Acute liver failure histopathology: A 5-year retrospective study.

BACKGROUND: Acute liver failure (ALF) is a rare, life-threatening disease of diverse etiology. It is defined as severe acute liver injury for fewer than 26 weeks' duration with encephalopathy and impaired synthetic function (international normalized ratio [INR] of 1.5 or higher) in a patient without cirrhosis or pre-existing liver disease. The diagnosis rests mainly on the clinical ground with wide range of pathological features. The present study seeks to explore the diverse histological patterns observed in cases for ALF and assess their usefulness in determining the underlying causes for the condition. METHODOLOGY: A retrospective cross-sectional study was conducted among patients of ALF who underwent liver transplant and transjugular liver biopsy over a five-year period. From 1082 explant liver and 2446 liver biopsies, 22 cases of ALF (10 explants and 12 liver biopsies) were included in the study. Clinical and laboratory details were retrieved and histological findings were reviewed. RESULT: Age ranged from 10 to 72 years (mean age, 40 years). There was a female predominance with a male:female ratio of 1:1.7. The commonest cause for ALF was virus-induced hepatocellular damage in 36.3% (eight patients), followed by autoimmune hepatitis in 22.7% (five patients), drug-induced liver injury (DILI) in 18.1% (four patients), cryptogenic in 13.6% (three patients) and ischemic injury secondary to large vein thrombosis in 9.0% (two) patients. The histological patterns identified were categorized into six categories. A more comprehensive morphological evaluation was conducted specifically for cases of ALF associated with autoimmune hepatitis (AIH) and compared with other cases of ALF. CONCLUSION: In summary, our present study illustrates a morphological overlap in various patterns for the purpose of etiological assessment. In cases of AIH ALF, the presence of portal plasma cell infiltrate and central perivenulitis were identified as significant histological features to guide diagnosis.

Clinicopathological Profile and Outcome of a Large Cohort of Patients with Nonalcoholic Fatty Liver Disease from South Asia: Interim Results of the Indian Consortium on Nonalcoholic Fatty Liver Disease.

Background: Previous data from South Asia and India had shown that patients with nonalcoholic fatty liver disease (NAFLD) have mild liver disease severity. There are no data regarding long-term clinical outcomes in patients with NAFLD from South Asia. The aim of the study was to evaluate the clinicopathological profile, severity of NAFLD, and clinical outcomes in a large cohort of patients with NAFLD from South Asia. Methods: In an ongoing real-life study [Indian Consortium on nonalcoholic fatty liver disease (ICON-D)], interim data captured across 23 centers in India over 18 months was analyzed for clinicopathological profile, severity of NAFLD, and hepatic/extrahepatic events on follow-up. Results: Of 4313 patients (mean age 45 ± 12.2 years, males 52%), data on metabolic risk factors in 3553 (82.3%) patients revealed that 378 (10.6%) were lean, 575 (16.2%) overweight, 2584 (72.7%) obese; metabolic syndrome in 1518 (42.7%) and at least one metabolic risk factor in 3292 (92.6%) patients. Evidence of significant or advanced fibrosis assessed with [aspartate transaminase to platelet ratio index (APRI), n = 3196 (74%)], [fibrosis-4 (FIB-4), n = 3554 (82.4%)], [NAFLD fibrosis score (NFS), n = 1924 (44.6%)], [Fibroscan, n = 2475, (57.3%)], and histology [n = 267 (6.2%)] was present in 682 (21.3%), 676 (19%), 397 (20.6%), 715 (29%), and 41 (15.4%) patients, respectively; 246 (10%) patients on Fibroscan and 22 (8.2%) on histology had evidence of cirrhosis. On a mean follow-up 43.5 months, hepatic and extrahepatic events recorded in 1353 (31.3%) patients showed that patients with compensated cirrhosis [71 (5.2%)] had more hepatic [26 (36.7%)] and extrahepatic events [8 (11.3%)] in comparison with those without cirrhosis (P < 0.0001). Conclusion: Around one fifth of patients with NAFLD in South Asia have significant liver disease. Both hepatic and extrahepatic events on follow-up are observed more commonly in patients with nonalcoholic steatohepatitis-related compensated cirrhosis.

An expert review on the use of tenofovir alafenamide for the treatment of chronic hepatitis B virus infection in Asia.

