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Background: The world health organization (WHO) classification of neuroendocrine neoplasms (NENs, i.e. neuroendocrine tumors (NETs) and neuroendocrine carcinomas (NECs)) of the gastrointestinal system involves grading of these tumors by mitotic count (i.e. H and E mitotic index or Haematoxylin and Eosin mitotic index [HE-MI] and Mindbomb E3 ubiquitin protein ligase 1 labelling index (MIB1-LI) into Grade 1 (G1), Grade 2 (G2), or Grade 3 (G3). However, the assessment of HE-MI and MIB1-LI is hindered by several factors that contribute to discordance between these two grading methods. Clinical data demonstrate the dependency of prognosis on grade., Objectives: The objective of this study was to compare the grading of NENs of the hepatopancreatobiliary (HPB) system using Anti-phosphohistone H3 mitotic index (i.e. PHH3-MI), HE-MI and MIB1-LI., Materials and Methods: In a cohort of 140 NENs selected from January 2011 to August 2019, the concordance and correlation between HE-MI, MIB1-LI and PHH3-MI grading methods were analysed using Cohen's weighted kappa (κ) statistics and Spearman's correlation (ρ), respectively. Receiver operating characteristic (ROC) curve and cut-off analyses were done to determine optimal PHH3-MI cut-off values to grade NENs., Results: The rates of discordance between HE-MI vs. MIB1-LI, PHH3-MI vs. MIB1-LI and PHH3-MI vs. HE-MI were 52% (κ =0.416), 29% (κ =0.64) and 41% (κ =0.508), respectively. There was a significant correlation between the grading methods. PHH3-MI had good overall sensitivity and specificity at cut-offs 2 and 17 in distinguishing between G1 vs. G2, and G2 vs. G3 tumors, respectively., Conclusion: PHH3 immunolabeling allowed for quick and easy identification of mitotic figures (MF). It had the highest concordance with MIB1-LI. At cut-off values of 2 and 17, there was good overall sensitivity and specificity. The interobserver agreement was excellent., (Copyright © 2024 Copyright: © 2024 Indian Journal of Pathology and Microbiology.)

Background: Low-volume plasma exchange (PLEX) and low-dose steroid improve survival in severe alcoholic hepatitis. We aimed to compare one-year survival of very severe alcoholic hepatitis (VSAH) patients treated with centrifugal PLEX (cPLEX), membrane PLEX (mPLEX) or standard medical treatment (SMT)., Methods: We retrospectively analyzed survival in consecutive VSAH patients treated at our department from November 2017 to September 2021. PLEX patients received low-volume PLEX along with low-dose steroid (tab. prednisolone 10 mg or 20 mg daily). To adjust for baseline differences between the three treatment (cPLEX, mPLEX or SMT) groups, propensity score (PS) matching was done. Acute-on-chronic liver failure (ACLF) was defined as per European Association for the Study of the Liver (EASL). The primary study outcome was one-year transplant-free survival of PS-matched VSAH patients treated with cPLEX compared to SMT., Results: Of 101 PLEX-eligible VSAH patients, 30 patients were treated with cPLEX, 21 with mPLEX and 50 with SMT. On comparing 30 PS-matched patients each in the cPLEX group vs. the SMT group, transplant-free survival in the cPLEX group was 86.7% at one month, 70% at three months and 52.4% at one year and in the SMT group was 33.3% at one month, 23.3% at three months and 16.7% at one year with hazard ratio (HR [95% CI]) in favor of the cPLEX group (0.29 [0.15-0.56], p < 0.001). Total 21 patients each (PS-matched) in cPLEX and mPLEX groups were compared and one-year survival was better with cPLEX (0.33 [0.16-0.69], p = 0.001). The sub-group analysis of VSAH (PS-matched cohort) patients with ACLF also showed better survival with cPLEX compared to SMT (0.38 [0.17-0.83], p = 0.003) and compared to mPLEX (0.43 [0.17-0.95], p = 0.03)., Conclusion: Better one-year transplant-free survival was noted among PS-matched VSAH patients treated with cPLEX (and low-dose steroid) compared to SMT (without steroid)., (© 2024. Indian Society of Gastroenterology.)

