Gut microbiome, liver immunology, and liver diseases.

Gut Microbiome and Alcohol-associated Liver Disease

The national Organ Procurement and Transplant Network (OPTN) reported the major indication for liver transplants in 2018 was for other/unknown causes. This study was undertaken to examine all causes and trends in liver disease and hepatocellular carcinoma (HCC) among adults who received liver transplants in the past 10 years. A national cohort study of all adults who received liver transplants from Jan 1, 2010 to Dec 31, 2019 recorded in the OPTN STAR database analyzed by etiology of liver disease and HCC, and gender. Adult liver transplants increased from 5,731 in 2010 to 8,345 in 2019 (45.6% increase). Between 2010 and 2014, liver disease and HCC associated with hepatitis C (HCV) was the major cause for liver transplantation. Proportion of liver transplants for HCV associated liver disease and HCC has since decreased to 18.7% in 2019 compared with 44.5% in 2010 [25.8%, (95% CI 24.3% to 27.3%), p<0.001], while liver transplants for liver disease and HCC associated with alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) increased from 12.7% to 28.8% [16.1%, (95% CI 14.8% to 17.4%), p<0.001], and from 9.1% to 21.5% [12.4%, (95% CI 11.2% to 13.5%), p<0.001], respectively. When all causes of liver disease were examined, only 1.7% of liver transplants had unspecified causes. The five major causes of liver disease and HCC among men receiving liver transplants in 2019 were ALD (33.1%), HCV (21.9%), NAFLD (18.5%), cholestatic liver disease (5.7%) and hepatitis B (4.9%), while the major causes among women were NAFLD (26.8%), ALD (21.1%), HCV (13.1%), cholestatic liver disease (11.1%), and autoimmune liver disease (5.6%). Our study found NAFLD in 2017 in women and ALD in 2019 in men have surpassed HCV as the leading causes of liver disease and HCC among adults receiving liver transplants.

Background and aimsThe national Organ Procurement and Transplant Network (OPTN) reported the major indication for liver transplants in 2018 was for other/unknown causes. This study was undertaken to examine all causes and trends in liver disease and hepatocellular carcinoma (HCC) among adults who received liver transplants in the past 10 years.MethodsA national cohort study of all adults who received liver transplants from Jan 1, 2010 to Dec 31, 2019 recorded in the OPTN STAR database analyzed by etiology of liver disease and HCC, and gender.ResultsAdult liver transplants increased from 5,731 in 2010 to 8,345 in 2019 (45.6% increase). Between 2010 and 2014, liver disease and HCC associated with hepatitis C (HCV) was the major cause for liver transplantation. Proportion of liver transplants for HCV associated liver disease and HCC has since decreased to 18.7% in 2019 compared with 44.5% in 2010 [25.8%, (95% CI 24.3% to 27.3%), p<0.001], while liver transplants for liver disease and HCC associated with alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) increased from 12.7% to 28.8% [16.1%, (95% CI 14.8% to 17.4%), p<0.001], and from 9.1% to 21.5% [12.4%, (95% CI 11.2% to 13.5%), p<0.001], respectively. When all causes of liver disease were examined, only 1.7% of liver transplants had unspecified causes. The five major causes of liver disease and HCC among men receiving liver transplants in 2019 were ALD (33.1%), HCV (21.9%), NAFLD (18.5%), cholestatic liver disease (5.7%) and hepatitis B (4.9%), while the major causes among women were NAFLD (26.8%), ALD (21.1%), HCV (13.1%), cholestatic liver disease (11.1%), and autoimmune liver disease (5.6%).ConclusionsOur study found NAFLD in 2017 in women and ALD in 2019 in men have surpassed HCV as the leading causes of liver disease and HCC among adults receiving liver transplants.

