Materiały źródłowe

• #1 Hepatocellular carcinoma: updates on epidemiology, surveillance, diagnosis and treatment

  https://dspace.kci.go.kr/handle/kci/2234212

  Hepatocellular carcinoma (HCC) is a major global burden, ranking as the third leading cause of cancer-related mortality. […] HCC due to chronic hepatitis B virus (HBV) or C virus (HCV) infection has decreased due to universal vaccination for HBV and effective antiviral therapy for both HBV and HCV, but HCC related to metabolic dysfunctionassociated steatotic liver disease and alcohol-associated liver disease is increasing. […] Biannual liver ultrasonography and serum -fetoprotein are the primary surveillance tools for early HCC detection among high-risk patients (e.g., cirrhosis, chronic HBV). […] Alternative surveillance tools such as blood-based biomarker panels and abbreviated magnetic resonance imaging (MRI) are being investigated. […] In this review article, we discuss the recent global epidemiology, risk factors, and HCC care continuum encompassing surveillance, diagnosis, staging, and treatments.

• #2 Hepatocellular Carcinoma: Surveillance, Diagnosis, Evaluation and Management

  https://www.mdpi.com/2072-6694/15/21/5118

  Hepatocellular carcinoma (HCC) is the most common primary liver cancer. High-risk patients should undergo semi-annual surveillance. Management of HCC is complex and requires multidisciplinary team evaluation and the consideration of patient’s goals of care. Early HCC is best managed by curative-intent treatment with liver resection, transplantation, or ablation. Intermediate-stage disease may be treated with transarterial therapies. Advanced-stage disease should be treated with systemic therapy. There are many therapies and therapy combinations currently under investigation. […] Hepatocellular carcinoma (HCC) ranks fourth in cancer-related deaths worldwide. Semiannual surveillance of the disease for patients with cirrhosis or hepatitis B virus allows for early detection with more favorable outcomes. The current underuse of surveillance programs demonstrates the need for intervention at both the patient and provider level.

• #3 Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide

  https://www.e-jlc.org/journal/view.php?number=557

  Despite a slowly decreasing trend in global age-standardized incidence rates of HCC since the late 1990s, the total number of HCC cases has been increasing owing to aging and population growth. […] In 2019, approximately 747,000 cases of HCC were reported worldwide, a 70% increase from 1990. […] While the global age-standardized incidence rates have been decreasing slowly since 2000, the rates have been increasing in countries with high sociodemographic indices since 1990. […] Chronic HBV infection is a major global health problem with high prevalence, that can lead to cirrhosis as well as HCC. […] Currently, the highest incidence and prevalence rates of HCC are observed in East Asia, North Africa, and Southeast Asia, regions where there is a higher prevalence of chronic HBV infection, contributing to over half of the global HCC cases.

• #4 Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide

  https://www.e-jlc.org/journal/view.php?number=557

  Despite a slowly decreasing trend in global age-standardized incidence rates of HCC since the late 1990s, the total number of HCC cases has been increasing owing to aging and population growth. […] In 2019, approximately 747,000 cases of HCC were reported worldwide, a 70% increase from 1990. […] While the global age-standardized incidence rates have been decreasing slowly since 2000, the rates have been increasing in countries with high sociodemographic indices since 1990. […] Chronic HBV infection is a major global health problem with high prevalence, that can lead to cirrhosis as well as HCC. […] Currently, the highest incidence and prevalence rates of HCC are observed in East Asia, North Africa, and Southeast Asia, regions where there is a higher prevalence of chronic HBV infection, contributing to over half of the global HCC cases.

• #5 Epidemiology and Surveillance for Hepatocellular Carcinoma: New Trends

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6986771/

  Hepatocellular carcinoma (HCC) burden is highest in East Asia and Africa, although its incidence and mortality are rapidly rising in the United States and Europe. […] Surveillance using ultrasound with or without alpha fetoprotein every 6 months has been associated with improved early detection and improved overall survival; however, limitations in implementation lead to a high proportion of HCC being detected at late stages in clinical practice. […] The worldwide incidence of HCC is heterogeneous because of the variable prevalence of underlying risk factors. It is estimated that 72% of cases occurs in Asia (more than 50% in China), 10% in Europe, 7.8% in Africa, 5.1% in North America, 4.6% Latin America and 0.5% in Oceania. […] Age-standardized mortality rates (ASMR) from HCC in 2018 are also highest in Eastern Asia (16.0) and Northern Africa (13.9) followed by South Eastern Asia (13.2).

• #6 Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide

  https://www.e-jlc.org/journal/view.php?number=557

  Approximately 80% of hepatocellular carcinoma (HCC) cases arise in sub-Saharan Africa and Eastern Asia, following a similarly high prevalence of chronic hepatitis B virus (HBV) carriers in these regions. […] The etiology and epidemiology of HCC have recently changed worldwide. […] Although HBV infection is the main contributor to HCC development, a slow but continuous decline in HBV infection rates has been reported since 1990. […] Owing to the widespread use of direct-acting antivirals, the incidence of hepatitis C virus-related HCC has remarkably decreased in Japan and European countries. […] In Korea, Taiwan, and Singapore, the incidence of HBV-related HCC has significantly decreased owing to vaccination against HBV. […] Globally, while HBV accounted for more than half of HCCs in 1990, this had decreased to 42% in 2019.

• #7 Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide

  https://www.e-jlc.org/journal/view.php?number=557

  The burden of HCC is expected to reach 22 million cases in the next 2 decades in this country. […] The incidence in Japan has dropped drastically with a significant reduction in the population infected by hepatitis C virus (HCV). […] Similarly, HCC incidence in China is declining owing to increasing vaccination against hepatitis B. […] In Korea, the age-standardized incidence of liver cancer significantly decreased from 28.9 in 1999 to 19.7 in 2014 and 16.1 in 2019. […] The age-standardized death rate from liver cancer notably declined from 24.7 in 1999 to 16.4 in 2014 and further to 11.5 in 2020. […] However, the annual crude incidence rate of liver cancer has risen over the last 2 decades, from 28.1 in 1999 to its peak at 32.8 in 2010 and 31-32 in 2015. […] In 2019, the Western Pacific region demonstrated the highest frequency of incident liver cancer cases (n=295,484), deaths (n=254,054), and disability-adjusted life-years (DALYs; 6.7 million).

• #8 Epidemiology of Hepatocellular Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7577946/

  Globally, hepatocellular carcinoma (HCC) is the dominant type of liver cancer, accounting for approximately 75% of the total. Incidence rates of HCC have been decreasing in some high-rate areas but increasing in many low-rate areas. In the interval between 1978 and 2012, HCC incidence declined in many Asian countries and Italy, but increased in India, the Americas, Oceania, and most European countries. In more recent years, however, the increase in some countries, such as the US, has abated, as rates in various subgroups have plateaued or declined. […] Prognosis of HCC is poor in all regions of the world. As a result, incidence and mortality rates are roughly equivalent. In 2018, the estimated global incidence rate of liver cancer per 100,000 person-years was 9.3 while the corresponding mortality rate was 8.5.

• #9 Epidemiology and Surveillance for Hepatocellular Carcinoma: New Trends

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6986771/

  Hepatocellular carcinoma (HCC) burden is highest in East Asia and Africa, although its incidence and mortality are rapidly rising in the United States and Europe. […] Surveillance using ultrasound with or without alpha fetoprotein every 6 months has been associated with improved early detection and improved overall survival; however, limitations in implementation lead to a high proportion of HCC being detected at late stages in clinical practice. […] The worldwide incidence of HCC is heterogeneous because of the variable prevalence of underlying risk factors. It is estimated that 72% of cases occurs in Asia (more than 50% in China), 10% in Europe, 7.8% in Africa, 5.1% in North America, 4.6% Latin America and 0.5% in Oceania. […] Age-standardized mortality rates (ASMR) from HCC in 2018 are also highest in Eastern Asia (16.0) and Northern Africa (13.9) followed by South Eastern Asia (13.2).

• #10 Epidemiology of Hepatocellular Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7577946/

  Globally, hepatocellular carcinoma (HCC) is the dominant type of liver cancer, accounting for approximately 75% of the total. Incidence rates of HCC have been decreasing in some high-rate areas but increasing in many low-rate areas. In the interval between 1978 and 2012, HCC incidence declined in many Asian countries and Italy, but increased in India, the Americas, Oceania, and most European countries. In more recent years, however, the increase in some countries, such as the US, has abated, as rates in various subgroups have plateaued or declined. […] Prognosis of HCC is poor in all regions of the world. As a result, incidence and mortality rates are roughly equivalent. In 2018, the estimated global incidence rate of liver cancer per 100,000 person-years was 9.3 while the corresponding mortality rate was 8.5.