Background: Data on non-O1/non-O139 Vibrio cholera (NOVC) infection in liver disease is limited. We studied the clinical features and outcome of patients with cirrhosis with non-NOVC bacteraemia and/or spontaneous bacterial peritonitis (SBP) when compared to non-extended spectrum beta lactamase (non-ESBL) Escherichia coli ( E. coli )., Methods: Hospital information system of patients with cirrhosis admitted with bacteraemia and/or SBP from 2010 to 2020 was searched to include patients with NOVC infection. Non-ESBL E. coli  bacteraemia/bacterascites were chosen as a comparator group, matched for the date of admission within 5 days of index case. Propensity score matching (PSM) was done for patient's age and Child score to compare outcome at discharge between NOVC-infected and E. coli -infected cirrhotic patients., Results: There were 2545 patients admitted with bacteraemia and/or SBP during the study period; 29 had NOVC isolated (M:F = 23:6; age: 39, 18-54 years; median, range; model for end-stage liver disease [MELD] score: 25, 12-38; Child score: 11, 10-12.5) from either blood (26), ascites (3), or both (8). Of these, 26 isolates were pan-sensitive to antibiotic sensitivity tests. Fifty-three patients with non-ESBL E. coli were isolated (M: F = 43:10; age: 48; 18-69 years; MELD score: 25, 20-32; Child score:12,11-13) from blood (31), ascites (17), or both (5) within the selected time frame. Of these, 48 isolates were sensitive to the empirical antibiotics initiated.After PSM, in comparison with 29 non-ESBL E. coli patients (age: 41, 18-55 years; MELD score: 24, 19-31; Child score: 12, 11-13), NOVC patients had higher incidence of circulatory failure at admission (14 [49 %] vs 4 [13 %]; P : 0.01) and significantly higher in-hospital mortality (15 [52 %] vs 6 [20 %]; P : 0.028]., Conclusions: Bacteraemia due to non-O1/non-O139 strains of V. cholera , is an uncommon cause of bacteraemia or bacterascites in patients with cirrhosis and is associated with high incidence of circulatory failure and significant mortality., (© 2024 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Idiosyncratic drug-induced liver injury (iDILI) causing acute liver failure (ALF) carries high short-term mortality and patients who meet King's College criteria for liver transplantation have 1-month survival of 34% without liver transplantation (PMID: 20949552). We present our experience with low-volume plasma exchange (PLEX-LV, 50% of estimated plasma volume exchanged per session) and low-dose steroid to treat iDILI ALF., Methods: We retrospectively analysed data of patients with iDILI (diagnosed as per RUCAM score), treated with PLEX-LV and low-dose steroid (prednisolone: 10 mg OD, with rapid taper) in our department from 2016 to 2022. Baseline and dynamic parameters (post-PLEX) were assessed as predictors of 1-month liver transplantation-free survival., Results: Twenty-two iDILI patients [probable: possible iDILI: 20:2, males: 9, age: 30 (14-84) years, median (range); MELD score: 30.5 (19-43)] underwent PLEX-LV for ALF during the study period. Causative agents were complementary and alternative medications (36%), antiepileptics (18%) antimicrobials (14%), antitubercular drugs (14%), antifungal drugs (9%) and others (9%). All patients had jaundice and encephalopathy; 9 patients also had ascites. None of the patients underwent liver transplantation. Study patients underwent 3 (1-7) PLEX sessions and 1.4 (0.6-1.6) litres of plasma was exchanged per session. One-month transplant-free survival was 59% (13/22) in the study population and 63% (12/19) among patients who fulfilled Kings College criteria for liver transplantation. Reduction of ≥25% in plasma von Willebrand factor (VWF) levels after PLEX-LV predicted improved survival (HR: 0.09, 95% CI: 0.01-0.65; AUROC: 0.81; 95% CI: 0.6-1.0)., Conclusion: Low-volume PLEX and low-dose steroid appears a promising treatment option in patients with iDILI-induced ALF not opting for liver transplantation. Dynamic changes in VWF level after PLEX predict 1-month survival in these patients., (© 2023 Indian National Association for Study of the Liver. Published by Elsevier B.V.)

