Ck Adarsh

Single-Center Experience With Drug-Induced Liver Injury From India: Causes, Outcome, Prognosis, and Predictors of Mortality

OBJECTIVES:Although drug-induced liver injury (DILI) is rare, it may result in significant morbidity or death. The causes and outcome vary according to regions, with acetaminophen and complementary medicines common in the West and the Far East, respectively. This study evaluates the causes, outcomes, predictors, and models for 90-day mortality from DILI from India.METHODS:Consecutive patients with DILI from 1997 to 2008 based on International Consensus Criteria from a medical college hospital setting were studied.RESULTS:Of the 313 patients, 58% were males. Leading causes were a combination of four anti-tuberculous drugs (ATDs) (58%), anti-epileptics (11%), olanzapine (5.4%), and dapsone (5.4%). The overall 90-day mortality of 17.3% was significantly higher for ATD hepatitis (21.5%) vs. those without (11.4%) (P=0.02). The highest mortality was for leflunomide (75%). Seventy-eight percent of patients received more than one drug. Fulminant hepatic failure developed more commonly in females than in males (23% vs. 17%). Of the 66% of cases with jaundice and/or icterus, mortality was 26%. Multivariable models for mortality using a combination of encephalopathy, ascites, and bilirubin, or a combination of albumin, prothrombin time, and white blood cell count yielded a C-statistic of at least 0.86 by recursive partitioning and 0.92 by logistic regression. Model for end stage liver disease (MELD) scores of 38 and 46 yield probabilities of death of 0.90 (confidence interval (CI): 0.71–0.97) and 0.99 (CI: 0.90–1.00), respectively.CONCLUSIONS:DILI results in significant overall mortality (17.3%). ATDs, anti-convulsants, sulphonamides, and olanzapine are the leading causes of DILI. Although common in males, more females developed fulminant hepatic failure. High-MELD score or a combination of ascites, encephalopathy, high bilirubin, prothrombin time, and leukocyte count are predictive of mortality.

Drug‐Induced liver injury with hypersensitivity features has a better outcome: A single‐center experience of 39 children and adolescents

Drug‐induced liver injury (DILI) is rare in children and adolescents, and, consequently, data are remarkably limited. We analyzed the causes, clinical and biochemical features, natural history, and outcomes of children with DILI. Consecutive children with DILI from 1997 to 2004 (retrospective) and 2005 to 2010 (prospective) were studied based on standard criteria for DILI. Thirty‐nine children constituted 8.7% of 450 cases of DILI. There were 22 boys and 17 girls. Median age was 16 years (range, 2.6‐17). Combination antituberculous drugs were the most common cause (n = 22), followed by the anticonvulsants, phenytoin (n = 10) and carbamazepine (n = 6). All of the 16 children (41%) who developed hypersensitivity features, such as skin rashes, fever, lymphadenopathy, and/or eosinophilia, including the 3 with Stevens‐Johnson syndrome, survived. Those with hypersensitivity presented earlier (24.5 versus 35 days; P = 0.24) had less severe disease (MELD, 16 versus 29; P = 0.01) and had no mortality (0/16 versus 12/23; P < 0.001), compared to those without hypersensitivity. The 12 fatalities were largely the result of antituberculous DILI (n = 11). The presence of encephalopathy and ascites were associated with mortality, along with hyperbilirubinemia, high international normalized ratio, and serum creatinine. According to the Roussel Uclaf Causality Assessment Method, 18 were highly probable, 14 probable, and 7 possible. Thirty‐two children were hospitalized. Conclusion: DILI is not uncommon in children and accounts for 8.7% of all patients with DILI. Antituberculous drugs and anticonvulsants are the leading causes of DILI in India. Overall mortality is high (30.7%), largely accounted by antituberculous drugs. Children with DILI and hypersensitivity features present early, have less severe disease, and, consequently, a better prognosis, compared to those without, and are often associated with anticonvulsants or sulfonamides. (HEPATOLOGY 2011;)

Outcome and determinants of mortality in 269 patients with combination anti-tuberculosis drug-induced liver injury

Worldwide anti‐tuberculosis (TB) drug‐induced liver disease (DILI) is an important cause of hepatotoxicity, and drug‐induced acute liver failure (ALF). Reported series on anti‐TB DILI are limited by a mix of cases with mild transaminase elevation or adaptation. Our aim was to analyze the clinical features, laboratory characteristics, outcome, and determine predictors of 90‐day mortality.

Factors that predict mortality in children with Wilson disease associated acute liver failure and comparison of Wilson disease specific prognostic indices

Wilson disease (WD) associated acute liver failure (ALF) affects children more than adults. The predictors of mortality and outcome in patients without encephalopathy are not clear. We investigated the ability of prognostic factors and various models including model for end‐stage liver disease (MELD) to predict mortality among children with WD and ALF.