• #11 Core Concepts – Surveillance for Hepatocellular Carcinoma – Evaluation, Staging, and Monitoring of Chronic Hepatitis C – Hepatitis C Online

  https://www.hepatitisc.uw.edu/go/evaluation-staging-monitoring/surveillance-hepatocellular-carcinoma/core-concept/all

  In 2020, hepatocellular carcinoma (HCC) was the seventh most common malignancy worldwide, with approximately 900,00 cases, and the second leading cause of cancer-related death. The rates of liver cancer are highest in Asia and in Northern Africa. Among all cases of liver cancer globally, the rates are much higher in males (14.1 per 100,000 people) than in females (5.2 per 100,000 people). […] In the United States, the National Cancer Institute (NCI) data for liver cancer combines liver and intrahepatic bile duct carcinoma. The annual reported rate of liver cancer in the United States has changed significantly in the past 30 years. In 2023, there were an estimated 41,210 new cases of liver and intrahepatic bile duct carcinoma reported in the United States, accounting for 2.1% of all new cancer cases. The significant increase in HCC incidence in the United States over the past 30 years has been largely attributable to HCV-related HCC. Rates of liver cancer in the United States show major differences based on sex, age, and race/ethnicity.

• #12 Core Concepts – Surveillance for Hepatocellular Carcinoma – Evaluation, Staging, and Monitoring of Chronic Hepatitis C – Hepatitis C Online

  https://www.hepatitisc.uw.edu/go/evaluation-staging-monitoring/surveillance-hepatocellular-carcinoma/core-concept/all

  In 2020, hepatocellular carcinoma (HCC) was the seventh most common malignancy worldwide, with approximately 900,00 cases, and the second leading cause of cancer-related death. The rates of liver cancer are highest in Asia and in Northern Africa. Among all cases of liver cancer globally, the rates are much higher in males (14.1 per 100,000 people) than in females (5.2 per 100,000 people). […] In the United States, the National Cancer Institute (NCI) data for liver cancer combines liver and intrahepatic bile duct carcinoma. The annual reported rate of liver cancer in the United States has changed significantly in the past 30 years. In 2023, there were an estimated 41,210 new cases of liver and intrahepatic bile duct carcinoma reported in the United States, accounting for 2.1% of all new cancer cases. The significant increase in HCC incidence in the United States over the past 30 years has been largely attributable to HCV-related HCC. Rates of liver cancer in the United States show major differences based on sex, age, and race/ethnicity.

• #13 Effect of Hepatocellular Carcinoma Surveillance Programmes on Overall Survival in a Mixed Cirrhotic UK Population: A Prospective, Longitudinal Cohort Study

  https://www.mdpi.com/2077-0383/10/13/2770

  Hepatocellular carcinoma (HCC) is the most common primary liver cancer and remains a major public health burden worldwide. Major increases have been reported in HCC incidence in the last 25 years, particularly in Europe and North America. In the UK, there has been a 63% increase in incidence and 55% increase in mortality from HCC over the past decade, which is highest in Scotland. Incidence rates for HCC are projected to rise by 38% (43% for males and 21% for females) in the UK by 2035, accompanied by a 58% rise in mortality. […] Cirrhosis is the main risk factor for HCC, with up to a third of patients developing HCC. Patients with cirrhosis have a 1 to 5.8% risk per year of developing HCC, but regular surveillance may allow early detection and increase access to potentially curative therapies. Five-year survival rates for early stage HCC is more than 70%, compared with less than 5% when diagnosed at an advanced stage. Most guidelines recommend surveillance is undertaken by 6-monthly ultrasound (US) scan, which has a sensitivity of 58–89% and specificity greater than 90%, and some centres also incorporate alpha-fetoprotein (AFP) measurement.

• #14 Effect of Hepatocellular Carcinoma Surveillance Programmes on Overall Survival in a Mixed Cirrhotic UK Population: A Prospective, Longitudinal Cohort Study

  https://www.mdpi.com/2077-0383/10/13/2770

  Hepatocellular carcinoma (HCC) is the most common primary liver cancer and remains a major public health burden worldwide. Major increases have been reported in HCC incidence in the last 25 years, particularly in Europe and North America. In the UK, there has been a 63% increase in incidence and 55% increase in mortality from HCC over the past decade, which is highest in Scotland. Incidence rates for HCC are projected to rise by 38% (43% for males and 21% for females) in the UK by 2035, accompanied by a 58% rise in mortality. […] Cirrhosis is the main risk factor for HCC, with up to a third of patients developing HCC. Patients with cirrhosis have a 1 to 5.8% risk per year of developing HCC, but regular surveillance may allow early detection and increase access to potentially curative therapies. Five-year survival rates for early stage HCC is more than 70%, compared with less than 5% when diagnosed at an advanced stage. Most guidelines recommend surveillance is undertaken by 6-monthly ultrasound (US) scan, which has a sensitivity of 58–89% and specificity greater than 90%, and some centres also incorporate alpha-fetoprotein (AFP) measurement.

• #15 Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide

  https://www.e-jlc.org/journal/view.php?number=557

  The burden of HCC is expected to reach 22 million cases in the next 2 decades in this country. […] The incidence in Japan has dropped drastically with a significant reduction in the population infected by hepatitis C virus (HCV). […] Similarly, HCC incidence in China is declining owing to increasing vaccination against hepatitis B. […] In Korea, the age-standardized incidence of liver cancer significantly decreased from 28.9 in 1999 to 19.7 in 2014 and 16.1 in 2019. […] The age-standardized death rate from liver cancer notably declined from 24.7 in 1999 to 16.4 in 2014 and further to 11.5 in 2020. […] However, the annual crude incidence rate of liver cancer has risen over the last 2 decades, from 28.1 in 1999 to its peak at 32.8 in 2010 and 31-32 in 2015. […] In 2019, the Western Pacific region demonstrated the highest frequency of incident liver cancer cases (n=295,484), deaths (n=254,054), and disability-adjusted life-years (DALYs; 6.7 million).

• #16 Epidemiology and Surveillance for Hepatocellular Carcinoma: New Trends

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6986771/

  The large majority of HCC cases occur in the setting of chronic liver disease, with cirrhosis being the primary risk factor for HCC independent of liver disease etiology. […] Hepatitis B virus (HBV) is the leading cause of incident cases of liver cancer and deaths in the world (33%), followed by alcohol (30%), hepatitis C virus (HCV) (21%) and other causes (16%). […] Implementation of infant HBV immunization programs in many countries in East Asia are expected to lower HBV-related HCC in the future. […] There is a growing evidence that non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) contribute to HCC development, and this is becoming an increasing common cause of HCC worldwide. […] Patients with cirrhosis have a differential distribution of cases by several sociodemographic factors. HCC has a strong male predominance for incidence and mortality, with a male-to-female ratio exceeding 2.5 for both. […] The global incidence and mortality of HCC is rising, particularly in the United States and Europe. Given the strong association between early detection and survival, improving uptake and performance of HCC surveillance must be defined as a priority for our community.

• #17 Core Concepts – Surveillance for Hepatocellular Carcinoma – Evaluation, Staging, and Monitoring of Chronic Hepatitis C – Hepatitis C Online

  https://www.hepatitisc.uw.edu/go/evaluation-staging-monitoring/surveillance-hepatocellular-carcinoma/core-concept/all

  In 2020, hepatocellular carcinoma (HCC) was the seventh most common malignancy worldwide, with approximately 900,00 cases, and the second leading cause of cancer-related death. The rates of liver cancer are highest in Asia and in Northern Africa. Among all cases of liver cancer globally, the rates are much higher in males (14.1 per 100,000 people) than in females (5.2 per 100,000 people). […] In the United States, the National Cancer Institute (NCI) data for liver cancer combines liver and intrahepatic bile duct carcinoma. The annual reported rate of liver cancer in the United States has changed significantly in the past 30 years. In 2023, there were an estimated 41,210 new cases of liver and intrahepatic bile duct carcinoma reported in the United States, accounting for 2.1% of all new cancer cases. The significant increase in HCC incidence in the United States over the past 30 years has been largely attributable to HCV-related HCC. Rates of liver cancer in the United States show major differences based on sex, age, and race/ethnicity.

