Materiały źródłowe

• #1 Non-alcoholic fatty liver disease: a practical approach to diagnosis and staging | Frontline Gastroenterology

  https://fg.bmj.com/content/5/3/211

  Non-alcoholic fatty liver disease (NAFLD) is now the commonest cause of abnormal liver function tests (LFTs) in the UK with approximately a third of the population being affected. […] The majority have simple steatosis, but approximately 10-30% develop NASH and the development of NASH cirrhosis is associated with a poor long-term prognosis. Patients with NASH have increased liver-related and cardiovascular mortality. […] The development of cirrhosis due to NASH is associated with a poor long-term prognosis. The 10-year mortality rate is 20% for subjects with Child-Pugh A disease and 45% will decompensate within 10 years of diagnosis. […] In addition, subjects with NASH cirrhosis are at significant risk of developing hepatocellular carcinoma (2.6% per year). […] It is important to note that, in addition to having an increased liver-related mortality rate compared with a reference population (2.8% vs 0.2%; p=0.04), patients with NASH also have an increased risk of cardiovascular death (15.5% vs 7.5%; p=0.04).

• #2 Nonalcoholic Fatty Liver Disease: Common Questions and Answers on Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2020/1115/p603.html

  Nonalcoholic fatty liver disease (NAFLD) is the most common form of liver disease in the United States, affecting up to 30% of adults. […] NAFL typically follows an indolent course, whereas patients with NASH are at higher risk of death from cardiovascular disease, cancer, and end-stage liver disease. […] Differentiating NAFL from NASH is important because they have different prognoses. NAFL follows a more indolent course, whereas patients with NASH are at risk of progression from fibrosis to cirrhosis and development of hepatocellular carcinoma. […] Most patients with NAFL will have a benign, nonprogressive disease course. Only 20% develop NASH, and 20% of those with NASH develop cirrhosis. Patients with a higher degree of fibrosis have a higher risk of death, mainly from cardiovascular disease, cancer, and end-stage liver disease.

• #3 Nonalcoholic Fatty Liver Disease: Common Questions and Answers on Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2020/1115/p603.html

  Two cohort studies found that 80% of patients with NAFLD had no progression to NASH. Of those who developed cirrhosis, 31% progressed to hepatic decompensation. About 2% of patients with NAFLD developed hepatocellular carcinoma. […] A community-based study of 420 patients with NAFLD found that these patients had a 34% higher risk of death (standard mortality ratio = 1.34; 95% CI, 1.003 to 1.76; P= .03) than would be expected in the general population; the three main causes of death were cancer, ischemic heart disease, and liver disease. […] A study of 817 patients with NAFLD echoed these results (hazard ratio = 1.038; 95% CI, 1.036 to 1.041; P.0001), with liver disease as the third leading cause of death after cardiovascular disease and malignancy. […] A meta-analysis also showed higher overall mortality in patients with NAFLD (odds ratio = 1.57; 95% CI, 1.18 to 2.10; P= .002). […] Further studies that stratified patients’ risk using fibrosis scoring tools found higher disease-specific mortality in those with NASH, indicating that fibrosis is the most important predictor of long-term outcomes.

• #4 Fatty liver disease – Wikipedia

  https://en.wikipedia.org/wiki/Fatty_liver_disease

  Prognosis Good if treated early[3] […] For people affected by NAFLD, the 10-year survival rate was about 80%. […] The rate of progression of fibrosis is estimated to be one per 7 years in NASH and one per 14 years in NAFLD, with an increasing speed.[9][10] […] Less than 10% of people with cirrhotic alcoholic FLD will develop hepatocellular carcinoma,[11] the most common type of primary liver cancer in adults, but up to 45% people with NASH without cirrhosis can develop hepatocellular carcinoma.[12] […] The progression to cirrhosis may be influenced by the amount of fat and degree of steatohepatitis and by a variety of other sensitizing factors.

• #5 Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss | BMC Endocrine Disorders | Full Text

  https://bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-022-00980-1

  Given the increasing prevalence of diabetes and obesity worldwide, the deleterious effects of non-alcoholic fatty liver disease (NAFLD) are becoming a growing challenge for public health. […] In these patients, advanced fibrosis is the major predictor of morbidity and liver-related mortality, and an accurate diagnosis of NASH and NAFLD is mandatory. […] The prevalence of liver disease (NAFLD) has risen rapidly in Western countries, with a worldwide prevalence of 25%. […] In the majority of the liver steatosis patients, the disease is non-progressive, however a small portion of these patients develop the earlier mentioned NASH, which can lead to liver failure and even hepatocellular carcinoma. […] NAFLD managements US guidelines define NAFLD as steatosis with 5% fat infiltration in imaging or histology and b) no alcohol, drug, or viral-induced steatosis.