Post- transplantation lymphoproliferative disorders (PTLD) are uncommon neoplasms that complicate the post transplantation period. The incidence of PTLD and outcome post liver transplantation is sparsely described. Children who undergo liver transplantation are at higher risk of PTLD than adults. Risk factors for PTLD include the level of immunosuppression and Epstein-Barr virus status. Immunosuppression in post-transplant patients can cause uncontrolled expansion of B cells. The diagnosis requires high degree of clinical suspicion, radiological evaluation, and tissue biopsy. Risk reduction depends mainly on decreasing patients' exposure to aggressive immunosuppressive regimens and is the initial step in management. Rituximab with or without chemotherapy is the mainstay of treatment. In refractory or persistent disease, alternative treatment options like adoptive immunotherapy and autologous stem cell transplant have been explored. Prognosis is determined by clonality of the PTLD and severity of the disease., (© 2023 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: Ultrasensitive HBsAg assays are replacing the previous versions. Unlike the sensitivity, the specificity, and its positioning to resolve weak-reactives (WR) are not studied. We investigated the ability of ARCHITECT HBsAg-Next (HBsAg-Nx) assay to resolve WR and sought its clinical validation and correlation with confirmatory/reflex testing., Methods: Among 99,761 samples between Jan 2022 - 2023, 248 reactive samples in HBsAg-Qual-II were compared with HBsAg-Nx assay. Sufficient samples were further subjected to neutralization (n = 108) and reflex (anti-HBc total/anti-HBs antibody) testing., Results: Out of 248 initial reactive samples in HBsAg-Qual-II, 180 (72.58%) were repeat reactive, and 68 (27.42%) were negative, whereas in HBsAg-Nx, 89 (35.89%) were reactive and 159 (64.11%) were negative (p<0.0001). Comparing the results of two assays (Qual-II/Next), 57.67% (n = 143) were concordant (++/-) and 105 (42.33%) were discordant (p = 0.0025). Testing of HBsAg-Qual-II + & HBsAg-Nx - samples revealed that 85.71% (n = 90) were anti-HBc total negative and 98.08% (n = 51) were not neutralized as well as significant proportion (89%) had no clinical correlation. The proportion of samples neutralized was significantly different between ≤5 S/Co (26.59%) and >5 S/Co (71.42%) (p = 0.0002). All samples (n = 26) with enhanced reactivity in HBsAg-Nx were effectively neutralized, while samples with no increase in reactivity, 89% (n = 72) failed neutralization (p=<0.001)., Conclusions: HBsAg-Nx assay is positioned better to resolve and refine challenging WR samples than Qual-II which correlated well with confirmatory/reflex tests and clinical disease. This superior internal benchmarking significantly reduced the cost and quantum of retesting, confirmatory/reflex testing in the diagnosis of HBV infection., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: HBsAg Next assay (HBsAgNx) claims improved detection of HBsAg. The aim was to investigate its performance in ascertaining HBsAg loss, ability to detect HBsAg in various phases of HBV infection, specificity and its amenability to in-house neutralization., Methods: Analytical sensitivity was investigated using NIBSC standard (3rd WHO-IS). For clinical performance, out of 91,962 samples tested for HBsAg (Qual-II), 512 samples consisting of 170 cases with evidence of HBsAg loss during treatment (n = 116) and without treatment (n = 54), acute-hepatitis B (n = 90) and acute exacerbation of chronic-hepatitis B (n = 41), acute-hepatitis A (n = 24) and acute-hepatitis E (n = 9) positive, HIV-1 positive (n = 20), non-HBV, HAV and HEV related acute-hepatitis (n = 81) and HBsAg prozone (n = 14) as well as in-house neutralization (n = 63) were included., Results: The calculated limit of detection (LOD) was 0.004 IU/mL. Of the 170 patients with apparent HBsAg loss, 18/116 (15.5%) among treated and 15/54 (27.7%) with spontaneous clearance were positive in HBsAgNx (p < 0.0001). Additionally, it detected HBsAg in 12/95 (12.6%) and 6/34 (17.6%) patients who were HBV DNA negative in treatment experienced and spontaneous clearance groups respectively (p < 0.001). The specificity of HBsAgNx was comparable to HBsAg Qual-II. The signal-intensity of HBsAgNx was significantly higher than HBsAg Qual-II across various phases of HBV infection and prozone samples., Conclusion: HBsAgNx significantly enhanced the accuracy of HBsAg detection without compromising the specificity in ascertaining HBsAg loss. The performance was superior in various phases of HBV infection including samples that exhibited prozone effect. Furthermore, it is amenable to cost-effective in-house neutralization to confirm low HBsAg levels., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: In the economy of therapeutic monitoring, an affordable viral marker is essential in the era of direct-acting antivirals (DAAs). We elucidated the kinetics of HCVcAg to delineate its precise role in monitoring therapeutic response., Methods: In this longitudinal study, 3208 patients were tested for HCV RNA. A total of 423 patients were started on DAAs. Treatment response and kinetics of HCVcAg/RNA were assessed in treatment-naïve (n = 383) and previously treated (n = 40) patients with follow-up for 2 years., Results: After the initiation of DAAs, the rate of relapse was significantly higher in the previously treated group than naive group [12.5% (5/40) Vs 2% (7/383), p<0.0001]. The response rate at RVR was significantly higher with HCVcAg than RNA in both groups (p<0.02). The kinetics of HCVcAg and RNA were significantly different at ETR and SVR12 in the naïve (p<0.04), but similar at all therapeutic points in the previously treated group. The correlation between HCVcAg and RNA was good at baseline, ETR and SVR, except RVR in both groups (r>0.6; p<0.0001). Furthermore, HCV genotypes, treatment regimen, CTP (<7/≥7) and MELD (<15/≥15) did not influence the therapeutic response and the viral replication kinetics (p>0.05)., Conclusions: It is the first longitudinal study from India shows that the response rate and kinetics of HCVcAg are comparable to HCV RNA for an extended duration, except at RVR, irrespective of the HCV genotypes, treatment regimen, and liver disease severity. Hence, HCVcAg can be considered as a pragmatic marker to monitor therapeutic response and predict relapse in the era of DAAs., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ponnuvel et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Overactivation of reticuloendothelial cells lining liver sinusoids - Kupffer cells (macrophages) and sinusoidal endothelial cells - may narrow the sinusoidal lumen, impair perfusion in liver microcirculation and contribute to disease severity in alcoholic hepatitis., Aim: The aim of the article was to assess reticuloendothelial activation in patients with severe alcoholic hepatitis (SAH)., Methods: In SAH patients, we prospectively studied baseline reticuloendothelial activation markers [serum ferritin, sCD163 and plasma von Willebrand factor (VWF) antigen] and Macrophage Activation Syndrome (MAS) criteria, correlated them with disease severity scores [model for end-stage liver disease (MELD) and Sequential Organ Failure Assessment (SOFA) scores] and analyzed their ability to predict survival over a 90-day follow-up period., Results: A total of 50 SAH patients [45 (37-49) years, median (interquartile range), 49 males, discriminant function, 76.2 (54.5-106.6); MELD score, 30 (26.2-36)] were studied. 41 SAH patients (82%) had ferritin >500 ng/mL, and all (100%) had markedly raised sCD163 and VWF levels. The median sCD163 level was 10-fold higher than healthy controls and the median VWF level was 5-fold above the upper limit of normal. In total, 37 SAH patients (74%) met MAS criteria. Reticuloendothelial activation markers correlated with MELD and SOFA scores (P < 0.05). VWF was an independent marker to predict mortality in SAH [adjusted hazard ratio, 1.002 (1.000-1.004)]., Conclusions: The reticuloendothelial system was markedly activated and correlated with disease severity scores in SAH patients.VWF predicted short-term mortality independent of MELD and sCD163. Further larger multicentric studies are needed to validate these findings., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Chronic immune activation is one of the most widely recognized hallmarks of HIV infection. T-cells that express CD38+ and HLA-DR+ show poor proliferative potential, signal transduction, and increased apoptotic potential. This affects HIV pathogenesis and its outcome and further complicates with a coinfection like HBV., Methods: Study Design: cross-sectional. Blood samples were collected and analyzed for virological markers using ELISA for HBeAg and RT-PCR for HIV&HBV Viral load. Chronic immune activation markers of CD8+ and CD4+ T cells were measured by Flow cytometry for both HIV and HBV., Results: There was a significant increase in HBV replication shown by higher HBV DNA (p=0.002), a higher proportion of HBeAg (p=0.0049), and lower CD4 counts (p=0.04) among HIV/HBV coinfected individuals, compared to the monoinfected groups. The frequencies of CD4+ CD38+ HLA-DR+ and CD8+ CD38+ HLA-DR+ in the HIV/HBV coinfection were significantly higher than HBV monoinfected group (P< 0.0001) and in the HIV monoinfected group (P < 0.0001). The Liver fibrosis score APRI and FIB-4, were higher in the coinfected group compared with HBV monoinfected group (0.67 vs. 0.25, p = 0.0085; 3.48 vs. 0.98, p = 0.0026) respectively. The cytokine levels of IL-17, Fas-L,TNF -α, IL-10, IL-2 and Granzyme B were also measured and compared among the study groups., Conclusion: Our data suggest that HIV probably influences immune activation of CD4+ and CD8+ T cells and this may play a significant role in accelerating the disease outcome among HIV/HBV coinfected individuals., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background and Aim: This aims to study incidence of re-bleeding on anticoagulation and survival of Budd-Chiari syndrome (BCS) patients presenting with variceal bleeding., Methods: Budd-Chiari syndrome patients presenting with variceal bleed between 01/01/2007 and 01/05/2019 were retrospectively studied. Patients underwent endoscopic treatment ± endovascular therapy, followed by anticoagulation. Variceal re-bleed (on anticoagulation) and survival were studied., Results: Of 376 BCS patients diagnosed during the study period, 40 (10.7%) patients, presenting with variceal bleed (age 33 [25-40] years; male patients 70%; Rotterdam score 1.13 [0.63-1.22]), Group 1 were compared with 40 randomly selected age-matched BCS patients presenting with ascites, no bleeds (40 [23-42] years; male patients 42.5%; Rotterdam score 1.11 [1.09-1.16]), Group 2. The commonest site of obstruction was hepatic vein (65%) in Group 1 and combined hepatic veins and inferior vena cava (57.5%) in Group 2 (P < 0.01). Thirty-six Group 1 patients underwent endoscopic intervention (variceal ligation, 33; sclerotherapy, 2; glue injection, 1). Endovascular intervention was performed in 30 Group 1 patients (angioplasty ± stent, 22; endovascular shunt, 8) and in 34 Group 2 patients (angioplasty ± stent, 26; endovascular shunt, 8). All 80 patients were started on anticoagulation. Variceal bleed on anticoagulation occurred in five patients in Group 1 and three patients in Group 2. One-year and 5-year survival were 94.2% and 87.5%, respectively, in Group 1 and 100% and 80%, respectively, in Group 2., Conclusions: About one-tenth of BCS patients present with variceal bleed. On management with endoscopic ± endovascular therapy, followed by anticoagulation, variceal re-bleed in these patients were comparable with those in BCS patients presenting with ascites and survival was excellent at 1 and 5 years., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Purpose: Human immunodeficiency virus-1 (HIV-1) and hepatitis B virus (HBV) coinfection has become a major health problem across the globe. The increased life expectancy of HIV-1 patients due to antiretroviral therapy has led to the emergence of liver disease as a major mortality factor among them. The purpose of the study was to examine the baseline characteristics of HBV in treatment-naïve HBV/HIV coinfection from southern India compared to monoinfected individuals., Materials and Methods: The study was cross sectional in design, and samples were examined from 80 HIV-1, 70 HBV and 35 HBV/HIV-coinfected individuals using chemiluminescent microparticle immunoassay, real-time polymerase chain reaction and flow cytometry assays., Results: There was a significant increase in HBV DNA (P = 0.0001), higher hepatitis B e antigen percentage difference (P = 0.027) and lower CD4 counts (P = 0.01) among the HBV/HIV-coinfected individuals, but no difference in the HIV-1 viral load compared to HIV-1-monoinfected individuals. Also, the aspartate aminotransferase levels, prothrombin time and the international normalised ratio were significantly high among coinfected individuals., Conclusion: These findings conclude that HIV-1 coinfection can have serious implications on the outcome of HBV-related liver disease. To the contrary, HBV infection had no consequence on the progression of HIV-1 disease but distinctly lowered CD4+ T-cells., Competing Interests: None