An unusual experience with endoscopic retrograde cholangiopancreatography

The endoscopic retrograde cholangiopancreatography (ERCP) is known for its varied diagnostic and therapeutic utility for a variety of disorders. However it has greater likelihood of procedure related complications among the endoscopic procedures of gastrointestinal tract. The extraluminal hemorrhagic complications following ERCP are potentially life threatening though relatively rare. We present a 50 year patient with choledocholithiasis and cholelithiasis developing rare complication of subcapsular hepatic hematoma, following ERCP due to guide wire injury.

Duodenal gastrointestinal stromal tumor presenting as massive gastrointestinal bleed

Editor Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal (GI) tract, derived from the malignant transformation of the interstitial cells of Cajal or their precursors. GISTs are more common in the 50– 60 years age group and occur commonly in the stomach (60% to 70 %) and small intestine (25 % to 35 %) [1]. Duodenal GISTs are rare, comprising about 12 % to 18 % of small intestine GIST and less than 4 % of all GISTs. They usually present with anemia due to chronic GI blood loss, but duodenal GIST presenting as massive GI bleed with shock is rare. Duodenal GISTs most frequently involve the second portion of the duodenum in close relationship to the ampulla of Vater, followed by the third, fourth, and first portions. The relationship to the ampulla determines surgical treatment strategies. We have treated four patients of GIST presenting with massive upper GI bleed and shock in the last 18 months. Their clinical, laboratory, operative, and histopathology details are outlined in Table 1. All four were between 40–60 years of age. Three out of four presented with hematemesis, and all four were critically ill with hemodynamic instability. Laboratory evaluations revealed severe microcytic hypochromic anemia in all four patients with hemoglobin ranging from 5.6 to 6.8 g/ dL. Coagulation parameters were normal. Gastroduodenoscopy showed submucosal nodule with surface ulceration and active ooze in the second part of the duodenum in three patients and submucosal nodule with active spurt of blood in the third part of the duodenum in one patient (Fig. 1). Hemostasis was achieved with injection of the diluted adrenaline. Contrast-enhanced computed tomography of abdomen confirmed intramural mass in duodenum with distinct fat planes and no lymph node enlargement. All four were operated with limited resection and primary anastomosis. All patients had small size tumors which presented early due to endoenteric growth and had mitosis less than 5 per 50 high-power fields. Their small size, endoenteric growth, complete resection, and lower mitosis were good prognostic signs in our patients. Immunohistochemical analysis revealed a positive CD117 in all four patients, positive CD34 in three patients, and positive smooth muscle actin (SMA) in one. All are alive with no recurrence, with a mean follow up of 10 months ranging from 5 to 18 months. Massive GI bleeding, as in our patients, is unusual in duodenal GIST. In a large study of 156 duodenal GIST patients, 75 cases presented with anemia due to chronic GI loss, but massive GI bleed with hemodynamic instability was only occasional [2]. In the same study, occasional massive GI bleed presented with melena, but none had hematemesis [2]. The typical features of GISTs on duodenoscopy include gross ulceration in the mucosa or an intramural mass with central ulceration. The most specific diagnostic criterion is strong and diffuse positive staining for CD117. GISTs harbor positivity for vimentin in nearly all cases, CD34 in 50 % to 70 %, smooth muscle actin in 30 % to 40 %, and platelet-derived growth factor receptor alpha (PDGFR-α) in about 5 %, while desmin (intermediate filament typical for muscle) and S-100 (a neural cell marker) are usually negative [3]. Poor prognostic parameters of GISTs include extragastric location, size greater than 5 cm, central necrosis, extension into adjacent organs, M. Patil (*) :K. A. Sheth :C. K. Adarsh :H. Devarbhavi Department of Gastroenterology, St. John’s Medical College, Bangalore 560 034, India e-mail: drmalli_arjun@yahoo.co.in

Tumour of the lowest probability

The diagnosis of neuroendocrine tumor, in general, seems to have increased in the recent years, most likely due to better diagnostic modalities. Ampulla represents an uncommon site for the occurrence of neuroendocrine tumor of gastrointestinal tract (0.05%). [1] A carcinoid tumor at the ampulla has varied presentations. Here, we report this rare case of neuroendocrine tumor at the ampulla in a young female presenting as abdominal pain and improving after pancreaticoduodenectomy.

An unusual cause of gastrointestinal bleed

Gastrointestinal (GI) bleed often brings the patient to the emergency medical service with great anxiety. Known common causes of GI bleed include ulcers, varices, Mallory-Weiss among others. All causes of GI bleed should be considered however unusual during the evaluation. Aortoenteric fistula (AEF) is one of the unusual causes of GI bleed, which has to be considered especially in patients with a history of abdominal surgery in general and aortic surgery in particular.