• #18 Hepatocellular carcinoma: Epidemiology, pathogenesis and surveillance – implications for sub-Saharan Africa

  http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S0256-95742018000900011

  The incidence and mortality of HCC is generally higher in males than in females, with an incidence ratio of 2:1 to 6:1, depending on the region. In males, HCC is the most commonly diagnosed cancer in 10 SSA countries (Mauritania, Republic of the Gambia, Mali, Burkina Faso, Cameroon, South Sudan, Democratic Republic of the Congo, Angola, Mozambique) and the most common cause of cancer deaths in most countries of western, eastern and central SSA. […] Currently, the incidence of HCC is underestimated in many countries, particularly developing countries, which is partially due to decreased access to care and poor reporting of health data. […] The age at the time of HCC diagnosis also varies based on aetiology of HCC and by region. In Africa, patients with HCC present at a younger age than in other regions of the world; therefore, surveillance of Africans with chronic HBV who are at risk for HCC is recommended from the age of 20 years.

• #19 Addressing the worldwide hepatocellular carcinoma: epidemiology, prevention and management – Samant – Journal of Gastrointestinal Oncology

  https://jgo.amegroups.org/article/view/36868/html

  The high mortality ratio of liver cancer made it fourth leading cause of cancer death globally. […] The overall incidence of HCC is heterogeneous probably due to variation in prevalence of hepatitis virus and environmental factors. […] In United states, incidence of HCC has tripled over the last four decades, possible from maturity of chronic hepatitis C patient pool. […] Burden of HCC is expected to reach 22 million cases in the next two decades. […] Population-based studies in the US have shown distribution of HCC differs amongst various racial and ethnic groups like Asians/Pacific Islanders (APIs) have higher rates of HCC compared with other Caucasians and Hispanics. […] American Association of the Study of Liver Diseases (AASLD) recommends enrollment in HCC surveillance program for all patients with cirrhosis regardless of etiology and high-risk chronic HBV carriers with ultrasound (US) with or without alpha-fetoprotein (AFP).

• #20 Epidemiology and Surveillance for Hepatocellular Carcinoma: New Trends

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6986771/

  The large majority of HCC cases occur in the setting of chronic liver disease, with cirrhosis being the primary risk factor for HCC independent of liver disease etiology. […] Hepatitis B virus (HBV) is the leading cause of incident cases of liver cancer and deaths in the world (33%), followed by alcohol (30%), hepatitis C virus (HCV) (21%) and other causes (16%). […] Implementation of infant HBV immunization programs in many countries in East Asia are expected to lower HBV-related HCC in the future. […] There is a growing evidence that non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) contribute to HCC development, and this is becoming an increasing common cause of HCC worldwide. […] Patients with cirrhosis have a differential distribution of cases by several sociodemographic factors. HCC has a strong male predominance for incidence and mortality, with a male-to-female ratio exceeding 2.5 for both. […] The global incidence and mortality of HCC is rising, particularly in the United States and Europe. Given the strong association between early detection and survival, improving uptake and performance of HCC surveillance must be defined as a priority for our community.

• #21 Core Concepts – Surveillance for Hepatocellular Carcinoma – Evaluation, Staging, and Monitoring of Chronic Hepatitis C – Hepatitis C Online

  https://www.hepatitisc.uw.edu/go/evaluation-staging-monitoring/surveillance-hepatocellular-carcinoma/core-concept/all

  Cirrhosis from any cause is the primary risk factor for HCC: approximately 80% of cases of HCC occur in individuals with cirrhosis and the risk of developing HCC increases with fibrosis stage. The most common underlying etiologies for HCC include chronic viral hepatitis (B or C), alcoholic liver disease, and metabolic-associated steatotic liver disease (MASLD). Chronic hepatitis B or C accounted for more than two-thirds of the global deaths from primary liver cancer each year between 1990-2019. […] The rationale for conducting HCC surveillance is that regular screening of asymptomatic persons at risk for HCC may detect tumors at an early stage when potentially curative treatment can be offered. Early detection of HCC is particularly important, given the very poor prognosis with lesions that are detected late.

• #22 Hepatocellular carcinoma surveillance: current practice and future directions

  https://www.oaepublish.com/articles/2394-5079.2021.131

  Patients with cirrhosis have HCC incident rates ranging from 1% to 8% annually and comprise more than 80% of newly diagnosed HCC cases. Therefore, all major guidelines recommend HCC surveillance in patients with cirrhosis, except in patients with transplant-ineligible Child-Pugh class C cirrhosis, as HCC surveillance will not provide survival benefit for them due to the competing risk of death from liver failure. […] Despite the absence of large-scale, generalizable RCT data, there is a clear association between receipt of HCC surveillance and improved outcomes. In general, surveillance is considered beneficial to an individual if it provides an increase in life expectancy of around 100 days, and cost-effective if surveillance costs $50,000 per year of life gained. A meta-analysis of 47 studies with 15,158 patients demonstrated that HCC surveillance was associated with significantly higher rates of early detection, curative treatments, and prolonged survival even after adjusting for lead-time bias.

• #23 Epidemiology and Surveillance for Hepatocellular Carcinoma: New Trends

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6986771/

  The large majority of HCC cases occur in the setting of chronic liver disease, with cirrhosis being the primary risk factor for HCC independent of liver disease etiology. […] Hepatitis B virus (HBV) is the leading cause of incident cases of liver cancer and deaths in the world (33%), followed by alcohol (30%), hepatitis C virus (HCV) (21%) and other causes (16%). […] Implementation of infant HBV immunization programs in many countries in East Asia are expected to lower HBV-related HCC in the future. […] There is a growing evidence that non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) contribute to HCC development, and this is becoming an increasing common cause of HCC worldwide. […] Patients with cirrhosis have a differential distribution of cases by several sociodemographic factors. HCC has a strong male predominance for incidence and mortality, with a male-to-female ratio exceeding 2.5 for both. […] The global incidence and mortality of HCC is rising, particularly in the United States and Europe. Given the strong association between early detection and survival, improving uptake and performance of HCC surveillance must be defined as a priority for our community.

• #24 Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide

  https://www.e-jlc.org/journal/view.php?number=557

  Despite a slowly decreasing trend in global age-standardized incidence rates of HCC since the late 1990s, the total number of HCC cases has been increasing owing to aging and population growth. […] In 2019, approximately 747,000 cases of HCC were reported worldwide, a 70% increase from 1990. […] While the global age-standardized incidence rates have been decreasing slowly since 2000, the rates have been increasing in countries with high sociodemographic indices since 1990. […] Chronic HBV infection is a major global health problem with high prevalence, that can lead to cirrhosis as well as HCC. […] Currently, the highest incidence and prevalence rates of HCC are observed in East Asia, North Africa, and Southeast Asia, regions where there is a higher prevalence of chronic HBV infection, contributing to over half of the global HCC cases.

• #25 Epidemiology of Hepatocellular Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7577946/

  The wide variability in incidence of HCC by geographic region, age, sex and race/ethnicity is largely, but not entirely, related to the prevalence, and age at acquisition, of major risk factors. […] HBV and HCV remain the most important global risk factors for HCC. However, the prevalence of both factors should decline in the coming years due to HBV vaccination of newborns, and more effective treatment of both HBV and HCV carriers. The prevalence of NAFLD/NASH is increasing and may soon overtake viral factors as the major cause of HCC globally. Excessive alcoholic consumption also remains an important risk factor. Due to climate change, so AFB1 could become a more dominant risk factor in the coming decades. These changing trends suggest that more effort needs to be focused on combating obesity and diabetes to decrease the incidence of NAFLD, and more effective strategies to control alcohol use and mycotoxin growth need to be implemented.

• #26 Epidemiology of Hepatocellular Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7577946/

  Liver cancer is a major contributor to the worlds cancer burden and incidence rates have increased in many countries in recent decades. As the principal histologic type of liver cancer, hepatocellular carcinoma (HCC) is responsible for the great majority of liver cancer diagnoses and deaths. Hepatitis B virus (HBV) and hepatitis C virus (HCV) remain, at present, the most important global risk factors for HCC, but it is likely their importance will decline in the coming years. The effect of HBV vaccination of newborns, already seen in young adults in some countries, will be more notable as vaccinated cohorts age. In addition, effective treatments for chronic infections with both HBV and HCV should contribute to declines in the rates of viral-associated HCC. Unfortunately, the prevalence of metabolic risk factors for HCC, including metabolic syndrome, obesity, type II diabetes and non-alcoholic fatty liver disease (NAFLD) are increasing and may jointly become the major cause of HCC globally. Excessive alcoholic consumption also remains an intractable risk factor, as does aflatoxin contamination of food crops in some parts of the world. While significant efforts in early diagnosis and better treatment are certainly needed for HCC, primary prevention efforts aimed at decreasing the prevalence and obesity and diabetes and controlling mycotoxin growth, and are just as urgently required.

