Impact of Diabetes, Drug-Induced Liver Injury, and Sepsis on Outcomes in MAFLD-Related Acute-on-Chronic Liver Failure.

BACKGROUND: The prevalence of Metabolic dysfunction associated fatty liver disease (MAFLD) and its complication, MAFLD-related acute on chronic liver failure (MAFLD-ACLF), is rising. Yet, factors determining patient outcomes in MAFLD-ACLF remain understudied. METHODS: Patients with MAFLD-ACLF were recruited from the AARC registry. The diagnosis of MAFLD-ACLF was made when the treating unit had identified the etiology of chronic liver disease (CLD) as MAFLD (or previous nomenclature such as NAFLD, NASH, or NASH-cirrhosis). Patients with coexisting other etiologies of CLD (such as alcohol, HBV, HCV, etc.) were excluded. Data was randomly split into derivation (n=258) and validation (n=111) cohorts at a 70:30 ratio. The primary outcome was 90-day mortality. Only the baseline clinical, laboratory features and severity scores were considered. RESULTS: The derivation group had 258 patients; 60% were male, with a mean age of 53. Diabetes was noted in 27%, and hypertension in 29%. The dominant precipitants included viral hepatitis (HAV and HEV, 32%), drug-induced injury (DILI, 29%) and sepsis (23%). MELD-Na and AARC scores upon admission averaged 32±6 and 10.4±1.9. At 90 days, 51% survived. Non-viral precipitant, diabetes, bilirubin, INR, and encephalopathy were independent factors influencing mortality. Adding diabetes and precipitant to MELD-Na and AARC scores, the novel MAFLD-MELD-Na score (+12 for diabetes, +12 for non-viral precipitant) and MAFLD-AARC score (+5 for each) were formed. These outperformed the standard scores in both cohorts. CONCLUSION: Almost half of MAFLD-ACLF patients die within 90 days. Diabetes and non-viral precipitants such as DILI and sepsis lead to adverse outcomes. The new MAFLD-MELD-Na and MAFLD-AARC scores provide reliable 90-day mortality predictions for MAFLD-ACLF patients.

Exploring the utility of EUS in Budd-Chiari syndrome: a multicenter multiobserver prospective cohort study.

BACKGROUND AND AIMS: The diagnosis of Budd-Chiari syndrome (BCS) is essentially radiologic and is needed to plan appropriate therapy. We therefore conducted this proof of concept study to assess the utility of EUS in assessing the anatomy of BCS. METHODS: This prospective, multicenter, observational study enrolled 50 consecutive patients with a diagnosis of BCS. All patients underwent a detailed EUS examination by 3 independent endosonographers, blinded to the anatomic details of BCS and others' findings. The EUS examination was compared between the endosonographers and with conventional angiography (where available) or magnetic resonance venography (MRV). Outcomes assessed were interobserver agreement, sensitivity, specificity, positive predictive value, negative predictive value, and overall accuracy in diagnosing pathologic lesions of BCS. RESULTS: Fifty BCS patients (mean age, 34 years [range, 13-65]) underwent EUS. Results showed good agreement among endosonographers for diagnosing right hepatic vein (κ = .716) and left hepatic vein lesions (κ = .722), moderate agreement for middle hepatic vein lesions (κ = .660), and very good agreement for inferior vena cava (IVC) lesions (κ = .823). EUS demonstrated high sensitivity and positive predictive value, low interobserver variability, and overall diagnostic accuracy for BCS lesions. CONCLUSIONS: EUS is a safe and accurate diagnostic tool for BCS. It can provide accurate mapping of hepatic veins, intrahepatic collaterals, and the IVC.

Navigating portal hypertension: Unlocking safe passage to healthy pregnancy in EHPVO.

