UNASSIGNED: Primary biliary cholangitis (PBC) is a chronic cholangiopathy characterised by immuno-mediated injury of interlobular bile ducts leading to intrahepatic cholestasis and progressive liver fibrosis. PBC histology is characterised by portal inflammation, progressive fibrosis, ductopenia, and the appearance of the so-called ductular reaction. The aim of the present study was to investigate the pathogenetic relevance of ductular reaction in PBC.
UNASSIGNED: Liver biopsies were collected from naïve people with PBC (N = 87). Clinical-serological parameters were obtained at diagnosis and after 1 year of ursodeoxycholic acid (UDCA) treatment. Histological staging was performed on all slides according to multiple scoring systems and criteria for PBC. Liver samples were obtained from Mdr2 -/- mice treated with or without UDCA. Samples were processed for histology, immunohistochemistry, and immunofluorescence.
UNASSIGNED: Ductular reaction in people with PBC correlated with the disease stage and liver fibrosis, but not with disease activity; an extensive ductular reaction correlated with serum alkaline phosphatase levels at diagnosis, response to UDCA, and individuals\' estimated survival, independently from other histological parameters, including disease stage. In people with PBC, reactive ductules were associated with the establishment of junctions with bile canaliculi and with fibrogenetic cell activation. Consistently, in a mouse model of intrahepatic cholestasis, UDCA treatment was effective in reducing ductular reaction and fibrosis and increasing ductular-canalicular junctions.
UNASSIGNED: Extensive ductular reaction outlines a severe histologic phenotype in PBC and is associated with an inadequate therapy response and a worse estimated prognosis.
UNASSIGNED: In people affected by primary biliary cholangitis (PBC), the histological appearance of extensive ductular reaction identifies individuals at risk of progressive fibrosis. Ductular reaction at diagnosis correlates with the lack of response to first-line therapy with ursodeoxycholic acid and serves to restore ductular-canalicular junctions in people with PBC. Assessing ductular reaction extension at diagnosis may add valuable information for clinicians.

UNASSIGNED: The FibroScan-AST (FAST) score was recently described to detect patients with nonalcoholic steatohepatitis (NASH) having elevated nonalcoholic fatty liver disease (NAFLD) activity score (NAS ≥ 4) and significant fibrosis (≥ F2) on liver biopsy (NASH+ NAS ≥ 4 + F ≥ 2).
UNASSIGNED: The aim of this study was to validate the FAST score in Indian patients with NAFLD and to derive optimal cut-offs.
UNASSIGNED: Sixty patients with biopsy-proven NAFLD [men: 38 (63.3%), age 40 (32-52) years] with all parameters for assessing the FAST score within 3 months of liver histology were retrospectively analysed.
UNASSIGNED: Histological NASH was present in 17 patients (28.3%), while 11 (18.3%) patients had NASH + NAS ≥ 4 + F ≥ 2. The area under the curve (AUROC) of the FAST score for discriminating NASH + NAS ≥ 4 + F ≥ 2 was 0.81. Using cut-offs by Newsome et al, the rule-out cut-off (FAST: ≤ 0.35) had a negative predictive value (NPV) of 0.88 [sensitivity: 0.91, specificity: 0.14, negative likelihood ratio (LR): 0.64], while the rule-in cut-off (FAST: ≥ 0.67) had a positive predictive value (PPV) of 0.33 (sensitivity: 0.73, specificity: 0.67, positive LR: 2.22). Fifteen (25%) patients were correctly classified as per histology, while 28 (46.67%) patients fell in the grey zone. On recalculating the optimal cut-offs for our patients, the rule-out cut-off (FAST: ≤ 0.55) had an NPV of 0.95 (sensitivity: 0.90, specificity: 0.45, negative LR: 0.21), while the optimal rule-in cut-off (FAST: ≥ 0.78) had a PPV of 0.70 (sensitivity: 0.64, specificity 0.94, positive LR: 10.39). With these cut-offs, 27 (45%) patients fell in the grey zone and 29 (48.3%) were correctly classified as per histology, performing better than the cut-offs by Newsome et al (P < 0.001).
UNASSIGNED: The FAST score demonstrates good AUROC for detecting NASH with significant fibrosis and inflammation on histology. Cut-offs should be recalibrated based on prevalence of disease.
UNASSIGNED: India has a high burden of NAFLD with an estimated 25 million patients at potential risk for significant liver disease. Liver biopsy remains the gold standard for diagnosing NASH, although its application in routine clinical practice is limited. Noninvasive tests for the simultaneous detection of steatosis, inflammation and fibrosis are thus the need of the hour. The FAST score has been recently suggested for the noninvasive detection of NASH with significant fibrosis (≥ F2) and inflammation (NAS ≥ 4) on liver biopsy. We validated the utility of the FAST score for detecting NASH with significant fibrosis and inflammation on liver biopsy in Indian patients with NAFLD. This noninvasive, easy-to-use and nonproprietary FAST score can correctly classify disease severity in more than 50% patients. However, our results suggest that cut-offs should be recalibrated based on the anticipated prevalence of NASH + NAS ≥ 4 + F ≥ 2 in the given population.

