Liver failure determines the outcome in patients of acute-on-chronic liver failure (ACLF): comparison of APASL ACLF research consortium (AARC) and CLIF-SOFA models.

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.

Autoimmune hepatitis in India: single tertiary referral centre experience.

BACKGROUND AND AIMS: Autoimmune hepatitis is considered to be rare in Asia-Pacific region. There a few long term studies available. This study was planned to estimate the burden, natural history of AIH and challenges associated with management in a single non-transplant tertiary referral center. METHODS: Prospectively maintained data of patients treated as AIH was screened and patients who qualified AIH by retrospective application of simplified criteria's were enrolled. 181 patients qualified. 125 patients with substantial follow up (65 Definite AIH; 81 females; median age 46, range 8 - 79) were included in study. RESULTS: Prevalence of AIH was 1.3% and 8.74% amongst all liver disease patients and chronic liver disease respectively. 89 patients qualified as Type I AIH, 14 as type II AIH and 22 were autoimmune markers negative. Modes of presentation was acute liver failure (n = 8), chronic hepatitis (n = 17), cirrhosis (n = 89), 50 patients were decompensated), ACLF (n = 7), while 2 were clinically asymptomatic. 19 patients had preceding history of drug intake. 33 patients didn't undergo pretreatment liver biopsy. Prednisolone alone was the predominant immunosuppressive agent used, especially in decompensated cirrhotics and those with acute liver failure. First remission rates after first immunosuppression course were 60%, 85% and 63% in type I, type II and autoantibody negative groups. After a median follow up of 7 years (range 1 - 17 years), 15 patients died (12 of liver related complications) and 2 underwent liver transplantation. Failure to normalize ALT had a high hazard ratio predicting liver related death or transplantation. 11 patients had improvement on repeat liver biopsy, with 5 showing complete cirrhosis reversal. 40 patients are on long term maintenance immunosuppression. CONCLUSION: AIH, though uncommon, needs to be kept in mind as early treatment is associated with significantly good long-term prognosis.

Risk of development of hepatocellular carcinoma in patients with NASH-related cirrhosis.

BACKGROUND AND AIMS: The risk of development of hepatocellular carcinoma (HCC) in hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is well established and is being recognized increasingly in non-alcoholic steatohepatitis (NASH)-related cirrhosis. This study aimed to assess the risk of development of HCC in patients with NASH-related cirrhosis. METHODS: From January 2010 to October 2011, we prospectively enrolled 585 patients with liver cirrhosis (men:women ratio 4.4:1, mean age 50.1 +/- 6.1 years, aetiology HBV 19%, HCV 14.2%, NASH-related 7%, cryptogenic cirrhosis 17.8%, already diagnosed cirrhosis 48.2%, and the remaining were newly diagnosed cases). The cumulative follow-up was for 5.9 +/- 0.5, 6.1 + 0.8 and 6.8 + 1.2 years for HBV, HCV and NASH-related cirrhosis, respectively. Patients with advanced cirrhosis, Child class C and associated comorbid conditions where survival was < 1 year were excluded from the study. The remaining patients were followed up 6-monthly with ultrasound examination and alpha-fetoprotein (AFP) test. Patients suspected of HCC underwent triple-phase computed tomography (CT) scan and liver biopsy was done to confirm the diagnosis. RESULTS: A total of 54 patients developed HCC, of which 26 had HBV, 14 had HCV, 9 had- cryptogenic and 6 had- NASH-related cirrhosis. The annual rate of development of HCC was 1.5%, 3.6%, 0.6% and 0.46 in HBV, HCV, cryptogenic and NASH-related cirrhosis, respectively. CONCLUSIONS: The incidence of HCC was highest in HCV and lowest in NASH-related cirrhosis. These figures suggest an intermediate risk of development of HCC when compared to western countries and Japan.

Protective effect of curcumin, silymarin and N-acetylcysteine on antitubercular drug-induced hepatotoxicity assessed in an in vitro model.

Tuberculosis (TB) is highly endemic in India. The first-line anti-TB therapy (ATT) involving isoniazid (INH), rifampicin and pyrazinamide causes hepatotoxicity in approximately 11.5% of Indian patients. Studies have shown that ATT-induced hepatotoxicity is primarily due to oxidative stress caused by the drugs and metabolites. Herbal drugs with antioxidative properties have been tested in animal studies and clinical trials for the management of hepatotoxicity. The objective of this study was to investigate the role of curcumin (CUR), silymarin (SILY) and N-acetylcysteine (N-ACET) on hepatotoxicity by ATT drugs using an in vitro model of human hepatocellular carcinoma cell line (HepG2). HepG2 cells were treated with ATT drugs alone or along with CUR, SILY or N-ACET for a 48-h duration. The cells were monitored for viability, morphology, respiring mitochondria and cell cycle. Our results suggest that the presence of hepatoprotective drugs during treatment of HepG2 cells with ATT drugs lowers the hepatotoxic effect of the latter. This is observed in terms of (a) increased cell viability, (b) healthy-looking cell morphology as revealed by phase contrast microscopy, (c) active respiring cells as observed with confocal microscopy upon staining with a mitochondrial membrane-specific dye, MitoTracker(®) Red, and reduction in the sub-G(1) peak in cell cycle analysis by flow cytometry. Our results suggest that these hepatoprotective drugs need to be further explored as potential adjuvant therapy along with ATT drugs.