BACKGROUND AND AIMS: Pregnancy is associated with hyperdynamic circulatory state and increased risk of portal hypertension related complications in patients with extra-hepatic portal vein obstruction (EHPVO). We aim to study the impact of EHPVO on pregnancy-related outcomes with focus on subset of patients with UGIB (upper GI bleed). METHODS: Retrospective analysis of obstetric, maternal and neonatal outcomes of patients with EHPVO registered between January 2006 and December 2022. Forty-five patients were included. Forty-five healthy females with low-risk pregnancies formed the control group. RESULTS: Adverse obstetric and neonatal outcomes were comparable between EHPVO and control group (22% vs. 28.6%; p > .05; low birth weight/ small for gestational age 17.8% vs. 36%, p = .0918 and 14.2% vs. 10%, p = .5698 respectively). Adverse outcomes were similar in patients with and without history of UGIB (26.3% vs. 19.4%, p = .0814; 17.8% vs. 36%, p = .0918; 14.2% vs. 10%, p = .5698). There was no maternal mortality in both the groups. A total of 7% pregnancies in EHPVO patients were complicated by ascites. CONCLUSIONS: EHPVO pregnancies have successful obstetric and neonatal outcomes with adequate management of portal hypertension.

Outcome of individuals with alcoholic cirrhosis hospitalized with first decompensation and their predictors.

BACKGROUND OBJECTIVES: Alcohol is one of most common aetiologies of cirrhosis and decompensated cirrhosis is linked to higher morbidity and death rates. This study looked at the outcomes and mortality associated risk variables of individuals with alcoholic cirrhosis who had hospitalization with their first episode of decompensation. METHODS: Individuals with alcoholic cirrhosis who were hospitalized with the first episode of decompensation [acute decompensation (AD) or acute-on-chronic liver failure (ACLF)] were included in the study and were prospectively followed up until death or 90 days, whichever was earlier. RESULTS: Of the 227 study participants analyzed, 167 (73.56%) and 60 (26.43%) participants presented as AD and ACLF, respectively. In the ACLF group, the mortality rate at 90 days was higher than in the AD group (48.3 vs 32.3%, P=0.02). In the AD group, participants who initially presented with ascites as opposed to variceal haemorrhage had a greater mortality rate at 90 days (36.4 vs 17.1%, P=0.041). The chronic liver failure-consortium AD score and the lactate-free Asian Pacific Association for the study of the Liver-ACLF research consortium score best-predicted mortality in individuals with AD and ACLF. INTERPRETATION CONCLUSIONS: There is significant heterogeneity in the type of decompensation in individuals with alcoholic cirrhosis. We observed significantly high mortality rate among alcoholic participants hospitalized with initial decompensation; deaths occurring in more than one-third of study participants within 90 days.

APASL-ACLF Research Consortium-Artificial Intelligence (AARC-AI) model precisely predicts outcomes in acute-on-chronic liver failure patients.

BACKGROUND AND AIMS: We hypothesized that artificial intelligence (AI) models are more precise than standard models for predicting outcomes in acute-on-chronic liver failure (ACLF). METHODS: We recruited ACLF patients between 2009 and 2020 from APASL-ACLF Research Consortium (AARC). Their clinical data, investigations and organ involvement were serially noted for 90-days and utilized for AI modelling. Data were split randomly into train and validation sets. Multiple AI models, MELD and AARC-Model, were created/optimized on train set. Outcome prediction abilities were evaluated on validation sets through area under the curve (AUC), accuracy, sensitivity, specificity and class precision. RESULTS: Among 2481 ACLF patients, 1501 in train set and 980 in validation set, the extreme gradient boost-cross-validated model (XGB-CV) demonstrated the highest AUC in train (0.999), validation (0.907) and overall sets (0.976) for predicting 30-day outcomes. The AUC and accuracy of the XGB-CV model (%Δ) were 7.0% and 6.9% higher than the standard day-7 AARC model (p < .001) and 12.8% and 10.6% higher than the day 7 MELD for 30-day predictions in validation set (p < .001). The XGB model had the highest AUC for 7- and 90-day predictions as well (p < .001). Day-7 creatinine, international normalized ratio (INR), circulatory failure, leucocyte count and day-4 sepsis were top features determining the 30-day outcomes. A simple decision tree incorporating creatinine, INR and circulatory failure was able to classify patients into high (~90%), intermediate (~60%) and low risk (~20%) of mortality. A web-based AARC-AI model was developed and validated twice with optimal performance for 30-day predictions. CONCLUSIONS: The performance of the AARC-AI model exceeds the standard models for outcome predictions in ACLF. An AI-based decision tree can reliably undertake severity-based stratification of patients for timely interventions.

Natural history of portal vein thrombosis in cirrhosis: A systematic review with meta-analysis.

