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Context: To review the imaging spectrum, clinical profile and disease outcome of patients with H1N1 influenza at a tertiary liver hospital., Aim: To review the imaging spectrum, clinical profile and disease outcome of patients with H1N1 influenza at a tertiary liver hospital., Settings and Design: A retrospective analysis of imaging findings of 21 patients with H1N1 flu, admitted to our hospital from September 2014-March 2015, was done., Methods and Material: All patients with H1N1 virus infection were included. Mode of hospital admission, concomitant liver disease, clinical findings, liver function tests and viral markers for hepatitis B and C infections were studied. Chest imaging findings on CXR or HRCT were analyzed. Correlation with CLD, clinical course, mortality and morbidity was reviewed., Statistical Analysis Used: Analysis was performed with SPSS version. Mean ± standard deviation (SD), number and percentage, chi-square or Fisher exact test, t-test and odds ratio were calculated as appropriate., Results: The mean age was 43.52 ± 14.2 years (18 males, 3 females). Positive CXR and HRCT findings were found in 14/21 (66.7%) and 19/21 (90.5%) respectively. Commonest abnormalities observed were bilateral consolidation and ground glass opacities (9/21, 42.9% each). Mid zone distribution was seen in 15/21(71.4%). Underlying CLD was seen in 14/21 (66.7%) with positive findings in 11/14 (78.6%) on CXR and 13/14 (92.9%) on HRCT. Presence of pleural effusion (PE)(57.1%) and lymphadenopathy(50%) were statistically significant (p<0.05). Median length of hospital stay was longer: 12 days (IQR 1-30) with significant mortality rate in this group., Conclusions: Imaging profile of patients with H1N1 influenza revealed that patients with underlying CLD were more likely to have imaging findings, pleural effusion, lymphadenopathy, receive intensive care and longer hospital stay with increased risk for mortality., (© Journal of the Association of Physicians of India 2011.)

Foamy viruses (FVs) or spumaviruses are retroviruses that are explored as vectors for gene therapy. The good feature of foamy viruses is its broad tropism; however, their infections result in non-targeted gene expression. Here, we attempted to design the liver targeted viral gene delivery by employing liver specific gene promoters like albumin (ALB), transthyretin (TTR) and hepatitis B virus (HBV) promoters. We compared the relative gene expression of liver specific promoters versus the U3 promoter in liver cell line (HepG2) and non-liver cell lines: human fibrosarcoma cell line (HT1080), baby hamster kidney cell line (BHK), human embryonic kidney cell line (HEK 293T) and cervical cancer cell line (HeLa). We have found that the promoter exchange didn't affect viral assembly. The ability to drive gene expression was best with TTR promoter which was followed by HBV and ALB promoter. The use of TTR, HBV and ALB promoters are helpful in achieving liver specific gene expression. Keywords: foamy virus; gene therapy; liver; albumin; transthyretin promoter; HBV promoter.

Introduction: Protein C (PrC), a physiological anticoagulant, regulates inflammation and cell death and has known predictive/therapeutic roles in sepsis. Accumulating evidences suggest plasma hypercoagulability results in progression of fibrosis and formation of microclots causing end-organ dysfunction. We investigated a possible association between natural anticoagulants-PrC, protein S (PrS) and antithrombin III (AT)-and clinical outcomes in cirrhotics., Methods: Functional PrC, PrS and AT were analysed in 515 cirrhotic patients and compared with 229 noncirrhotics. Among those with cirrhosis, we conducted multivariable predictive model on 3-month survival to assess the prognostic ability of anticoagulants., Results: Protein C (P < .001), PrS (P < .001) and AT (P < .001) levels were lower in cirrhotics compared with noncirrhotics. In addition, patients with Child-Pugh (CP)-C had significantly lower (P < .05) functional PrC, PrS and AT levels than CP-B, CP-A and noncirrhotic patients. Low PrC function correlated with markers of liver dysfunction and inflammation: INR(r = -.72, P < .001), bilirubin (r = -.620, P < .001), albumin (r = .539, P < .001), creatinine (r = -.417, P < .001), ferritin (r = -.68, P = .035), procalcitonin (r = -.79, P = .01), raised ESR (r = .56, P < .001) and liver fibrosis (r = -.840, P < .001). Patients who died (n = 160) had significantly lower median PrC function (23.8%, 16.3-33.0]) compared with those who remained alive (74.9%, [59.7-92.5]); P < .001. In a multivariable predictive model using PrC, and MELD score, we found a significant impact of low PrC levels on survival (P < .001, IRR = 0.97, 95% CI = 0.96-0.98). Receiver operating characteristic (ROC) curve analysis revealed that functional PrC levels <52% were associated with increased mortality (P < .001)., Conclusion: Low functional protein C level correlated with markers of liver dysfunction, inflammation and sepsis and independently predicted mortality at 3 months in cirrhotics, especially if functional levels were <52%., (© 2018 John Wiley & Sons Ltd.)

Background: Liver fibrosis is often accompanied by steatosis, particularly in patients with non-alcoholic fatty liver disease (NAFLD), and its non-invasive characterisation is of utmost importance. Vibration-controlled transient elastography is the non-invasive method of choice; however, recent research suggests that steatosis may influence its diagnostic performance. Controlled Attenuation Parameter (CAP) added to transient elastography enables simultaneous assessment of steatosis and fibrosis., Aim: To determine how to use CAP in interpreting liver stiffness measurements., Methods: This is a secondary analysis of data from an individual patient data meta-analysis on CAP. The main exclusion criteria for the current analysis were unknown aetiology, unreliable elastography measurement and data already used for the same research question. Aetiology-specific liver stiffness measurement cut-offs were determined and used to estimate positive and negative predictive values (PPV/NPV) with logistic regression as functions of CAP., Results: Two thousand and fifty eight patients fulfilled the inclusion criteria (37% women, 18% NAFLD/NASH, 42% HBV, 40% HCV, 51% significant fibrosis ≥ F2). Youden optimised cut-offs were only sufficient for ruling out cirrhosis (NPV of 98%). With sensitivity and specificity-optimised cut-offs, NPV for ruling out significant fibrosis was moderate (70%) and could be improved slightly through consideration of CAP. PPV for significant fibrosis and cirrhosis were 68% and 55% respectively, despite specificity-optimised cut-offs for cirrhosis., Conclusions: Liver stiffness measurement values below aetiology-specific cut-offs are very useful for ruling out cirrhosis, and to a lesser extent for ruling out significant fibrosis. In the case of the latter, Controlled Attenuation Parameter can improve interpretation slightly. Even if cut-offs are very high, liver stiffness measurements are not very reliable for ruling in fibrosis or cirrhosis., (© 2018 John Wiley & Sons Ltd.)