• #27 Epidemiology of Hepatocellular Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7577946/

  Liver cancer is a major contributor to the worlds cancer burden and incidence rates have increased in many countries in recent decades. As the principal histologic type of liver cancer, hepatocellular carcinoma (HCC) is responsible for the great majority of liver cancer diagnoses and deaths. Hepatitis B virus (HBV) and hepatitis C virus (HCV) remain, at present, the most important global risk factors for HCC, but it is likely their importance will decline in the coming years. The effect of HBV vaccination of newborns, already seen in young adults in some countries, will be more notable as vaccinated cohorts age. In addition, effective treatments for chronic infections with both HBV and HCV should contribute to declines in the rates of viral-associated HCC. Unfortunately, the prevalence of metabolic risk factors for HCC, including metabolic syndrome, obesity, type II diabetes and non-alcoholic fatty liver disease (NAFLD) are increasing and may jointly become the major cause of HCC globally. Excessive alcoholic consumption also remains an intractable risk factor, as does aflatoxin contamination of food crops in some parts of the world. While significant efforts in early diagnosis and better treatment are certainly needed for HCC, primary prevention efforts aimed at decreasing the prevalence and obesity and diabetes and controlling mycotoxin growth, and are just as urgently required.

• #28 Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide

  https://www.e-jlc.org/journal/view.php?number=557

  Notably, in Taiwan, the mortality rate from HCC significantly dropped among individuals aged 5 to 29 years, from 0.81 deaths per 100,000 to 0.05 per 100,000, during 2001-2004, among those born in 1977-1980, attributed to the immunization campaign in 1984. […] Similarly, Hong Kong has witnessed a significant decline in HCC incidence across all age groups over the past 25 years, partly due to a decline in HBV infection rates since the introduction of universal HBV vaccination in 1988. […] According to the Global Burden of Disease study, there are temporal and geographical differences in HCC etiologies. […] Clearly, there was a transition from chronic viral hepatitis to a non-viral etiology between 1990 and 2019. […] In Korea, the hepatitis B surface antigen (HBsAg) positivity rates were high, exceeding 8% in the 1980s.

• #29 Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide

  https://www.e-jlc.org/journal/view.php?number=557

  Notably, in Taiwan, the mortality rate from HCC significantly dropped among individuals aged 5 to 29 years, from 0.81 deaths per 100,000 to 0.05 per 100,000, during 2001-2004, among those born in 1977-1980, attributed to the immunization campaign in 1984. […] Similarly, Hong Kong has witnessed a significant decline in HCC incidence across all age groups over the past 25 years, partly due to a decline in HBV infection rates since the introduction of universal HBV vaccination in 1988. […] According to the Global Burden of Disease study, there are temporal and geographical differences in HCC etiologies. […] Clearly, there was a transition from chronic viral hepatitis to a non-viral etiology between 1990 and 2019. […] In Korea, the hepatitis B surface antigen (HBsAg) positivity rates were high, exceeding 8% in the 1980s.

• #30 Epidemiology of Hepatocellular Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7577946/

  Liver cancer is a major contributor to the worlds cancer burden and incidence rates have increased in many countries in recent decades. As the principal histologic type of liver cancer, hepatocellular carcinoma (HCC) is responsible for the great majority of liver cancer diagnoses and deaths. Hepatitis B virus (HBV) and hepatitis C virus (HCV) remain, at present, the most important global risk factors for HCC, but it is likely their importance will decline in the coming years. The effect of HBV vaccination of newborns, already seen in young adults in some countries, will be more notable as vaccinated cohorts age. In addition, effective treatments for chronic infections with both HBV and HCV should contribute to declines in the rates of viral-associated HCC. Unfortunately, the prevalence of metabolic risk factors for HCC, including metabolic syndrome, obesity, type II diabetes and non-alcoholic fatty liver disease (NAFLD) are increasing and may jointly become the major cause of HCC globally. Excessive alcoholic consumption also remains an intractable risk factor, as does aflatoxin contamination of food crops in some parts of the world. While significant efforts in early diagnosis and better treatment are certainly needed for HCC, primary prevention efforts aimed at decreasing the prevalence and obesity and diabetes and controlling mycotoxin growth, and are just as urgently required.

• #31 Epidemiology and Surveillance for Hepatocellular Carcinoma: New Trends

  https://pmc.ncbi.nlm.nih.gov/articles/PMC6986771/

  The large majority of HCC cases occur in the setting of chronic liver disease, with cirrhosis being the primary risk factor for HCC independent of liver disease etiology. […] Hepatitis B virus (HBV) is the leading cause of incident cases of liver cancer and deaths in the world (33%), followed by alcohol (30%), hepatitis C virus (HCV) (21%) and other causes (16%). […] Implementation of infant HBV immunization programs in many countries in East Asia are expected to lower HBV-related HCC in the future. […] There is a growing evidence that non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) contribute to HCC development, and this is becoming an increasing common cause of HCC worldwide. […] Patients with cirrhosis have a differential distribution of cases by several sociodemographic factors. HCC has a strong male predominance for incidence and mortality, with a male-to-female ratio exceeding 2.5 for both. […] The global incidence and mortality of HCC is rising, particularly in the United States and Europe. Given the strong association between early detection and survival, improving uptake and performance of HCC surveillance must be defined as a priority for our community.

• #32 Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide

  https://www.e-jlc.org/journal/view.php?number=557

  In contrast, the proportion of patients with alcoholic- and nonalcoholic steatohepatitis (NASH) increased from 13% to 18% and from 5% to 6%, respectively. […] NASH-related HCC has characteristics that differ from those of virus-associated HCC. […] Compared with other etiologies, patients with NASH-associated HCC are older, have a higher body mass index, and have higher rates of type 2 diabetes mellitus, hypertension, hyperlipidemia, and cardiovascular disease. […] Nonalcoholic fatty liver disease (NAFLD)-associated HCC is also known to develop in the absence of cirrhosis, unlike alcohol-related and autoimmune liver diseases. […] Because patients with NAFLD usually have diabetes or obesity, surveying this population is challenging. […] Optimal selection of the target population and surveillance tools among patients with NAFLD needs to be determined.

• #33 Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide

  https://www.e-jlc.org/journal/view.php?number=557

  In contrast, the proportion of patients with alcoholic- and nonalcoholic steatohepatitis (NASH) increased from 13% to 18% and from 5% to 6%, respectively. […] NASH-related HCC has characteristics that differ from those of virus-associated HCC. […] Compared with other etiologies, patients with NASH-associated HCC are older, have a higher body mass index, and have higher rates of type 2 diabetes mellitus, hypertension, hyperlipidemia, and cardiovascular disease. […] Nonalcoholic fatty liver disease (NAFLD)-associated HCC is also known to develop in the absence of cirrhosis, unlike alcohol-related and autoimmune liver diseases. […] Because patients with NAFLD usually have diabetes or obesity, surveying this population is challenging. […] Optimal selection of the target population and surveillance tools among patients with NAFLD needs to be determined.

• #34 Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide

  https://www.e-jlc.org/journal/view.php?number=557

  The prevalence of NAFLD-related HCC increased from 2.6% (1995-1999) to 19.5% (2010-2014) in a French study with 323 patients with HCC who received liver resection at two centers between 1995 and 2014. […] However, with increasing numbers of patients with NAFLD, estimated to be 243.7 million currently, and in the near future due to aging population, the prevalence of NAFLD-related HCC is projected to rise from 14,090 cases in 2016 to 26,240 cases by 2030.

• #35 Changing etiology and epidemiology of hepatocellular carcinoma: Asia and worldwide

  https://www.e-jlc.org/journal/view.php?number=557

  The prevalence of NAFLD-related HCC increased from 2.6% (1995-1999) to 19.5% (2010-2014) in a French study with 323 patients with HCC who received liver resection at two centers between 1995 and 2014. […] However, with increasing numbers of patients with NAFLD, estimated to be 243.7 million currently, and in the near future due to aging population, the prevalence of NAFLD-related HCC is projected to rise from 14,090 cases in 2016 to 26,240 cases by 2030.