This Research Topic is part of a series with: Herbal Medicines for Gastrointestinal and Hepatic Diseases - Novel Pharmacological and Toxicological approaches, Volume II Ethnopharmacology deals with the exchange of knowledge about people's use of herbal medicines and their pharmacological effects. The information related to therapeutic agents of plant origin and their toxic effects was preserved by oral tradition as well as recorded in materia medica. Many drugs that are now available on the market have been developed from this valuable information. Today, scientists that specialize in medicinal chemistry use these existing herbal drugs to develop and produce more therapeutically active agents with less toxic side effects. The gastrointestinal tract (GIT) is a multi-organ system, consisting of bacteria, and digestive enzymes that have the capacity of degrading food and other molecules. Diseases associated with this organ system include peptic ulcer, inflammatory bowel disease, gastric cancer to name a few. The liver receives seventy percent of its blood supply from the GIT via the hepatic portal vein. The disruption in the gut–liver axis is associated with liver diseases including alcohol-associated liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), and autoimmune liver disease (AILD). NAFLD can cause non-alcoholic steatohepatitis, which can develop into liver cirrhosis through inflammation and fibrosis. Liver cirrhosis is categorized as an end-stage of chronic liver disease, which impairs innate immunity-related genes. Growing evidence from preclinical studies proposes that the gut–liver axis leads to targeted therapeutic modalities for various liver injuries. Therefore, therapeutic treatment of these conditions is essential to prevent progression to these more harmful late-stage diseases.

Long-term Liver-related Outcomes of Patients With Chronic Liver Diseases in Australia

These recommendations are based on the following: (1) a formal review and analysis of the recently published world literature on the topic [Medline search up to June 2011]; (2) the American College of Physicians’ Manual for Assessing Health Practices and Designing Practice Guidelines; (3) guideline policies of the three societies approving this document; and (4) the experience of the authors and independent reviewers with regards to NAFLD. Intended for use by physicians and allied health professionals, these recommendations suggest preferred approaches to the diagnostic, therapeutic and preventive aspects of care. They are intended to be flexible and adjustable for individual patients. Specific recommendations are evidence-based wherever possible, and when such evidence is not available or inconsistent, recommendations are made based on the consensus opinion of the authors. To best characterize the evidence cited in support of the recommendations, the AASLD Practice Guidelines Committee has adopted the classification used by the Grading of Recommendation Assessment, Development, and Evaluation (GRADE) workgroup with minor modifications (Table 1). The strength of recommendations in the GRADE system is classified as strong (1) or weak (2). The quality of evidence supporting strong or weak recommendations is designated by one of three levels: high (A), moderate (B) or low-quality (C). This is a practice guideline for clinicians rather than a review article and interested readers can refer to several comprehensive reviews published recently.

Sarcoïdose conjonctivale et cornéenne

Contribution of gut microbiota to nonalcoholic fatty liver disease: Pathways of mechanisms.

The role of the gut microbiome in chronic liver disease: the clinical evidence revised.

Nonalcoholic fatty liver disease (NAFLD), an increasingly prevalent paediatric disorder, is diagnosed and managed not only by both pediatric gastroenterologists/hepatologists but also frequently by the general pediatrician. This article updates recent advances in diagnostic and therapeutic approach, which may be applied to everyday practice. Diagnosis of NAFLD takes into account the risk factor profile and is a diagnosis of exclusion. Techniques such as transient elastography and specific biomarkers aimed at improving diagnosis and monitoring of NAFLD need further validation in the pediatric population. Defining the risk to develop cirrhosis seems to be of primary importance already in childhood and a combination of genetic, clinical, and environmental factors can help in monitoring and making decisions on therapy. Weight reduction therapy should be the aim of treatment approach, but the compliance is poor and pharmacological treatment would be helpful; docosahexaenoic acid, some probiotics, and vitamin E are to be considered, but evidence is not sufficient to recommend widespread use.