Aims and Objectives: To evaluate technical feasibility, long-term primary patency and clinical outcome of the transjugular intrahepatic portosystemic shunt (TIPS) through the struts of the previously placed stents., Materials and Methods: Retrospective evaluation of seven consecutive patients (three male and four female, age range 13-65 years, median 28) out of a total 95 patients, who underwent TIPS through the strut of the previously placed stents of hepatic vein (HV), inferior vena cava (IVC) or TIPS in a single tertiary care hospital. Six of the patients were diagnosed with Budd-Chiari syndrome (BCS) and one with alcohol-induced chronic liver disease (CLD). Kaplan-Meier test was used to calculate 18- and 60-month primary patency rate of TIPS stent., Results: TIPS through the strut of a previously placed stent was technically successful in all the patients (100%). The TIPS was direct intrahepatic portosystemic shunt (DIPS) in 5/7 cases, due to occluded HV. Mean portosystemic pressure gradient (PPG) reduced from 24 mmHg ± 5.9 (range, pre-TIPS 15-31 mmHg) to 8.57 mmHg ± 4.4 (range, post-TIPS, 3-14 mmHg). One patient required three sessions of TIPS revisions. Another patient needed TIPS revision after 5 years of TIPS creation. All the patients showed improvement in clinical symptoms and in mean Child-Turcotte-Pugh (CTP) score and modified end-stage liver disease (MELD) score during mean follow-up period 40.57 month ± 34.9 (range 3-100 month). Primary patency rates of TIPS stent measured with Kaplan-Meier estimate at 18- and 60-month follow-up were 80% (95% CI, 37-97%) and 40% (95% CI, 10-97%), respectively., Conclusion: TIPS through the strut of a previously placed stent is technically feasible with good long-term primary patency and clinical outcome.

