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Digestive Diseases and Sciences Aug 2023Hepatitis D virus (HDV) depends on hepatitis B virus (HBV) to enter and exit hepatocytes and to replicate. Despite this dependency, HDV can cause severe liver disease.... (Review)
Review
Hepatitis D virus (HDV) depends on hepatitis B virus (HBV) to enter and exit hepatocytes and to replicate. Despite this dependency, HDV can cause severe liver disease. HDV accelerates liver fibrosis, increases the risk of hepatocellular carcinoma, and hastens hepatic decompensation compared to chronic HBV monoinfection. The Chronic Liver Disease Foundation (CLDF) formed an expert panel to publish updated guidelines on the testing, diagnosis, and management of hepatitis delta virus. The panel group performed network data review on the transmission, epidemiology, natural history, and disease sequelae of acute and chronic HDV infection. Based on current available evidence, we provide recommendations for screening, testing, diagnosis, and treatment of hepatitis D infection and review upcoming novel agents that may expand treatment options. The CLDF recommends universal HDV screening for all patients who are Hepatitis B surface antigen-positive. Initial screening should be with an assay to detect antibodies generated against HDV (anti-HDV). Patients who are positive for anti-HDV IgG antibodies should then undergo quantitative HDV RNA testing. We also provide an algorithm that describes CLDF recommendations on the screening, diagnosis, testing, and initial management of Hepatitis D infection.
Topics: Coinfection; Humans; Hepatitis Delta Virus; Hepatitis D; Superinfection; Hepatitis B virus
PubMed: 37338616
DOI: 10.1007/s10620-023-07960-y -
Journal of Hepatology Oct 2023Alcohol-related liver disease is a major cause of liver disease-associated mortality, with inpatient care being a major contributor to its clinical and economic burden.... (Review)
Review
Alcohol-related liver disease is a major cause of liver disease-associated mortality, with inpatient care being a major contributor to its clinical and economic burden. Alcohol-related hepatitis (AH) is an acute inflammatory form of alcohol-related liver disease. Severe AH is associated with high short-term mortality, with infection being a common cause of death. The presence of AH is associated with increased numbers of circulating and hepatic neutrophils. We review the literature on the role of neutrophils in AH. In particular, we explain how neutrophils are recruited to the inflamed liver and how their antimicrobial functions (chemotaxis, phagocytosis, oxidative burst, NETosis) may be altered in AH. We highlight evidence for the existence of 'high-density' and 'low-density' neutrophil subsets. We also describe the potentially beneficial roles of neutrophils in the resolution of injury in AH through their effects on macrophage polarisation and hepatic regeneration. Finally, we discuss how manipulation of neutrophil recruitment/function may be used as a therapeutic strategy in AH. For example, correction of gut dysbiosis in AH could help to prevent excess neutrophil activation, or treatments could aim to enhance miR-223 function in AH. The development of markers that can reliably distinguish neutrophil subsets and of animal models that accurately reproduce human disease will be crucial for facilitating translational research in this important field.
Topics: Animals; Humans; Neutrophils; Hepatitis, Alcoholic; Phagocytosis
PubMed: 37290590
DOI: 10.1016/j.jhep.2023.05.017 -
The American Journal of Gastroenterology Jan 2024Alcohol-associated liver disease (ALD) is the most common cause of advanced hepatic disease and frequent indication for liver transplantation worldwide. With harmful...
Alcohol-associated liver disease (ALD) is the most common cause of advanced hepatic disease and frequent indication for liver transplantation worldwide. With harmful alcohol use as the primary risk factor, increasing alcohol use over the past decade has resulted in rapid growth of the ALD-related healthcare burden. The spectrum of ALD ranges from early asymptomatic liver injury to advanced disease with decompensation and portal hypertension. Compared with those with other etiologies of liver disease, patients with ALD progress faster and more often present at an advanced stage. A unique phenotype of advanced disease is alcohol-associated hepatitis (AH) presenting with rapid onset or worsening of jaundice, and acute on chronic liver failure in severe forms conveying a 1-month mortality risk of 20%-50%. The model for end stage disease score is the most accurate score to stratify AH severity (>20 defined as severe disease). Corticosteroids are currently the only available therapeutic with proven efficacy for patients with severe AH, providing survival benefit at 1 month in 50%-60% of patients. Abstinence of alcohol use, a crucial determinant of long-term outcomes, is challenging to achieve in ALD patients with concurrent alcohol use disorder (AUD). As patients with ALD are rarely treated for AUD, strategies are needed to overcome barriers to AUD treatment in patients with ALD and to promote a multidisciplinary integrated care model with hepatology, addiction medicine providers, and social workers to comprehensively manage the dual pathologies of liver disease and of AUD. Liver transplantation, a definitive treatment option in patients with advanced cirrhosis, should be considered in selected patients with AH, who are unresponsive to medical therapy and have a low risk of relapse to posttransplant alcohol use. Level of evidence and strength of recommendations were evaluated using the Grading of Recommendations, Assessment, Development, and Evaluations system. This guideline was developed under the American College of Gastroenterology Practice Parameters Committee.
