-
Liver Transplantation : Official... Jul 2020
Topics: Consensus; Hepatitis, Alcoholic; Humans; Liver Transplantation
PubMed: 32198966
DOI: 10.1002/lt.25763 -
Annals of Hepatology 2023Liver diseases are a major cause of morbidity and mortality globally. In the Philippines, a lower middle-income country in Southeast Asia, liver diseases accounted for... (Review)
Review
Liver diseases are a major cause of morbidity and mortality globally. In the Philippines, a lower middle-income country in Southeast Asia, liver diseases accounted for 27.3 cases per 1000 deaths. In this review, we discussed the prevalence, risk factors, and management of hepatitis B, hepatitis C and other viral hepatitis, non-alcoholic fatty liver disease, alcohol-associated liver disease, liver cirrhosis, and hepatocellular carcinoma. The true burden of liver disease in the Philippines is likely underestimated due to limited epidemiological studies. Thus, surveillance of liver disease should be strengthened. Clinical practice guidelines tailored to the local needs of the country have been developed for important liver diseases. Multisectoral cooperation among different stakeholders is needed to manage the burden of liver disease in the Philippines.
Topics: Humans; Philippines; Liver Diseases, Alcoholic; Liver Cirrhosis; Risk Factors; Carcinoma, Hepatocellular; Non-alcoholic Fatty Liver Disease; Liver Neoplasms
PubMed: 36889673
DOI: 10.1016/j.aohep.2023.101085 -
Clinics in Liver Disease Aug 2021Malnutrition is common in alcohol-associated hepatitis (AH); almost all patients with severe AH have some component of malnutrition. The classic phenotype of... (Review)
Review
Malnutrition is common in alcohol-associated hepatitis (AH); almost all patients with severe AH have some component of malnutrition. The classic phenotype of malnutrition in AH is sarcopenia, but this has become more difficult to discern clinically as patients have become more obese. Patients with AH are often drinking 10 to 15 standard drinks per day. This substantial alcohol consumption becomes a major source of calories, but these are considered "empty" calories that contain little nutritional value. Malnutrition is associated with liver complications, such as hepatic encephalopathy, and worse liver outcomes. Nutrition support can improve nutrition status and reduce complications.
Topics: Hepatic Encephalopathy; Hepatitis, Alcoholic; Humans; Malnutrition; Nutritional Status; Nutritional Support
PubMed: 34229839
DOI: 10.1016/j.cld.2021.03.002 -
Topics in Antiviral Medicine Sep 2019Among individuals with HIV infection, liver disease remains an important cause of morbidity and mortality, even with the availability of agents that cure hepatitis C...
Among individuals with HIV infection, liver disease remains an important cause of morbidity and mortality, even with the availability of agents that cure hepatitis C infection and suppress hepatitis B replication. The causes of liver disease are multifaceted and continue to evolve as the population ages and new etiologies arise. Nonalcoholic fatty liver disease and nonalcoholic steatohepatitis and hepatitis viruses such as A, D, and E have emerged even as hepatitis C has receded. Newer antiretroviral agents may increase risk of weight gain and subsequent fatty infiltration, and prior use of nucleotide-based therapies may continue to impact liver health. Several barriers including economics, social stigma, and psychiatric disease impact identification of liver disease, as well as management and treatment interventions. Hepatocellular carcinoma is emerging as a more common and late-diagnosed complication in those with HIV infection and liver disease.
Topics: Antirheumatic Agents; Carcinoma, Hepatocellular; Fatty Liver; Fatty Liver, Alcoholic; HIV Infections; Hepatitis A; Hepatitis B; Hepatitis C; Hepatitis D; Hepatitis E; Hepatitis Viruses; Hepatitis, Viral, Human; Humans; Liver; Liver Diseases; Non-alcoholic Fatty Liver Disease
PubMed: 31634861
DOI: No ID Found -
Seminars in Liver Disease Feb 2023Alcohol-associated liver disease is a leading cause of mortality and morbidity worldwide. Patients with alcohol-associated liver disease are often diagnosed at advanced... (Review)
Review
Alcohol-associated liver disease is a leading cause of mortality and morbidity worldwide. Patients with alcohol-associated liver disease are often diagnosed at advanced stage and disease spectrum including alcoholic hepatitis, a severe manifestation with a high short-term mortality. Corticosteroid, recommended first-line treatment for patients with alcoholic hepatitis, is a very suboptimal treatment. Although the use of early liver transplantation has increased with consistent benefit in select patients with alcoholic hepatitis, its use remains heterogeneous worldwide due to lack of uniform selection criteria. Over the last decade, several therapeutic targets have evolved of promise with ongoing clinical trials in patients with cirrhosis and alcoholic hepatitis. Even with availability of effective medical therapies for alcohol-associated liver disease, long-term outcome depends on abstinence from alcohol use in any spectrum of alcohol-associated liver disease. However, alcohol use disorder treatment remains underutilized due to several barriers even in patients with advanced disease. There is an urgent unmet need to implement and promote integrated multidisciplinary care model with hepatologists and addiction experts to provide comprehensive management for these patients. In this review, we will discuss newer therapies targeting liver disease and therapies targeting alcohol use disorder in patients with alcohol-associated liver disease.