BACKGROUND AND AIM: Progression of liver disease in cirrhosis is associated with an increased incidence of portal vein thrombosis (PVT) in cirrhosis. However, evidence suggests that spontaneous recanalization of PVT may occur even without anti-thrombotic therapy. Thus, the present meta-analysis was conducted to study the natural history of PVT in cirrhosis, facilitating decisions regarding anticoagulation. METHODS: Three electronic databases were searched from 2000 to August 2022 for studies reporting the outcome of PVT in cirrhotics without anticoagulation. The pooled proportions with their 95% confidence intervals (CIs) were calculated using a random-effect model. RESULTS: A total of 26 studies (n = 1441) were included in the final analysis. Progression of PVT on follow-up was seen in 22.2% (95% CI 16.1-28.4), while 77.7% (95% CI 71.6-83.9) remained non-progressive (improved or stable). The most common outcome was a stable PVT with a pooled event rate of 44.6% (95% CI 34.4-54.7). The pooled rates of regression and complete recanalization of PVT in cirrhotics were 29.3% (95% CI 20.9-37.7) and 10.4% (95% CI 5.0-15.8), respectively. On follow-up after improvement, pooled recurrence rate of PVT was 24.0% (95% CI 14.7-33.4). MELD score, and presence of ascites had a negative association, while a longer follow-up duration had positive association with PVT regression. CONCLUSION: Approximately 25% of the cases of PVT in cirrhosis are progressive, 30% cases improve, and 45% remain stable. Future studies are needed to analyze the predictors of spontaneous regression.

An Indian perspective for umbilical cord blood haematological parameters reference interval.

BACKGROUND: The Haematological Reference Intervals (RIs) are prone to vary on the basis of various factors such as altitude, age, sex, socioeconomic status, etc. These values play a major role in laboratory data interpretation and determine the necessary clinical treatment. Currently, India has no well-established RI for cord blood haematological parameters of newborns. This study aims to establish these intervals from Mumbai, India. METHOD: A cross sectional study was conducted in a tertiary care hospital of India from October 2022 to December 2022 on healthy and term neonates having normal birth weight and born to healthy pregnant mothers. About 2 - 3 mL of cord blood was collected from the clamped cord into EDTA tubes from 127 term neonates. The samples were analysed in the haematology laboratory of the institute and the data was analysed. The upper and lower limits were determined using non-parametric method. The Mann-Whitney U test was used to compare the distribution of the parameters between sex of infant, modes of deliveries, maternal age and obstetric history. P value less than 0.05 was considered to declare statistical significance. RESULT: The median values and 95% RI for umbilical cord blood haematological parameters of newborns were as follows: WBC = 12.35 [2.56-21.19] × 109/L, RBC = 4.34 [2.45-6.27] × 1012/L, HGB = 14.7 [8.08-21.44] g/dL, HCT = 48 [29-67]%, MCV = 109.6 [59.04-159.1] fL, MCH = 34.5 [30.54-37.79] pg, MCHC = 31.3 [29.87-32.75] %, PLT = 249 [16.97-479.46] × 109/L,LYM = 38 [17-62] %, NEU = 50 [26-74] %, EOS = 2.3 [0.1-4.8] %, MON = 7.3 [3.1-11.4], BAS = 0 [0-1]. This study found no statistically significant difference between sex of infants, except MCHC, and obstetric history. A significant difference was observed in WBC, EOS% and absolute NEU, LYM, MON and BAS by delivery type. A higher platelet count and absolute LYM was observed in the cord blood compared to venous blood. CONCLUSIONS: For the first time, haematological reference intervals in cord blood were established for newborns in Mumbai, India. The values are applicable for newborns from this area. Larger study throughout the country is required.

Contextual and individual factors associated with knowledge, awareness and attitude on liver diseases: A large-scale Asian study.