BACKGROUND: Hyaline globules (HGs) in the cytoplasm of Kupffer cells (KCs) have been appraised for being a typical feature of autoimmune hepatitis (AIH). This study aimed to determine how useful Kupffer cell hyaline globules (KCHGs) are in diagnosing AIH vs. other causes of pediatric chronic liver diseases (PCLDs).
METHODS: This retrospective study recruited 124 children; 58 with AIH, 50 with chronic hepatitis C virus (HCV) infection, and 16 with Wilson\'s disease (WD). Two pathologists retrieved paraffin blocks of liver biopsies and prepared new cut sections for Periodic acid-Schiff-Diastase (PAS-D) stain. They independently examined liver biopsies before starting treatment. Two pediatricians reviewed medical records for demographic, clinical, laboratory, and serological findings.
RESULTS: Females represented 48.6% of the studied children with a median age of 5.8 (4.9) years. Pathologists identified KCHGs in 67.24%, 12.5%, and 6.0% of AIH, WD, and HCV affected children respectively, P < 0.001. A significantly higher proportion of seropositive than seronegative AIH patients had KCHGs (77.5% vs. 50.0%), (P < 0.05). In multivariate analysis, KCHGs and prolonged prothrombin time were the only significant predictors that differentiate between AIH and the other studied PCLDs. The odds ratio of having AIH increased 68 times if KCHGs were seen. Among children with AIH, the presence of KCHGs was associated with higher median levels of direct bilirubin 2.2 (1.3) vs. 1.2 (2.2), and immunoglobulin G 3.2 (1.9) vs. 2.0 (1.7), (P < 0.05), but not to histopathological findings or hepatic fibrosis and activity.
CONCLUSIONS: KCHGs are key indicators that can differentiate between AIH and other PCLDs, and between seropositive and seronegative AIH.

UNASSIGNED: The present study is planned to assess etiologies, course, and outcome in patients with acute-on-chronic liver failure (ACLF).
UNASSIGNED: Two hundred and eight (182 males and 26 females) patients of ACLF fulfilling modified Asia Pacific Association For Study Of Liver Consensus criteria 2009 admitted to the gastroenterology department of SMS Medical College and hospital, Jaipur, between October 2015 and December 2017 were included. We evaluated etiology of underlying chronic disease and the acute event precipitating decompensation in ACLF.
UNASSIGNED: Most common etiology of chronic liver disease (CLD) was alcohol with 133 (63.94 %) patients. Viral hepatitis, cryptogenic cirrhosis, autoimmunity, nonalcoholic steatohepatitis, and Wilson disease as causes of CLD were present in 32 (15.4%), 29 (13.94%), 9 (4.3%), 3 (1.4%), and 2 (1%) cases, respectively. Alcohol, sepsis, bleeding, reactivation of hepatitis B, hepatitis E, antitubercular drugs, and autoimmune hepatitis as the causes of acute event were present in 100 (48.08%), 34 (16.35%), 19 (9.1%), 17 (8.2 %), 15 (7.2%), 13 (6.25%), and 2 (0.96%) patients, respectively. In 8 (3.85%) patients, the precipitating event could not be known. Mortality (in-hospital) in this study was 37.5%. Higher model for end-stage liver disease score and high Child-Turcotte-Pugh score score were significantly associated with mortality (P <0.001). Patients with higher ACLF grade were associated with higher mortality. Alcohol as a cause of CLD was significantly associated with mortality (p=0.0146, 95% confidence interval between 3.802 and 30.979). There was no significant difference regarding acute precipitating events between survivors and nonsurvivors.
UNASSIGNED: Alcohol was the most common cause for chronic etiology as well as acute precipitating event. Alcohol as a cause of CLD was significantly associated with mortality.