Topics: Humans; Hepatitis, Alcoholic; Alcoholism; Liver Diseases, Alcoholic; Alcohol Drinking; Treatment Outcome
PubMed: 36572032
DOI: 10.1055/s-0042-1759614 -
Cells Feb 2022Viral infections or persistent alcohol or drug abuse, together with intrinsic factors, lead to hepatitis, which often ends in the development of liver cirrhosis or... (Review)
Review
Viral infections or persistent alcohol or drug abuse, together with intrinsic factors, lead to hepatitis, which often ends in the development of liver cirrhosis or hepatocellular carcinoma (HCC). With this review, we describe inflammatory liver diseases, such as acute liver failure, virus-induced hepatitis, alcoholic- and non-alcoholic steatohepatitis, and autoimmune hepatitis, and highlight their driving mechanisms. These include external factors such as alcohol misuse, viral infection and supernutrition, as well as intrinsic parameters such as genetic disposition and failure, in immune tolerance. Additionally, we describe what is known about the translational machinery within all these diseases. Distinct eukaryotic translation initiation factors (eIFs) with specific functional roles and aberrant expression in HCC are reported. Many alterations to the translational machinery are already triggered in the precancerous lesions described in this review, highlighting mTOR pathway proteins and eIFs to emphasize their putative clinical relevance. Here, we identified a lack of knowledge regarding the roles of single eIF proteins. A closer investigation will help to understand and treat HCC as well as the antecedent diseases.
Topics: Carcinogenesis; Carcinoma, Hepatocellular; Ethanol; Hepatitis, Viral, Human; Humans; Inflammation; Liver Cirrhosis; Liver Neoplasms; Non-alcoholic Fatty Liver Disease; TOR Serine-Threonine Kinases
PubMed: 35159342
DOI: 10.3390/cells11030533 -
Hepatology International Sep 2020Alcoholic hepatitis (AH) is a clinical syndrome characterized by jaundice and progressive inflammatory liver injury in patients with a history of prolonged periods of... (Review)
Review
Alcoholic hepatitis (AH) is a clinical syndrome characterized by jaundice and progressive inflammatory liver injury in patients with a history of prolonged periods of excess alcohol consumption and recent heavy alcohol abuse. Severe AH is a life-threatening form of alcohol-associated liver disease with a high short-term mortality rate around 30-50% at one month from the initial presentation. A large number of pro-inflammatory mediators, metabolic pathways, transcriptional factors and epigenetic factors have been suggested to be associated with the development and progression of AH. Several factors may contribute to liver failure and mortality in patients with severe AH including hepatocyte death, inflammation, and impaired liver regeneration. Although the pathogeneses of AH have been extensively investigated and many therapeutic targets have been identified over the last five decades, no new drugs for AH have been successfully developed. In this review, we discuss interleukin-22 (IL-22) biology and its roles of anti-apoptosis, anti-fibrosis, anti-oxidation, anti-bacterial infection and regenerative stimulation in protecting against liver injury in many preclinical models including several recently developed models such as chronic-plus-binge ethanol feeding, acute-on-chronic liver failure, C-X-C motif chemokine ligand 1 plus high-fat diet-induced nonalcoholic steatohepatitis. Finally, clinical trials of IL-22 for the treatment of AH are also discussed, which showed some promising benefits for AH patients.
Topics: Hepatitis, Alcoholic; Humans; Interleukins; Liver; Liver Regeneration; Models, Biological; Interleukin-22
PubMed: 32892258
DOI: 10.1007/s12072-020-10082-6 -
Gastroenterology Nov 2019Activation of TGFB (transforming growth factor β) promotes liver fibrosis by activating hepatic stellate cells (HSCs), but the mechanisms of TGFB activation are not...
BACKGROUND & AIMS
Activation of TGFB (transforming growth factor β) promotes liver fibrosis by activating hepatic stellate cells (HSCs), but the mechanisms of TGFB activation are not clear. We investigated the role of ECM1 (extracellular matrix protein 1), which interacts with extracellular and structural proteins, in TGFB activation in mouse livers.