Background: Severe alcoholic hepatitis patients have high mortality and limited response to corticosteroids. Microvesicles reflect cellular stress and disease conditions., Aims: To investigate whether microvesicles are associated with severity, response to steroid therapy and inflammation in severe alcoholic hepatitis., Methods: Microvesicles originating from different cells were studied pre-therapy in 101 patients; (71 responder to corticosteroid therapy and 30 nonresponders) and 20 healthy controls. Microvesicles and cells were determined in peripheral and hepatic vein samples using flow cytometry and correlated with outcomes. Inflammatory signalling pathways and functional alterations of immune cells after stimulation with microvesicles were also investigated., Results: Microvesicles mean levels were higher in nonresponders for T cells (CD3 + CD4 + ; 10.1 MV/μL vs 5.4; P = 0.06), macrophages (CD68 + CD11b + ; 136.5 vs 121.9 MV/μL; P = 0.01), haematopoietic stem-cells (CD45 + CD34 + ; 116.8 vs 13.4 MV/μL; P = 0.0001) and hepatocytes (ASGPR + ; 470 vs 361 MV/μL; P = 0.01); the latter two predicting steroid nonresponse in 94% patients at baseline in peripheral plasma. Microvesicle levels correlated with histological and liver disease severity indices. Whereas, in non-responders hepatic vein CD34+ cells were lower (P = 0.02), the CD34+ microvesicles there from were higher (P = 0.04), thus suggesting impaired regeneration. Also, microvesicles of 0.2-0.4 μm size were higher in nonresponders (P < 0.03) at baseline. Microvesicles from patients trigger more (P = 0.04) ROS generation, TNF-α production (P = 0.04) and up-regulate pro-inflammatory cytokine related genes in neutrophils in vitro., Conclusions: Pre-therapy peripheral plasma levels of CD34 + and ASGPR + microvesicles are reliable non-invasive markers of steroid nonresponse and mortality in patients with severe alcoholic hepatitis., (© 2018 John Wiley & Sons Ltd.)

Background and Aims: Acute-on-chronic liver failure (ACLF) is a progressive disease associated with rapid clinical worsening and high mortality. Early prediction of mortality and intervention can improve patient outcomes. We aimed to develop a dynamic prognostic model and compare it with the existing models., Methods: A total of 1402 ACLF patients, enrolled in the APASL-ACLF Research Consortium (AARC) with 90-day follow-up, were analyzed. An ACLF score was developed in a derivation cohort (n = 480) and was validated (n = 922)., Results: The overall survival of ACLF patients at 28 days was 51.7%, with a median of 26.3 days. Five baseline variables, total bilirubin, creatinine, serum lactate, INR and hepatic encephalopathy, were found to be independent predictors of mortality, with AUROC in derivation and validation cohorts being 0.80 and 0.78, respectively. AARC-ACLF score (range 5-15) was found to be superior to MELD and CLIF SOFA scores in predicting mortality with an AUROC of 0.80. The point scores were categorized into grades of liver failure (Gr I: 5-7; II: 8-10; and III: 11-15 points) with 28-day cumulative mortalities of 12.7, 44.5 and 85.9%, respectively. The mortality risk could be dynamically calculated as, with each unit increase in AARC-ACLF score above 10, the risk increased by 20%. A score of ≥11 at baseline or persisting in the first week was often seen among nonsurvivors (p = 0.001)., Conclusions: The AARC-ACLF score is easy to use, dynamic and reliable, and superior to the existing prediction models. It can reliably predict the need for interventions, such as liver transplant, within the first week.

Objective: To investigate dual-energy spectral CT in characterization of hepatocellular Carcinoma (HCC) in patients with chronic liver disease., Methods: Dynamic computed tomography (CT) was performed in 3600 patients (2879 males; 721 females, mean age 50.9 ± 11.9 years) with working clinical diagnosis of liver cirrhosis for hepatocellular carcinoma screening and other clinical indications. The study was conducted over a period of 3 years. During dynamic CT scanning, spectral (monochromatic) and routine (polychromatic) CT acquisitions were obtained on a single tube, dual energy, 64 slice multi-detector CT scanner. Imaging findings were studied on routine CT. On the basis of routine CT findings, indeterminate lesions (lesions not showing characteristic hypervascularity followed by washout on dynamic routine CT scan) that were referred for biopsy or surgery were segregated. A retrospective blinded review of the lesions, acquired by the spectral CT acquisitions was done with the help of gem stone imaging (GSI) software to characterize these lesions. All the above lesions were analyzed qualitatively in the arterial phase for lesion conspicuity as well as quantitatively using the monochromatic data sets and nodule Iodine concentration on material density maps, respectively. This data was studied with respect to predictability of HCC using the spectral CT technique. Iodine density of the lesion, surrounding liver parenchyma, and lesion to liver parenchyma ratio (LLR) were derived and statistically analyzed. Histopathology of the lesion in question was treated as gold standard for analysis., Results: It was observed via statistical analysis that the value of iodine density of the lesion on material density sets of ≥29.5 mg/dl, enabled a discriminatory power of 86.5%, sensitivity of 90.5% with 95% confidence Interval (CI) (69.2-98.8%) and specificity of 81.2% with 95% Confidence Interval (54.4-95.9%) in predicting HCC. Qualitative assessment also showed higher lesion conspicuity with spectral CT image sets as compared to routine CT data., Conclusion: This study reveals that spectral imaging is an excellent qualitative as well as a quantitative tool for assessing and predicting hepatocellular carcinoma in cirrhotic patients.

Acute on chronic liver failure (ACLF) is a distinct clinical entity; however, there is still debate in the way it is defined in the East as compared to the West, especially with respect to incorporation of kidney dysfunction or failure in the definition of ACLF. Kidney dysfunction is defined as serum creatinine between 1.5 and 1.9 mg/dl and kidney failure as serum creatinine of more than 2 mg/dl or requirement of renal replacement therapy according to the EASL-CLIF Consortium. Kidney dysfunction or failure is universally present in patients with ACLF according to the definition by the EASL-CLIF Consortium while on the contrary the APASL definition of ACLF does not incorporate kidney dysfunction or failure in its definition. Recently, both the diagnosis and management of renal failure in patients with cirrhosis has changed with the advent of the acute kidney injury (AKI) criteria defined as an abrupt decline in renal functions, characterized by an absolute increase in serum creatinine of 0.3 mg/dl within 48 h or an increase of more than 50 % from baseline, which is known or presumed to have occurred in the previous 7 days. Further, recent studies in patients with cirrhosis have shown the utility of biomarkers for the diagnosis of AKI. The present review covers the pathogenetic mechanisms, diagnosis, prognosis as well as management of AKI in patients with ACLF from both a Western as well as an Eastern perspective. The review identifies an unmet need to diagnose AKI and prevent this ominous complication in patients with ACLF.

Background: Systemic inflammatory response syndrome (SIRS) is associated with an increased risk of hepatic encephalopathy, renal failure, and poor outcome in patients with cirrhosis; however, there is a paucity of studies on this entity for severe alcoholic hepatitis (SAH)., Aim: To evaluate SIRS at baseline as a predictor of development of acute kidney injury (AKI) and mortality in patients with SAH., Methods: Consecutive in-patients with SAH (discriminant function ≥ 32) without AKI at baseline were followed up for the development and progression of AKI (AKIN criteria)., Results: Of the 365 patients (mean age 45.5 ± 9.5, 356 males), SIRS at baseline was present in 236 (64.6%). AKI developed in 122 (33.4%), of which 50 (40.9%) had progression of AKI. SIRS was associated with bacterial infections in 96 (40.6%) and in 140 (59.3%) occurred in the absence of proven infection microbiologically. The presence of SIRS predicted both AKI development (p < 0.001, OR 2.9, 95% CI 1.7-4.8) and AKI progression (p = 0.002, OR 3.27, 95% CI 1.48-7.21). Resolution of AKI also had a significant inverse association with SIRS (p = 0.001). High MELD score (p = 0.002, HR 1.1, 95% CI 1.02-1.09), in-hospital progression of AKI (p = 0.04, HR 1.54, 95% CI 1.003-2.38), and SIRS (p = 0.004, HR 1.98, 95% CI 1.25-3.1) were significant predictors of 90-day mortality (model 1), while high MELD score (p < 0.001, HR 1.1, 95% CI 1.04-1.12) and bacterial infections (p = 0.001, HR 1.8, 95% CI 1.27-2.6) were independent predictors of mortality in the second multivariate model (model 2)., Conclusion: SIRS at admission predicts both the development of AKI and 90-day mortality in patients with SAH. This could definitely have a therapeutic and prognostic implication.

Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.

Background and Aims: The current definitions of acute kidney injury (AKI) including HRS have been derived from patients with decompensated cirrhosis. No studies have carefully addressed AKI in patients with acute on chronic liver failure (ACLF). We evaluated the prevalence, spectrum, natural history and mortality of AKI at admission and new-onset AKI in hospitalized patients with ACLF and compared the results with patients with acute decompensation of cirrhosis (ADC)., Patients and Methods: Consecutive patients with ACLF (n = 382) and ADC (n = 451) were prospectively studied. Serial renal and liver functions were recorded and correlated with the disease course and outcome., Results: AKI at admission and new onset AKI in the hospital were not different in patients with ACLF and ADC (p > 0.05). However, a significant difference in the spectrum of AKI was noted; functional volume-responsive AKI was more common (p < 0.05) in ADC, while patients with ACLF more frequently had the structural form of AKI (p < 0.05). Moreover, patients with ADC had significantly less AKI progression (p < 0.05) and prolonged duration (p < 0.05), a lower requirement of RRT (p < 0.05) and also less AKI resolution (p < 0.05) compared to ACLF patients. Patients with ACLF (versus ADC) had a significantly higher mortality on multivariate analysis., Conclusions: The kidneys are differentially affected in patients with cirrhosis with or without liver failure. Patients with ACLF with AKI have more structural AKI, greater potential for reversibility despite higher progression as well as higher mortality compared to patients with ADC. Prevention and early detection of AKI should be considered in patients with ACLF.

Aim: The aim of this study was to investigate the clinical and pathological features of hepatic sarcoidosis in symptomatic cases., Methods: Twenty-two symptomatic hepatic sarcoidosis cases were included in the study. Hepatic sarcoidosis was determined by typical imaging, histopathology, and high angiotensin-converting enzyme levels. Demographic data, laboratory data, imaging findings, liver biopsies, and clinical findings were analyzed. Portal hypertension (PH) was defined by the presence of ascites and/or varices; imaging findings suggestive of PH-splenomegaly (> 12 cm on longest axis); portal vein dilation (> 13 mm); collateral vessel formation; and hepatic venous pressure gradient ≥ 6 mmHg., Results: Mean age was 49.63 ± 10.7 years. Liver tests showed elevated serum alkaline phosphatase and gamma-glutamyl transpeptidase levels (95%). Serum albumin levels were low (< 3 g/dl) in 32% of the patients. Histologically, hepatic granulomas were located in the portal/periportal areas, with or without parenchymal involvement (77%). Duct damage (27%), absent portal veins (32%), and hepatomegaly (41%) were also observed. Clinically, chronic cholestatic symptoms and PH features were observed in 41% and 50% of the patients, respectively. Three-quarters of patients with PH features were non-cirrhotic. Cirrhosis and bleeding varices were observed in 14%. Hepatic sarcoidosis overlaps with primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) was observed in two cases., Conclusions: Sarcoidosis causes significant hepatic disease. PH and jaundice are main clinical presentations in liver sarcoidosis patients. Imaging findings of PH should be carefully reviewed, as it can occur even before the establishment of cirrhosis. Hepatic sarcoidosis mimics and overlaps with PBC and PSC., (© Acta Gastro-Enterologica Belgica.)

Purpose: Hepatitis B surface Antigen (HBsAg) is the hallmark in diagnosing hepatitis B virus (HBV) infection. In India many commercial assays are available for detection of HBsAg but very few can measure it quantitatively. The present study presents the comparative evaluation of two methods and their correlation with serum HBsAg in chronic hepatitis B (CHB) patients., Materials and Methods: Consecutive patients of CHB were included and there HBsAg levels were measured by two methods: (i) Elecsys, Roche Diagnostics, a qualitative assay and (ii) Architect, Abbott Diagnostics, a quantitative assay. The HBV DNA was measured by real-time polymerase chain reaction (qPCR)., Results: Total of 136 patients were included in the study and there was a significant overall correlation between both the assays (correlation coefficient [r] = 0.83; P < 0.001). Assays correlated well with each other across all subgroups of CHB: treatment naοve (r = 0.73; P < 0.001, n = 32), on treatment (r = 0.56; P < 0.05, n = 104), hepatitis Be (HBe) antigen positive (r = 0.67; P < 0.001, n = 62) and anti-HBe positive (r = 0.61; P < 0.05, n = 74) group. On correlation with serum HBV DNA, Architect assay demonstrated good correlation (r = 0.73; P < 0.001, n = 136) as compared to the Elecsys assay (r = 0.27; P = 0.068, n = 136). Architect HBsAg QT assay (A1) also correlated well with HBV DNA in the treatment naοve group (r = 0.69; P < 0.001, n = 32)., Conclusions: Our study hence proved that both the assays are comparable and a simple qualitative assay with in-house modification can be used easily for quatitation of HBsAg in clinical samples.

Background & Aims: Serum ferritin is a known marker of hepatic necro-inflammation and has been studied to predict 1 year mortality and post-transplant survival in decompensated cirrhotics. However, there are no studies evaluating ferritin as a predictor of early mortality. We investigated whether serum ferritin levels could predict 15 day and 30 day mortality in patients with decompensated cirrhosis., Methods: 318 patients with decompensated cirrhosis were included., Results: Patients of decompensated cirrhosis [257 males, mean age of 51 [±13]years, were followed for a median of 31 days. Serum ferritin levels were significantly different between survivors and non-survivors [p<0.001] and showed significant correlation with MELD score [p<0.001], CTP score [p<0.001], leucocyte counts [TLC] [p<0.001], serum sodium [p<0.001], ACLF grades [p=0.005], spontaneous bacterial peritonitis [SBP] [p=0.02], hepatic encephalopathy [HE] [p<0.001] and hepatorenal syndrome [HRS] [p=0.012]. Serum ferritin, etiology, MELD, HE, CTP score, sodium, TLC, and ACLF grades were significant predictors of mortality on univariate analysis. Ferritin [p=0.04, HR 1.66 95% CI (1.02-2.73)] was a significant predictor of early mortality on multivariate analysis along with HE [p=0.006, HR 3.47 95% CI (2.13-8.41)] (Model 1), TLC [p=0.02, HR 1.81 95% CI (1.06-3.07)] (Model 2), ACLF grades [p=0.018, HR 2.013,95% CI (1.126-3.60)], and CTP score [p<0.0001, HR 1.36 95% CI (1.17-1.59)] (Model 3)., Conclusion: Serum ferritin levels correlate with severity of hepatic decompensation and are associated with early liver related death independent of the MELD score in hospitalized patients with decompensated cirrhosis. This could also have a potential therapeutic implication., (Copyright © 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

The role of quantitative hepatitis B surface antigen (HBsAg) levels in patients receiving highly potent oral antiviral therapy is controversial, and here, we determined the HBsAg response in 121 chronic hepatitis B patients treated with tenofovir 300 mg daily. During tenofovir treatment, HBsAg decline of ≥ 1.0 log from baseline was seen in 16.1%, 16.3%, 18.4%, 34.6%, 36.4% and 11.8%, 15.2%, 14.8%, 28.6%, 20% at years 1, 2, 3, 4, 5 for HBeAg-positive and HBeAg-negative patients, respectively. Early decline in HBsAg levels at week 4 was predictive of subsequent significant HBsAg level decline. HBeAg seroconversion occurred in 29.9% of HBeAg-positive patients. On multinomial logistic regression, HBsAg level decline from baseline at week 4 and week 12 or any time subsequently did not correlate with HBeAg seroconversion and HBV DNA level decline from baseline at week 4 and week 12 (OR = 3.704; 95% CI = 1.511-9.076; P = 0.006 and OR = 1.732; 95% CI = 1.032-2.867; P = 0.037, respectively) was significantly predictive of seroconversion. A small proportion of chronic HBV-infected patients treated with tenofovir exhibit a significant (≥ 1.0 log) decline in HBsAg levels. Early decline in HBsAg levels at week 4 was predictive of subsequent and significant HBsAg level decline. The HBsAg decline did not correlate with HBeAg seroconversion in HBeAg-positive patients. Reduction in HBV DNA levels at week 4 and 12 correlated with seroconversion., (© 2013 John Wiley & Sons Ltd.)