There are limited data to provide better understanding of the knowledge/awareness of general population towards liver health in Asia. We sought to identify the knowledge gaps and attitudes towards liver health and liver diseases as well as evaluate associated individual-level and macro-level factors based on contextual analysis. An online survey assessing knowledge, awareness and attitudes towards liver health and disease was conducted among 7500 respondents across 11 countries/territories in Asia. A liver index was created to measure the respondents' knowledge level and the degree of awareness and attitudes. Multilevel logistic regression was performed to identify individual factors and contextual effects that were associated with liver index. The overall liver index (0-100-point scale) was 62.4 with 6 countries/territories' liver indices greater than this. In the multilevel model, the inclusion of geographical information could explain for 9.6% of the variation. Residing in a country/territory with higher HBV prevalence (80% IOR: 1.20-2.79) or higher HCV death rate (80% IOR: 1.35-3.13) increased the individual probability of obtaining a high overall liver index. Individual factors like age, gender, education, household income, disease history and health screening behaviour were also associated with liver index (all p-values<0.001). The overall liver index was positively associated with the two macro-level factors viz. HBV prevalence and HCV death rate. There is a need to formulate policies especially in regions of lower HBV prevalence and HCV death rate to further improve the knowledge, awareness and attitudes of the general public towards liver diseases.

Paroxysmal nocturnal hemoglobinuria and vascular liver disease: Eculizumab therapy decreases mortality and thrombotic complications.

A total of 2%-10% of patients with vascular liver disease (VLD) have paroxysmal nocturnal hemoglobinuria (PNH). Eculizumab reduces complement-mediated haemolytic activity in PNH. This study was aimed at assessing the impact of eculizumab on VLD outcome. Retrospective cohort of PNH patients, in Valdig registry, who had VLD diagnosed between 1997 and 2019 is considered. Eculizumab was the exposure of interest. Studied outcomes were death, venous thrombosis, bleeding, arterial ischemic event, infection, and liver-related complications. We compared survival and new thrombotic events from PNH/VLD cohort to Envie2 non-PNH cohort. Sixty-two patients (33 women), median age 35 years (28-48) and median follow-up VLD diagnosis 4.7 years (1.2-9.5), were included. Clone size was 80% (70-90), median hemoglobin concentration was 10.0 g/dl (8-11), and lactate dehydrogenase (LDH) was 736 IU (482-1744). Forty-two patients (68%) had eculizumab; median exposure time was 40.1 [9.3-72.6] months. Mortality was significantly lower in exposed versus nonexposed period: 2.6 versus 8.7 per 100 (PY), incidence rate ratio (IRR) was 0.29, 95% CI (0.1-0.9), p = .035. Thrombosis recurrence occurred less frequently during the exposure to eculizumab: 0.5 versus 2.8 per 100 PY, IRR 0.22 (0.07-0.64). Other secondary end points (i.e., bleeding, arterial ischemic lesions, infection, and liver complications) were less common during the exposure to eculizumab, although not reaching statistical significance. Six-year thrombosis-free survival was 70%, 95% CI [0.60-0.83] for PNH cohort and 83%, 95% CI [0.70-1.00] for non-PNH Envie 2 patients, (p < .001). In conclusion, patients with PNH and VLD are at higher risk of recurrent thrombosis than non-PNH patients. Eculizumab is significantly associated with a lower mortality and less thrombotic recurrence in patients with PNH and VLD.

Efficacy and Safety of Transjugular Intrahepatic Portosystemic Shunt Creation for Budd-Chiari Syndrome: A Systematic Review and Meta-Analysis.

PURPOSE: To assess the critical role of transjugular intrahepatic portosystemic shunt (TIPS) in the management of Budd-Chiari syndrome (BCS), as the data with respect to the safety and outcome of TIPS in patients with BCS are scarce because of the rarity of the disease. MATERIALS AND METHODS: A comprehensive search of literature of various databases from 2000 to October 2021 was conducted for studies evaluating the outcome of TIPS in patients with BCS. The primary outcomes of the analysis were technical and clinical success, adverse events and mortality associated with TIPS, dysfunction of TIPS, need for TIPS revision, need for liver transplantation (LT), and 1-year survival. RESULTS: A total of 33 studies (1,395 patients) were included in this meta-analysis. The pooled rates and 95% confidence intervals of various outcomes were 98.6% (97.6-99.7) for technical success, 90.3% (86.0-94.6) for clinical success, 10.0% (6.5-13.6) for major adverse events, 0.5% (0.2-1.0) for TIPS-related mortality, 11.6% (7.8-15.4) for post-TIPS hepatic encephalopathy (HE), 40.1% (32.5-47.7) for TIPS dysfunction, 8.6% (4.9-12.4) for the need for TIPS revision, 4.5% (2.8-6.2) for the need for LT, and 94.6% (93.1-96.1) for 1-year survival. Publication bias was seen with all outcomes except for post-TIPS HE, TIPS dysfunction, and the need for LT. CONCLUSIONS: The existing literature supports the feasibility, safety, and efficacy of TIPS in the treatment of BCS. Deciding the optimal timing of TIPS in BCS needs further studies.