Hepatitis C virus (HCV) infection in kidney transplantation is an important issue with effects on patient and graft survival. The current standard of care involves using oral Direct Acting Antiviral drugs. Till recently, pre-transplant treatment with interferon was the only option for treatment. We studied 677 consecutive kidney transplant recipients with HCV infection. 5.2% patients had evidence of HCV infection. 2.0% were newly detected to have HCV infection after transplant (de novo HCV group). Nearly 28.6% had negative antibody tests but positive Nucleic Acid Test at the time of diagnosis. Eighty-five percent of pre-transplant HCV-positive patients were treated with interferon-based regimens. Early virologic response was seen in 66.6%. End of treatment response was achieved by 94.1%. Sustained virologic response was seen in 81.2%. Overall, patient and graft survival were not different between HCV and control groups (log-rank P = 0.154). Comparing HCV and control groups, there was a tendency toward increased fungal (11.4% vs. 5.6%, P = 0.144) and CMV infections (25.7% vs. 17.1%, P = 0.191) in the HCV group, though it did not reach statistical significance. Eighty-percent of the interferon-treated patients suffered side effects. On comparing, the pre-transplant HCV-positive group (85% treated) with the de novo HCV group (none treated), the de novo group had significantly reduced patient survival (P = 0.020) and NODAT (35.7 vs 4.8%, P = 0.028), and a tendency toward higher CMV infections (35.7% vs 19%, P = 0.432). In addition, death and hepatic complications (decompensated liver disease, fibrosing cholestatic hepatitis) occurred only in de novo HCV group. These results highlight the need for continued post-transplant treatment of HCV positive patients. The newer anti-HCV drugs are expected to fulfill this felt-need in kidney transplantation but long-term results are awaited. This study can serve as a benchmark for future studies to compare the long-term effect of Direct Acting Antiviral drugs., Competing Interests: None declared.