Topics: Humans; Liver Diseases, Alcoholic; Risk Factors; Hepatitis, Alcoholic; Liver Cirrhosis; Alcoholism
PubMed: 38174913
DOI: 10.14309/ajg.0000000000002572 -
Clinics in Liver Disease Aug 2023Acute-on-chronic liver failure (ACLF) is a potentially reversible syndrome that develops in patients with cirrhosis or with underlying chronic liver disease (CLD) and is... (Review)
Review
Acute-on-chronic liver failure (ACLF) is a potentially reversible syndrome that develops in patients with cirrhosis or with underlying chronic liver disease (CLD) and is characterized by acute decompensation, organ failure, and high short-term mortality. Hepatitis A and hepatitis E are major causes of ACLF. Hepatitis B may also cause ACLF through a flare of hepatitis B, acute infection, or reactivation. Besides supportive care, nucleoside/nucleotide analog therapy should also be initiated in this setting. Nonhepatotropic viruses may rarely also cause ACLF with the severe acute respiratory syndrome coronavirus 2 virus recently being identified with poorer outcomes in those with underlying CLD.
Topics: Humans; Acute-On-Chronic Liver Failure; COVID-19; Hepatitis B; Hepatitis E; Liver Cirrhosis
PubMed: 37380286
DOI: 10.1016/j.cld.2023.03.006 -
HIV Medicine Nov 2023The European AIDS Clinical Society (EACS) guidelines were revised in 2023 for the 19th time, and all aspects of HIV care were updated.
BACKGROUND
The European AIDS Clinical Society (EACS) guidelines were revised in 2023 for the 19th time, and all aspects of HIV care were updated.
KEY POINTS OF THE GUIDELINES UPDATE
Version 12.0 of the guidelines recommend the same six first-line treatment options for antiretroviral treatment (ART)-naïve adults as versions 11.0 and 11.1: tenofovir-based backbone plus an unboosted integrase inhibitor or doravirine; abacavir/lamivudine plus dolutegravir; or dual therapy with lamivudine or emtricitabine plus dolutegravir. The long-acting section has been expanded in the ART and drug-drug interaction (DDI) panels. Tables for preferred and alternative ART in children and adolescents have been updated, as has the section on prevention of vertical transmission, particularly with new guidance for breastfeeding. A new DDI table has been included for the ART and anti-infective drugs used for opportunistic infections, sexually transmitted infections, and other infectious conditions; lenacapavir has been included in all DDI tables. New sections on alcohol use and patient-reported outcome measures (PROMs) have been included in the comorbidity panel, in addition to updates on many relevant topics, such as new resource guidance for deprescribing in people with HIV. Other sections, including travel, cognitive impairment, cancer screening, sexual health, and diabetes have also been revised extensively. The algorithm for the management of acute hepatitis C virus infection has been removed, as current guidelines recommend immediate treatment of all people with recently acquired hepatitis C virus. Updates on vaccination for hepatitis B virus and recommendations for simplification to tenofovir-free two-drug regimens in people with isolated anti-hepatitis B core antibodies are provided. In the opportunistic infections and COVID-19 panel, guidance on the management of COVID-19 in people with HIV has been updated according to the most up-to-date evidence, and a new section on monkeypox has been added.
CONCLUSIONS
In 2023, the EACS guidelines were updated extensively and now include several new sections. The recommendations are available as a free app, in interactive web format, and as a pdf online.
Topics: Adolescent; Adult; Child; Humans; Acquired Immunodeficiency Syndrome; AIDS-Related Opportunistic Infections; Anti-HIV Agents; Anti-Retroviral Agents; COVID-19; Hepatitis C; HIV Infections; Lamivudine; Tenofovir; Practice Guidelines as Topic
PubMed: 37849432
DOI: 10.1111/hiv.13542 -
The Lancet. Public Health Sep 2023In 2016, the World Health Assembly adopted the resolution to eliminate viral hepatitis by 2030. This study aims to provide an overview of the burdens of hepatitis B...
BACKGROUND
In 2016, the World Health Assembly adopted the resolution to eliminate viral hepatitis by 2030. This study aims to provide an overview of the burdens of hepatitis B virus (HBV) and hepatitis C virus (HCV) in Europe and their changes from 2010 to 2019 using estimates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019.
METHODS
We used GBD 2019 estimates of the burden associated with HBV-related and HCV-related diseases: acute hepatitis, cirrhosis and other chronic liver diseases, and liver cancer. We report total numbers and age-standardised rates per 100 000 for mortality, prevalence, incidence, and disability-adjusted life-years (DALYs) from 2010 to 2019. For each HBV-related and HCV-related disease and each measure, we analysed temporal changes and percentage changes for the 2010-19 period.