• #36 Epidemiology of Hepatocellular Carcinoma

  https://pmc.ncbi.nlm.nih.gov/articles/PMC7577946/

  The wide variability in incidence of HCC by geographic region, age, sex and race/ethnicity is largely, but not entirely, related to the prevalence, and age at acquisition, of major risk factors. […] HBV and HCV remain the most important global risk factors for HCC. However, the prevalence of both factors should decline in the coming years due to HBV vaccination of newborns, and more effective treatment of both HBV and HCV carriers. The prevalence of NAFLD/NASH is increasing and may soon overtake viral factors as the major cause of HCC globally. Excessive alcoholic consumption also remains an important risk factor. Due to climate change, so AFB1 could become a more dominant risk factor in the coming decades. These changing trends suggest that more effort needs to be focused on combating obesity and diabetes to decrease the incidence of NAFLD, and more effective strategies to control alcohol use and mycotoxin growth need to be implemented.

• #37 Imaging Techniques for the Surveillance, Diagnosis, and Staging of Hepatocellular Carcinoma | Effective Health Care (EHC) Program

  https://effectivehealthcare.ahrq.gov/products/liver-cancer/research-protocol

  The American Association for the Study of Liver Diseases (AASLD) has identified the following groups as being at high risk for developing HCC and recommends that these population groups undergo surveillance: Asian male HBV carriers over age 40, Asian female HBV carriers over age 50, HBV carriers with a family history of HCC, African/North American black HBV carriers, HBV or HCV carriers with cirrhosis, all individuals with other causes for cirrhosis (including alcoholic cirrhosis), and patients with stage 4 primary biliary cirrhosis. […] Surveillance is the use of periodic testing to monitor lesions in the liver that give rise to a clinical suspicion of HCC. The diagnosis phase involves the use of additional tests (radiological and/or histopathological) to confirm that the lesion detected in the liver is HCC. Staging of HCC is based on the size and number of lesions and helps to determine appropriate treatments.

• #38 Imaging Techniques for the Surveillance, Diagnosis, and Staging of Hepatocellular Carcinoma | Effective Health Care (EHC) Program

  https://effectivehealthcare.ahrq.gov/products/liver-cancer/research-protocol

  In surveillance, the objective is early detection, and the use of imaging techniques for surveillance has been proposed as a means of identifying HCC at earlier stages in high-risk patients, such as those with cirrhosis. […] Surveillance strategies for HCC use available imaging techniques alone or in a particular sequence. For example, some centers use ultrasound (US) alternatively with either computed tomography (CT) or magnetic resonance imaging (MRI) every 6 months. […] In addition to imaging tests, biomarkers for HCC have also been used in surveillance and diagnosis. Alpha-fetoprotein is the most widely used serological marker for HCC, but it is recommended only as an adjunct to imaging. […] There is clinical uncertainty about which imaging technique to use to diagnose and stage HCC. It is possible to confirm the diagnosis with the availability of either a combination of tests or specific sequences of tests; however, the test performance of these combinations and sequences against a single test should be evaluated before employing them in regular clinical practice. […] Finally, other factors, including risk factors for HCC and disease characteristics like etiology, tumor size, and level of liver dysfunction may impact the diagnostic accuracy or clinical utility of various imaging strategies.

• #39

  https://www.hksmp.com/journals/gfm/article/view/439

  Hepatocellular carcinoma (HCC) surveillance of individuals with cirrhosis or other conditions that confer a high risk of HCC development is essential for early detection and improved overall survival. […] HCC surveillance is a complex process, with failure at any step in the process contributing to a gap between its efficacy and effectiveness. […] Biannual ultrasonography with or without alpha-fetoprotein is widely recommended as the standard method for HCC surveillance, but it has limited sensitivity in early disease and may be inadequate in certain individuals. […] The strong association between early detection and improved survival has been the impetus behind professional society guidelines for HCC surveillance among at-risk individuals, including those with cirrhosis. […] The American Association for the Study of Liver Disease (AASLD), the European Association for the Study of Liver (EASL) and Asian Pacific Association for the Study of Liver (APASL) recommend HCC surveillance for patients with cirrhosis with liver ultrasound with or without serum alpha-fetoprotein (AFP) test every 6 months.

• #40 Core Concepts – Surveillance for Hepatocellular Carcinoma – Evaluation, Staging, and Monitoring of Chronic Hepatitis C – Hepatitis C Online

  https://www.hepatitisc.uw.edu/go/evaluation-staging-monitoring/surveillance-hepatocellular-carcinoma/core-concept/all

  Cirrhosis from any cause is the primary risk factor for HCC: approximately 80% of cases of HCC occur in individuals with cirrhosis and the risk of developing HCC increases with fibrosis stage. The most common underlying etiologies for HCC include chronic viral hepatitis (B or C), alcoholic liver disease, and metabolic-associated steatotic liver disease (MASLD). Chronic hepatitis B or C accounted for more than two-thirds of the global deaths from primary liver cancer each year between 1990-2019. […] The rationale for conducting HCC surveillance is that regular screening of asymptomatic persons at risk for HCC may detect tumors at an early stage when potentially curative treatment can be offered. Early detection of HCC is particularly important, given the very poor prognosis with lesions that are detected late.

• #41

  https://www.hksmp.com/journals/gfm/article/view/439

  Hepatocellular carcinoma (HCC) surveillance of individuals with cirrhosis or other conditions that confer a high risk of HCC development is essential for early detection and improved overall survival. […] HCC surveillance is a complex process, with failure at any step in the process contributing to a gap between its efficacy and effectiveness. […] Biannual ultrasonography with or without alpha-fetoprotein is widely recommended as the standard method for HCC surveillance, but it has limited sensitivity in early disease and may be inadequate in certain individuals. […] The strong association between early detection and improved survival has been the impetus behind professional society guidelines for HCC surveillance among at-risk individuals, including those with cirrhosis. […] The American Association for the Study of Liver Disease (AASLD), the European Association for the Study of Liver (EASL) and Asian Pacific Association for the Study of Liver (APASL) recommend HCC surveillance for patients with cirrhosis with liver ultrasound with or without serum alpha-fetoprotein (AFP) test every 6 months.

• #42

  https://www.hksmp.com/journals/gfm/article/view/439

  This systematic review and meta-analysis highlighted that HCC surveillance continued to be underutilized, with only 1 in 4 patients with cirrhosis receiving surveillance. […] The intended benefits of entering a patient into a surveillance programme are clear. […] The aim is to detect early cancers in at-risk groups and enable potentially curative treatments for this group of patients. […] HCC surveillance is associated with significant improvements in early tumour detection, receipt of curative therapy, and overall survival in patients with cirrhosis. […] When considering the risk versus benefits of HCC surveillance we must consider the possible harm to the patient. […] Such concerns include false-positive testing resulting in unnecessary and risk-associated procedures such as liver biopsy, overdiagnosis of HCC among patients with cirrhosis, as well as false-negative investigations resulting in delayed diagnosis of HCC.

• #43 NHS England » Hepatocellular carcinoma surveillance: minimum standards

  https://www.england.nhs.uk/long-read/hepatocellular-carcinoma-surveillance-minimum-standards/

  On average, patients in regular ultrasound surveillance have their cancers detected earlier and receive more curative intent treatment. […] Regular 6-monthly surveillance of adults with cirrhosis or advanced fibrosis and conditions including hepatitis B and hepatitis C (as set out in the eligibility criteria below) increases the chance of detecting HCC early so that patients can benefit from potentially curative treatment, and improved chances of survival. […] With a growing array of effective treatments, all patients with early-stage cirrhosis who would be fit for and benefit from treatment should be offered enrolment into liver surveillance. […] The above criteria set a minimum standard for patients who should be offered HCC surveillance. Providers may choose to offer HCC surveillance to additional patients in line with local protocols, but these protocols should be published and implemented consistently.

• #44 Hepatocellular carcinoma surveillance: current practice and future directions

  https://www.oaepublish.com/articles/2394-5079.2021.131

  Patients with cirrhosis have HCC incident rates ranging from 1% to 8% annually and comprise more than 80% of newly diagnosed HCC cases. Therefore, all major guidelines recommend HCC surveillance in patients with cirrhosis, except in patients with transplant-ineligible Child-Pugh class C cirrhosis, as HCC surveillance will not provide survival benefit for them due to the competing risk of death from liver failure. […] Despite the absence of large-scale, generalizable RCT data, there is a clear association between receipt of HCC surveillance and improved outcomes. In general, surveillance is considered beneficial to an individual if it provides an increase in life expectancy of around 100 days, and cost-effective if surveillance costs $50,000 per year of life gained. A meta-analysis of 47 studies with 15,158 patients demonstrated that HCC surveillance was associated with significantly higher rates of early detection, curative treatments, and prolonged survival even after adjusting for lead-time bias.