Introduction: Acute decompensation of pre-existing chronic liver disease (CLD), known as acute-on-chronic liver failure (ACLF), is associated with high mortality. Hepatitis E virus (HEV) as a potential cause was studied., Objectives: The objectives of this study are to evaluate the role of HEV in ACLF patients using an IgM anti-HEV antibody enzyme-linked immunosorbent assay (ELISA), HEV antigen ELISA, and a quantitative HEV polymerase chain reaction (PCR)., Materials and Methods: In this prospective cross-sectional study, blood samples were collected from 50 ACLF (cases) as defined by the standard guidelines (APASL, 2014) and 50 patients with stable CLD (controls) from January 2015 to August 2016, after obtaining informed consent. Two IgM ELISAs (MP Diagnostics HEV IgM ELISA 3.0, Singapore and Wantai HEV IgM ELISA, Beijing, China) were compared using plasma from cases and controls. In addition, an HEV antigen detection by ELISA (Wantai, Beijing, China) and a real-time PCR for quantification of HEV RNA in plasma and stool were employed., Results: Ethanol was the leading cause of acute insult in ACLF (54%) cases. HEV infection accounted for 20% of cases. Ten ACLF patients (20%) had 1-3 markers of HEV versus two (4%) among controls (P = 0.0138). Among ACLF cases, one had HEV viraemia (403 IU/ml), faecal shedding (2790 IU/ml) and detectable HEV antigenaemia. Agreement between the two anti-HEV IgM ELISAs was 0.638 (kappa value)., Conclusion: This study shows that alcohol is a major contributing factor for both underlying CLD and ACLF while HEV is the most common infectious cause for ACLF, suggesting a need for a vaccination in such patients, whenever made available., Competing Interests: There are no conflicts of interest