A retrospective clinico-pathological analysis of neuroendocrine tumors of the gastrointestinal tract.

AIM: Gastrointestinal tract is the commonest site for neuroendocrine tumors. Appendix, ileum and rectum were considered to be common sites for these tumors. However, there has been change in pattern of gastrointestinal neuroendocrine tumors over last few years. There is limited data available on epidemiology and patterns of these tumors in India. METHODS: Analysis of 74 patients with gastrointestinal and pancreatic neuroendocrine tumors over a period of 7 years at a single center in Mumbai, India was done. Clinical details, surgical outcome with follow up and treatment were reviewed. All these patients were analyzed with special emphasis on the site of the tumor. RESULTS: The results showed a male preponderance (ratio of 2.5:1) with a mean age of 53.01 +/- 15.13 years. Of the 74 tumors, the commonest site was found to be stomach 22 (30.2%), followed by pancreas 17 (23.3%) and duodenum 14 (18.9%). Only 3 (4.1%) patients presented with carcinoid syndrome. The disease was localized in 46 (62.2%), regional spread was seen in 14 (18.9%) and distant spread in 14 (18.9%). Majority of gastric and duodenal tumors had localized disease while pancreatic NETs led to most of the cases with distant disease. CONCLUSION: This analysis showed that gastrointestinal and pancreatic neuroendocrine tumors are not rare. Pattern of these tumors has definitely changed over last few years. Stomach was found to be commonest site for gastrointestinal neuroendocrine tumors followed by pancreas and duodenum.

Prevalence of tuberculosis in patients with cirrhosis of liver in western India.

Tuberculosis is a common disease in India. Its prevalence is higher in patients with cirrhosis of the liver. This study was conducted to determine the prevalence of tuberculosis in patients with liver cirrhosis in Western India. The prevalence was fifteen times higher than in the general population. It was significantly higher in alcoholics. The response to treatment and outcome were found to be favourable.

Intrinsic factor antibody negative atrophic gastritis; is it different from pernicious anaemia?

INTRODUCTION: H. pylori gastritis and autoimmune gastritis are the two main types of chronic atrophic gastritis. Parietal cell antibody (PCA) and intrinsic factor antibody (IFA) are characteristic of autoimmune gastritis, of which IFA is more specific. Patients who are IFA negative are considered under the category of chronic atrophic gastritis. AIM: To differentiate IFA positive from IFA negative chronic atrophic gastritis. METHODS: Fifty consecutive patients of biopsy proven chronic atrophic gastritis were included in this study. All patients underwent haematological and biochemical tests including serum LDH, vitamin B12 and fasting serum gastrin levels. PCA and IFA antibodies were tested in all patients. Multiple gastric biopsies from body and antrum of the stomach were taken and evaluated for presence of intestinal metaplasia, endocrine cell hyperplasia, carcinoid and H. pylori infection. Patients were grouped as group A (IFA positive) and group B (IFA negative). The mean laboratory values and histological parameters were compared between the two groups using appropriate statistical methods. RESULTS: Eighteen patients were in group A (mean age 55.5 +/- 13 years, male: female = 16:2) and thirty-two in group B (mean age 49.7 +/- 13 years, male: female = 25:7). There was no statistically significant difference between median values of haemoglobin, MCV, LDH, Vitamin B12 and serum gastrin in both the groups. None of the histological parameters showed any significant difference. CONCLUSION: There was no statistically significant difference in haematological, biochemical and histological parameters in IFA positive and negative gastritis. These may be the spectrum of the same disease, where H. pylori may be responsible for initiating the process.

Portopulmonary hypertension in a case of non-cirrhotic portal fibrosis.

Portopulmonary hypertension (PPHT) is the unusual association of portal hypertension (HT) with pulmonary HT. We report a case of noncirrhotic portal fibrosis (NCPF) leading to PPHT which is exceedingly rare with only very few cases reported in the literature. This is an autopsy report of a 30 years old man, a known case of portal HT who died suddenly due to a syncopal attack. Autopsy revealed massive pulmonary thromobembolism with pulmonary HT. Liver showed changes of NCPF. The rarity of NCPF causing PPHT prompted this case report.