Hepatocellular Carcinoma Evaluation and Management for Physicians: Joint Gastroenterology Research Society and Association of Physicians of India Guidelines.

Hepatocellular carcinoma (HCC) is the most common cause of, and accounts for almost 90% of all liver cancers. Data from India is limited especially due to cancer not being a reportable disease and in view of wide variation in diagnostic modalities. This document is a result of a consensus meeting comprising Hepatologists, Interventional Radiologists, Hepatobiliary surgeons, medical and surgical Oncologists nominated by the Association of Physicians of India and Gastroenterology Research Society of Mumbai. The following Clinical Practice Guidelines for practicing physicians is intended to act as an up to date protocol for clinical management of patients with hepatocellular carcinoma. The document comprises seven sections with statements and sub-statements with strength of evidence and recommendation.

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.

Impact of metabolic risk factors on the severity and outcome of patients with alcohol-associated acute-on-chronic liver failure.

BACKGROUND: Metabolic risk factors may impact the severity and outcome of alcoholic liver disease. The present study evaluated this effect in patients with alcohol-associated acute-on-chronic liver failure (ACLF). METHODOLOGY: One thousand two hundred and sixteen prospectively enrolled patients with ACLF (males 98%, mean age 42.5 ± 9.4 years, mean CTP, MELD and AARC scores of 12 ± 1.4, 29.7 ± 7 and 9.8 ± 2 respectively) from the Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) database were analysed retrospectively. Patients with or without metabolic risk factors were compared for severity (CTP, MELD, AARC scores) and day 30 and 90 mortality. Information on overweight/obesity, type 2 diabetes mellitus (T2DM), hypertension and dyslipidaemia were available in 1028 (85%), 1019 (84%), 1017 (84%) and 965 (79%) patients respectively. RESULTS: Overall, 392 (32%) patients died at day 30 and 528 (43%) at day 90. Overweight/obesity, T2DM, hypertension and dyslipidaemia were present in 154 (15%), 142 (14%), 66 (7%) and 141 (15%) patients, respectively, with no risk factors in 809 (67%) patients. Patients with overweight/obesity had higher MELD scores (30.6 ± 7.1 vs 29.2 ± 6.9, P = .007) and those with dyslipidaemia had higher AARC scores (10.4 ± 1.2 vs 9.8 ± 2, P = .014). Overweight/obesity was associated with increased day 30 mortality (HR 1.54, 95% CI 1.06-2.24, P = .023). None of other metabolic risk factors, alone or in combination, had any impact on disease severity or mortality. On multivariate analysis, overweight or obesity was significantly associated with 30-day mortality (aHR 1.91, 95% CI 1.41-2.59, P < .001), independent of age, CTP, MELD and AARC scores. CONCLUSION: Overweight/obesity and dyslipidaemia increase the severity of alcohol-associated ACLF, and the former also increases the short-term mortality in these patients.

Asian consensus recommendations on optimizing the diagnosis and initiation of treatment of hepatitis B virus infection in resource-limited settings.

Asia has an intermediate-to-high prevalence of and high morbidity and mortality from hepatitis B virus (HBV) infection. Optimization of diagnosis and initiation of treatment is one of the crucial strategies for lowering disease burden in this region. Therefore, a panel of 24 experts from 10 Asian countries convened, and reviewed the literature, to develop consensus guidance on diagnosis and initiation of treatment of HBV infection in resource-limited Asian settings. The panel proposed 11 recommendations related to diagnosis, pre-treatment assessment, and indications of therapy of HBV infection, and management of HBV-infected patients with co-infections. In resource-limited Asian settings, testing for hepatitis B surface antigen may be considered as the primary test for diagnosis of HBV infection. Pre-treatment assessments should include tests for complete blood count, liver and renal function, hepatitis B e-antigen (HBeAg), anti-HBe, HBV DNA, co-infection markers and assessment of severity of liver disease. Noninvasive tests such as AST-to-platelet ratio index, fibrosis score 4 or transient elastography may be used as alternatives to liver biopsy for assessing disease severity. Considering the high burden of HBV infection in Asia, the panel adopted an aggressive approach, and recommended initiation of antiviral therapy in all HBV-infected, compensated or decompensated cirrhotic individuals with detectable HBV DNA levels, regardless of HBeAg status or alanine transaminase levels. The panel also developed a simple algorithm for guiding the initiation of treatment in noncirrhotic, HBV-infected individuals. The recommendations proposed herein, may help guide clinicians, to optimize the diagnosis and improvise the treatment rates for HBV infection in Asia.