Sudden Onset Abdominal Wall Swellings in Patient of Liver Cirrhosis

Spontaneous hematomas in cirrhotic patients are uncommon. Severe coagulopathy in advanced hepatic disease is characterized by both coagulation factor deficiencies and accelerated fibrinolysis. Hyperfibrinolysis in cirrhosis is a result of excess fibrin breakdown leading to defective hemostasis. We present a case of spontaneous hematomas with an acute drop in hemoglobin level, in a patient with cirrhosis which was due to primary hyperfibrinolysis.

Comparative Study of Terlipressin, Somatostatin and Octreotide in Acute Esophageal Variceal Bleed: A Prospective Randomized Study

© 2011, INASL 13 CIRRHOSIS AND ITS COMPLICATIONS Comparative Study of Terlipressin, Somatostatin and Octreotide in Acute Esophageal Variceal Bleed: A Prospective Randomized Study CK Adarsh, KS Prasanna, H Devarbhavi, D Karanth, Mallikarjuna, B Girisha Department of Gastroenterology, St. Johns Medical College Hospital, Bangalore Background and Aims: Terlipressin, somatostatin and octreotide are known to reduce portal pressures and hence used as adjuvant therapy to endoscopic management of acute variceal bleed. However head to head comparison of above drugs has not been carried out. We evaluated the efficacy of these drugs with respect to control of acute variceal bleed, rebleed and mortality at 6 weeks. Methods: A total of 210 cirrhotic patients with esophageal variceal bleed were randomized to receive either somatostatin (group A = 73), terlipressin (group B = 69), or octreotide (group C = 68) prior to the endoscopic therapy. The drug was continued for 48 hours after endotherapy. Failure to control bleeding and rebleeding were defined according to Baveno-IV criteria. Results: Baseline characteristics of the three groups were comparable with respect to age, gender, etiology, Child-Pugh class, MELD score, duration of hospital stay, serum creatinine, serum sodium, active bleed seen during endoscopy and ascites. No significant difference was seen in failure to control bleed (group A vs. group B vs. group C: 15.1% vs. 18.8% vs. 25% p > 0.05), in hospital mortality (2.7% vs. 2.9% vs. 2.9%), rebleed at 6 weeks (13.7% vs. 15.9% vs. 26.5%, p > 0.05) and mortality at 6 weeks (13.7% vs. 10.1% vs. 17.6%, p > 0.05) among the three groups. On multivariate analysis, presence of portal hypertensive gastropathy, number of units of blood transfused and serum creatinine levels were independent predictors of failure to control bleed. Etiology of liver disease (ethanol and hepatitis C) and active bleed during endoscopy were independent predictors of mortality at 6 weeks. Child-Pugh class and serum sodium levels were independent predictors of rebleed at 6 weeks. Conclusion: The efficacy of somatostatin, terlipressin and octreotide as an adjuvant therapy for the control of acute esophageal variceal bleed, in-hospital survival, rebleed at 6 weeks and mortality at 6 weeks was comparable. Conflict of Interest: None A Study on Seroprevalence of Hepatitis A Antibody (IgG Anti-HAV) in Cirrhotic Patients DJ Payeng*, AK Das** *PGT, **Professor, Department of Medicine, Assam Medical College, Dibrugarh, Assam Background: Hepatitis A virus (HAV) vaccination is recommended in worldwide for cirrhotic patients to prevent decompensation due to superinfection with HAV. The prevalence of pre-existing antibodies against HAV due to subclinical exposure to the virus in childhood among cirrhotic patients may be high and, therefore, vaccination may not be needed. However, little data are available on the prevalence of HAV antibody among patients with chronic liver disease in India, especially in North East part of our country. Aims: To evaluate the seroprevalence of Hepatitis A virus anti-body (IgG anti-HAV) in cirrhotic patients and necessity of uniform vaccination against hepatitis A in these patients. Methods: Eighty cirrhotic patients attended in Department of Medicine, Assam Medical College and Hospital, during the period of 1 year were tested for the presence of IgG anti-HAV antibody (using a commercial ELISA kit). In addition, 100 apparently healthy subjects without liver disease were tested for the presence of IgG anti-HAV antibody in their sera. Results: Mean age of these cirrhotics and healthy group was 48.07 and 33.08 years and 67 (84%) and 70 (70%) of them were males, respectively. The seroprevalence of anti-HAV in two groups were 95% and 89%, respectively. In apparently healthy group, lower seroprevalence was observed in young adult (70%) than the rest. The prevalence of anti-HAV positivity was similar among patients with various etiologies. Conclusion: As there is a very high prevalence of pre-existing antibodies in these patients, uniform vaccination is not required. However those with negative anti-HAV are increased risk especially in young adult for developing fulminant hepatic failure should be vaccinated rendering cost effectiveness of vaccine. Conflict of Interest: None 03_JCEH-Abstract.indd 13 3/18/2011 11:13:03 AM