Materiały źródłowe

• #1

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3002533/

  Hepatitis C virus (HCV) is a major cause of chronic liver disease infecting more than 170 million people worldwide. […] Predicting the probable outcome of treatment in patients with HCV infection has always been a challenging task. […] Accurately predicting the patients who will respond to therapy is becoming increasingly important, both from the point of patient care and also with respect to the healthcare cost as clinicians need to continue treatment in patients who will respond and stop treatment in patients who are unlikely to respond. […] The presence of severe fibrosis/cirrhosis on pretreatment liver biopsy predicts a poor response to treatment. […] Recent studies on gene expression profiling and characterization of the liver and serum proteome provide options to accurately predict the outcome of patients infected with HCV in the future.

• #2 Can You Die from Hepatitis C? Prognosis and Life Expectancy

  https://www.healthline.com/health/hepatitis-c/hepatitis-prognosis-and-life-expectancy

  Acute hepatitis C may resolve on its own, while chronic cases have different outcomes depending on the degree of liver damage. […] The life expectancy and outlook of chronic hepatitis C may depend on different factors. […] The outlook and life expectancy for people with chronic hepatitis C depend on the existence and severity of complications. It also depends on how well a person responds to early treatment. […] The 5-year survival rate for liver cancer is about 22%, while the life expectancy of someone with early-stage cirrhosis is about 9-12 years. […] According to the World Health Organization (WHO), it is possible to recover from hepatitis C and live a healthy life. The prognosis of chronic hepatitis C cases depends on the extent of liver damage, individual responses to treatment, virus genotype, and other personal factors. […] The outlook for hepatitis C depends on different factors, like treatment response, genotypes, and complications. […] Overall, the outlook improves with early diagnosis and intervention.

• #3

  https://www.who.int/news-room/fact-sheets/detail/hepatitis-c

  Hepatitis C is a viral infection that affects the liver. It can cause both acute (short term) and chronic (long term) illness. It can be life-threatening. […] Early detection and treatment can prevent serious liver damage and improve long-term health. […] Of those with chronic HCV infection, the risk of cirrhosis ranges from 15% to 30% within 20 years. […] After a person has been diagnosed with chronic HCV infection, an assessment should be conducted to determine the degree of liver damage (fibrosis and cirrhosis). This can be done by liver biopsy or through a variety of non-invasive tests. The degree of liver damage is used to guide treatment decisions and management of the disease. […] The goal of treatment is to cure the disease and prevent long-term liver damage. […] Treatment is always needed for chronic hepatitis C.

• #4 Predicting spontaneous clearance of acute hepatitis C virus in a large cohort of HIV-1-infected men | Gut

  https://gut.bmj.com/content/60/6/837

  15% of patients cleared HCV spontaneously, while 85% progressed towards chronicity. […] Spontaneous clearance was strongly associated with a 2.2 log10 viral load drop within 100 days of infection (HR=1.78; p0.0001), elevated bilirubin (40mol/l; HR=5.04; p=0.006), elevated alanine aminotransferase (ALT; 1000IU/ml; HR=2.62; p=0.048) and baseline CD4 count 650106/l (HR=2.66; p=0.045), and only occurred in patients with genotype 1 infection. […] Spontaneous clearance of acute HCV in HIV-positive men can be predicted by a rapid decline in viral load, high CD4 count, elevated bilirubin and ALT, and is associated with low viral diversity and strong T cell responses.

• #5

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3002533/

  Understanding the probable outcome of treatment either before treatment (pretreatment predictors) or during treatment (on-treatment predictors) is absolutely vital in determining the optimal therapy and duration of treatment. […] A number of host, genetic and viral factors are responsible for the variable outcome of patients with HCV infection. […] Achieving RVR has recently been shown to be important in treatment duration and predicting outcome as studies show that the positive predictive value using RVR for predicting SVR is 89%. […] Thus, viral kinetics is more useful to determine the probable outcome of treatment. […] The presence of advanced fibrosis and cirrhosis is a major independent predictor of nonresponse to antiviral therapy. […] The frequency of steatosis in chronic HCV infection is around 50%, significantly higher in patients with genotype-3 infections.

• #6 Predicting Treatment Outcome in Chronic Hepatitis C | AAFP

  https://www.aafp.org/pubs/afp/issues/1998/0415/p1973.html

  Infection with hepatitis C virus often leads to chronic hepatitis, after which cirrhosis and hepatocellular carcinoma may develop. […] Many factors influence treatment outcome, including patient age and duration of infection, absence of cirrhosis, body weight, gamma-glutamyl transpeptidase levels, viral genotype and pre-treatment serum titer of hepatitis C RNA. However, these factors are not useful in predicting response to treatment in individual patients. […] Clearance of serum hepatitis C RNA after one month of treatment was the strongest independent predictor of sustained response. Negative viremia after one month of treatment resulted in a predicted probability of long-term response of 50 percent, with wide variability depending on age. Persistent viremia more accurately indicated a low probability of long-term response.

