Beta-blocker plus nitrates for secondary prevention of variceal bleeding

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Maternal and fetal outcomes in pregnant women with acute hepatitis E virus infection

Background: Hepatitis E virus (HEV) infection is known to cause severe liver disease in pregnant women. It is unclear whether obstetric and fetal outcomes are worse in pregnant women with HEV infection than in women with other forms of viral hepatitis. Objective: To compare maternal, obstetric, and fetal outcomes in pregnant women with acute viral hepatitis caused by HEV and other hepatitis viruses. Design: Observational cohort. Setting: Tertiary care hospital, New Delhi, India. Patients: 220 consecutive pregnant women presenting with jaundice caused by acute viral hepatitis. Measurements: Maternal mortality and medical complications, obstetric complications, deliveries, and fetal outcomes. Results: Infection with HEV caused acute viral hepatitis in 60% of included women. Fulminant hepatic failure was more common (relative risk, 2.7 [95% CI, 1.7 to 4.2]; P = 0.001) and maternal mortality was greater (relative risk, 6.0 [CI, 2.7 to 13.3]; P < 0.001) in HEV-infected women than in non-HEV-infected women. Women with HEV infection were more likely than those with other forms of viral hepatitis to have obstetric complications (relative risk, 4.1 [CI, 1.7 to 10.2] for antepartum hemorrhage and 1.9 [CI, 1.3 to 2.7] for intrauterine fetal death; P < 0.001 for both) and poor fetal outcomes (relative risk, 1.2 [CI, 1.0 to 1.4] for preterm delivery [P = 0.005] and 1.8 [CI, 1.2 to 2.5] for stillbirth [P = 0.026]). Limitations: The findings may not apply to community settings, to women who are asymptomatic or have only minor symptoms, or in the setting of an HEV epidemic. Conclusions: Pregnant women with jaundice and acute viral hepatitis caused by HEV infection had a higher maternal mortality rate and worse obstetric and fetal outcomes than did pregnant women with jaundice and acute viral hepatitis caused by other types of viral hepatitis

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

Predicting prognosis in large cohort of decompensated cirrhosis of liver (DCLD)- a machine learning (ML) approach

Background and aims: Onset of decompensation in cirrhosis is associated with poor outcome. The current clinico-biochemical tools have limited accuracy in predicting outcomes reliably. Identifying the predictors with precision model on the big data using artificial intelligence may improve predictability. We aimed to develop a machine learning (ML) based prognostic model for predicting 90 day survival in patients of cirrhosis presenting with decompensation. Method: We analysed electronic medical records retrospectively of hospitalised cirrhosis patients at the ILBS, with a complete 90-day follow-up. Clinical data, laboratory parameters and organ involvement were serially noted. AI-modelling was done after appropriate mining, feature engineering, splitted randomly into train and testsets (20:80). The class imbalance problem was handled by random over-sampling technique, to make balanced 50:50 ratios. After 10- fold cross validation, 3 repetitions and grid search for optimal hyper parameters, the XGB-CV model was chosen. AUC was the primary selection criteria and confusion matrix was used to compare AUCs between AI-models and existing indices; CTP and MELD-score. Results: Total of 6326 patients [mean age 48.2 ± 11.5 years, 84% male, Mean CTP 10.4 ± 2.2 and MELD Na-30.4 ± 11.9, alcohol 49.4%] were included. Ninety day mortality was 29.2%. Acute insult was identified in 80% cases; of which extra-hepatic 49%, hepatic 46% and unknown 5% cases respectively. The XGB-CV model had the best accuracy for prediction of 90 days event in the train set 0.90 (0.90–0.93), validation set 0.80 (0.79–0.81) and for overall dataset 0.80 (0.79– 0.81). The AUC of the XGB-CV model was better than CTP and MELD Na-score by 16% and 15% respectively. The prediction model considered 43 variables; 18 of which predicted the outcome, and 10 maximum contributors are shown in concordance classifier. The most contributors to poor outcome included, index presentation as HE, diagnosis of AD/ACLF/ESLD, PT-INR, serum creatinine, total bilirubin, acute insult etiology, prior decompensation, acute hepatic or extrahepatic insult, leukocyte count and present duration of illness. In the Decision Tree Model, the presence of HE, PT-INR and syndromic diagnosis of AD or ACLF/ESLD was able to stratify the patients into low (22%), intermediate (23–46%) and high risk (\u3e75%) of mortality at 90 days. Conclusion: The AI based current model developed using a large data base of CLD patients presenting with decompensation immensely adds to the current indices of liver disease severity and can stratify patients at admission. Simple ML algorithms using HE and INR besides syndromic presentation, could help treatment decisions and prognostication

Characterization of naturally occurring and lamivudine-induced surface gene mutants of hepatitis B virus in patients with chronic hepatitis B in India

