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Multiple predictive models of mortality exist for acute-on-chronic liver failure (ACLF) patients that often create confusion during decision-making. We studied the natural history and evaluated the performance of prognostic models in ACLF patients.Prospectively collected data of ACLF patients from APASL-ACLF Research Consortium (AARC) was analyzed for 30-day outcomes. The models evaluated at days 0, 4, and 7 of presentation for 30-day mortality were: AARC (model and score), CLIF-C (ACLF score, and OF score), NACSELD-ACLF (model and binary), SOFA, APACHE-II, MELD, MELD-Lactate, and CTP. Evaluation parameters were discrimination (c-indices), calibration [accuracy, sensitivity, specificity, and positive/negative predictive values (PPV/NPV)], Akaike/Bayesian Information Criteria (AIC/BIC), Nagelkerke-RThirty-day survival of the cohort (n = 2864) was 64.9% and was lowest for final-AARC-grade-III (32.8%) ACLF. Performance parameters of all models were best at day 7 than at day 4 or day 0 (p 0.05 for C-indices of all models except NACSELD-ACLF). On comparison, day-7 AARC model had the numerically highest c-index 0.872, best accuracy 84.0%, PPV 87.8%, RAPASL-ACLF is often a progressive disease, and models assessed up to day 7 of presentation reliably predict 30-day mortality. Day-7 AARC model is a statistically robust tool for classifying risk of death and accurately predicting 30-day outcomes with relatively lower prediction errors. Day-7 AARC score 12 may be used as a futility criterion in APASL-ACLF patients.

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

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.

The World Health Organization (WHO) South-East Asia Regional Office (SEARO) covers 11 countries with a combined population of about 2 billion people, making it the most populous of the six WHO regions. In 1992, the WHO advocated including the hepatitis B vaccine in the Expanded Program of Immunization (EPI) and vaccinating all infants and children three times within 1 year of birth (HepB3). Recently, the WHO advocate birth-dose hepatitis B vaccination (HepB-BD) as soon as possible after birth, preferably within 24 hours. In 2016, the SEARO endorsed a regional hepatitis B control goal with a target of hepatitis B surface antigen (HBsAg) seroprevalence of ≤1% among children aged ≥5 years by 2020. Of the 11 SEARO countries, four achieved this target on schedule. Out of these four countries, two countries (Bangladesh and Nepal) have not adopted HepB-BD in EPI program. On the other hand, the coverage of HepB3 is not satisfactory in some SEARO countries, including India which adopted HepB-BD but could not achieve the overall target of SEARO. Thus, it is a point of debate whether emphasis should be placed on proper implementation of HepB3 or whether a new agenda of HepB-BD should be incorporated in developing countries of SEARO. The article discusses strengthening and expanding the Hepatitis B vaccination program in SEARO countries with an emphasis on HepB and HepB-BD programs.

Background & Objectives:Chronic hepatitis C is one of the leading causes of chronic liver disease in our country. With the introduction of directly acting antivirals, many patients are benefitted these days. Transient elastography is one of the newer technologies for measuring liver stiffness and quantifying liver fibrosis and has excellent accuracy for the diagnosis of fibrosis in patients with chronic hepatitis C. Our study analyzes changes of liver stiffness and its associated factors in patients with chronic hepatitis C treated with directly acting antivirals (DAAs).Materials & Methods: One hundred and seven patients with chronic hepatitis C, who were treated with DAAs (Sofosbuvir 400 mg and velpatasvir 100mg) and have significant fibrosis (>7.0 kPa) at baseline were included. Liver stiffness was measured at the time of enrollment, and after completion of DAAs with fibroscan and changes of stiffness and its associated factors were analyzed. Results:The study showed significant decrease in liver stiffness at the end of treatment, which continued after treatment only in patients who achieved a sustained virological response.Conclusion: Liver stiffness decreased following 12 weeks of successful DAAs therapy in patients with chronic hepatitis C at the end of treatment who achieved sustained virological response.

Hepatocellular carcinoma (HCC) is highly incidental in South Asian countries. Nepal, however, has low incidence for HCC owing to low prevalence for hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. Nepal lacked national cancer registry until 2003. Though there has been some effort in having one, the current registry incorporates twelve centers and may not properly represent the total cancer burden in the country. Serology for HBV and HCV is seen to be positive in nearly 25 to 30% and 5 to 10% of HCCs respectively. Clinical characteristics of HCCs in Nepal have been discussed in this mini-review and it features poor performance status and advanced stage at presentation, making only a small fraction of these subjects eligible for curative treatment options. Most of the standard treatment modalities are available in Nepal and appear to be reasonably affordable as compared with other developed nations. How to cite this article: Shrestha A. Liver Cancer in Nepal. Euroasian J Hepato-Gastroenterol 2018;8(1):63-65.