• #7 Predicting Treatment Outcome in Chronic Hepatitis C | AAFP

  https://www.aafp.org/pubs/afp/issues/1998/0415/p1973.html

  The authors conclude that early determination of viral status during therapy is the principal predictor of the final outcome of treatment. The negative predictive value of this measurement is quite high, although a small percentage of patients (less than 5 percent) would be misclassified as nonresponders. When viremia becomes negative, the probability of sustained response is likely to vary between 20 and 70 percent, depending on patient age.

• #8 Baseline Prediction of Combination Therapy Outcome in Hepatitis C Virus 1b Infected Patients by Discriminant Analysis Using Viral and Host Factors | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0014132

  Baseline Prediction of Combination Therapy Outcome in Hepatitis C Virus 1b Infected Patients by Discriminant Analysis Using Viral and Host Factors […] Current treatment of chronic hepatitis C virus (HCV) infection has limited efficacy especially among genotype 1 infected patients, is costly, and involves severe side effects. Thus, predicting non-response is of major interest for both patient wellbeing and health care expense. At present, treatment cannot be individualized on the basis of any baseline predictor of response. We aimed to identify pre-treatment clinical and virological parameters associated with treatment failure, as well as to assess whether therapy outcome could be predicted at baseline. […] Lower alanine transaminase levels (ALT, p=0.009), a higher number of quasispecies variants in the E1E2 region (number of haplotypes, nHap_E1E2) (p=0.003), and the absence of both amino acid arginine at position 70 and leucine at position 91 in the Core region (p=0.039) were significantly associated with treatment failure. Therapy outcome was most accurately predicted by discriminant analysis (90.5% sensitivity and 95.5% specificity, 85.7% sensitivity and 81.8% specificity after cross-validation); the most significant variables included in the predictive model were the Core amino acid pattern, the nHap_E1E2, and gamma-glutamyl transferase and ALT levels.

• #9

  https://pmc.ncbi.nlm.nih.gov/articles/PMC3002533/

  Steatosis is suggested to be independently associated with progression of fibrosis and in a recent meta-analysis of more than 3000 patients with chronic HCV infection from Europe, Australia, and the US, steatosis was significantly and independently associated with fibrosis in these patients. […] RVR is rapidly becoming a new tool for predicting patients with hepatitis C who are more likely to achieve SVR. […] A number of host, genetic and viral factors interact to predict the probable outcome of patients with HCV infection. […] HCV genotype other than 1 and low baseline viral load are the most important baseline predictors of SVR. […] RVR has become an important determinant of treatment duration irrespective of the genotype and the presence or absence of other determinants and has come to be recognized as one of the most powerful predictors of SVR.

• #10

  https://haematologica.org/article/view/6965

  A specific prognostication score for hepatitis C virus-positive diffuse large B-cell lymphomas is not available. […] We combined these 3 factors in a new HCV Prognostic Score able to discriminate 3 risk categories with different overall and progression-free survival (low=0; intermediate=1; high-risk 2 factors; P0.001). […] The new score performed better than the International Prognostic Index at multivariate analysis and Harrel C-statistic. […] With the use of three readily available factors (performance status, albumin level and HCV-RNA viral load), the new HCV Prognostic Score is able to identify 3 risk categories with different survival, and may be a useful tool to predict the outcome of hepatitis C virus-associated diffuse large B-cell lymphomas. […] The prediction of the prognosis in HCV-positive DLBCL is still a subject for debate.

• #11 Hepatitis C-related hepatocellular carcinoma in the era of new generation antivirals | BMC Medicine | Full Text

  https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0815-7

  Hepatitis C virus infection is a major cause of hepatocellular carcinoma worldwide. […] However, access to therapies remains limited due to the high costs and under-diagnosis of infection in specific subpopulations, e.g., baby boomers, inmates, and injection drug users, and therefore, hepatocellular carcinoma incidence is predicted to increase in the next decades even in high-resource countries. […] Moreover, cancer risk persists even after 10 years of viral cure, and thus a clinical strategy for its monitoring is urgently needed. […] Several risk-predictive host factors, e.g., advanced liver fibrosis, older age, accompanying metabolic diseases such as diabetes, persisting hepatic inflammation, and elevated alpha-fetoprotein, as well as viral factors, e.g., core protein variants and genotype 3, have been reported.