Paraduodenal pancreatitis is a distinct clinicopathological entity involving the duodenum and the pancreatic tissue in the vicinity of the minor papilla. Most afflicted patients are young alcoholic males who present clinically with upper abdominal pain, weight loss, nausea, and vomiting. Pancreatic tissue elements in the duodenal wall and impedance to exocrine pancreatic secretions at the minor papilla are key factors in the pathogenesis of this condition. On imaging, the condition may manifest as a solid fibrotic mass around the minor papilla or as cysts in the duodenum and the pancreaticoduodenal groove. Duodenal stenosis, biliary strictures, chronic calcifying pancreatitis, and pancreatic ductal dilatation are also often observed., (Copyright © 2013. Published by Elsevier Ltd.)

Hepatitis B Virus (HBV) infection in infancy or early childhood leads to high rate of persistent infection (25-90%). The immunological basis of high rate of viral persistence in vertically acquired HBV infections is not completely understood. CD8 T cells play a pivotal role in clearing the Hepatitis B virus infection in adults. Herein, we sought to delineate the role of T cells in viral persistence in HBsAg+ve newborns. At birth peripheral and cord blood of HBsAg+ve (N = 12), HBsAg-ve (N = 10) and healthy newborns (HC: N = 15) were evaluated for T-cell frequency and functionality by flow cytometry. No significant differences were observed in the frequency of CD8 and CD4 T cells in all the three groups. However, significantly higher frequency of FoxP3 expressing regulatory T cells were observed in HBsAg+ve (63.79%) compared with HBsAg-ve (28.12%) and HC (11.06%) (P < 0.05). Moreover, HBsAg+ve newborns showed functional defect in CD8 T cells by decreased IFN-γ production and lower CD107A expression (cytotoxic capacity) compared with HBsAg-ve and HC, which positively correlated with decreased TCRζ-chain expression CD8 T cells (r(2) > 0.93, P < 0.05). Despite equal frequency of CD8 T cells in all the three groups, CD8 T cells in HBsAg+ve newborns are dysfunctional. An expansion of regulatory T cells and impaired TCR signalling may represent the immune tolerant state of the adaptive immune system in response to chronic HBV infection., (© 2013 John Wiley & Sons Ltd.)

Acute kidney injury (AKI) is a relatively frequent problem, occurring in approximately 20 % of hospitalized patients with cirrhosis. Although serum creatinine (S Cr) is the most commonly used method to determine AKI because of easy availability and low cost, practically it underestimates the extent of kidney injury in patients with chronic liver disease. AKI is defined as an abrupt rise in S Cr of 0.3 mg/dl or more (>26.4 mmol/l) or an increase of 150 % or more (1.5-fold) from baseline. The cause of AKI in cirrhosis is multifactorial and is unique in terms of pathogenesis. The most common causes of AKI in cirrhosis can be subdivided into either functional or structural. The functional group includes volume-responsive (prerenal azotemia) and volume-unresponsive states (hepatorenal syndrome). Volume responsive is the most common type of AKI due to frequent use of diuretics, large volume abdominal paracentesis and gastrointestinal bleeding in patients with liver disease. The structural causes include acute tubular necrosis, tubulointerstitial and glomerular diseases. Patients with decompensated cirrhosis are in a vasodilatory state leading to a decrease in effective arterial blood volume, predisposing to AKI. Therefore, management of AKI depends on the underlying cause, and therapy should be directed toward removal of the cause. The outcome in cirrhosis when patients are on dialysis is very dismal. Every effort should be made to prevent AKI.

Rare interstitial lung disease cases have been reported with albinterferon alfa-2b (albIFN) and pegylated interferon alfa-2a (Peg-IFNα-2a) in chronic hepatitis C virus (HCV) patients. Systematic pulmonary function evaluation was conducted in a study of albIFN q4wk vs Peg-IFNα-2a qwk in patients with chronic HCV genotypes 2/3. Three hundred and ninety-one patients were randomly assigned 4:4:4:3 to one of four, open-label, 24-week treatment groups including oral ribavirin 800 mg/d: albIFN 900/1200/1500 μg q4wk or Peg-IFNα-2a 180 μg qwk. Standardized spirometry and diffusing capacity of the lung for carbon monoxide (DLCO) were recorded at baseline, weeks 12 and 24, and 6 months posttreatment, and chest X-rays (CXRs) at baseline and week 24. Baseline spirometry and DLCO were abnormal in 35 (13%) and 98 (26%) patients, respectively. Baseline interstitial CXR findings were rare (4 [1%]). During the study, clinically relevant DLCO declines (≥15%) were observed in 173 patients (48%), and were more frequent with Peg-IFNα-2a and albIFN 1500 μg; 24 weeks posttreatment, 57 patients (18%) still had significantly decreased DLCO, with a pattern for greater rates with albIFN vs Peg-IFNα-2a. One patient developed new interstitial CXR abnormalities, but there were no clinically relevant interstitial lung disease cases. The risk of persistent posttreatment DLCO decrease was not related to smoking, alcohol, HCV genotype, sustained virologic response, or baseline viral load or spirometry. Clinically relevant DLCO declines occurred frequently in chronic HCV patients receiving IFNα/ribavirin therapy and commonly persisted for ≥6 months posttherapy. The underlying mechanism and clinical implications for long-term pulmonary function impairment warrant further research., (© 2013 Blackwell Publishing Ltd.)

Patients with decompensated cirrhosis owing to chronic hepatitis B viral (HBV) infection have a high morbidity/mortality rate, and the treatment remains a challenge. We studied the safety and efficacy of telbivudine and lamivudine in such patients. This noninferiority, double-blind trial randomized 232 treatment-naive patients with decompensated HBV (1:1) in 80 academic hospitals to receive once-daily telbivudine 600 mg or lamivudine 100 mg for 104 weeks. Primary composite endpoint was proportion of patients with HBV DNA <10 000 copies/mL, normal alanine aminotransferase (ALT) and Child-Turcotte-Pugh score improvement/stabilization at week 52. Response rates using a post hoc modified endpoint (HBV DNA <300 copies/mL [57 IU/mL] and ALT normalization) in intent-to-treat analysis (missing = failure) were 56.3%vs 38.0% after 76 weeks (P = 0.018) and 45.6%vs 32.9% after 104 weeks (P = 0.093) for telbivudine vs lamivudine. Telbivudine treatment was an independent predictive factor for HBV DNA <300 copies/mL and ALT normalization (P = 0.037). Response rates with protocol-defined composite endpoint in intent-to-treat analysis (M = F) were 56.2 vs 54.0% (noninferiority not achieved) and 39.1%vs 36.4% (noninferiority achieved) in telbivudine and lamivudine groups at 52 and 104 weeks. Telbivudine treatment was associated with a significant improvement in glomerular filtration rate compared to lamivudine treatment and was also associated with a trend for improvement in survival (87%vs 79%). No cases of lactic acidosis were reported. Telbivudine compared to lamivudine was associated with a higher rate of patients with both viral suppression and ALT normalization, a trend towards a higher rate of survival and significant improvement in glomerular filtration., (© 2012 Blackwell Publishing Ltd.)