FINDINGS
In 2019, across all age groups, there were an estimated 2·08 million (95% uncertainty interval [UI] 1·66 to 2·54) incident cases of acute hepatitis B and 0·49 million (0·42 to 0·57) of hepatitis C in Europe. There were an estimated 8·24 million (7·56 to 8·88) prevalent cases of HBV-related cirrhosis and 11·87 million (9·77 to 14·41) of HCV-related cirrhosis, with 24·92 thousand (19·86 to 31·03) deaths due to HBV-related cirrhosis and 36·89 thousand (29·94 to 45·56) deaths due to HCV-related cirrhosis. Deaths were estimated at 9·00 thousand (6·88 to 11·62) due to HBV-related liver cancer and 23·07 thousand (18·95 to 27·31) due to HCV-related liver cancer. Between 2010 and 2019, the age-standardised incidence rate of acute hepatitis B decreased (-22·14% [95% UI -35·44 to -5·98]) as did its age-standardised mortality rate (-33·27% [-43·03 to -25·49]); the age-standardised prevalence rate (-20·60% [-22·09 to -19·10]) and mortality rate (-33·19% [-37·82 to -28·13]) of HBV-related cirrhosis also decreased in this time period. The age-standardised incidence rate of acute hepatitis C decreased by 3·24% (1·17 to 5·02) and its age-standardised mortality rate decreased by 35·73% (23·48 to 47·75) between 2010 and 2019; the age-standardised prevalence rate (-6·37% [-8·11 to -4·32]), incidence rate (-5·87% [-11·24 to -1·01]), and mortality rate (-11·11% [-16·54 to -5·53]) of HCV-related cirrhosis also decreased. No significant changes were observed in age-standardised rates of HBV-related and HCV-related liver cancer, although we observed a significant increase in numbers of cases of HCV-related liver cancer across all ages between 2010 and 2019 (16·41% [2·81 to 30·91] increase in prevalent cases). Substantial reductions in DALYs since 2010 were estimated for acute hepatitis B (-27·82% [-36·92 to -20·24]), acute hepatitis C (-27·07% [-15·97 to -39·34]), and HBV-related cirrhosis (-30·70% [-35·75 to -25·03]). A moderate reduction in DALYs was estimated for HCV-related cirrhosis (-6·19% [-0·19 to -12·57]). Only HCV-related liver cancer showed a significant increase in DALYs (10·37% [4·81-16·63]). Changes in age-standardised DALY rates closely resembled those observed for overall DALY counts, except for HCV-liver related cancer (-2·84% [-7·75 to 2·63]).
INTERPRETATION
Although decreases in some HBV-related and HCV-related diseases were estimated between 2010 and 2019, HBV-related and HCV-related diseases are still associated with a high burden, highlighting the need for more intensive and coordinated interventions within European countries to reach the goal of elimination by 2030.
FUNDING
Bill & Melinda Gates Foundation.
Topics: Humans; Europe; Global Burden of Disease; Hepatitis B; Hepatitis C; Liver Cirrhosis; Liver Neoplasms
PubMed: 37633679
DOI: 10.1016/S2468-2667(23)00149-4 -
Viruses Nov 2023Acute hepatitis B infection is associated with severe liver disease and chronic sequelae in some cases. The purpose of this review was to determine the efficacy of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Acute hepatitis B infection is associated with severe liver disease and chronic sequelae in some cases. The purpose of this review was to determine the efficacy of nucleoside analogues (NA) (lamivudine versus entecavir) compared to placebo or no intervention for treating acute primary HBV infection.
METHODS
A meta-analysis for drug intervention was performed, following a fixed-effect model. Randomized controlled trials (RCTs) and quasi-randomized studies that evaluated the outcomes of NA in acute hepatitis B infection were included. The following outcomes were considered: virological cure (PCR negative), elimination of acute infection (seroconversion of HBsAg), mortality, and serious adverse events.
RESULTS
Five trials with 627 adult participants with severe acute hepatitis B defined by biochemical and serologic parameters were included. Virological cure did not favor any intervention: OR 0.96, 95% CI 0.54 to 1.7 ( = 0.90), I2 = 58%. Seroconversion of HBsAg to negative favored placebo/standard-of-care compared to lamivudine: OR 0.54, 95% CI 0.33 to 0.9 ( = 0.02), I2 = 31%. The only trial that compared entecavir and lamivudine favored entecavir over lamivudine (OR: 3.64, 95% CI 1.31-10.13; 90 participants). Adverse events were mild.
CONCLUSION
There is insufficient evidence that NA obtain superior efficacy compared with placebo/standard-of-care in patients with acute viral hepatitis, based on low quality evidence.
Topics: Adult; Humans; Lamivudine; Antiviral Agents; Hepatitis B Surface Antigens; Hepatitis B; Hepatitis B virus; Hepatitis B, Chronic; Treatment Outcome; DNA, Viral
PubMed: 38005918
DOI: 10.3390/v15112241