• #6 Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss | BMC Endocrine Disorders | Full Text

  https://bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-022-00980-1

  Patients with NAFLD often have one or more components of the metabolic syndrome (MS) like systemic hypertension, dyslipidaemia, Insulin resistance, or overt diabetes. […] There is increasing evidence that visceral obesity is a risk factor for NAFLD and it also has to be taken into account that MS is a known risk factor in cardiovascular disease development. […] The spectrum of NAFLD and related disease, including its complex relationship with MS poses challenges for clinicians. […] The treatment of NAFLD and related diseases (including but not limited to components of MS) consists of several tiers of which conservative and surgical therapies are known treatments. […] Weight loss is the primary therapy for most patients with NAFLD. Weight loss can improve liver biochemical tests, liver histology, serum insulin levels, and quality of life in patients with NAFLD.

• #7 Predicting Liver-Related Outcomes in People With Nonalcoholic Fatty Liver Disease: The Prognostic Value of Noninvasive Fibrosis Tests – PubMed

  https://pubmed.ncbi.nlm.nih.gov/34783191/

  It remains unclear whether screening for advanced fibrosis in the community can identify the subgroup of people with nonalcoholic fatty liver disease (NAFLD) at higher risk for development of liver-related complications. […] We aimed to determine the prognostic value of baseline noninvasive fibrosis tests for predicting liver-related outcomes and mortality in patients with NAFLD from type 2 diabetes (T2D) clinics or primary care. […] During a median follow-up of 50 months, decompensated liver disease or primary liver cancer occurred in 6 of 35 (17.1%) patients with baseline LSM 13 kPa, 1 of 17 (5.9%) patients with LSM 9.5-13 kPa, and in no patients with LSM 9.5 kPa. […] No patient with low-risk NFS developed liver decompensation or liver-related mortality. […] Following repeat NFSs at the end of follow-up, all patients with a liver-related complication were in the high-risk NFS category.

• #8 Predicting Liver-Related Outcomes in People With Nonalcoholic Fatty Liver Disease: The Prognostic Value of Noninvasive Fibrosis Tests – PubMed

  https://pubmed.ncbi.nlm.nih.gov/34783191/

  Patients who developed liver-related complications were also more likely to have baseline high-risk FIB-4 scores or ELF test 9.8 compared to patients who did not develop liver outcomes. […] Conclusion: Liver fibrosis risk stratification in non-hepatology settings can identify the subset of patients at risk of liver-related complications. […] Although the rate of development of a decompensation event or hepatocellular carcinoma was low (2.1% per year) in our patients with compensated cirrhosis (LSM 13 kPa), these events are projected to lead to a substantial increase in NAFLD-related disease burden over the next decade due to the high prevalence of NAFLD in people with obesity and T2D.

• #9 Liver stiffness thresholds to predict disease progression and clinical outcomes in bridging fibrosis and cirrhosis | Gut

  https://gut.bmj.com/content/72/3/581

  In retrospective studies, liver stiffness (LS) by vibration-controlled transient elastography (VCTE) is associated with the risk of liver decompensation in patients with non-alcoholic steatohepatitis (NASH), but prospective data in biopsy-confirmed cohorts with advanced fibrosis are limited. […] The optimal baseline LS thresholds were 16.6 kPa for predicting progression to cirrhosis, and 30.7 kPa for predicting liver-related events. […] Baseline LS 16.6 kPa (adjusted HR 3.99; 95% CI 2.66 to 5.98, p0.0001) and a 5 kPa (and 20%) increase (adjusted HR 1.98; 95% CI 1.20 to 3.26, p=0.008) were independent predictors of progression to cirrhosis in participants with bridging fibrosis, while baseline LS 30.7 kPa (adjusted HR 10.13, 95% CI 4.38 to 23.41, p0.0001) predicted liver-related events in participants with cirrhosis.