• #45

  https://www.hksmp.com/journals/gfm/article/view/439

  Hepatocellular carcinoma (HCC) surveillance of individuals with cirrhosis or other conditions that confer a high risk of HCC development is essential for early detection and improved overall survival. […] HCC surveillance is a complex process, with failure at any step in the process contributing to a gap between its efficacy and effectiveness. […] Biannual ultrasonography with or without alpha-fetoprotein is widely recommended as the standard method for HCC surveillance, but it has limited sensitivity in early disease and may be inadequate in certain individuals. […] The strong association between early detection and improved survival has been the impetus behind professional society guidelines for HCC surveillance among at-risk individuals, including those with cirrhosis. […] The American Association for the Study of Liver Disease (AASLD), the European Association for the Study of Liver (EASL) and Asian Pacific Association for the Study of Liver (APASL) recommend HCC surveillance for patients with cirrhosis with liver ultrasound with or without serum alpha-fetoprotein (AFP) test every 6 months.

• #46 Hepatocellular Carcinoma (HCC) Guidelines: Guidelines Summary

  https://emedicine.medscape.com/article/197319-guidelines

  Guidelines for the screening, surveillance, diagnosis, and treatment of hepatocellular carcinoma (HCC) have been issued by the following organizations: American Association for the Study of Liver Diseases (AASLD), National Comprehensive Cancer Network (NCCN), American College of Gastroenterology (ACG), European Association for the Study of the Liver (EASL)European Organisation for Research and Treatment of Cancer (EORTC), European Society for Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO), American Gastroenterological Association (AGA), International Stereotactic Radiosurgery Society. […] In its 2018 guidelines for the management of HCC, the AASLD recommends surveillance for HCC in adults with cirrhosis, because it improves overall survival. Surveillance should be conducted with ultrasonography (US), with or without alpha-fetoprotein (AFP) testing, every 6 months. Computed tomography (CT) and magnetic resonance imaging (MRI) are not recommended as the primary modality for surveillance but may be used in select patients with a high likelihood of having an inadequate US or if US is attempted but inadequate.

• #47 Hepatocellular Carcinoma (HCC) Guidelines: Guidelines Summary

  https://emedicine.medscape.com/article/197319-guidelines

  Guidelines for the screening, surveillance, diagnosis, and treatment of hepatocellular carcinoma (HCC) have been issued by the following organizations: American Association for the Study of Liver Diseases (AASLD), National Comprehensive Cancer Network (NCCN), American College of Gastroenterology (ACG), European Association for the Study of the Liver (EASL)European Organisation for Research and Treatment of Cancer (EORTC), European Society for Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO), American Gastroenterological Association (AGA), International Stereotactic Radiosurgery Society. […] In its 2018 guidelines for the management of HCC, the AASLD recommends surveillance for HCC in adults with cirrhosis, because it improves overall survival. Surveillance should be conducted with ultrasonography (US), with or without alpha-fetoprotein (AFP) testing, every 6 months. Computed tomography (CT) and magnetic resonance imaging (MRI) are not recommended as the primary modality for surveillance but may be used in select patients with a high likelihood of having an inadequate US or if US is attempted but inadequate.

• #48

  https://www.hksmp.com/journals/gfm/article/view/439

  This strategy has been shown to increase early detection and improve survival in a large randomized controlled trial (RCT) in hepatitis B virus (HBV) patients and several cohort studies in patients with cirrhosis. […] All major guidelines recommend surveillance of high-risk groups. […] These groups include most patients with cirrhosis but not those with advanced liver failure unless they are on the transplant waiting list. […] Patients with non-cirrhotic HBV infection and patients with HCV infection and advanced fibrosis are also recommended to have surveillance due to high incidence of HCC in these groups. […] Most HCC cases are attributable to chronic HBV and/or HCV infection, especially in the setting of advanced fibrosis and established cirrhosis. […] There is regional variation in the importance of different risk factors for cirrhosis.

• #49 Hepatocellular Carcinoma (HCC) Guidelines: Guidelines Summary

  https://emedicine.medscape.com/article/197319-guidelines

  Although the risk of HCC is reduced in patients with hepatitis C virus (HCV) infection who have a sustained virologic response after direct-acting antiviral therapy, the risk is not eliminated, and continuing surveillance is recommended. However, the AASLD advises that risk for HCC is too low to justify surveillance in patients with HCV infection or nonalcoholic fatty liver disease (NAFLD) who do not have cirrhosis. The AASLD recommends not performing surveillance of patients with Child-Pugh class C cirrhosis unless they are on the transplant waiting list, given their low anticipated survival. […] Similarly, the NCCN guidelines recommend screening with US, with or without AFP testing, every 6 months in patients with cirrhosis due to any of the following: Hepatitis B or C, Alcohol, Genetic hemochromatosis, NAFLD, Stage 4 primary biliary cholangitis, Alpha-1-antitrypsin deficiency, Other causes.

• #50

  https://www.hksmp.com/journals/gfm/article/view/439

  Liver ultrasonography every 6 months with or without serum AFP level is widely recommended as the standard modality for HCC surveillance. […] There is no universal agreement about adding AFP to ultrasound (US) in HCC screening. […] A prospective surveillance study at a tertiary care centre compared the HCC detection rate of US and MRI in patients with cirrhosis who are at high risk for HCC. […] The study concluded that screening using MRI with liver-specific contrast resulted in a higher HCC detection rate and lower false-positive findings compared with US. […] Most guidelines recommend ultrasonographic screening every 6 months. […] Reports of HCC surveillance in patients with cirrhosis consistently show poor uptake and adherence to the published guidance. […] The study showed that adherence to HCC surveillance guidelines has remained poor over time.

• #51

  https://www.hksmp.com/journals/gfm/article/view/439

  In Japan, around 70% of cases diagnosed with HCC over the last 10 years were HCV antibody (HCV-Ab)-positive. […] A retrospective epidemiological study from Egypt on 1313 patients found that HCV Ab was detected in 91.32% of the studied patients. […] Although only a minority of patients with non-alcoholic fatty liver disease (NAFLD) progress to cirrhosis, NAFLD has become the commonest cause of cirrhosis in western nations. […] In Northern England, the number of HCC cases referred to the tertiary centre in Newcastle upon Tyne has increased over tenfold with NAFLD accounting for 35% of cases. […] The incidence of HCC in patients with non-cirrhotic NAFLD is very low. Hence, no guidelines recommend screening of HCC in patients with NAFLD without cirrhosis. […] All international societies agree that US is the cornerstone of HCC screening, due to its widespread availability, low costs, lack of ionizing radiation, repeatability, and well-tolerability by patients.

• #52 Hepatocellular carcinoma surveillance — utilization, barriers and the impact of changing aetiology | Nature Reviews Gastroenterology & Hepatology

  https://www.nature.com/articles/s41575-023-00818-8

  Hepatocellular carcinoma (HCC) is the third leading cause of cancer death worldwide. Surveillance for HCC is critical for early detection and treatment, but fewer than one-quarter of individuals at risk of HCC undergo surveillance. […] Multiple failures across the screening process contribute to the underutilization of surveillance, including limited disease awareness among patients and health-care providers, knowledge gaps, and difficulty recognizing patients who are at risk. Non-alcoholic fatty liver disease and alcohol-associated liver disease are the fastest-rising causes of HCC-related death worldwide and are associated with unique barriers to surveillance. […] In particular, more than one-third of patients with HCC related to non-alcoholic fatty liver disease do not have cirrhosis and therefore lack a routine indication for HCC surveillance on the basis of current practice guidelines. Semi-annual abdominal ultrasound with measurement of -fetoprotein levels is recommended for HCC surveillance, but the sensitivity of this approach for early HCC is limited, especially for patients with cirrhosis or obesity.

• #53 Hepatocellular carcinoma surveillance — utilization, barriers and the impact of changing aetiology | Nature Reviews Gastroenterology & Hepatology

  https://www.nature.com/articles/s41575-023-00818-8

  Ultrasonography has a suboptimal sensitivity for the detection of early-stage HCC and its performance can be poorer in the presence of obesity and non-alcoholic fatty liver disease-related or alcohol-related cirrhosis. […] Novel blood-based and imaging-based biomarkers for HCC surveillance are emerging but require validation.

• #54 Addressing the worldwide hepatocellular carcinoma: epidemiology, prevention and management – Samant – Journal of Gastrointestinal Oncology

  https://jgo.amegroups.org/article/view/36868/html

  Systemic reviews demonstrate US alone has sensitivity for HCC from 30-70%. […] At present, the concern is adherence to such surveillance program as data from Surveillance, Epidemiology, and End Results registry shows that less than 20% of patients who developed HCC had received regular surveillance.