Flare of Autoimmune Hepatitis Causing Acute on Chronic Liver Failure: Diagnosis and Response to Corticosteroid Therapy.

Autoimmune hepatitis (AIH) is considered less common in the Asia Pacific region. Due to this, AIH flare as a cause of acute on chronic liver failure (ACLF) is often overlooked and treatment delayed. We aimed at the defining clinical and histopathological spectrum and role of steroid therapy in AIH-ACLF. Patients with AIH-ACLF, prospectively recruited and followed between 2012 and 2017, were analyzed from the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) data base. Diagnosis of AIH was confirmed using International Autoimmune Hepatitis Group score or simplified AIH score with histopathological evidence. Of 2,825 ACLF patients, 82 (2.9%) fulfilled criteria of AIH (age 42.1 ± 18.1 years, 70% female). At baseline, mean bilirubin was 18.6 ± 8.2 mg/dL, Child-Turcotte-Pugh score was 11.7 ± 1.4, and Model for End-Stage Liver Disease (MELD) score was 27.6 ± 6.5. Mean immunoglobulin G was 21.61 ± 7.32 g/dL, and this was elevated ≥1.1 times in 97% of cases; 49% were seronegative. Liver histology was available in 90%, with median histological activity index of 10 (interquartile range, 7-12); 90% with moderate to severe interface activity; 56% showing significant parenchymal necrosis (bridging and confluent necrosis); and cirrhosis in 42%. Twenty-eight (34%) patients received steroid therapy and showed shorter intensive care unit (ICU) stay (median 1.5 versus 4 days, P < 0.001) and improved 90-day survival (75% versus 48.1%, P = 0.02) with comparable incidence of sepsis (P = 0.32) compared to those who did not. Patients of advanced age, more severe liver disease (MELD >27; 83.3% sensitivity, 78.9% specificity, area under the receiver operating characteristic curve 0.86), presence of hepatic encephalopathy, and fibrosis grade ≥F3 had an unfavorable response to corticosteroid therapy. Conclusion: AIH presenting as ACLF is not uncommon in Asian patients; a low threshold for liver biopsy is needed to confirm the diagnosis as nearly half the patients are seronegative; early stratification to steroid therapy or liver transplantation (MELD >27, hepatic encephalopathy in ≥F3) would reduce ICU stay and improve outcomes.

Lactate-free AARC ACLF Score (LaFAS) - A Simple Userfriendly Score is the Best Prognostic Marker for Patients with Alcohol Induced ACLF in Western Indian Population in a Nontransplant Resource-limited Setting.

INTRODUCTION: Acute-on-Chronic liver failure (ACLF) is a disease with a distinct spectrum of liver injury, with a rapid downhill course Here we describe three new scores - Albumin Bilirubin Index (ALBI), platelet albumin bilirubin index (PALBI) and Lactate-free AARC ACLF score(LaFAS), in predicting short-term mortality in patients with alcohol induced ACLF when compared to standard validated scores. METHODS: Consecutive patients diagnosed as alcohol induced ACLF as per the APASL 2014 definition were included in the study. Standard scores - MELD, MELD-Na, Maddreys' discriminant function, CLIF-OF and CLIF-C ACLF scores, APACHE II, ALBI, PALBI and LaFAS were calculated. The endpoints of the study were to predict short term mortality in alcohol induced ACLF patients using ALBI, PALBI and LaFAS and finding the cut-offs of these new scores and comparing it with standard validated scores. RESULTS: 67 patients were studied with 97% being male. Mean age was 45.78 + 8.15 years.44 patients died. The cut-offs, area under the ROC curve; sensitivity and specificity, positive and negative predictive values of the new prognostication scores were, respectively: ALBI (-0.57; 0.948; 90.9% and 82.6%; 77.69% and 93.15%),LaFAS(7; 0.968; 95.5% and 96.7%; 95.075 and 96.99%), PALBI(-0.28; 0.59; 61.4% and 52.2%; 46.13% and 66.98%). LaFAS and ALBI outnumbered the valid prognostic scores in predicting short-term mortality. PALBI underperformed when compared to all other scores. CONCLUSION: Thus incorporating albumin and bilirubin in a mathematical equation (for ALBI) or combining it with creatinine and grade of hepatic encephalopathy (for LaFAS) would help in prognosticate the patients with ACLF on admission in a resource limited setting thus enabling them to be transferred to a transplant center.