Albinterferon alfa-2b (albIFN) is a fusion protein of recombinant human albumin/recombinant interferon (IFN)-α-2b, with ∼200-h half-life. Safety/efficacy of albIFN q4wk was evaluated in 391 treatment-naive patients with chronic hepatitis C virus (HCV) genotype 2/3. Patients were randomized 3:4:4:4 to one of four open-label treatment groups: pegylated IFN (Peg-IFN)-α-2a 180 μg qwk or albIFN 900, 1200 or 1500 μg q4wk, plus oral ribavirin 800 mg/day, for 24 weeks. Primary efficacy endpoint was sustained virologic response (SVR; HCV RNA <20 IU/mL 24 weeks post-treatment). SVR rates were as follows: 85%, 76%, 76% and 78% with Peg-IFNα-2a and albIFN 900, 1200 and 1500 μg, respectively (P = NS); corresponding rapid virologic response rates (HCV RNA <43 IU/mL at week 4) were as follows: 78%, 49% (P < 0.001), 60% (P = 0.01) and 71%. SVR rates were not influenced by interleukin 28B genotype, although rapid virologic response rates were greater with interleukin 28B CC (P = NS). Serious adverse event rates were as follows: 4%, 11%, 3% and 3% with Peg-IFNα-2a and albIFN 900, 1200 and 1500 μg, respectively. No increase in serious/severe respiratory events was noted with albIFN. Fewer absolute neutrophil count reductions <750/mm(3) occurred with albIFN (P = 0.03), leading to fewer IFN dose reductions. Haemoglobin reductions <10 g/dL were less frequent with albIFN 900 and 1200 μg vs 1500 μg and Peg-IFNα-2a (P = 0.02), leading to fewer ribavirin dose reductions. albIFN administered q4wk produced fewer haematologic reductions than Peg-IFNα-2a, but had numerically lower SVR rates (P = NS) in patients with chronic HCV genotype 2/3., (© 2012 Blackwell Publishing Ltd.)

Purpose: The hallmark of chronic hepatitis B (CHB) infection is the presence of hepatitis B surface antigen (HBsAg) positivity for at least 6 months. Recently, serum levels of HBsAg have been compared with serum HBV DNA as a surrogate marker to monitor CHB patients. However, data correlating these two markers are scarce. Hence, the present study was done to correlate HBV DNA with HBsAg in CHB patients., Materials and Methods: Consecutive patients of CHB were included. HBV DNA was measured by real-time polymerase chain reaction (PCR). Serum HBsAg was measured by Architect HBsAg., Results: Of the 198 patients enrolled, 166 fulfilled the inclusion criteria (mean age 43 ± 14 years, 87% males) and the median HBV DNA was 1.7 × 10 3 (range 6.0-1.1 × 10 8 ) IU/ml. Median HBsAg was 8.7 × 10 3 (range 5.0-3.2 × 10 5) IU/ml. Overall correlation between HBV DNA and HBsAg was weak but significant (Spearman ρ = 0.443, P < 0.01). Correlation in HBe antigen-positive group was better (ρ = 0.402, P < 0.01) in comparison to HBe antigen-negative group (ρ = 0.193 P = 0.05). Good correlation existed in treatment-naïve group (ρ = 0.538, P < 0.01) .Correlation was regardless of normal or raised alanine transaminase (ALT). Eighty (48%) patients had high HBV DNA (≥ 2000 IU/ml). Correlation in high DNA group was significant (P < 0.01). The best cut-off of HBsAg for diagnosing high DNA is 3.36 ×10 3 IU/ml., Conclusions: Serum HBsAg correlates with HBV DNA in CHB patients, especially in high serum HBV DNA, HBe antigen-positive and treatment-naïve group. HBsAg levels can be used for predicting high serum HBV DNA levels.

Background: Non-alcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease globally and commonly associated with insulin resistance and metabolic syndrome (MS). Peroxisome proliferator-activated receptor-γ (PPARγ) is a transcription factor abundantly expressed in adipocytes and plays a key role in the regulation of adipocyte differentiation, lipid and glucose homeostasis. Pro12Ala variant has been earlier associated with obesity, type 2 diabetes and MS., Aim: The present study aimed to determine the genotype frequencies of the Pro12Ala variant in NAFLD patients and any further association with other phenotype in the patients., Patients and Methods: Ninety-eight NAFLD patients and 280 matched controls were genotyped for presence of the Pro12Ala variant. Genomic DNA was extracted and polymerase chain reaction-restriction fragment length polymorphism using Bst-UI was performed for the detection of C-G change at codon 12 position of PPAR γ2 gene. Genotype and allele frequencies were compared between patients and controls. The Hardy-Weinberg equilibrium was tested by comparing expected/observed genotype frequencies by χ(2) test., Results: The frequencies of Pro/Ala genotype were comparable between NAFLD patients and controls. In the controls, 213 (75.7%) were homozygous for the wild-type (Pro/Pro) genotype and 67 (23.9%) were heterozygous (Pro/Ala). In NAFLD patients, genotypic distribution of wild type, heterozygous and homozygous were 63 (64.3%), 34 (34.7%) and 1 (1%), respectively. Heterozygous genotype was found to be significantly higher in the patients (P = 0.01). We also analyzed related phenotypic association of the patients with Pro12Ala genotype. We observed that the Pro12Ala (heterozygous) genotype was significantly higher in the patients who had body mass index >25 kg/m(2) (P = 0.025)., Conclusions: Pro12Ala variation of the PPAR γ2 gene is associated with NAFLD and might play a role in the pathogenesis of NAFLD.

Background: Cirrhosis with arterial hypertension is not uncommon. Haemodynamic alterations in these patients and the effects of beta-blocker on hepatic venous pressure gradient (HVPG) and systemic haemodynamics have not been evaluated., Aims: To compare the systemic haemodynamic alterations in hypertensive and normotensive cirrhotics, and to investigate the effects of propranolol on these parameters., Methods: A retrospective analysis of consecutive hypertensive cirrhotic patients (n = 33) who underwent haemodynamic assessment and paired HVPG measurement was done. Normotensive cirrhotics (n = 50) served as controls., Results: Hypertensive patients had a significantly higher heart rate, systemic (SVRI), and pulmonary vascular resistance. There was a significant reduction in mean arterial pressure (MAP) in the hypertensive cirrhotic group from 112 (107-130) mmHg to 95 (77-114) mmHg (P < 0.01), but no change in the normotensives. SVRI remained the same in the hypertensive cirrhotic group, but it increased in the normotensives. There was no correlation between MAP reduction and HVPG reduction., Conclusions: The frequency of HVPG response with propranolol treatment in hypertensive cirrhotics is similar to normotensive cirrhotics. Propranolol treatment reduces MAP significantly in hypertensive patients with cirrhosis. Treatment with a nonselective beta-blocker is a good strategy for hypertensive cirrhotic patients.