• #55

  https://www.hksmp.com/journals/gfm/article/view/439

  Liver ultrasonography every 6 months with or without serum AFP level is widely recommended as the standard modality for HCC surveillance. […] There is no universal agreement about adding AFP to ultrasound (US) in HCC screening. […] A prospective surveillance study at a tertiary care centre compared the HCC detection rate of US and MRI in patients with cirrhosis who are at high risk for HCC. […] The study concluded that screening using MRI with liver-specific contrast resulted in a higher HCC detection rate and lower false-positive findings compared with US. […] Most guidelines recommend ultrasonographic screening every 6 months. […] Reports of HCC surveillance in patients with cirrhosis consistently show poor uptake and adherence to the published guidance. […] The study showed that adherence to HCC surveillance guidelines has remained poor over time.

• #56

  https://www.hksmp.com/journals/gfm/article/view/439

  HCC surveillance underuse appears particularly problematic among patients with non-viral liver disease and those followed by primary care providers or outside academic centres. […] The effectiveness of HCC surveillance at improving outcomes in high-risk patients relies not only on the accuracy of surveillance tests but also on the real-life implementation of surveillance. […] HCC surveillance implementation can be affected by either provider or patient-related factors; patients must be engaged in healthcare and have a clinic visit, providers must accurately identify at-risk patients, providers must order appropriate surveillance tests; surveillance tests must be scheduled, and the patient must adhere with the surveillance recommendations. […] A recent systematic review and meta-analysis included was conducted to assess utilization of hepatocellular carcinoma surveillance in patients with cirrhosis.

• #57

  https://www.hksmp.com/journals/gfm/article/view/439

  HCC surveillance underuse appears particularly problematic among patients with non-viral liver disease and those followed by primary care providers or outside academic centres. […] The effectiveness of HCC surveillance at improving outcomes in high-risk patients relies not only on the accuracy of surveillance tests but also on the real-life implementation of surveillance. […] HCC surveillance implementation can be affected by either provider or patient-related factors; patients must be engaged in healthcare and have a clinic visit, providers must accurately identify at-risk patients, providers must order appropriate surveillance tests; surveillance tests must be scheduled, and the patient must adhere with the surveillance recommendations. […] A recent systematic review and meta-analysis included was conducted to assess utilization of hepatocellular carcinoma surveillance in patients with cirrhosis.

• #58

  https://www.hksmp.com/journals/gfm/article/view/439

  Liver ultrasonography every 6 months with or without serum AFP level is widely recommended as the standard modality for HCC surveillance. […] There is no universal agreement about adding AFP to ultrasound (US) in HCC screening. […] A prospective surveillance study at a tertiary care centre compared the HCC detection rate of US and MRI in patients with cirrhosis who are at high risk for HCC. […] The study concluded that screening using MRI with liver-specific contrast resulted in a higher HCC detection rate and lower false-positive findings compared with US. […] Most guidelines recommend ultrasonographic screening every 6 months. […] Reports of HCC surveillance in patients with cirrhosis consistently show poor uptake and adherence to the published guidance. […] The study showed that adherence to HCC surveillance guidelines has remained poor over time.

• #59

  https://www.hksmp.com/journals/gfm/article/view/439

  This systematic review and meta-analysis highlighted that HCC surveillance continued to be underutilized, with only 1 in 4 patients with cirrhosis receiving surveillance. […] The intended benefits of entering a patient into a surveillance programme are clear. […] The aim is to detect early cancers in at-risk groups and enable potentially curative treatments for this group of patients. […] HCC surveillance is associated with significant improvements in early tumour detection, receipt of curative therapy, and overall survival in patients with cirrhosis. […] When considering the risk versus benefits of HCC surveillance we must consider the possible harm to the patient. […] Such concerns include false-positive testing resulting in unnecessary and risk-associated procedures such as liver biopsy, overdiagnosis of HCC among patients with cirrhosis, as well as false-negative investigations resulting in delayed diagnosis of HCC.

• #60 Addressing the worldwide hepatocellular carcinoma: epidemiology, prevention and management – Samant – Journal of Gastrointestinal Oncology

  https://jgo.amegroups.org/article/view/36868/html

  Systemic reviews demonstrate US alone has sensitivity for HCC from 30-70%. […] At present, the concern is adherence to such surveillance program as data from Surveillance, Epidemiology, and End Results registry shows that less than 20% of patients who developed HCC had received regular surveillance.

• #61 Surveillance for Hepatocellular Carcinoma Reduces Mortality: an Inverse Probability of Treatment Weighted Analysis | Annals of Hepatology

  https://www.elsevier.es/en-revista-annals-hepatology-16-articulo-surveillance-for-hepatocellular-carcinoma-reduces-S1665268119304156

  A number of guidelines universally recommend screening and surveillance for HCC using ultrasonography and/or serum alpha-fetoprotein (AFP) among at-risk populations. […] Screening and active surveillance has been shown to enhance rate of early HCC detection, increase potential access to curative treatment and possibly improve survival outcome. […] Although it has been suggested that the HCC surveillance may have potential benefits, yet its use in clinical practice remains disappointing. For example, in Europe and the US, the use of HCC surveillance is less than 20%. […] The rate of surveillance in this cohort was approximately 20%, highlighting the underutilization of the surveillance program for HCC in clinical practice. […] Given the benefits of surveillance in improving survival and reducing mortality, it is important to enhance the surveillance rate by identifying barriers to surveillance, and developing strategies and effective intervention to overcome these obstacles.

• #62

  https://www.hksmp.com/journals/gfm/article/view/439

  HCC surveillance underuse appears particularly problematic among patients with non-viral liver disease and those followed by primary care providers or outside academic centres. […] The effectiveness of HCC surveillance at improving outcomes in high-risk patients relies not only on the accuracy of surveillance tests but also on the real-life implementation of surveillance. […] HCC surveillance implementation can be affected by either provider or patient-related factors; patients must be engaged in healthcare and have a clinic visit, providers must accurately identify at-risk patients, providers must order appropriate surveillance tests; surveillance tests must be scheduled, and the patient must adhere with the surveillance recommendations. […] A recent systematic review and meta-analysis included was conducted to assess utilization of hepatocellular carcinoma surveillance in patients with cirrhosis.

• #63 Hepatocellular Carcinoma: Surveillance, Diagnosis, Evaluation and Management

  https://www.mdpi.com/2072-6694/15/21/5118

  The goal of surveillance programs is to identify early-stage HCC in at-risk patients (cirrhosis from any etiology, HBV in the absence of cirrhosis, and HCV in the absence of cirrhosis), when curative-intent treatment is an option. The American Association for the Study of Liver Diseases (AASLD), Asian Pacific Association for the Study of the Liver (APASL), the National Comprehensive Cancer Network (NCCN), and the European Association for the Study of the Liver (EASL) all recommend surveillance every six months for these high-risk patients. Abdominal ultrasonography (US) is the recommended surveillance modality. […] Although the HCC surveillance of patients with cirrhosis has been found to increase survival, surveillance is underused in clinical practice. Barriers have been identified at the patient level, provider level, and system level. Identified patient-level barriers include financial constraints, lack of awareness of surveillance recommendations, and scheduling issues. At the provider level, there is a lack of clinician orders for surveillance and cirrhosis unrecognition.

• #64 Hepatocellular Carcinoma: Surveillance, Diagnosis, Evaluation and Management

  https://www.mdpi.com/2072-6694/15/21/5118

  Due to the continued underuse of surveillance programs, it is recommended that interventions be implemented to improve HCC surveillance rates. A variety of interventions have been evaluated. Patient-level interventions commonly involve patient education on the importance of screening, assistance with scheduling, and programs for transportation to screening appointments. Provider-level interventions include adherence to screening guidelines, reminders via electronic medical records, and compliance reports. On the macro-level, initiatives that aim to decrease the cost of screening and increase the accessibility could positively impact the surveillance of HCC.

• #65 Hepatocellular carcinoma: Epidemiology, pathogenesis and surveillance – implications for sub-Saharan Africa

  http://www.scielo.org.za/scielo.php?script=sci_arttext&pid=S0256-95742018000900011

  Countries such as Taiwan and Japan that have established effective national HCC surveillance programs have substantially better overall survival of patients with HCC compared with countries with less effective programs such as the US, Canada, most European countries, South Korea, China and SSA countries.