METHODS
We performed studies with C57BL/6J mice (controls), ECM1-knockout (ECM1-KO) mice, and mice with hepatocyte-specific knockout of EMC1 (ECM1). ECM1 or soluble TGFBR2 (TGFB receptor 2) were expressed in livers of mice after injection of an adeno-associated virus vector. Liver fibrosis was induced by carbon tetrachloride (CCl) administration. Livers were collected from mice and analyzed by histology, immunohistochemistry, in situ hybridization, and immunofluorescence analyses. Hepatocytes and HSCs were isolated from livers of mice and incubated with ECM1; production of cytokines and activation of reporter genes were quantified. Liver tissues from patients with viral or alcohol-induced hepatitis (with different stages of fibrosis) and individuals with healthy livers were analyzed by immunohistochemistry and in situ hybridization.
RESULTS
ECM1-KO mice spontaneously developed liver fibrosis and died by 2 months of age without significant hepatocyte damage or inflammation. In liver tissues of mice, we found that ECM1 stabilized extracellular matrix-deposited TGFB in its inactive form by interacting with αv integrins to prevent activation of HSCs. In liver tissues from patients and in mice with CCl-induced liver fibrosis, we found an inverse correlation between level of ECM1 and severity of fibrosis. CCl-induced liver fibrosis was accelerated in ECM1 mice compared with control mice. Hepatocytes produced the highest levels of ECM1 in livers of mice. Ectopic expression of ECM1 or soluble TGFBR2 in liver prevented fibrogenesis in ECM1-KO mice and prolonged their survival. Ectopic expression of ECM1 in liver also reduced the severity of CCl-induced fibrosis in mice.
CONCLUSIONS
ECM1, produced by hepatocytes, inhibits activation of TGFB and its activation of HSCs to prevent fibrogenesis in mouse liver. Strategies to increase levels of ECM1 in liver might be developed for treatment of fibrosis.
Topics: ATP Binding Cassette Transporter, Subfamily B; Animals; Carbon Tetrachloride; Chemical and Drug Induced Liver Injury; Extracellular Matrix Proteins; Hepatic Stellate Cells; Hepatitis, Alcoholic; Hepatitis, Viral, Human; Humans; Liver; Liver Cirrhosis, Alcoholic; Liver Cirrhosis, Experimental; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Signal Transduction; Transforming Growth Factor beta; ATP-Binding Cassette Sub-Family B Member 4
PubMed: 31362006
DOI: 10.1053/j.gastro.2019.07.036 -
Current Opinion in Organ Transplantation Apr 2023Early liver transplantation is emerging as a treatment option for severe alcohol-associated hepatitis refractory to pharmacotherapies. This review outlines the current... (Review)
Review
PURPOSE OF REVIEW
Early liver transplantation is emerging as a treatment option for severe alcohol-associated hepatitis refractory to pharmacotherapies. This review outlines the current status of transplantation for alcohol-associated hepatitis and the treatment of alcohol use disorder after liver transplantation.
RECENT FINDINGS
Rates of early liver transplantation for alcohol-associated hepatitis are increasing with significant heterogeneity in practices across the Unites States. Recent studies have demonstrated a substantial survival benefit in patients transplanted for alcohol-associated hepatitis with improved outcomes in early vs. late transplantation, first vs. prior hepatic decompensation, and posttransplant abstinence/delayed relapse vs. early return to alcohol use. Several prediction algorithms have been developed to ascertain patients' risk of alcohol relapse and aid in candidate selection, though data on treatment of alcohol use disorders in transplant recipients remains limited.
SUMMARY
Although controversial, early liver transplantation for severe alcohol-associated hepatitis has shown to be a lifesaving intervention. Additional research is needed to evaluate its long-term outcomes, optimize candidate selection, and understand treatment of alcohol use disorder posttransplant.
Topics: Humans; Liver Transplantation; Alcoholism; Hepatitis, Alcoholic; Alcohol Drinking; Recurrence
PubMed: 36512482
DOI: 10.1097/MOT.0000000000001044 -
Translational Gastroenterology and... 2020Alcoholic hepatitis (AH) is associated with a high short-term mortality. Currently, most transplant centers require minimum six months of abstinence from alcohol use... (Review)
Review
Alcoholic hepatitis (AH) is associated with a high short-term mortality. Currently, most transplant centers require minimum six months of abstinence from alcohol use before considering liver transplant for patients with end stage liver disease. Some recent data are emerging on the benefits and safety of early liver transplantation for patients with severe AH, a population who cannot meet the minimum six months sobriety. This article reviews the current status, benefits, challenges, barriers, and future prospects on early liver transplantation in patients with severe, acute AH.
PubMed: 32258530
DOI: 10.21037/tgh.2019.11.17