• #10 Liver stiffness thresholds to predict disease progression and clinical outcomes in bridging fibrosis and cirrhosis | Gut

  https://gut.bmj.com/content/72/3/581

  The LS thresholds identified in this study may be useful for risk stratification of NASH patients with advanced fibrosis. […] In this analysis of four large, prospective, international, multicentre, randomised placebo-controlled trials of participants with NASH and biopsy-proven advanced fibrosis (F3F4), clinical disease progression was associated with higher liver stiffness by vibration-controlled transient elastography at baseline. […] The liver stiffness thresholds identified in this study will be useful for risk stratification of patients with NASH in clinical trials and in clinical practice. […] The optimal LS threshold at baseline was 16.6 kPa, with a c-statistic of 0.72 (95% CI 0.66 to 0.77). […] A 5 kPa (and 20%) increase in LS was associated with a nearly 1.6-fold risk (HR 1.59, 95% CI 0.97 to 2.59) of progression to cirrhosis in participants with bridging (F3) fibrosis.

• #11 Liver stiffness thresholds to predict disease progression and clinical outcomes in bridging fibrosis and cirrhosis | Gut

  https://gut.bmj.com/content/72/3/581

  The optimal LS threshold at baseline was 30.7 kPa, which had a c-statistic of 0.77 (95% CI 0.67 to 0.87). […] Baseline LS by VCTE 30.7 kPa was associated with an 8-fold risk (HR 8.24; 95% CI 3.61 to 18.82) of clinical events in participants with cirrhosis (F4). […] The LS thresholds identified in this study may be useful for risk stratification of patients with NASH in clinical trials and in clinical practice and lend further support to the use of non-invasive surrogates rather than liver histology to predict the risk of clinically meaningful outcomes.

• #12 Non-invasive score identifies ultrasonography-diagnosed non-alcoholic fatty liver disease and predicts mortality in the USA | BMC Medicine | Full Text

  https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-014-0154-x

  In this study, we aimed to validate and compare the performance of four NAFLD prediction scores: fatty liver index, hepatic steatosis index, lipid accumulation product, and NAFLD liver fat score (LFS), and to evaluate the ability of the best NAFLD prediction score to predict mortality. […] LFS is the best non-invasive prediction score for NAFLD, and people with a high LFS score have an increased risk for cardiovascular and liver-related mortality. […] During a median follow-up of 14.7 years (range 0.1 to 18.2 years) and 83,830.5 person-years, participants in the high LFS group (LFS 1.257) had a higher cardiovascular and liver-related mortality than participants in the low (LFS1.413; cardiovascular hazard ratio (HR)=2.24, 95% CI 1.03 to 4.88; liver HR=31.25, 95% CI 3.13 to 333.33) or intermediate (-1.413LFS1.257; cardiovascular HR=2.3, 95% CI 1.19 to 4.48; liver HR=30.3, 95% CI 4 to 250) LFS groups in the fully adjusted model.

• #13 Non-invasive score identifies ultrasonography-diagnosed non-alcoholic fatty liver disease and predicts mortality in the USA | BMC Medicine | Full Text

  https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-014-0154-x

  Higher LFS were associated with all causes of mortality tested, except malignancy-related causes. […] Participants in the high LFS group had a 60% higher risk (HR=1.6; 95% CI 1.01 to 2.54; P=0.048 in full model) of all-cause mortality than the intermediate LFS group. For cardiovascular mortality, participants in the high LFS group was associated with 2.24-fold (95% CI 1.03 to 4.88; P=0.042 in full model) and 2.3-fold (95% CI 1.19 to 4.48; P=0.015 in full model) increase in risk of death compared with the low and intermediate LFS groups. For liver mortality, participants in the high LFS group had a 31.25-fold (95% CI 3.13 to 333.33; P=0.004 in full model) and 30.3-fold (95% CI 4 to 250; P=0.001 in full model) increase in risk of death compared with the low and intermediate LFS groups. […] Using a large, nationally representative cohort with more than 10 years of follow-up and ultrasonographic data, we have demonstrated that LFS is the best prediction score for ultrasonography-diagnosed NAFLD, and can predict mortality, including cardiovascular- and liver-related mortality. […] Our findings suggest that LFS may be a promising tool for large-scale NAFLD screening. If confirmed in future studies, LFS may be a useful marker for large-scale NAFLD screening and prediction of long-term clinical outcomes.