Drug-Induced Acute-on-Chronic Liver Failure in Asian Patients.

OBJECTIVES: Acute insults from viruses, infections, or alcohol are established causes of decompensation leading to acute-on-chronic liver failure (ACLF). Information regarding drugs as triggers of ACLF is lacking. We examined data regarding drugs producing ACLF and analyzed clinical features, laboratory characteristics, outcome, and predictors of mortality in patients with drug-induced ACLF. METHODS: We identified drugs as precipitants of ACLF among prospective cohort of patients with ACLF from the Asian Pacific Association of Study of Liver (APASL) ACLF Research Consortium (AARC) database. Drugs were considered precipitants after exclusion of known causes together with a temporal association between exposure and decompensation. Outcome was defined as death from decompensation. RESULTS: Of the 3,132 patients with ACLF, drugs were implicated as a cause in 329 (10.5%, mean age 47 years, 65% men) and other nondrug causes in 2,803 (89.5%) (group B). Complementary and alternative medications (71.7%) were the commonest insult, followed by combination antituberculosis therapy drugs (27.3%). Alcoholic liver disease (28.6%), cryptogenic liver disease (25.5%), and non-alcoholic steatohepatitis (NASH) (16.7%) were common causes of underlying liver diseases. Patients with drug-induced ACLF had jaundice (100%), ascites (88%), encephalopathy (46.5%), high Model for End-Stage Liver Disease (MELD) (30.2), and Child-Turcotte-Pugh score (12.1). The overall 90-day mortality was higher in drug-induced (46.5%) than in non-drug-induced ACLF (38.8%) (P = 0.007). The Cox regression model identified arterial lactate (P < 0.001) and total bilirubin (P = 0.008) as predictors of mortality. DISCUSSION: Drugs are important identifiable causes of ACLF in Asia-Pacific countries, predominantly from complementary and alternative medications, followed by antituberculosis drugs. Encephalopathy, bilirubin, blood urea, lactate, and international normalized ratio (INR) predict mortality in drug-induced ACLF.

Correlation of Computed Tomography of Colonic Wall Thickening with Colonoscopy.

INTRODUCTION: Computed Tomography of abdomen frequently shows bowel wall thickening with different grades and characteristic of thickening. The correlation of bowel wall thickening (BWT) with endoscopic findings is not well described in Indian population. Therefore we did this study to determine the correlation of BWT with endoscopic findings. METHODS: Its Prospective single center study with 85 Consecutive patients with age group more than 12 years with CT scan abdomen showing bowel wall thickening were included in the study. Colonoscopy was done subsequently within a span of 15 days with appropriate bowel preparation. Colonoscopic correlation was done in relation to site, degree and characteristic of thickening. Biopsies were taken at the site of visible abnormalities on endoscopy and from normal appearing mucosa in case of strong suspicious of disease. RESULTS: Total of 85 (37 men) consecutive symptomatic patients with colonic wall thickening on computed tomography underwent colonoscopy. The mean age group was 34.2 (SD±17.35) years. Endoscopy was normal in 20 patients (24%) and abnormal in 65 patients (76.5%). Patients with mild thickening were more likely to have normal endoscopy than those with moderate/severe thickening (19 versus 1 patient; p<0.001). The abnormality rate was similar across different bowel segments (left vs right side; 85.7% versus 76.5%, p< 0.57). Out of 65 patients with endoscopic abnormality, 41 (62.12%) had tuberculosis, 10 (15.16%) had malignancy. Most common cause of IC thickening was secondary to tuberculosis (n=40, 95.2%). CONCLUSION: A proportion of patients with thickening on CT scan, especially mild, may have normal colonoscopy. Patients should be counseled about the same prior to colonoscopy. However, colonoscopy should be done to rule out abnormality even when CT shows mild thickening.

