Beta-blocker plus nitrates for secondary prevention of variceal bleeding

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Portal biliopathy

In patients with portal hypertension, particularly with extrahepatic portal vein obstruction, portal biliopathy producing biliary ductal and gallbladder wall abnormalities are common. Portal cavernoma formation, choledochal varices and ischemic injury of the bile duct have been implicated as causes of these morphological alterations. While a majority of the patients are asymptomatic, some present with a raised alkaline phosphatase level, abdominal pain, fever and cholangitis. Choledocholithiasis may develop as a complication and manifest as obstructive jaundice with or without cholangitis. Endoscopic sphincterotomy and stone extraction can effectively treat cholangitis when jaundice is associated with common bile duct stone(s). Definitive decompressive shunt surgery is sometimes required when biliary obstruction is recurrent and progressive

Gene expression signatures of peripheral CD4+ T cells clearly discriminate between patients with acute and chronic hepatitis B infection

CD4+ T and regulatory T cells (Tregs) seem to play a key role in persistence of hepatitis B virus (HBV) infection. However, the molecular events by which Tregs exert their modulatory activity are largely unknown. The transcriptional profiles of CD4+ T cells of healthy controls (HCs) and patients affected by acute hepatitis B (AVH-B) or chronic hepatitis B (CHB) infection were established using a custom expression array consisting of 350 genes relevant for CD4+ T cell and Treg function. These studies were complemented by real-time reverse-transcription polymerase chain reaction. Peripheral blood mononuclear cells (PBMCs) were also analyzed for the presence of Tregs, which were more abundant in the acute stage of the disease (7%) than in HCs and CHB infection (HCs versus AVH-B, P = 0.003; AVH-B versus CHB, P = 0.04). One hundred eighteen genes (34%) intrinsically differentiate HBV-infected patients from HCs. Using gene ontology, we identified T cell receptor signaling and clusterization, mitogen-activated protein kinase kinase signaling, cell adhesion, cytokines and inflammatory responses, cell cycle/cell proliferation, and apoptosis as the most prominent affected modules. A higher expression of CCR1, CCR3, CCR4, CCR5, and CCR8 was seen in AVH-B than in CHB-infected patients and HCs. Annotation of the interconnected functional network of genes provided a unique representation of global immune activation during acute infection. Almost all genes were down-regulated in patients with CHB infection. Conclusion: The fingerprints enable clear discrimination between patients suffering from AVH-B or CHB infection. The observed profiles suggest accumulation of effector T cells with a potential role in necro-inflammation during the acute stage. Subsequent down-regulated effector functions support the hypothesis of suppressed CD4+ effector T cells favoring viral persistence in the chronic infection stage

Congenital extrahepatic portosystemic shunts (Abernethy malformation): An international observational study

Congenital extrahepatic portosystemic shunt (CEPS) or Abernethy malformation is a rare condition in which splanchnic venous blood bypasses the liver draining directly into systemic circulation through a congenital shunt. Patients may develop hepatic encephalopathy (HE), pulmonary hypertension (PaHT), or liver tumors, among other complications. However, the actual incidence of such complications is unknown, mainly because of the lack of a protocolized approach to these patients. This study characterizes the clinical manifestations and outcome of a large cohort of CEPS patients with the aim of proposing a guide for their management. This is an observational, multicenter, international study. Sixty-six patients were included; median age at the end of follow-up was 30 years. Nineteen patients (28%) presented HE. Ten-, 20-, and 30-year HE incidence rates were 13%, 24%, and 28%, respectively. No clinical factors predicted HE. Twenty-five patients had benign nodular lesions. Ten patients developed adenomas (median age, 18 years), and another 8 developed HCC (median age, 39 years). Of 10 patients with dyspnea, PaHT was diagnosed in 8 and hepatopulmonary syndrome in 2. Pulmonary complications were only screened for in 19 asymptomatic patients, and PaHT was identified in 2. Six patients underwent liver transplantation for hepatocellular carcinoma or adenoma. Shunt closure was performed in 15 patients with improvement/stability/cure of CEPS manifestations. Conclusion: CEPS patients may develop severe complications. Screening for asymptomatic complications and close surveillance is needed. Shunt closure should be considered both as a therapeutic and prophylactic approach

Regional differences in clinical presentation and prognosis of patients with post-sustained virologic response (SVR) hepatocellular carcinoma.

Background& Amis: Widespread use of direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection has resulted in increased numbers of patients with hepatocellular carcinoma (HCC) after achieving sustained virologic response ('post-SVR HCC') worldwide. Few data compare regional differences in presentation and prognosis of patients with post-SVR HCC.MethodsWe identified patients with advanced fibrosis (F3/F4) who developed incident post-SVR HCC between March, 2015 and October, 2021 from 30 sites in Europe, North America, South America, Middle East, South Asia, East Asia, and Southeast Asia. We compared patient demographics, liver dysfunction, and tumor burden by region. We compared overall survival by region using Kaplan-Meier analysis and identified factors associated with survival using multivariable Cox regression analysis.ResultsAmong 8,796 patients with advanced fibrosis or cirrhosis who achieved SVR, 583 (6.6%) developed incident HCC. There was marked regional variation in the proportion of detection by surveillance (range: 59.5-100%), median maximum tumor diameter (range: 1.8-5.0 cm), and proportion with multinodular HCC (range: 15.4-60.8%). Prognosis of patients highly varied by region (HR range: 1.82-9.92), with the highest survival in East Asia, North America, and South America, and lowest in the Middle East and South Asia. After adjusting for geographic region, HCC surveillance was associated with early-stage detection (BCLC stage 0/A: 71.0% vs. 21.3%, pConclusionsClinical characteristics, including early-stage detection, and prognosis of post-SVR HCC significantly differed across geographic regions. Surveillance utilization appears to be a high-yield intervention target to improve prognosis among patients with post-SVR HCC globally