• #14 An integrated gene-to-outcome multimodal database for metabolic dysfunction-associated steatotic liver disease | Nature Medicine

  https://www.nature.com/articles/s41591-023-02602-2

  Metabolic dysfunction-associated steatotic liver disease (MASLD) is the commonest cause of chronic liver disease worldwide and represents an unmet precision medicine challenge. […] We constructed a 15-gene transcriptional risk score to predict future hepatic decompensation events (area under the receiver operating characteristic curve 0.86, 0.81 and 0.83 for 1-, 3- and 5-year risk, respectively). […] The importance of histological fibrosis in predicting outcomes in MASLD has been highlighted by several studies, with discrete fibrosis stages dramatically influencing the risk of all-cause mortality and liver-related morbidity and mortality. […] The predictive value of the computationally derived PSR-positive proportion in the biopsy cases where a value was available was also separately examined. Increased PSR content in a biopsy was associated with increased risk of death, hazard ratio 1.06 (95% confidence interval 1.0451.075, P21016).

• #15 An integrated gene-to-outcome multimodal database for metabolic dysfunction-associated steatotic liver disease | Nature Medicine

  https://www.nature.com/articles/s41591-023-02602-2

  KaplanMeier estimator curves for liver-related events (excluding death) associated with F0, F1 and F2 were placed in the same cluster by an unbiased clustering approach, but those associated with F3 and F4 were distinct. […] Cox regression modeling of hepatic decompensation events on the cause-specific hazard, with death as a competing risk, using age at biopsy, gender and NASH-CRN fibrosis stage, showed that NASH-CRN fibrosis stages F3 and F4 were associated with increased decompensation events. […] The annotated patient timelines in SteatoSITE allow predictive tools to be developed. […] The risk scores were calculated using the formula indicated in the Methods. According to the median risk score, patients were split into high- and low-risk groups. […] All the biopsy samples could be stratified using the TRS into high- and low-risk groups with substantially different decompensation trajectories. […] The predictive model requires external validation, ideally in prospective longitudinal studies. However, to our knowledge, there are at present no available MASLD datasets with integrated pathology, transcriptomics and clinical outcome data to enable this.

• #16 The Predictive Value of Time-Varying Noninvasive Scores on Long-Term Prognosis of NAFLD in South Korea – PubMed

  https://pubmed.ncbi.nlm.nih.gov/39314528/

  This study aimed to examine whether repeated measurements on noninvasive fibrosis scores during follow-up improve long-term nonalcoholic fatty liver disease (NAFLD) outcome prediction. […] Higher baseline NFS (high versus low probability for advanced fibrosis groups) was associated with higher risk of mortality (adjusted hazard ratio (aHR), (95% confidence interval (CI)), 2.80, [1.39-5.63]) and liver-related outcomes (3.70, [1.27-10.78]). […] In models considering designated time-point measurements of the scores, stronger associations were noted. […] Higher aHRs describing the associations of FIB-4/NFS with overall mortality and liver-related outcomes were observed in the models that included designated time-point measurements of the scores. […] In addition to the baseline measurement, a routine monitoring on these scores may be important in predicting prognosis of NAFLD patients.

• #17 Non-Alcoholic Fatty Liver Disease as a Predictor of Atrial Fibrillation in Middle-Aged Population (OPERA Study) | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142937

  Non-alcoholic fatty liver disease (NAFLD) and atrial fibrillation (AF) are widespread diseases and have multiple common risk factors and comorbidities. […] The goal of this prospective study was to study the value of NAFLD as a predictor of atrial fibrillation. […] In conclusion, our data shows that NAFLD is independently associated with the risk of AF. […] Our main finding was that NAFLD was an independent risk factor of atrial fibrillation in this OPERA study of nearly 1,000 subjects with a long follow-up time. […] In multivariate Cox regression analysis of the NAFLD group, see Table 3, relevant covariates (not medications and plasma lipids) were chosen as potential confounding factors on the basis of their significance in univariate analyses. […] In this model, NAFLD (p = 0.041), older age (p = 0.009), higher LVMI (p = 0.016) and ANP (p = 0.004) were independently associated with AF.

• #18 Non-Alcoholic Fatty Liver Disease as a Predictor of Atrial Fibrillation in Middle-Aged Population (OPERA Study) | PLOS One

  https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0142937

  Subjects in the NAFLD group had greater probability of developing atrial fibrillation during the follow-up time in comparison to the subjects in the non-NAFLD group (Hazard ratio (HR) 1.96 (95%CI) 1.292.97). […] In conclusion, the present study provides strong epidemiological evidence that NAFLD is an independent risk factor for atrial fibrillation.