Utilization of antihepatocyte clone OCH1E5 (Hep Par 1) in histological evaluation of liver tumors.

Diagnosis of hepatocellular carcinoma (HCC) is not always easy on simple hematoxylin and eosin (H&E) stain. The diagnostic problems arise when tumor shows pseudoglandular, pleomorphic or clear cell differentiation. Various tumors markers have been described with varying sensitivity and specificity. Monoclonal antibody Hep Par 1 (OCH1E5) which is specific for hepatocytes offers great help in separation of these tumors. The aim of the present study was to determine utility of Hep Par 1 (OCH1E5) in differentiating HCC from metastatic tumors and cholangiocarcinoma. Total of 62 cases of liver tumors obtained from biopsies, resected or autopsy specimens were included in the study. Slides having representative sections were subjected to immunohistochemistry with monoclonal antibody Hep Par 1 (Dako Corp) using avidin biotin technique with primary antibody dilution of 1:40. Adjacent nontumorous hepatocytes were taken as positive control. Slides were examined by experienced pathologist without any information of clinical or H&E diagnosis. Cases were considered positive for Hep Par 1 if tumor cells showed cytoplasmic brown colored granules. The intensity and distribution (diffuse/ focal) of immunoreactivity was noted. Subsequently immunohistochemistry results were correlated with histology and clinical diagnosis. Hep Par 1 antibody was positive in 26 (42 %) and negative in 36 (58 %) liver tumors. On correlating with H&E sections, out of 26 positive cases, 25 (89.2%) were HCC and one was the case of metastasis of mucin secreting adenocarcinoma. From 36 tumors with negative staining 3 were cases of HCC, 27 metastatic adenocarcinomas and 6 cholangiocarcinomas. Only one case of liver metastasis of mucin secreting adenocarcinoma showed positivity. None of the cases of cholangiocarcinoma showed positivity for Hep Par 1. The three HCCs which did not take up staining for Hep Par 1 were 2 cases of moderately differentiated HCC having pseudoglandular pattern and a case of well differentiated HCC with trabecular arrangement. In 11(44%) cases staining was diffuse while in 14 (56%) it was focal but intense. Hep Par 1 is a useful marker in differentiating HCC from metastaic tumors and cholangiocarcinoma with sensitivity and specificity of 89 % and 97 % respectively and positive predictive value of 96 %. However one should be aware of limitations of immunohistochemistry.

Gastric antral vascular ectasia (GAVE) syndrome.

Gastric antral vascular ectasia (GAVE) syndrome is an uncommon cause of chronic gastrointestinal bleeding and iron deficiency anaemia. We describe two cases of GAVE, one pernicious anaemia related and the other portal hypertension related. In both the cases, progressive mucosal changes, which lead to development of GAVE, were documented. Those changes were progression of multiple antral erythematous spots into linear configuration and lastly to watermelon stomach. One of the cases was treated with tranexamic acid with good response.

Tissue polymerase chain reaction in diagnosis of intestinal tuberculosis and Crohn's disease.

AIMS AND OBJECTIVES: 1) To evaluate the utility of PCR in differentiating intestinal tuberculosis from Crohn's disease. 2) To compare histological features of tuberculosis and Crohn's disease. MATERIAL AND METHODS: A total of 60 cases of diagnosed intestinal tuberculosis and 20 Crohn's disease were included in the study. Clinical data, radiological and endoscopic findings and response to treatment were taken into consideration. Endoscopic biopsies from affected areas were subjected to histopathological examination and polymerase chain reaction (PCR) assay. Acid fast staining on tissue and culture was done whenever possible. RESULTS: Clinical symptoms, radiological and endoscopic findings were almost similar between intestinal tuberculosis and Crohn's disease. PCR was positive in 21.6% cases of intestinal tuberculosis and 5% Crohn's disease. Nine out of 42 cases (21.4%) without granuloma were also positive by PCR. There was no statistical difference for PCR positivity between patients with intestinal tuberculosis with or without granuloma on histology and also between caseating and non-caseating granuloma. CONCLUSION: PCR assay showed high specificity (95%) for the diagnosis of intestinal tuberculosis hence may be valuable method to differentiate intestinal tuberculosis from Crohn's disease.

Management of large hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world. There is increasing incidence of HCC in India. More than 70% of HCC are not suitable for curative treatment. Majority of the HCCs are large when diagnosed all over the world. There is no standard treatment for large HCCs. Different palliative treatments like arterial embolization/chemoembolization, intraarterial lipoidol chemotherapy, hormonal compounds like tamoxifene, octerotide systemic chemotherapy, immuno therapy with interferon, internal radiation with 131I or 99Yttrium. Arterial chemoembolization is the treatment of choice with proved efficacy in selected group of patients. The newer modalities and strategies need to be tried in controlled randomized trials.