Bleeding from gastric varices (GVs) is generally more severe than bleeding from esophageal varices (EVs), but is thought to occur less frequently. Although several recent developments in the agents and the techniques have improved the outcome of GV bleeds no consensus has been reached on the optimum treatment. Because the blood flow in the GVs is relatively large and the bleeding is rapid and often profuse endoscopic means of treating bleeding GVs are the treatments of choice. Endoscopic injection of cyanoacrylate glue is the treatment of choice for the control of active bleeding of gastric avarices and to prevent rebleeding. This article reviews the current endoscopic treatment modalities used in gastric variceal bleeding, and the primary and secondary prophylaxis of gastric variceal bleeding., (2010 Elsevier Inc. All rights reserved.)

Metastasis-associated protein 1 (MTA1), a master chromatin modifier, has been shown to regulate cancer progression and is widely upregulated in human cancer, including hepatitis B virus-associated hepatocellular carcinomas (HCCs). Here we provide evidence that hepatitis B virus transactivator protein HBx stimulates the expression of MTA1 but not of MTA2 or MTA3. The underlying mechanism of HBx stimulation of MTA1 involves HBx targeting of transcription factor nuclear factor (NF)-kappaB and the recruitment of HBx/p65 complex to the NF-kappaB consensus motif on the relaxed MTA1 gene chromatin. We also discovered that MTA1 depletion in HBx-expressing cells severely impairs the ability of HBx to stimulate NF-kappaB signaling and the expression of target proinflammatory molecules. Furthermore, the presence of HBx in HBx-infected HCCs correlated well with increased MTA1 and NF-kappaB-p65. Collectively, these findings revealed a previously unrecognized integral role of MTA1 in HBx stimulation of NF-kappaB signaling and consequently, the expression of NF-kappaB targets gene products with functions in inflammation and tumorigenesis.

Background: A beta-blocker is recommended for primary prophylaxis of variceal bleeding; however, only one-third have hepatic venous pressure gradient (HVPG) response. The role of addition of isosorbide-5-mononitrate (ISMN) to beta-blocker and benefits of HVPG-guided 'a la carte' approach remain unclear., Aim: To determine the benefits of HVPG-guided pharmacotherapy in primary prophylaxis of variceal bleeding using beta-blocker and ISMN., Patients and Methods: Consecutive patients of cirrhosis, with high-risk varices, with no previous variceal bleeding were included. After baseline HVPG, patients received incremental propranolol to achieve HR of 55/min. After one-month, HVPG was repeated to determine response (<12 mmHg or >or=20% reduction). ISMN was added in nonresponders and HVPG repeated. Patients were followed up for 24 months., Results: Of 56 patients (age 47 +/- 13, males 79%) from 89 eligible patients, 21 (38%) responded to beta-blocker alone. Six additional patients responded to combination. Thus, overall 48% (27/56) patients responded. Variceal bleeding occurred in seven of 56 (13%) patients [one of 27 (4%) responder, five of 23 (22%) nonresponders and one of six (17%) with unknown response; P = N.S.]. The actuarial probability of variceal bleeding at median 24 months was 4% in responders and 22% in nonresponders (P < 0.05). Ten (18%) patients developed adverse effects to propranolol and six of 35 (17%) to nitrates requiring dose reduction. Risk factors of variceal bleed were grade IV varices and haemodynamic nonresponse., Conclusions: For primary prophylaxis, a beta-blocker is effective in 38% and addition of ISMN raises the response rate to about half of patients. The HVPG-guided 'a la carte' approach may be considered for these patients.

Background: Small-intestinal bacterial overgrowth (SIBO) is known to be present in patients with cirrhosis, predisposing to various complications., Aim: To determine the frequency of SIBO in cirrhotics and correlate with severity of cirrhosis., Methods: Small-intestinal bacterial overgrowth was determined by glucose-hydrogen breath test (GHBT). A basal breath-hydrogen >20 ppm or a rise by > or = 12 ppm above baseline following glucose administration was taken as positive test. Prevalence of SIBO in cirrhotics was compared with healthy controls and correlated with severity of cirrhosis., Results: Of the 53 cirrhotics, 26 (49%) had SIBO, compared to one (8%) control (P = 0.010). The prevalence of SIBO increased with severity of cirrhosis (Child-Pugh A 20%, B 52% and C 73%; P = 0.013). On multivariate analysis, SIBO was independently associated with serum bilirubin and ascites. The best cut-off of serum bilirubin was >/=2 mg/dL [AUROC 0.77 (95% CI 0.64-0.90)] predicting SIBO with sensitivity 65%, specificity 81%, positive predictive value 77%, negative predictive value 71% and accuracy 74%. Patients having combination of ascites and serum bilirubin > or = 2 mg/dL had 82% chance, while patients having neither had only 10% chance of having SIBO., Conclusions: Small-intestinal bacterial overgrowth was prevalent in about half of cirrhotics. Its frequency increased with increase in severity of cirrhosis. Ascites and raised serum bilirubin reliably predicted presence of SIBO.

Background and Study Aims: Endoscopic biliary drainage is an established mode of treatment for acute cholangitis. We compared the safety and efficacy of 7 Fr and 10 Fr stent placement for biliary drainage in patients with acute cholangitis., Patients and Methods: We recruited 40 patients with severe cholangitis who required endoscopic biliary drainage. Patients were randomized to have either a 7 Fr or a 10 Fr straight flap stent placement during endoscopy. Outcome measures included complications related to endoscopic retrograde cholangiopancreatography (ERCP) and clinical outcome., Results: Of 40 patients, 20 were randomized to the 7 Fr stent group and 20 to the 10 Fr stent group. All patients had biliary obstruction due to stones in the common bile duct. Indications for biliary drainage were: fever >100.4 degrees F (n = 27), hypotension (n = 6), peritonism (n = 10), impaired consciousness (n = 8), and failure to improve with conservative management (n = 13). Biliary drainage was achieved in all patients. Abdominal pain, fever, jaundice, hypotension, peritonism, and altered sensorium improved after a median period of 3 days in both groups. Leukocyte counts became normal after a median time of 4 days in the 7 Fr stent group and 6 days in the 10 Fr stent group. There were no ERCP-related complications. There were no instances of occlusion or migration of stent. The success rates of biliary drainage in cholangitis were not affected by the size of stent used., Conclusions: Biliary drainage by 7 Fr stent or 10 Fr stent is equally safe and effective treatment for patients with severe cholangitis.

Introduction: Interleukin (IL)-18 plays an important dual role in Th1 polarization and viral clearance, as well as in the development of liver fibrosis. Single-nucleotide promoter polymorphisms influence the transcription of IL-18 mRNA. Promoter polymorphisms are linked to delayed virus clearance and disease susceptibility in many diseases. However, there is no information about their role in hepatitis C virus (HCV) infection., Aim: To investigate the association between -607 or -137 polymorphism with susceptibility and severity of HCV infection., Patients and Methods: Two hundred and four serologically proven patients with chronic HCV infection and 350 matched healthy controls were included in this study. Patients were segregated in 2 groups: group A with mild liver disease and group B with severe liver disease on the basis of histological activity index (HAI 5) and hepatic fibrosis score (2). IL-18 promoter genotyping was performed with sequence-specific primers., Results: There was no significant difference in the frequencies of -607 and -137 allelic distribution in patients and controls. The -607 A/A allele was more common in group A patients with mild liver disease than in patients with severe liver disease on the basis of HAI (38.6% vs. 21%, P = 0.05; odds ratio [OR] = 0.424, confidence interval [CI] = 0.233-0.773; R (2) = 0.631) and stage of fibrosis (38.7% vs. 16.7%, P = 0.008; OR = 0282, CI = 0.134-0.596; R (2) = 0.434)., Conclusions: IL-18 promoter polymorphism at -607 position with A/A allele is a potential protective marker, as it is associated with milder liver disease in patients with chronic HCV infection.