• #66 Hepatocellular carcinoma surveillance: the often-neglected practice – Sammon – Hepatobiliary Surgery and Nutrition

  https://hbsn.amegroups.org/article/view/28548/html

  Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer worldwide and as such represents a significant global health burden. The clinical societies dedicated to the study of liver diseases all recommend routine surveillance for those at risk. […] Worldwide, only small minorities of patients at risk for HCC undergo the recommended surveillance regimen. Japan and Korea remain the only two countries with a national surveillance program. Elsewhere, the utilization of regular ultrasound screening is low, with only 12-29% of patients diagnosed with HCC receiving regular (annual or biannual) ultrasound surveillance prior to diagnosis. […] In conclusion, Kanwal and Singal highlight the need for surveillance and the need to improve the uptake of surveillance in those at-risk of developing HCC. It is important to note that there has been a significant change in ultrasound technology over the last few decades and the sensitivity of the detection of HCC in studies published before the mid 2000s is not applicable to today’s ultrasound surveillance. Better, more accessible surveillance tools are being developed. But in the meanwhile, far more effort is needed to identify at-risk patients and direct them to surveillance as recommended by current guidelines.

• #67 Hepatocellular carcinoma surveillance — utilization, barriers and the impact of changing aetiology | Nature Reviews Gastroenterology & Hepatology

  https://www.nature.com/articles/s41575-023-00818-8

  Ultrasonography has a suboptimal sensitivity for the detection of early-stage HCC and its performance can be poorer in the presence of obesity and non-alcoholic fatty liver disease-related or alcohol-related cirrhosis. […] Novel blood-based and imaging-based biomarkers for HCC surveillance are emerging but require validation.

• #68 Hepatocellular carcinoma: updates on epidemiology, surveillance, diagnosis and treatment

  https://dspace.kci.go.kr/handle/kci/2234212

  Hepatocellular carcinoma (HCC) is a major global burden, ranking as the third leading cause of cancer-related mortality. […] HCC due to chronic hepatitis B virus (HBV) or C virus (HCV) infection has decreased due to universal vaccination for HBV and effective antiviral therapy for both HBV and HCV, but HCC related to metabolic dysfunctionassociated steatotic liver disease and alcohol-associated liver disease is increasing. […] Biannual liver ultrasonography and serum -fetoprotein are the primary surveillance tools for early HCC detection among high-risk patients (e.g., cirrhosis, chronic HBV). […] Alternative surveillance tools such as blood-based biomarker panels and abbreviated magnetic resonance imaging (MRI) are being investigated. […] In this review article, we discuss the recent global epidemiology, risk factors, and HCC care continuum encompassing surveillance, diagnosis, staging, and treatments.

• #69 Hepatocellular carcinoma surveillance in Australia: current and future perspectives | The Medical Journal of Australia

  https://www.mja.com.au/journal/2023/219/9/hepatocellular-carcinoma-surveillance-australia-current-and-future-perspectives

  HCC prediction models and novel surveillance tools such as biomarker panels, computed tomography and magnetic resonance imaging may have a future role in personalised HCC surveillance. […] Analyses suggest surveillance may be costeffective, but Australian data remain limited. […] A centralised HCC surveillance program may ultimately have a role in delivering improved and more equitable care.

• #70 Hepatocellular carcinoma surveillance after HBsAg seroclearance

  https://www.explorationpub.com/Journals/edd/Article/100546

  Existing HCC risk scores have a reasonably good performance in patients after HBsAg seroclearance. […] HBsAg seroclearance reduces but does not eliminate the risk of HCC, especially when HBsAg seroclearance occurs later in life and after the development of cirrhosis. […] Current guidelines only provide recommendations on HCC surveillance in patients with positive HBsAg. The optimal management after HBsAg seroclearance is poorly defined. […] HBsAg seroclearance confers a substantially reduced risk of development of HCC compared to that with complete viral suppression, however, the risk is not eliminated. […] The current evidence substantially indicates a non-negligible risk of HCC despite HBsAg seroclearance and thus may still benefit from regular HCC surveillance. […] Cirrhosis is the most important disease factor contributing to HCC development after HBsAg seroclearance with unifying evidence showing cirrhotic patients have a 210 times risk of HCC than non-cirrhotic patients despite HBsAg seroclearance from large-scale retrospective studies.

• #71 Global trends in hepatocellular carcinoma epidemiology: implications for screening, prevention and therapy | Nature Reviews Clinical Oncology

  https://www.nature.com/articles/s41571-023-00825-3

  Hepatocellular carcinoma (HCC) mortality rates are increasing globally, and particularly in the Western world. […] However, epidemiological shifts in the incidence of HCC from patients with virus-related liver disease to those with non-viral aetiologies, including alcohol-associated and metabolic dysfunction-associated steatotic liver disease, have important implications for prevention, surveillance and treatment. […] Secondary prevention of HCC via semi-annual surveillance is associated with improvements in early detection and thus reduced mortality; however, current tools, including abdominal ultrasonography, have suboptimal sensitivity for the detection of early stage HCC, particularly in patients with obesity and/or non-viral liver disease. […] Moreover, HCC surveillance is underused in clinical practice, particularly among patients with non-viral liver disease and those followed outside of gastroenterology and/or hepatology practices, highlighting a need for multi-level interventions to increase use. […] In this Review, we discuss trends in the epidemiology of HCC and their implications for screening, prevention and therapy.

• #72 Hepatocellular carcinoma surveillance: current practice and future directions

  https://www.oaepublish.com/articles/2394-5079.2021.131

  Liver cancer is among the leading causes of global cancer incidence and is the second-most common cause of cancer mortality. Hepatocellular carcinoma (HCC) is the most dominant form of primary cancer, accounting for roughly 80% of all cases of liver cancer, and occurs in patients with chronic liver diseases of various causes. The burden of HCC has historically been high in Asia, with China accounting for over 51% of the global liver cancer burden. While a recent analysis has projected a decrease in the incidence and mortality rates of liver cancer in China through 2030, it also emphasized that the overall disease burden would still be serious, especially in rural and western areas due to the persistently high prevalence of HBV and HCV, as well as aflatoxin and alcohol-related liver diseases. In the Western world, the HCC incidence rates remain elevated due to the rising prevalence of cirrhosis due to non-alcoholic steatohepatitis (NASH) and alcohol-related liver diseases. While there have been significant advances in the treatment of HCC, the overall prognosis in patients with large tumor burden, vascular invasion, or extrahepatic spread continues to remain extremely poor. Therefore, surveillance of high-risk patients is critical for the detection of HCC at earlier stages where curative options are still available. This review article will provide a comprehensive overview of the indications and rationale for HCC surveillance, currently available surveillance methods and their utilization, effectiveness, and limitations, as well as novel surveillance tools which are emerging as alternatives.

• #73 Hepatocellular carcinoma surveillance in Australia: current and future perspectives | The Medical Journal of Australia

  https://www.mja.com.au/journal/2023/219/9/hepatocellular-carcinoma-surveillance-australia-current-and-future-perspectives

  Hepatocellular carcinoma (HCC) is a leading cause of cancerrelated death worldwide, and is increasing in incidence in Australia. […] For most people with cirrhosis and chronic hepatitis B, HCC screening and surveillance is recommended with 6monthly ultrasound. However, most patients with HCC are still diagnosed outside of surveillance with incurable disease. […] While HCC surveillance almost certainly reduces cancerrelated mortality, the potential harms of surveillance are incompletely understood. […] Surveillance uptake remains suboptimal in many contexts, and stems from a combination of patient, clinician and system level barriers. […] Improved casefinding strategies may be required to identify high risk individuals in need of surveillance, as cirrhosis and viral hepatitis are often asymptomatic.

• #74 Hepatocellular carcinoma surveillance in Australia: current and future perspectives | The Medical Journal of Australia

  https://www.mja.com.au/journal/2023/219/9/hepatocellular-carcinoma-surveillance-australia-current-and-future-perspectives

  Hepatocellular carcinoma (HCC) is a leading cause of cancerrelated death worldwide, and is increasing in incidence in Australia. […] For most people with cirrhosis and chronic hepatitis B, HCC screening and surveillance is recommended with 6monthly ultrasound. However, most patients with HCC are still diagnosed outside of surveillance with incurable disease. […] While HCC surveillance almost certainly reduces cancerrelated mortality, the potential harms of surveillance are incompletely understood. […] Surveillance uptake remains suboptimal in many contexts, and stems from a combination of patient, clinician and system level barriers. […] Improved casefinding strategies may be required to identify high risk individuals in need of surveillance, as cirrhosis and viral hepatitis are often asymptomatic.

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