UNASSIGNED: Acute exacerbation of Autoimmune Hepatitis (AIH) poses a significant challenge for diagnosis as it can mimic acute viral hepatitis especially in absence of autoantibodies and hypergammaglobulinemia.
UNASSIGNED: To determine the clinical, laboratory, histopathological characteristics and response to treatment in AIH patients with acute exacerbation.
UNASSIGNED: A retrospective analysis of 16 patients with acute exacerbation of AIH diagnosed over a period of eight years (2008-2016).
UNASSIGNED: Out of the 111 patients diagnosed with AIH, acute exacerbation of AIH was diagnosed in 16 (14.4%) patients. All patients were females with median age of 35 years. Nine patients (56%) had Type 1 AIH and seven (44%) patients were diagnosed with seronegative AIH. All 16 (100%) patients had acute viral hepatitis like illness at presentation. The median bilirubin was 4.2 mg/dl (range, 2.2-20), aspartate transaminase was 568 IU/L (range, 390-908), alanine transaminase was 430 IU/L (range, 257-1026) and serum alkaline phosphatase was 395 IU/L (range, 112-890) during symptomatic period. The histopathological examination showed underlying chronic hepatitis in 10 (71.4%) patients, only fibrosis in 2 (14.2) patients and cirrhosis with activity in 2 (14.2%). All 16 (100%) patients were treated with a combination of steroids and azathioprine. Thirteen (81%) patients achieved complete biochemical remission and three (19%) patients achieved partial remission out of which one (6%) patient succumbed to illness because of the complications of cirrhosis.
UNASSIGNED: A suspicion of acute exacerbation of AIH should be considered in patients with unexplained acute hepatitis mimicking acute viral hepatitis in the absence of positive viral markers. Through evaluation with immunoserological markers and liver biopsy can clinch the diagnosis of acute exacerbation of AIH in such cases.

BACKGROUND: Oxidative stress and cytokines play an important role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We compared the presence of oxidative stress and cytokines in 25 patients with NAFLD with 25 age, sex and BMI-matched patients with chronic viral hepatitis (CVH) and 25 healthy volunteers (HV).
METHODS: Oxidative stress was studied biochemically by markers of lipid peroxidation and biochemical assessment of anti-oxidant status and various cytokines were studied by ELISA.
RESULTS: Patients with NAFLD had significantly higher levels of malondialdehyde (MDA) (p = 0.000) and conjugated dienes (CD) (p = 0.000) in comparison to HVs. Patients with NAFLD also had significantly higher MDA levels (p = 0.000) in comparison to CVH patients. Patients with NAFLD had significantly lower GSH levels (p = 0.004) in comparison to HVs. Patients with NAFLD had higher GPx activity (p = 0.028) in comparison to HVs. Catalase activity was significantly decreased in both NAFLD (p = 0.001) and CVH patients (p = 0.000) in comparison to HVs. Patients with NAFLD had significantly higher SOD activity (p = 0.000) in comparison to CVH patients. There was no difference in serum levels of IL-1β and TNF-α amongst three groups. Patients with CVH were found to have higher IL-8 serum levels (p = 0.039) in comparison to HVs. CVH patients also had higher TGF-β levels (p = 0.002) in comparison to both NAFLD patients and HVs.
CONCLUSIONS: Differences in the markers of oxidative stress and anti-oxidant status between NAFLD, CVH and healthy volunteers suggest presence of higher oxidative stress in patients with NAFLD.