Background and Study Aims: Endoscopic retrograde cholangiopancreaticography (ERCP) has been found to be useful for the diagnosis and treatment of post-traumatic bile leaks, but data on outcome after therapeutic ERCP is limited. We performed a prospective study on evaluation of ERCP for diagnosis and treatment of bile leaks following blunt abdominal trauma., Patients and Methods: Ten patients of bile leaks following blunt abdominal trauma were evaluated for modes of injury, clinical presentations, investigations, ERCP findings, modes of therapy and outcome. The time interval between trauma and ERCP, ERCP and healing of bile leak and complications of ERCP were also recorded., Results: Ten patients (age 21.9 +/- 14.5 years, 6 males) presented 24.6 +/- 17.1 days following trauma. The modes of injury were motor vehicle accident (n = 6), and fall from height (n = 4). The ERCP revealed bile leak from the right hepatic duct (n = 7), both right and left hepatic ducts (n = 1), mid-common bile duct (n = 1), and peripheral branches of right hepatic duct (n = 1). Procedures for ERCP included endoscopic sphincterotomy (ES) with stenting in nine patients and ES with nasobiliary drainage in one patient. Bile leak resolved in all the patients in 8.5 +/- 8.2 days. Biliary stents and the nasobiliary drain were removed after 36.4 +/- 16.2 days of their insertion and all the patients remain asymptomatic for follow up of 33 +/- 20.8 months., Conclusions: Therapeutic ERCP procedures like endoscopic sphincterotomy with stenting or nasobiliary drainage are effective in management of bile leaks following blunt abdominal trauma.

Background: There is a renewed interest in use of combination therapies in treatment-naïve chronic hepatitis B (CHB) because of limitations of monotherapies., Aim: To discuss the current status of combination therapies in treatment-naïve CHB., Methods: PubMed search was done using 'combination', 'sequential' and 'chronic hepatitis B' as the search terms., Results: The two most popular combination therapies include 'combination of nucleos(t)ide analogues' and 'combination of interferons and nucleos(t)ide analogues'. Combination therapies using two nucleos(t)ide analogues do not lead to higher long-term efficacy. However, addition of a nucleos(t)ide analogue with a good resistance profile to a nucleos(t)ide analogue with a lower genetic barrier to resistance decreases the risk of emergent resistance to the latter. Greater sustained virological, biochemical and seroconversion rates are observed with addition of lamivudine to conventional interferon, but pegylated-interferon monotherapy is equally effective as combination with lamivudine. Again, resistance to lamivudine is lower with its combination with interferons., Conclusions: The answer to the question whether hepatitis B can be treated better with combination or monotherapy remains largely unknown. Additional trials are warranted of combination therapies of peginterferon and potent nucleos(t)ide analogues or therapies with the combined use of nucleos(t)ide analogues or immunomodulators.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. The outcome of the disease is related to the stage of presentation. A comprehensive analysis of patients with this disease is not available in India., Methods: Retrospective chart review of 246 patients with HCC was done. One hundred ninety-one patients (male 160, female 31; median age 52 years, range 9-85 years) fulfilling diagnostic criteria for HCC adopted by Barcelona-2000 EASL conference were analyzed for clinical, etiological, radiological and cytohistological profile., Results: Underlying cirrhosis was seen in 60% cases with hepatitis B being the most common etiologic agent. HCC caused new onset ascites and recent worsening in three-fourth cases with ascites. Paraneoplastic syndrome was a rare event in HCC in India. Diagnostic level of serum AFP was seen in only 46% with significant difference between cirrhosis HCC patients compared with non-cirrhosis HCC patients (53% vs. 26%; P = 0.046). Most cases (83%) presented at advanced stage (Okuda III or IV) and cytohistology was the best method to diagnose HCC. Vascular invasion was seen in half the patients (53%) by the time they presented with extrahepatic spread of tumor in 13% cases., Conclusion: The prevalence of advanced stage HCC makes most of the detectable lesions unsuitable for curative resection. However, universal hepatitis B vaccination program may become the most effective preventive measure to control this disease in India.

Background: Determining a relationship between specific histological parameters in cirrhosis and hepatic venous pressure gradient can be used to subclassify cirrhosis., Aim: To determine the relationship between hepatic venous pressure gradient and specific histological parameters in cirrhosis., Methods: Forty-seven patients (mean age: 46.2 +/- 13.6 years; 36 male) with biopsy-proven cirrhosis and hepatic venous pressure gradient measurements within 1 month of biopsy were studied. The following histological parameters were scored semiquantitatively: nodule size, loss of portal tracts and central veins, portal inflammation, periportal inflammation, bile duct proliferation, lobular inflammation, ballooning, fatty change, cholestasis and septal thickness., Results: On multiple ordinal regression analysis, small nodule size (odds ratio: 21.0; 95% confidence interval: 2.1-208.2, P = 0.009) and thick septa (OR: 42.6; CI: 2.3-783.7, P = 0.011) were significantly associated with the presence of clinically significant portal hypertension. A score was assigned to each of the two parameters (nodule size: large = 1, medium = 2, small = 3 and septal thickness: thin = 1, medium = 2, thick = 3). Two subcategories were devised based on the composite score: category A (n = 12): score 1-3 and category B (n = 35): score 4-6. On ordinal regression, subcategory B (OR: 15.5; CI: 3.3-74.2, P = 0.001) was significantly associated with clinically significant portal hypertension., Conclusion: Small nodularity and thick septa are independent predictors of the presence of clinically significant portal hypertension.

Background/aims: Minimal hepatic encephalopathy (MHE) is associated with poorer quality of life and increased work disability. Diagnosis requires cumbersome psychometric and neurophysiological tests. We evaluated critical flicker frequency (CFF) to diagnose MHE., Methods: 156 cirrhotic patients (age 41+/-12.5 yr) without overt encephalopathy (Child A 63, Child B 56, Child C 37) were evaluated by psychometric (number connection tests A, B or figure connection tests A, B), P300 auditory event related potential (ERP) and CFF. MHE was diagnosed by abnormal psychometric and/or P300 auditory event related potential., Results: Prevalence of MHE was 53% with 27 (43%) in Child's A, 33 (59%) in Child's B and 23 (62%) in Child's C cirrhosis (p=NS). Of 83 patients, 72 (87%) had abnormal psychometry, 64 (77%) had abnormal P300 auditory event related potential (ERP) (380.6+/-28.8 ms) and in 66 (80%) CFF was below 39 Hz. 60 (83%) patients with abnormal psychometry and 51 (80%) with abnormal P300 auditory event related potential had CFF below 39 Hz. CFF sensitivity (96%), specificity (77%) and positive predictive value (68%), negative predictive value (98%) and diagnosis accuracy was 83.3% when compared to patients with both abnormal psychometry and P300ERP., Conclusions: Critical flicker frequency is a simple, reliable and accurate test without any age or literacy dependence for the diagnosis of MHE.

Extensive and persistent hepatic fibrosis has for a long time been considered irreversible. Accumulating evidence suggests that liver fibrosis is reversible and that recovery from cirrhosis may be possible. The application of molecular techniques to models of reversible fibrosis are helping to establish the events and processes that are critical to recovery. The problem consists in identifying and eliminating its cause. Although fibrosis in the liver has little functional significance by itself, its severity derives from associated vascular changes. Disappearance of fibrosis can be accompanied by remodeling of vascular changes. However, depending on its duration, the fibrosis may be irreversible.