An Expert Review and Recommendations on the Rational Use of Proton Pump Inhibitors: Indian Perspective.

BACKGROUND: Proton pump inhibitors (PPIs) are the mainstay of treatment for acid peptic diseases (APDs), but are often irrationally prescribed in clinical practice. Appropriate prescription of PPIs is needed to optimize outcomes, and minimize risks and cost burden on the healthcare system. OBJECTIVE: To review available literature on efficacy and safety of proton pump inhibitors (PPIs) and give recommendations for rational use of PPIs from an Indian perspective. METHODS: Twelve healthcare professionals (9 gastroenterologists, 1 cardiologist, 1 orthopedist, 1 clinical pharmacologist) comprised the expert group; members disclosed conflicts of interest. The creation of the expert review was through a process that included meetings (in-person, online, telephone) where each professional contributed their experiences with regards to efficacy and safety of PPIs. Articles published between the years 2000 and 2017 were reviewed for evaluation of safety and efficacy of PPIs in treatment of various APDs. CONCLUSION: This expert review provides key recommendations for decision making in order to minimize the irrational use of PPIs. Some significant recommendations include: patients with GERD and acid-related complications should take a PPI for minimum 12 weeks for healing of esophagitis, and for maximum up to 48 weeks for symptom control. Patients with Barrett's esophagus should take long-term PPI. Patients at high risk for ulcer-related bleeding from NSAIDs including aspirin should take a PPI if they continue to take NSAIDs. Best practice recommendations are meant to merely assist with decision making in conjunction with patients' clinical history, and are not intended to dictate mandatory rules.

Pregnancy in idiopathic non-cirrhotic portal hypertension: A multicentric study on maternal and fetal management and outcome.

BACKGROUND & AIMS: A total of 15% of patients with idiopathic non-cirrhotic portal hypertension (INCPH) are women of childbearing age. We aimed to determine maternal and fetal outcome of pregnancies occurring in women with INCPH. METHODS: We retrospectively analyzed the charts of women with INCPH followed in the centers of the VALDIG network, having had ≥1 pregnancy during the follow-up of their liver disease. Data are represented as median (interquartile range). RESULTS: A total of 24 pregnancies occurred in 16 women within 24 (5-66) months after INCPH diagnosis. Four women had associated partial portal vein thrombosis before pregnancy. At conception, 2 out of the 16 women had detectable ascites and others were asymptomatic. Out of these 24 pregnancies, there were four miscarriages, one ectopic pregnancy, and one medical termination of pregnancy at 20 weeks of gestation. Out of the 18 other pregnancies reaching 20 weeks of gestation (in 14 patients), there were nine preterm and nine term deliveries. All infants were healthy at delivery, but one died at day 1 of unknown cause and one at day 22 of infectious meningitis; both were preterm. Concerning mothers, two had worsening of ascites, two had variceal bleeding despite non-selective betablockers during pregnancy and one developed a main portal vein thrombosis in early postpartum. Genital bleeding occurred in three patients, including two receiving anticoagulation. All 16 women were alive and asymptomatic after a median follow-up of 27 (9-93) months after last delivery. CONCLUSION: The overall outcome of women with INCPH who become pregnant is favorable despite a significant incidence of complications related to portal hypertension. Fetal outcome is favorable in most pregnancies reaching 20 weeks of gestation. LAY SUMMARY: About 15% of patients with idiopathic non-cirrhotic portal hypertension are women of childbearing age, who can become pregnant. As available reports on pregnancy in these women are scarce and heterogeneous, it is unclear whether or not pregnancy should be contraindicated in this setting. We provide detailed data showing that, regardless of the associated conditions, the overall outcome of women with idiopathic non-cirrhotic portal hypertension becoming pregnant is good despite a significant incidence of complications related to portal hypertension, and that fetal outcome is favorable in most pregnancies reaching 20 weeks of gestation.