• #12 Baseline Prediction of Combination Therapy Outcome in Hepatitis C Virus 1b Infected Patients by Discriminant Analysis Using Viral and Host Factors | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0014132

  Discriminant analysis has been shown as a useful tool to predict treatment outcome using baseline HCV genetic variability and host characteristics. The discriminant models obtained in this study led to accurate predictions in our population of Spanish HCV-1b treatment nave patients. […] As combination treatment failure occurs in about half of all patients with chronic hepatitis C infected by genotype 1, prediction of treatment outcome at baseline would be highly beneficial. Although several factors have been identified as predictors of treatment outcome, none of them can provide a reliable individualized prediction when used independently. Based on our results in Spanish patients infected with HCV-1b, we propose the use of discriminant statistical models based on host and viral characteristics to provide an aggregate prediction of the treatment outcome at baseline.

• #13 LecT-Hepa facilitates estimating treatment outcome during interferon therapy in chronic hepatitis C patients | Clinical Proteomics | Full Text

  https://clinicalproteomicsjournal.biomedcentral.com/articles/10.1186/1559-0275-11-44

  A combination treatment of interferon and ribavirin is the standard and the commonly used treatment for chronic hepatitis C (CHC). […] Developing noninvasive tests like serum indicators that can predict treatment outcome at an early stage of therapy is beneficial for individualized treatment and management of CHC. […] We found that LecT-Hepa might reflect the change in fibrosis regression during the treatment process. Moreover, the change of LecT-Hepa at the first 12 weeks of treatment could already predict the antiviral treatment response, which was more superior to FIB-4 index and aspartate aminotransferase-to-platelet ratio index (APRI) in this study. […] These results provide a new perspective that serum glycoprotein could be used as a joint diagnosis indicator for estimation treatment outcome of viral hepatitis at earlier stage of therapy.

• #14 LecT-Hepa facilitates estimating treatment outcome during interferon therapy in chronic hepatitis C patients | Clinical Proteomics | Full Text

  https://clinicalproteomicsjournal.biomedcentral.com/articles/10.1186/1559-0275-11-44

  Our data also showed that the change in LecT-Hepa was well correlated with the treatment outcome of CHC (p=0.0031). If patients had an increased R value in LecT-Hepa (R=124 weeks), they were more likely to experience relapse and become non-SVR. […] The prognostic value of serum LecT-Hepa level is superior to that of other biochemical markers such as FIB-4 and APRI just at the first 12 weeks of therapy. […] Our study revealed that the change in serum level of LecT-Hepa after viral elimination may serve as an early predictor of antiviral treatment response in CHC patients treated with IFN and ribavirin, and may provide additional information for individualizing treatment.

• #15 Core Concepts – Goals and Benefits with HCV Treatment – Evaluation and Preparation for Hepatitis C Treatment – Hepatitis C Online

  https://www.hepatitisc.uw.edu/go/evaluation-treatment/treatment-goals-predicting-response/core-concept/all

  The goals for treating persons with chronic hepatitis C virus (HCV) are threefold: (1) eradicate HCV, (2) improve HCV-related health outcomes and survival, and (3) reduce transmission of HCV to others. […] The health outcome benefits following successful treatment of persons with chronic HCV infection are multiple and include reduced prevalence of hepatic fibrosis, lower risk of developing hepatic failure, decreased occurrence of hepatocellular carcinoma (HCC), improved survival, and amelioration of some extrahepatic HCV-related manifestations. […] In persons with chronic HCV infection, treatment with achievement of SVR12 or SVR24 has been shown to markedly reduce the risk of death, including liver-related and non-liver-related deaths. […] Studies have shown survival benefit in persons with chronic HCV (with or without advanced liver disease) who achieve SVR with DAA therapy.

• #16 Core Concepts – Goals and Benefits with HCV Treatment – Evaluation and Preparation for Hepatitis C Treatment – Hepatitis C Online

  https://www.hepatitisc.uw.edu/go/evaluation-treatment/treatment-goals-predicting-response/core-concept/all

  Individuals with advanced fibrosis who underwent antiviral therapy and achieved an SVR had reduced overall mortality, liver-related death, liver failure, and hepatocellular carcinoma compared with those who did not achieve an SVR. […] In a meta-analysis of 35 studies that included 33,360 persons with chronic HCV infection, investigators showed a clear benefit in 5-year overall survival in persons who achieved an SVR with treatment when compared with those who had not achieved an SVR. […] The mortality rate in persons who achieved an SVR was significantly lower than in those who did not achieve an SVR with treatment, after adjusting for baseline demographics, clinical characteristics, and comorbidity. […] A number of studies evaluating contemporary trends have suggested an early signal of benefit since the introduction of DAA therapy with decreased hospitalization, longer survival, and reduced liver transplantation rates in patients with advanced HCV liver disease.