Unlabelled: The role of antivirals in patients with acute viral hepatitis B (AVH-B) has not been evaluated in controlled trials. The aim of this study was to evaluate the efficacy of lamivudine in patients with AVH-B. AVH-B patients with serum bilirubin of more than 5 mg/dL were randomized to receive either 100 mg of lamivudine daily for 3 months (group 1, n = 31) or placebo (group 2, n = 40). Patients were considered to have severe AVH-B if they fulfilled 2 of 3 criteria: (1) hepatic encephalopathy; (2) serum bilirubin > or = 10.0 mg/dL; and (3) international normalized ratio (INR) > or = 1.6. At week 4, HBV DNA levels were significantly lower (P = 0.037) in group 1 (median: 3.6721 log copies/mL) than group 2 (median: 4.2721 log copies/mL). Thereafter, HBV DNA levels were comparable in the 2 groups. The improvement in serum bilirubin, ALT, and INR values was similar in the 2 groups. Twenty-two patients (71%) in group 1 and 25 patients (62.5%) in group 2 had severe AVH-B. Results were similar when patients with severe AVH-B were analyzed separately. After 12 and 18 months, 93.5% and 92.5%, respectively, of patients in the lamivudine group and 96.7% and 97.5%, respectively, of patients in the placebo group lost HBsAg. There were no deaths in either group. After 1 year, 21 patients (67.7%) in group 1 and 34 patients (85%) in group 2 developed protective anti-HBs titers (P = 0.096). All HBeAg-positive patients in both groups lost e antigen and anti-HBe developed in 71% and 87.5% of patients in groups 1 and 2, respectively (P = 0.132)., Conclusion: Though lamivudine causes a greater decrease in levels of HBV DNA, it does not cause significantly greater biochemical and clinical improvement as compared to placebo in patients with acute hepatitis B.

The hepatic venous pressure gradient (HVPG) clearly reflects portal pressure in cirrhotic portal hypertension. Its relation with variceal bleeding has been well studied. We undertook to study the relation of HVPG to variceal size, Child's status, and etiology of cirrhosis. Patients with cirrhotic portal hypertension with esophageal varices underwent HVPG measurement as part of a prospective evaluation. One hundred seventy-six cirrhotics with varices (M:F, 140:36; mean age, 42.6 +/- 13.4 years), 104 with CLD related to viral etiology, 40 with alcoholic liver disease, 26 cryptogenic with cirrhosis, and 6 with miscellaneous causes of CLD underwent HVPG measurement. The mean HVPG was lower in patients with small varices (n = 77; 14.6 +/- 5.9 mm Hg) than in patients with large varices (n = 99; 19.2 +/- 6.6 mm Hg; P < 0.01). In patients with large varices, the mean HVPG in bleeders (n = 37) was higher than in nonbleeders (n = 62) (21.7 +/- 7.2 vs 17.9 +/- 6.2 mm Hg; P < 0.01). The mean HVPG was significantly higher in Child's B (n = 97; 17.4 +/- 6.9 mm Hg) and C (n = 56; 19.0 +/- 5.7 mm Hg) compared to Child's A cirrhotics (n = 23; 12.2 +/- 5.9 mm Hg; P < 0.01), and Child's C compared to Child's B cirrhotics (P = 0.05). HVPG was higher in alcoholic compared to nonalcoholic cirrhotics (20.8 +/- 7.3 vs 16.4 +/- 6.3 mm Hg; P < 0.05), but this was not significant in multivariate analysis. The HVPG was comparable between hepatitis B- and hepatitis C virus-related cirrhotics (P = 0.8). Cirrhotics with ascites had a higher HVPG than those without ascites (18.5 +/- 5.6 vs 16.6 +/- 7.6 mm Hg; P = 0.02). In multivariate analysis, only Child's status, size of varices, and variceal bleed predicted higher HVPG. HVPG is higher in cirrhotics with large varices and a history of bleed. There is a good correlation between HVPG and large varices, bleeder status, and ascites. A higher HVPG reflects more severe liver disease. The etiology of liver disease did not influence the portal pressure.

Host immunity plays an important role in viral persistence and progression of liver disease in HCV infected patients. IL-12 induces production of IFN-gamma, a potent antiviral agent. IL-12 comprises two subunits; IL-p35 and IL-12p40, which are encoded by two different genes located on chromosome 3 and 5, respectively. Single nucleotide polymorphism at A1188C in the 3'UTR of IL-12p40 gene is associated with immune mediated diseases. Association of IL-12p40 A1188C polymorphism with the outcome of HCV infection was investigated in this study. Two hundred and fifty three histologically proven chronic hepatitis C patients (43 +/- 13 years, male:female: 185:68) and 380 matched controls were included. Genotyping was performed by RFLP and confirmed by direct sequencing. To assess correlation of immune gene polymorphism with severity of HCV-related liver disease, patients were divided into those with fibrosis score of < or = 2 (mild) or > 2 (severe), and histological activity index (HAI) of = 5 (mild) or > 5 (severe). The distribution of A/A, A/C or C/C alleles in the controls was comparable to the patients. The distribution of C/C allele was significantly more common in patients with mild as compared to severe fibrosis (23.7% vs. 6.25%, P = 0.004). No significant difference was observed for any of the genetic markers with HAI or with normal or raised alanine aminotransferase (ALT). These results show that the C/C allele of IL-12p40 gene could render genetic protection against development of severe liver disease in patients infected with HCV., (2006 Wiley-Liss, Inc.)

Ibuprofen is a member of the propionic acid class of NSAID. We report a 35-year-old man with ibuprofen-induced acute severe cholestatic liver injury. He recovered after seven months.

Background: Predictors of response of chronic hepatitis B (CHB) to lamivudine therapy need better definition. Whether hepatitis B virus (HBV) genotypes could serve as such a predictor has not been well studied., Aim: To study the association of HBV genotypes with the outcome of lamivudine treatment in patients with CHB., Methods: Seventy-six patients with CHB (45 HBeAg +ve) received lamivudine 100 mg/day, orally for 12 mo. Infecting HBV genotypes were determined in pre-treatment specimens using restriction fragment length polymorphism. End-of-treatment response (ETR) and sustained viral response (SVR) were defined as undetectable HBV DNA (< 0.5 pg/mL) at 12 and 18 months, respectively., Results: ETR was observed in 26 (34%) and SVR in 11 (14%) patients receiving lamivudine. The pre-treatment characteristics of the responders and non-responders were comparable. Genotypes A and D were observed in 28 (37%) and 48 (63%) patients, respectively. The frequency of genotypes A and D was comparable between responders (28.6% vs. 37.5%) and non-responders (71.4% vs. 62.5%), respectively (p=ns). Of the 26 responders, SVR could be evaluated in 20 subjects; 9 (45%) relapsed and 11 achieved SVR. Patients with genotype D achieved higher SVR rate than genotype A (10 of 48, 28.8% vs. 1 of 28, 3.5% p =0.0359)., Conclusions: Forty-five percent of Indian patients with CHB who achieve ETR relapse, and SVR to lamivudine therapy is achieved in 14%. Patients with genotype D achieve higher SVR rate than with genotype A.

We report our experience with endoscopic management of 3 men (aged 62, 63 and 65 years) with duodenal diaphragm disease following NSAID use for 5-15 years. In the first patient a 24 F through-the-scope balloon dilatation was attempted but failed; he subsequently underwent gastro-jejunostomy. The other two patients subsequently underwent radial incisions of the web with mixed cutting and coagulation current using a standard 5 F sphincterotome.