Asia has intermediate-to-high prevalence and high morbidity of hepatitis B virus (HBV) infection. The use of guideline-recommended nucleos(t)ide analogs with high barrier to resistance, such as entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF), is one of the key interventions for curbing HBV infection and associated morbidity in Asia. However, there are some challenges to the use of ETV and TDF; while ETV is associated with high resistance in lamivudine (LAM)-exposed (especially LAM-refractory) patients; bone and renal safety issues are a major concern with TDF. Hence, a panel of twenty-eight expert hepatologists from Asia convened, reviewed the literature, and developed the current expert opinion-based review article for the use of TAF in the resource-constrained settings in Asia. This article provides a comprehensive review of two large, phase 3, double-blind, randomized controlled trials of TAF versus TDF in HBeAg-negative (study 0108) and HBeAg-positive (study 0110) chronic HBV patients (> 70% Asians). These studies revealed as follows: (1) non-inferiority for the proportion of patients who had HBV DNA < 29 IU/mL; (2) significantly high rate of normalization of alanine aminotransferase levels; (3) no incidence of resistance; and (4) significantly better bone and renal safety, with TAF vs. TDF up to 144 weeks. Considering the benefits of TAF, the expert panel proposed recommendations for optimizing the use of TAF in Asia, along with guidance on specific patient groups at risk of renal or bone disease suitable for TAF therapy. The guidance provided in this article may help clinicians optimize the use of TAF in Asia.

Anti-endothelial cell antibody rich sera from rheumatic heart disease patients induces proinflammatory phenotype and methylation alteration in endothelial cells.

Rheumatic heart disease (RHD) is a major cause of cardiovascular morbidity and mortality in developing nations like India. RHD commonly affects the mitral valve which is lined by a single layer of endothelial cells (ECs). The role of ECs in mitral valve damage during RHD is not well elucidated. In here, anti-endothelial cell antibody from RHD patients has been used to stimulate the ECs (HUVECs and HMVECs). ECs proinflammatory phenotype with increased expression of TNFα, IL-6, IL-8, IFNγ, IL-1ß, ICAM1, VCAM1, E-selectin, laminin B, and vimentin was documented in both ECs. The promoter hypomethylation of various key inflammatory cytokines (TNFα, IL-6, and IL-8), integrin (ICAM1) associated with leukocyte transendothelial migration, and extracellular matrix genes (vimentin, and laminin) were also observed. Further, the in-vitro data was in accordance with ex-vivo observations which correlated significantly with the etiological factors such as smoking, socioeconomic status, and housing. Thus, the study sheds light on the role of ECs in RHD which is a step forward in the elucidation of disease pathogenesis.

A report on three patients with Echinococcus multilocularis: Lessons learned.

Echinococcus multilocularis (EM) is the most virulent species of the genus Echinococcus. It causes a highly lethal helminthic disease in humans. The disease may present as hepatic mass mimicking a malignant neoplasm. Due to the vascular and neural invasion, protean clinical manifestations including Budd-Chiari syndrome (BCS) may be the clinical presentation of this condition. We herein report three cases of Echinococcus multilocularis; the first case presenting as multiple hepatic space-occupying lesions, second as liver mass infiltrating the nerve bundles, and the third as a hepatic mass infiltrating the large vessels including inferior vena cava and right hepatic vein presenting as BCS. EM is a parasite with capabilities of mass-forming effect, neural and vascular invasion. Though cases of BCS have been described, most of these are due to secondary compression and rarely by direct parasitic invasion.

Association of rheumatic fever & rheumatic heart disease with plausible early & late-stage disease markers.

BACKGROUND & OBJECTIVES: Rheumatic fever (RF) and rheumatic heart disease (RHD) are the autoimmune sequelae caused by Group A Streptococcus. RHD still remains a major concern in the developing countries due to its poor diagnosis, lack of vaccines and social awareness among population. This study was aimed to identify the plausible early- and late-stage disease markers associated with RF/RHD. METHODS: A total of 84 patients with confirmed pharyngitis (n=18), RF (n=23) and RHD (n=43) were included in the comparative analysis of different factors involved in host-pathogen interaction during RF/RHD pathogenesis. RESULTS: This study revealed high titre of serum antistreptolysin O (ASO) antibody in pharyngitis compared to RF and RHD patients, whereas procollagen type 1 C-peptide (PICP) level was elevated in RHD which showed an inverse correlation with serum ASO titre. The significant elevation of serum anti-peptide associated with RF (PARF) antibody in RF patients was correlated as a probable stage-specific determinant. In addition, pro-inflammatory cytokine profile revealed high levels of interleukin-12 (IL-12)/IL-23p40, IL-17A in RF, whereas IL-6 concentration was higher in RHD compared to healthy controls. INTERPRETATION & CONCLUSIONS: The overall assessment of the factors/ disease markers involved in host-pathogen interaction in RF/RHD may be suggestive of plausible disease marker in different groups of patients. Further studies with larger sample need to be done to better understand RF/RHD pathogenesis.