One of the major successes in the area of vaccinology is the emergence, development and usage of hepatitis B vaccine (a prophylactic vaccine against HBV). Hepatitis B vaccine has protected millions of individuals from acquiring HBV infection and has prevented liver cancer in the majority of vaccinated subjects. Although initially designed as prophylactic vaccines, accumulative evidence has shown that these vaccines may also be used to treat patients with chronic hepatitis B. At present, there are two main areas of discussion in hepatitis B vaccination; development of more effective prophylactic hepatitis B vaccine that can provide protection to all vaccine recipients, and designing hepatitis B-based therapeutic vaccines for treatment of chronic hepatitis B patients.

Hepatitis E virus (HEV) seropositivity may confer an increased risk of liver fibrosis in immunosuppressed individuals. We studied this effect in HIV-infected individuals in Nepal, a country hyperendemic for HEV.We prospectively evaluated 200 HIV-positive individuals. Serum samples were tested for components of fibrosis scores and cytokeratin-18.Of 200 patients, 43% were HEV-immunoglobulin G+. The mean fibrosis-4 score was 8.02 in the HEV-positive and 1.17 in the HEV-negative group (P0.001). The mean nonalcoholic fatty liver disease score was 2.12 in the HEV-positive and -2.53 in the HEV-negative group (P=0.02). The mean aminotransferase-platelet ratio index score was 0.37 in the HEV-positive and 0.38 in the HEV-negative group (P=0.9). The mean cytokeratin-18 levels were 119.9 in the HEV-positive group and 158.6 in the HEV-negative group (P=0.08).We found higher fibrosis-4 and nonalcoholic fatty liver disease scores in HEV-HIV-positive individuals, suggesting an increased liver fibrosis profile in this group. Further studies using liver stiffness measurements should be carried out.

Over the last four decades, the diagnosis and therapy of viral hepatitis has evolved substantially all over the world. Although Nepal is a developing nation, it has been keeping pace with these developments in terms of the implementation of diagnostic and therapeutic strategies. However, because of a lack of infrastructure and logistics, Nepal still depends on its neighboring countries for molecular diagnostics in viral hepatitis B and C. Though most of the recent antivirals for hepatitis B and directly acting antivirals for hepatitis C are available at a highly subsidized cost, affordability still remains an issue. A lack of comprehensive national program for hepatitis B and C has been a major barrier for access to health care in patients with chronic viral hepatitis. Similarly, hepatitis E still remains an important public health issue with major epidemics at periodic intervals. Recent developments in understanding hepatitis E virus have unveiled important aspects of the virus, particularly with regard to why these epidemics occur. In this manuscript we try to elaborate the evolution in understanding, diagnosing, and treating viral hepatitis in Nepal. How to cite this article Shrestha A. Viral Hepatitis in Nepal: Past, Present, and Future. Euroasian J Hepato-Gastroenterol 2016;6(1):59-61.

Although several antiviral drugs are now available for treatment of patients with chronic hepatitis B (CHB), sustained off-treatment clinical responses and containment of CHB-related complications are not achieved in majority of CHB patients by antiviral therapy. In addition, use of these drugs is endowed with substantial long term risk of viral resistance and drug toxicity. The infinite treatment regimens of antiviral drugs for CHB patients are also costly and usually unbearable by most patients of developing and resource-constrained countries. Taken together, there is a pressing need to develop new and innovative therapeutic approaches for CHB patients. Immune therapy seems to be an alternate therapeutic approach for CHB patients because impaired or distorted or diminished immune responses have been detected in most of these patients. Also, investigators have shown that restoration or induction of proper types of immune responses may have therapeutic implications in CHB. Various immunomodulatory agents have been used to treat patients with CHB around the world and the outcomes of these clinical trials show that the properties of immune modulators and nature and designing of immune therapeutic regimens seem to be highly relevant in the context of treatment of CHB patients. In this review, the general properties and specific features of immune therapy for CHB have been discussed for developing the guidelines of effective regimens of immune therapy for CHB.

Hepatitis E virus (HEV) infection results in nearly 20 million new infections, resulting in 70,000 deaths globally each year. Previously thought as a disease limited to developing nations with poor sanitation and hygiene, it is increasingly recognized that even the most developed nations are not spared. A clear dichotomy in epidemiology of HEV is noted between developing and industrialized nations. The HEV genotypes 1 and 2 are common in Asia and Africa and are transmitted mainly by contaminated drinking water. Sporadic as well as large-scale epidemics of acute hepatitis have been noted with HEV genotype 1 infection in developing countries of Asia and Africa. On the contrary, HEV genotypes 3 and 4 are common in industrialized nations and unlike genotypes 1 and 2, they are transmitted by consumption of raw meat products, fruits, and blood transfusion. Large epidemics have not been reported with HEV genotypes 3 and 4 and manifestation is usually indolent, though severe acute hepatitis has been reported. How to cite this article: Shrestha A, Gupta BP, Lama TK. Current Treatment of Acute and Chronic Hepatitis E Virus Infection: Role of Antivirals. Euroasian J Hepato-Gastroenterol 2017;7(1):73-77.