• #17 Response to antiviral therapy for chronic hepatitis C and risk of hepatocellular carcinoma occurrence in Japan: a systematic review and meta-analysis of observational studies | Scientific Reports

  https://www.nature.com/articles/s41598-023-30467-5

  In Japan, hepatocellular carcinoma (HCC) is a leading cause of cancer mortality and hepatitis C virus infection is a major cause of HCC. […] The pooled estimate (95% confidence interval [CI]) of 25 studies was 0.37 (0.330.43) for sustained virologic response (SVR) and 1.70 (1.611.80) for non-SVR for the HCC incidence rate per 100 person-years, and 0.22 (0.190.26) for the incidence rate ratio (SVR vs. non-SVR). […] SVR to interferon therapy for chronic hepatitis C reduces the risk of HCC occurrence. […] Based on pooled estimates of both the crude incidence rate ratio calculated using data from individual studies and the HR adjusted for potential confounders reported by the studies, we concluded that SVR to IFN-based therapy for chronic hepatitis C reduces the risk of HCC occurrence. […] Eradication of HCV by IFN is thought to reduce HCC occurrence by improving hepatic inflammation, regression of hepatic fibrosis, and the antitumor effects of IFN including tumoricidal, antiproliferative, or immunomodulatory effects. […] The findings of the present study suggest that eradication of HCV by IFN therapy may reduce HCC occurrence in Japanese patients.

• #18 Hepatitis C-related hepatocellular carcinoma in the era of new generation antivirals | BMC Medicine | Full Text

  https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0815-7

  This result suggests that the anti-inflammatory and/or immunomodulatory effects of interferon may have HCC-preventive effects irrespective of HCV presence, although the adverse effects (flu-like symptoms, neuropsychiatric and myelosuppressive effects) hamper its wider use. […] Despite the anticipated improvement in SVR rate with wider use of DAAs, model-based simulation studies have predicted further increases of HCC incidence over the next decade even with SVR rates of 80-90% by DAAs. […] It is noteworthy that SVR does not necessarily mean elimination of HCC risk despite the substantially decreased incidence. […] In fact, HCC can occur even more than 10 years after successful HCV clearance. […] The annual post-SVR HCC incidence of approximately 1% is still higher than the cancerous conditions in other organs, and the volume of HCC-developing patients will remain substantial given the vast size of the HCV-infected population.

• #19 Hepatitis C-related hepatocellular carcinoma in the era of new generation antivirals | BMC Medicine | Full Text

  https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0815-7

  More advanced liver fibrosis as well as biochemical or imaging surrogates of histological fibrosis before and/or after antiviral treatment are the most prominent features associated with higher post-SVR HCC risk. […] Current practice guidelines recommend regular biannual HCC screening for cirrhotic patients with active HCV infection, but it is still undetermined whether and how post-SVR patients should be monitored for future HCC development and if any of the risk-associated variables has clinical utility. […] A pan-etiology HCC risk-predictive gene signature in the liver, which was shown to predict post-SVR HCC development, may serve as a biomarker to identify a subset of SVR patients who should be regularly monitored for future HCC. […] Accumulating clinical experience of DAA-based treatment has suggested that post-SVR HCC development and recurrence may be more frequent compared to interferon-based treatment.

• #20 Real-world treatment outcome of direct-acting antivirals and patient survival rates in chronic hepatitis C virus infection in Eritrea | Scientific Reports

  https://www.nature.com/articles/s41598-023-47258-7

  Reliable real-world data on direct acting anti-retroviral (DAA) uptake and treatment outcomes are lacking for patients with hepatitis C virus (HCV) in sub-Saharan Africa. This study provides data on HCV DAA-based treatment outcomes, mortality, loss-to-follow up, and associated factors among patients in Eritrea. The SVR rates achieved in this cohort were high. However, high LTFU and high mortality driven largely by late presentation and suboptimal population screening/case finding, were uncovered. Death occurred in 18 (7.5% (95% CI 1.74.1) patients while 67 cases were LTFU (28.1%, 95% CI 22.333.9). Following 29,786 person-days of follow-up, incidence rate of death was 6.04 (95% CI 3.89.5) per 10,000 person-days. The high mortality rate observed in this cohort is probably linked to late presentation of patients. Moreover, patients who died had a higher median FIB-4 score, 6.9 (IQR 4.56.9) as compared to positive outcome 3.1 (IQR 1.66.2) and LTFU 1.3 (IQR: 0.96); p value 0.001. In the adjusted model, independent predictors of LTFU included enrollment year (2020: aHR=2.2, 95% CI 14.7; p value=0.04); Hospital (Hospital B: aHR=2.2, 95% CI 14.7; p value=0.03) and FIB-4 score (3.25: aHR=3.7, 95% CI 1.211.5; p value =0.02). Overall, better diagnostic performance for FIB-4 score has been reported by multiple investigators.