• #19 Machine learning prediction of hepatic steatosis using body composition parameters: A UK Biobank Study | npj Aging

  https://www.nature.com/articles/s41514-023-00127-z

  We found several significant associations with traditional measurements such as abdominal obesity, as defined by waist-to-hip ratio (OR=2.50 (male), 3.35 (female)), android-gynoid ratio (OR=3.35 (male), 6.39 (female)) and waist circumference (OR=1.79 (male), 3.80 (female)) with hepatic steatosis. […] Lifestyle modification, as with other chronic diseases, is the cornerstone of NAFLD management regardless of the disease stage, so while end-stage liver disease has a poor prognosis, NAFLD is clinically manageable at its early onset. […] Early detection of NAFLD is important in order that timely intervention can be prescribed to patients (e.g., lifestyle and diet modification) by healthcare practitioners. […] As NAFLD cases rise to epidemic proportions, new tools that can potentially be used as opportunistic screening may be helpful particularly as early detection is important.

• #20 Non-alcoholic fatty liver disease (NAFLD): a review of pathophysiology, clinical management and effects of weight loss | BMC Endocrine Disorders | Full Text

  https://bmcendocrdisord.biomedcentral.com/articles/10.1186/s12902-022-00980-1

  A significant body of literature has shown that weight loss induces a clinical improvement in patients with NAFLD or NASH. […] Bariatric and metabolic surgery has not been taken into account as treatment option in many meta-analyses to date, despite the increasing body of evidence and properly designed studies on this subject. […] It has to be said that a small proportion of the patients undergoing bariatric and metabolic surgery develop NASH or suffer from aggravation of the disease (NAFLD/NASH/ live fibrosis) after bariatric surgery.

• #21 Journal of Medical Internet Research – Predicting the 5-Year Risk of Nonalcoholic Fatty Liver Disease Using Machine Learning Models: Prospective Cohort Study

  https://www.jmir.org/2023/1/e46891/

  Background: Nonalcoholic fatty liver disease (NAFLD) has emerged as a worldwide public health issue. Identifying and targeting populations at a heightened risk of developing NAFLD over a 5-year period can help reduce and delay adverse hepatic prognostic events. […] Developing and validating machine learning models can aid in predicting which populations are at the highest risk of developing NAFLD over a 5-year period, thereby helping delay and reduce the occurrence of adverse liver prognostic events. […] In conclusion, based on a long-term follow-up study in Ningbo, China, we found a 5-year incidence of NAFLD of 18.65% in health checkups. Further, we developed and externally validated a 5-year NAFLD risk prediction model, which is important for the reduction and prevention of adverse liver prognostic events.

• #22 Predicting and elucidating the etiology of fatty liver disease: A machine learning modeling and validation study in the IMI DIRECT cohorts | PLOS Medicine

  https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003149

  Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in individuals with and without type 2 diabetes (T2D). Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and, ultimately, hepatocellular carcinomas. […] We sought to expand etiological understanding and develop a diagnostic tool for NAFLD using machine learning. […] The IMI DIRECT prediction models outperformed existing noninvasive NAFLD prediction tools. […] In this study, we developed several models with different combinations of clinical and omics data and identified biological features that appear to be associated with liver fat accumulation. […] In general, the clinical variables showed better prediction ability than the complex omics variables. However, the combination of omics and clinical variables yielded the highest accuracy.

• #23 Predicting and elucidating the etiology of fatty liver disease: A machine learning modeling and validation study in the IMI DIRECT cohorts | PLOS Medicine

  https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.1003149

  We envisage that these new approaches to predicting fatty liver may be of clinical value when screening at-risk populations for NAFLD. […] The identification of specific molecular features that underlie the development of NAFLD provides novel insights into the diseases etiology, which may lead to the development of new treatments.

• #24 Nonalcoholic Fatty Liver Disease: Diagnosis and Management | AAFP

  https://www.aafp.org/pubs/afp/issues/2013/0701/p35.html

  A large prospective cohort study in the United States involving 11,371 adults found that nonalcoholic fatty liver disease was not associated with an increased risk of all-cause mortality, cardiovascular disease, cancer, or liver disease. […] Although hepatic steatosis rarely progresses to cirrhosis, 15% to 30% of patients with nonalcoholic steatohepatitis progress to advanced fibrosis, and 12% to 35% with advanced fibrosis progress to cirrhosis. […] Patients with cirrhosis should be monitored for signs of portal hypertension, disease progression, and hepatocellular carcinoma.

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