Hepatology : Official Journal of the American Association for the Study of Liver Diseases

AIMS: Men who have sex with men (MSM) are vulnerable to contracting hepatitis B virus (HBV) as a sexually transmitted infection (STI). We evaluated the incidence of HBV infection (HBI) and the prophylactic effect of tenofovir-based pre-exposure prophylaxis (PrEP) on HBI in an MSM cohort. METHODS: MSM who were older than 16 years were enrolled from January 2018 and followed up until June 2021 and tested for HIV, bacterial STIs, and hepatitis B surface antigen (HBsAg)/hepatitis B surface antibody (HBsAb) and hepatitis B core antibody (HBcAb) every 3 months based on inclusion criteria, including HBsAg, HBcAb, HBsAb, and human immunodeficiency virus (HIV) negativity at enrollment...

BACKGROUND: Adolescents constitute a unique waitlist cohort that is distinct from younger children. MELD 3.0, which was developed in an adult population of liver transplant candidates, is planned to replace MELD-Na in the current liver allocation system for both adult and adolescents aged 12-17. We evaluated the predictive performance of MELD-Na, MELD 3.0, and PELD, for 90-day waitlist mortality risk among adolescent liver transplant registrants. METHODS: New waitlist registrations for primary liver transplant among individuals aged 12-17 and aged 18-25 for comparison were identified using OPTN data from Nov 17 2004 to Dec 31 2021...

BACKGROUND AND AIMS: Acute-on-chronic liver failure (ACLF) is an acute liver and multisystem failure in patients with previously stable cirrhosis. A common cause of ACLF is sepsis secondary to bacterial infection. Sepsis-associated ACLF involves a loss of differentiated liver function in the absence of direct liver injury, and its mechanism is unknown. We aimed to study the mechanism of sepsis associated ACLF using a novel mouse model. APPROACH AND RESULTS: Sepsis-associated ACLF was induced by cecal ligation and puncture procedure (CLP) in mice treated with thioacetamide (TAA)...

BACKGROUND AIMS: Parathyroid hormone receptor-1 (PTH1R) is a class B G protein-coupled receptor central to skeletal development, bone turnover, and calcium homeostasis. However, the role of PTH1R signaling in liver fibrosis is largely unknown. Here, the role of PTH1R signaling in the activation of hepatic stellate cells (HSCs) and hepatic fibrosis was examined. APPROACH RESULTS: PTH1R was highly expressed in activated HSCs and fibrotic liver by using human liver specimens or carbon tetrachloride (CCl4)-treated or methionine and choline-deficient diet (MCD)-fed C57/BL6 mice...

Alcohol-associated liver disease due to harmful alcohol use and non-alcoholic fatty liver disease associated with metabolic syndrome are the two most common liver diseases worldwide. Control of respective risk factors is the cornerstone in the long-term management of these diseases. Furthermore, there are no effective therapies. Both diseases are characterized by metabolic derangements, thus, the focus of this review is to broaden our understanding of metabolic targets investigated in non-alcoholic fatty liver disease, and how these can be applied to alcohol-associated liver disease...

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BACKGROUND: We evaluated the diagnostic accuracy of simple non-invasive tests(NITs) in NAFLD patients with type 2 diabetes(T2D). METHODS: This was an individual patient data meta-analysis of 1780 patients with biopsy-proven NAFLD and T2D. The index tests of interest were FIB-4, NAFLD Fibrosis Score(NFS), APRI, liver stiffness measurement(LSM) by vibration-controlled transient elastography(VCTE) and AGILE 3+. The target conditions were advanced fibrosis, nonalcoholic steatohepatitis(NASH) and fibrotic NASH(NASH plus F2-F4 fibrosis)...

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BACKGROUND AND AIMS: Beta-blockers have been studied for the prevention of variceal bleeding and, more recently, for the prevention of all cause decompensation. Some uncertainties regarding the benefit of beta-blockers for the prevention of decompensation remain. Bayesian analyses enhance the interpretation of trials. The purpose of this study was to provide clinically meaningful estimates of both the probability and magnitude of benefit with beta-blocker treatment across a range of patient types...

Current recommendations for the surveillance of hepatocellular carcinoma are based on semiannual liver ultrasound (with or without serum alpha fetoprotein) in patients with cirrhosis and in subgroups with chronic hepatitis B infection. However, the sensitivity of this strategy is suboptimal for the detection of early-stage tumors especially in obese patients, due to inter-operator variability, and poor adherence. The detection rate of focal liver lesions is excellent with Magnetic Resonance Imaging (MRI), making it the best alternative candidate for surveillance...

BACKGROUND AND AIMS: Long-term maintenance of viral control, even HBsAg loss, remains a challenge for chronic hepatitis B (CHB) patients undergoing nucleos(t)ide analogue (NA) discontinuation. This study aimed to investigate the relationship between HBV-specific T cell responses targeting peptides spanning the whole proteome and clinical outcomes in CHB patients after NA discontinuation. APPROACH AND RESULTS: Eighty-eight CHB patients undergoing NA discontinuation were classified as responders (remained relapse-free up to 96 wk) or relapsers (relapsed patients who underwent NA re-treatment for up to 48 weeks and re-achieved stable viral control)...

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BACKGROUND AND AIMS: Mutations within the precore (PC) and basal core promoter (BCP) regions of the HBV genome are associated with fulminant hepatitis and HBV reactivation. These mutations may enhance viral replication, but little is known about whether they directly induce damage to the liver. We investigated mechanisms of direct cytopathic effects induced by infection with PC/BCP mutants in the absence of immune response in vitro and in vivo. APPROACH RESULTS: Mice with humanized livers and hepatocytes derived from humanized mice were infected with either wild-type or mutant-type PC/BCP HBV, and HBV replication and human hepatocyte damage were evaluated...

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