The fungal microbiota plays an important role in the pathogenesis of alcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD). In this study, we aimed to compare changes of the fecal fungal microbiota between patients with ALD and NAFLD and to elucidate patterns in different disease stages between the two conditions. We analyzed fungal internal transcribed spacer 2 (ITS2) sequencing using fecal samples from a cohort of 48 patients with ALD, 78 patients with NAFLD, and 34 controls. The fungal microbiota differed significantly between ALD and NAFLD. The genera Saccharomyces, Kluyveromyces, Scopulariopsis, and the species Candida albicans (C. albicans), Malassezia restricta (M. restricta), Scopulariopsis cordiae (S. cordiae) were significantly increased in patients with ALD, whereas the genera Kazachstania and Mucor were significantly increased in the NAFLD cohort. We identified the fungal signature consisting of Scopulariopsis, Kluyveromyces, M. restricta, and Mucor to have the highest discriminative ability to detect ALD vs NAFLD with an area under the curve (AUC) of 0.93. When stratifying the ALD and NAFLD cohorts by fibrosis severity, the fungal signature with the highest AUC of 0.92 to distinguish ALD F0-F1 vs NAFLD F0-F1 comprised Scopulariopsis, Kluyveromyces, Mucor, M. restricta, and Kazachstania. For more advanced fibrosis stages (F2-F4), the fungal signature composed of Scopulariopsis, Kluyveromyces, Mucor, and M. restricta achieved the highest AUC of 0.99 to differentiate ALD from NAFLD. This is the first study to identify a fungal signature to differentiate two metabolic fatty liver diseases from each other, specifically ALD from NAFLD. This might have clinical utility in unclear cases and might hence help shape treatment approaches. However, larger studies are required to validate this fungal signature in other populations of ALD and NAFLD.

Comment on: Impact of the COVID-19 pandemic on liver disease-related mortality rates in the United States

BackgroundCirrhosis is a major global health concern with increasing mortality secondary to cirrhosis and chronic liver diseases observed both in the United States and Canada. However, population-level causes of death among patients with cirrhosis in North America have not been reported.AimsThe aim of this study was to describe cause-specific mortality in patients with cirrhosis stratified by cirrhosis etiology.MethodsRetrospective cohort study using linked administrative healthcare data from Ontario, Canada. Adult patients with cirrhosis 2000/01/01-2017/12/31 were identified and etiology of liver disease was assigned as hepatitis C (HCV), hepatitis B (HBV), alcohol-associated liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), or autoimmune liver disease (AI)/other using validated algorithms for cirrhosis (sensitivity [sn] 99%, specificity [sp] 79%) and cirrhosis etiology (sn 75%-97%, sp 95%-100%). Patients were followed until death, liver transplant, or end of study. The primary outcome of cause of death was defined based on the top 10 causes of death reported by Statistics Canada; however, hepatocellular carcinoma and cholangiocarcinoma were included in liver-related deaths as opposed to malignant neoplasms. The proportion of deaths by each cause was described, stratified by cirrhosis etiology. The cumulative incidence of death with liver transplant and hepatocellular carcinoma as competing risks were calculated at 1, 5 and 10 years.Results202,022 patients with cirrhosis were identified (60% male sex, median age 56 years [IQR 46–67], 52% NAFLD, 26% ALD, 11% HCV, 5% HBV, 6% AI/Other). Overall, 81,428 (40%) patients died after a median follow-up of 5 years (IQR 2–12) and 3,024 (2%) patients received liver transplant. The overall leading cause of death was liver-related (32%) but varied substantially by cirrhosis etiology. Liver-related deaths were highest among those with viral hepatitis (HBV 56%, HCV 52%), and lowest in NAFLD (20%). In NAFLD cirrhosis, the most common causes of death were non-hepatic malignancy (26%), followed by a composite of cardiovascular disease, cerebrovascular disease, or diabetes (22%).ConclusionsAlthough the overall leading cause of death in patients with cirrhosis is liver-related, the most common causes of mortality in patients with NAFLD cirrhosis is non-hepatic malignancy, cerebrovascular disease, and diabetes. This supports the involvement of multidisciplinary teams and healthcare providers for patients with NAFLD cirrhosis to optimize appropriate cancer screening and management of co-morbid cardiovascular and metabolic conditions.Funding AgenciesNone

Focus

Bile Acids as Modulators of Gut Microbiota Linking Dietary Habits and Inflammatory Bowel Disease: A Potentially Dangerous Liaison