Hepatic sarcoidosis.

We describe six cases of hepatic sarcoidosis. Clinical presentation was with weight loss, hepatomegaly and abnormal liver function tests. In addition there was fever, itching, splenomegaly and abdominal lymphadenopathy in some. CT scan revealed mediastinal lymphadenopathy in all. Liver biopsy showed noncaseating epithelioid granulomas. Serum angiotensin converting enzyme was elevated in four cases. All patients had received anti-tuberculosis treatment with clinical diagnosis of hepatic tuberculosis. None of them improved, while some showed clinical deterioration. All patients responded to corticosteroids with disappearance of symptoms and normalization of liver function tests.

Gastric lipoma presenting with dyspepsia.

Gastric lipoma is one of the rare benign gastric tumors. Its preoperative diagnosis obviates the need of an extended gastrectomy. We report a case of gastric lipoma who presented with symptoms of dyspepsia and was treated by surgical gastrectomy and tumour enucleation.

HLA genotyping in type-I autoimmune hepatitis in Western India.

OBJECTIVES: To analyze association of different HLA genotypes for predisposition to type-I autoimmune hepatitis in Western India. METHODS: This study was undertaken on patients of type-I autoimmune hepatitis (defined by international criteria by IAHG, 1999). HLA genotyping for class I and II was done in 20 patients of autoimmune hepatitis and 100 healthy controls. Statistics were done using Halden's modification of Woolfs formula. RESULT: Significant association of autoimmune hepatitis was found amongst class I antigens--HLA B27 [20 vs. 0 %] & HLA cw4 [40 vs. 15 %] and amongst class II antigens--DRBI*01XX [25 vs. 2%], DRB1*14XX [30 vs. 12%], DRB1*15XX [40 vs. 25%] and DRB1*07XX [20 vs. 9 %] at DRB1 locus. Stronger association was found with HLA B27, cw4 & HLA DRB1 *01XX. CONCLUSION: Our data indicate that predisposition to autoimmune hepatitis is different in Indian patients and not associated with HLA DRB1*03XX or *04XX, as seen in Western world.

Chronic liver disease in diabetes mellitus.

BACKGROUND: The association of diabetes with liver disease is well known. AIM: To study the spectrum of liver disease in patients of chronic liver disease (CLD) with diabetics and compare it with age and sex matched patients of CLD without diabetes. METHODS: We studied the patients of chronic liver disease presenting over a period of one year and their diagnosis were established by biochemical studies, imaging, endoscopic examination and liver biopsy when required. They were evaluated for the aetiological causes of liver diseases. RESULTS: A total of 53 patients of CLD with diabetes, M:F 43:8, with an age range of 35-70 years, median age of 51 years were taken as study group. Demographic picture of control group was n = 115, with M:F = 100: 15, age range of 37-68 years, with a median age of 52 years. Spectrum of liver disease in diabetic group were as follows: 56.6% cirrhosis, 15.1% chronic hepatitis, 22.6% fatty liver, 5.7% cirrhosis + hepatocellular carcinoma (HCC). The spectrum in control group was as follows, cirrhosis 46.1%, chronic hepatitis 36.5%, fatty liver 14.8%, cirrhosis and HCC 2.6%. Aetiology of chronic liver disease in diabetic group was as follows: Non-alcoholic steatohepatitis (NASH) with cirrhosis 11.3%, NASH 18.9%, cryptogenic cirrhosis 22.6%, hepatitis B virus (HBV) 17%, hepatitis C virus (HCV) 13.2%, alcohol 17%. Aetiology of chronic liver disease in nondiabetic group was as follows: NASH with cirrhosis 1.7%, NASH 13.0%, cryptogenic cirrhosis 7.8%, HBV 30.43%, HCV 13%, alcohol 29.6% and autoimmune in 4.3%. Incidence of NASH with cirrhosis and cryptogenic cirrhosis were found to be statistically significantly high in diabetic group. Incidence of diabetes in cryptogenic cirrhosis was found to be 57% versus 30% in noncryptogenic cirrhosis. CONCLUSION: NASH, NASH with cirrhosis and cryptogenic cirrhosis are the major causes of chronic liver disease in patients with diabetes mellitus. Alcohol and viral causes are found to be important aetiologies in nondiabetic control group. Diabetes mellitus is an important risk factor for chronic liver disease and progression of NASH to cirrhosis, which may present as cryptogenic cirrhosis.