Background: Hepatitis E virus (HEV) is endemic in India and causes epidemics and sporadic cases. However, the exact transmission route for sporadic hepatitis E remains unclear. This study investigated HEV in sporadic hepatitis cases and sewage samples, as sewage is the major source of contamination of water in developing countries., Methods: Monthly sampling and testing for HEV in sewage samples from Vellore, India was carried out for 1 year (November 2009-October 2010) and plasma and/or fecal samples from sporadic hepatitis cases presenting to a hospital in Vellore during 2006-2010 were tested for HEV RNA. A total of 144 raw sewage samples and 94 samples from sporadic hepatitis cases were tested for HEV RNA using RT-PCR., Results: The prevalence of HEV RNA in sewage and sporadic cases was 55.6% and 9.6%, respectively. HEV strains isolated from sewage showed 94-100% nucleotide sequence similarity with the HEV strains isolated from the sporadic hepatitis cases. HEV RNA in sewage was identified more often during the summer (81.2%) than the monsoon season (14.5%) (p < 0.001)., Conclusion: This study indicates that sewage may be a source of contamination for sporadic hepatitis and also underscores the need for preventive measures to protect drinking water from sewage contamination, particularly in the summer. GENBANK ACCESSION NUMBERS: HEV strains isolated from this study were deposited in GenBank under accession numbers JF972766-JF972773, JN705651-JN705659 and JN705660-JN705662.

Aim: The study was conducted with an aim to evaluate the clinico-pathological profile, the correlation of AST: ALT ratio and APRI with histological fibrosis, and the frequency of two specific polymorphisms (-238, -308) in the TNF alpha promoter region in patients with NAFLD., Methods: The present study compared aspartate transaminase/alanine transaminase (AST/ALT) ratio and AST-to-platelet ratio index (APRI) with fibrosis score in 29 patients who underwent liver biopsy for NAFLD. Single nucleotide polymorphisms (SNP) in the tumor necrosis factor-alpha (TNF-alpha) promoter region at positions -308 and -238 were examined by polymerase chain reaction-restriction fragment length polymorphism., Results: AST/ALT ratio correlated better than the APRI with liver fibrosis in patients with NAFLD (AUROC of 0.9 compared to 0.68). TNF-alpha promoter region SNPs were present in only a minority of patients, and did not correlate with fibrosis severity., Conclusions: AST/ALT ratio correlated well with liver fibrosis in Indian patients with NAFLD. The SNPs studied had no role in development of fibrosis in Indian patients with NAFLD.

Esophageal or gastric varices may be incidentally seen during endoscopy for dyspeptic or reflux symptoms. However, the frequency of their occurrence in these patients is unknown. Our center follows the scope and treat strategy for adult patients with dyspeptic or reflux symptoms and this provided us an opportunity to study this. Apart from providing an idea on the etiological spectrum, our data suggests that patients with incidentally detected varices have well preserved liver function which may provide a window for better management.