Different Nodules Identified during Liver Explant Gross Examination: Relevance and Need for Sectioning-Experience from India.

Objective. The goal of this study was to determine the etiopathological association of various hepatic nodules identified during gross examination of liver explants specimen and the grossing aspects of these abnormal nodules especially those smaller than 1 cm in diameter. Our aim was to analyze whether there is any association of macroregenerative and dysplastic nodule with hepatocellular carcinoma. Materials and Methods. Fifty consecutive liver explants specimens were analyzed for the presence of any abnormal nodule (abnormal nodule defined as any nodule different in color, texture, and appearance from adjacent liver tissue). Results. Of the total 40 abnormal nodules identified in 50 liver explant specimens, there were 12 (30%) HCC [including 5 small HCC (41% of total HCC) and 1 steatohepatitic HCC (8% of total HCC)], 11 (27%) MRNs, 8 (20%) dysplastic nodules, and 9 (22%) necrotic nodules. Most cases (72%) of MRN are seen in hepatitis C virus related cirrhosis with only 2 cases having associated HCC. Most cases of HCC were seen in cases of HBV associated cirrhosis (60%). The association of MRN was not found to be significantly associated with HCC with a p value of 1.0. Dysplastic nodules were found to be significantly associated with HCC with a p value of 0.02. Conclusion. In hepatic carcinogenesis, the role of MRN does not appear to be significant. However, the presence of dysplastic nodules is significantly associated with HCC. The study identified another variant of cirrhotic nodules herein called necrotic nodules that are mostly tan greenish in color and <0.5 cm in diameter. No dysplastic changes were identified in any of these nodules disqualifying the need of sectioning in such nodules.

Peritransplant management of chronic hepatitis C.

Hepatitis C infection is the commonest cause of cirrhosis worldwide. Management of chronic hepatitis C in peritransplant period is challenging. Patients with compensated/ Child class A cirrhosis due to HCV infection are treated like non-cirrhotics, with PEG IFN and Ribavirin, albeit with a higher incidence of complications. Treatment is not recommended for decompensated cirrhotics due to higher complication rate including risk of death. After liver transplant, immunosuppression should be adjusted to prevent/delay recurrent HCV disease. Incidence and severity of recurrent HCV disease as well as patient and graft survival is similar between living donor and deceased donor liver transplants. It is currently recommended to treat established recurrent hepatitis C i.e. raised ALT with HAI > 4 and/or F > 1. Pre-emptive/prophylactic antiviral therapy is poorly tolerated and has low efficacy. Standard dose regimen (PEG IFN 1.5 mcg/kg or 180 mcg weekly + Ribavirin 800-1200 mg/ day) for 48 weeks irrespective of genotype is the recommended treatment protocol. Therapy poses significant problems in the form of anemia, neutropenia, and a higher risk of rejection.

Endoscopic management of pancreatic duct disruption following a bullet injury: a case report.

CONTEXT: A pancreatic fistula is the most common complication of pancreatic injury. Although spontaneous closure of pancreatic ductal disruption has been reported, surgical treatment is accepted as the single most carried-out intervention in major ductal injury. We report a case of pancreatic duct disruption due to a bullet injury managed successfully by endoscopic pancreatic duct stenting. CASE REPORT: A 28-year old male sustained a bullet injury leading to proximal pancreatic duct disruption with leakage of dye. After a month of unsuccessful conservative management, graded endoscopic pancreatic duct stenting was carried out, leading to closure of the leak. The patient has gained 15 kilograms of weight at one year of follow-up without any complications. CONCLUSION: This is probably the first case of successful endoscopic management of pancreatic duct disruption due to a bullet injury. In carefully selected patients, successful non-surgical management of traumatic pancreatic duct disruption is feasible.