• #21 Hepatitis C-related hepatocellular carcinoma in the era of new generation antivirals | BMC Medicine | Full Text

  https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0815-7

  HCV-related HCC will remain a major health problem in the coming decades despite the clinical deployment of DAAs. […] Post-SVR HCC is an emerging problem, with urgent unmet needs for the clinical strategy of early tumor detection and intervention, as well as elucidation of its molecular mechanisms for therapeutic target and biomarker discovery.

• #22

  https://www.who.int/news-room/fact-sheets/detail/hepatitis-c

  With proper treatment, many people can be cured from hepatitis C infection and live healthy lives. […] Access to HCV treatment is improving but remains limited. Of the 50 million people living with HCV infection globally in 2022, an estimated 36% people knew their diagnosis, and of those diagnosed with chronic HCV infection, around 20% (12.5 million) people had been treated with DAAs by the end of 2022.

• #23 LecT-Hepa facilitates estimating treatment outcome during interferon therapy in chronic hepatitis C patients | Clinical Proteomics | Full Text

  https://clinicalproteomicsjournal.biomedcentral.com/articles/10.1186/1559-0275-11-44

  Early prediction of the outcome during or after treatment is expected to provide additional information for individualizing treatment, and thus improves the cure rates for patients with chronic HCV infection. […] Continuous monitoring of the degree of liver fibrosis should be beneficial for early estimation of the therapeutic efficacy and long-term follow-up of patients, which provides clues for the prognosis and management of CHC. […] We found that the change of LecT-Hepa just at the first 12 weeks of therapy could already distinguish CHC patients attainment of SVR. […] These results suggest that the new indicator LecT-Hepa may be superior to the routine clinical indicators for the evaluation of fibrosis in this cohort. […] These results indicated that LecT-Hepa was effective for evaluation of the progression of fibrosis, at least in this cohort.

• #24 Prediction of Outcome of Newly Onset Cerebrovascular Stroke in HCV Infected Patients – Biomedical and Pharmacology Journal

  https://biomedpharmajournal.org/vol16no1/prediction-of-outcome-of-newly-onset-cerebrovascular-stroke-in-hcv-infected-patients/

  Chronic Vascular Diseases (CVD) is a major health burden. Hepatitis C Virus (HCV) infection has been implicated in the development of carotid artery atherosclerosis and has recently been associated with poor prognosis in stroke patients. […] The outcome and predictors of prognosis had been documented and estimated statistically. […] We found there is a significant association between chronic HCV infections and Ischemic Stroke severity and bad prognosis. […] The prognosis of a recent stroke may be influenced by patients who have cirrhosis and concomitant conditions. […] This study indicates a strong connection between chronic HCV infection and severity of ischemic stroke and a bad prognosis result from it. […] Prognosis of stroke in HCV positive patient is more unfavorable than in HCV negative groups, and mortality rate among HCV patients with newly onset Ischemic Stroke is higher than negative group due to more comorbidities and bad general condition of HCV cirrhotic patients.

• #25 Spatial patterns and MRI-based radiomic prediction of high peritumoral tertiary lymphoid structure density in hepatocellular carcinoma: a multicenter study | Journal for ImmunoTherapy of Cancer

  https://jitc.bmj.com/content/12/12/e009879

  Patients with HCC and a high pTLS density experienced prolonged median overall survival (p0.05) and favorable immunotherapy response (p=0.03). […] We identified key regulators of pTLS density in patients with HCC and proposed a non-invasive radiomic classifier capable of assisting in stratification for prognosis and treatment. […] High pTLS density group significantly correlated with improved overall survival (OS) and relapse-free survival (RFS) (both log-rank p0.05) in the TCGA-LIHC (n=363) and in-house (n=660) cohorts. […] The predicted pTLShigh group exhibited prolonged mST for OS (HR 0.200.44, p=0.005to 0.001) and RFS (HR 0.250.73, p=0.015to 0.001) compared with predicted pTLSlow group across three data sets. […] Our study identifies potential novel targets of pTLS density, shedding light on its clinical application in immunotherapy. Developing a non-invasive method for assessing pTLS density could aid in clinical decision-making and treatment selection in hepatocellular carcinoma.

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