Aims: To evaluate the accuracy of measurement of hepatic venous pressure gradient by catheter wedge as compared to balloon wedge (the gold standard)., Materials and Methods: Forty-five patients having a clinical diagnosis of intrahepatic portal hypertension were subjected to the two different types of pressure measurements (catheter wedge and balloon wedge) during transjugular liver biopsy under fluoroscopic guidance., Statistical Analysis: Spearman's rank correlation coefficient, Bland-Altman plot for agreement, and single measure intraclass correlation were used for analysis of data., Results: There was a close correlation between the results obtained by both the techniques, with highly significant concordance (P < 0.0001). Hepatic venous pressure gradients as measured by the catheter wedge technique were either equal to or less than those obtained by the balloon wedge technique., Conclusions: The difference in hepatic venous pressure gradients measured by the two techniques is insignificant.

Budd-Chiari syndrome (BCS) and portal hypertension is an uncommon complication of hydatid cyst of the liver. Previous reports describe cyst excision or portosystemic shunt surgery for such patients. Here we present a case of hydatid cyst of the liver with BCS that was treated successfully with hepatic venoplasty and transjugular stent placement.

Transjugular intrahepatic portocaval shunt (TIPS) is performed in patients with symptomatic Budd-Chiari syndrome (BCS) who do not have repairable hepatic veins. We report the case of a patient who had an inferior vena cava (IVC) stent placed previously as part of the management for BCS, and who subsequently required TIPS. The TIPS tract was created through the strut of the previously placed IVC stent; the TIPS stent was placed after dilatation of the liver parenchyma as well as the strut of the IVC stent. This novel technique of "strutplasty" of a previously placed stent as part of TIPS has not been reported in the literature.

The aetiological profile of paediatric portal hypertension in our hospital, a tertiary care centre in South India, showed that the commonest causes were extrahepatic portal venous obstruction (EHPVO) and cirrhosis. Wilson's disease was the most common cause of cirrhosis.

Background and Aim: The data available on subacute hepatic failure due to hepatitis E virus is scarce. The aim of this study is to analyze the clinical spectrum and outcome of this condition., Methods: This is a retrospective hospital-based study of patients with acute hepatitis E and subacute hepatic failure from January 2001 to June 2006., Results: We encountered 12 patients with this condition during the study period. There were four females and eight males (age 39 +/- 16). Jaundice and ascites were present in all. The model for end stage liver disease (MELD) score was 25 +/- 8. All of them had normal-sized liver on ultrasonogram. Transjugular liver biopsies were done in nine patients and revealed extensive bridging, submassive necrosis and cholestasis. Complications included spontaneous bacterial peritonitis (four) and urinary tract infections (two), renal failure (three) and encephalopathy (three). The in-hospital mortality was 25% (3/12). The remaining nine patients left the hospital alive with normalization of liver functions in eight of them over the next few months., Conclusion: Subacute hepatic failure caused by hepatitis E is a distinct entity with a better prognosis compared with the previously published series of subacute hepatic failure. Liver biopsy is useful to differentiate from hepatitis E virus superinfection on underlying chronic disease. Poor prognostic factors were female sex, younger age, encephalopathy and persistent renal failure. These patients should be considered for liver transplantation.

Human serum albumin binds ligands such as fatty acids and metals in circulation. Oxidative stress can modify albumin and affect ligand binding. This study examines the role of oxidative stress and fatty acids in modulating cobalt binding to albumin in patients with fatty liver. Elevated levels of malondialdehyde and protein carbonyls, indicative of oxidative stress were evident in serum of patients with fatty liver. A significant decrease in albumin-cobalt binding was also observed. Albumin isolated from patient serum also showed an increase in bound fatty acids. In vitro experiments indicated that while oxidant exposure or removal of fatty acids independently decreased cobalt binding to albumin, removal of fatty acids from the protein prior to oxidant exposure did not influence the oxidant effect on albumin-cobalt binding. These results suggest that oxidative stress and fatty acids on albumin can influence albumin-cobalt binding in patients with fatty liver by independent mechanisms.