Background: Besides vaccine escape or immune escape hepatitis B virus (HBV) mutants, naturally occurring and drug-induced mutations have been reported in the surface gene (S-gene) of HBV. Aim: To investigate the frequency and profile of naturally occurring S-gene mutants and the influence of long-term lamivudine therapy in patients with chronic hepatitis B (CHB). Materials and Methods: 57 patients with histologically proven CHB, on lamivudine 100 mg/day for more than 24 months, were included. Viral DNA was extracted at baseline and from on-therapy serum samples. The region encoding the complete major hydrophilic region (MHR) and flanking regions (nucleotides 425-840) of major S-gene that overlapped with the viral polymerase was PCR amplified and sequenced. End-of-therapy response (ETR) was assessed. Results: Two (3.5%) patients had naturally occurring HBV mutants, sP127S and sS143L seen in the 'a' determinant of the S-gene. Following lamivudine therapy, 14 of 57 (24.5%) patients developed 16 types of S-gene mutations (sP120S, sA128V, sS143L, sW182St., sT189I, sV190A, sS193L, sI195M, sW196L, sW196St., sS207R, sI208T, sS210E, sF219S, sF220L and sC221G). Thirteen (81.2%) of these mutations emerged downstream to the MHR. Nine of 16 types of S-gene mutations observed with lamivudine therapy were also associated with the corresponding changes in the polymerase gene. Baseline viral DNA was significantly higher (2,093 vs. 336 pg/ml; p < 0.05) among patients developing S-gene mutants and the ETR in them was significantly lower [3 of 16 (18.8%) vs. 17 of 41 (41.5%); p < 0.05]. Conclusions: Naturally occurring S-gene mutations are uncommon and are restricted to the 'a' determinant region. Mutations develop in about a quarter of the patients on lamivudine therapy, mostly downstream to the MHR. They may contribute to non-response to the antiviral therapy

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

Acute-on-chronic liver failure: Consensus recommendations of the Asian pacific association for the study of the liver (APASL): An update

The first consensus report of the working party of the Asian Pacific Association for the Study of the Liver (APASL) set up in 2004 on acute-on-chronic liver failure (ACLF) was published in 2009. With international groups volunteering to join, the APASL ACLF Research Consortium (AARC) was formed in 2012, which continued to collect prospective ACLF patient data. Based on the prospective data analysis of nearly 1400 patients, the AARC consensus was published in 2014. In the past nearly four-and-a-half years, the AARC database has been enriched to about 5200 cases by major hepatology centers across Asia. The data published during the interim period were carefully analyzed and areas of contention and new developments in the field of ACLF were prioritized in a systematic manner. The AARC database was also approached for answering some of the issues where published data were limited, such as liver failure grading, its impact on the \u27Golden Therapeutic Window\u27, extrahepatic organ dysfunction and failure, development of sepsis, distinctive features of acute decompensation from ACLF and pediatric ACLF and the issues were analyzed. These initiatives concluded in a two-day meeting in October 2018 at New Delhi with finalization of the new AARC consensus. Only those statements, which were based on evidence using the Grade System and were unanimously recommended, were accepted. Finalized statements were again circulated to all the experts and subsequently presented at the AARC investigators meeting at the AASLD in November 2018. The suggestions from the experts were used to revise and finalize the consensus. After detailed deliberations and data analysis, the original definition of ACLF was found to withstand the test of time and be able to identify a homogenous group of patients presenting with liver failure. New management options including the algorithms for the management of coagulation disorders, renal replacement therapy, sepsis, variceal bleed, antivirals and criteria for liver transplantation for ACLF patients were proposed. The final consensus statements along with the relevant background information and areas requiring future studies are presented here

APASL consensus statements and recommendations for hepatitis C prevention, epidemiology, and laboratory testing

The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on “APASL consensus statements and recommendations for management of hepatitis C” in March 2015 to revise the “APASL consensus statements and management algorithms for hepatitis C virus infection” (Hepatol Int 6:409–435, 2012). The working party consisted of expert hepatologists from the Asian–Pacific region gathered at the Istanbul Congress Center, Istanbul, Turkey on 13 March 2015. New data were presented, discussed, and debated during the course of drafting a revision. Participants of the consensus meeting assessed the quality of the cited studies. The finalized recommendations for hepatitis C prevention, epidemiology, and laboratory testing are presented in this review

Minimal hepatic encephalopathy: consensus statement of a working party of the Indian National Association for study of the liver

Hepatic encephalopathy (HE) is a major complication that develops in some form and at some stage in a majority of patients with liver cirrhosis. Overt HE occurs in approximately 30-45% of cirrhotic patients. Minimal HE (MHE), the mildest form of HE, is characterized by subtle motor and cognitive deficits and impairs health-related quality of life. The Indian National Association for Study of the Liver (INASL) set up a Working Party on MHE in 2008 with a mandate to develop consensus guidelines on various aspects of MHE relevant to clinical practice. Questions related to the definition of MHE, its prevalence, diagnosis, clinical characteristics, pathogenesis, natural history and treatment were addressed by the members of the Working Party