Drug Induced Liver Injury at a Tertiary Hospital in India: Etiology, Clinical Features and Predictors of Mortality

ABSTRACT Introduction and aims. Drug-induced liver injury (DILI) is rare; however, it is one of the important causes of acute liver failure which results in significant morbidity or mortality. Material and methods. Patients with suspected DILI were enrolled based on predefined criteria and followed up for at least 6 months or until normalization of liver tests. Causality assessment was done by applying the Roussel Uclaf Causality Assessment Method model. Results. We collected data from 82 individuals diagnosed with DILI at our hospital from 2014 through 2015 (41 men; median age, 38 years). The most commonly implicated drugs were antitubercular therapy (ATT) (49%), antiepileptic drugs (12%), complementary and alternative medicine (CAM) in 10%, antiretroviral drugs (9%) and non-steroidal anti-inflammatory drugs (6%). 8 out of 13 deaths were liver related. Also, liver related mortality was significantly higher for ATT DILI (17.5%) vs. those without (2.4%) (P = 0.02). There was no significant difference in overall as well as liver related mortality in hepatocellular, cholestatic or mixed pattern of injury. Laboratory parameters at one week after discontinuation of drug predicted mortality better than those at the time of DILI recognition. On multivariate logistic regression analysis, jaundice, encephalopathy, MELD (Model for end stage liver disease) score and alkaline phosphatase at one week, independently predicted mortality. Conclusion. DILI results in significant overall mortality (15.85%). ATT, anti-epileptic drugs, CAM and antiretroviral drugs are leading causes of DILI in India. Presence of jaundice, encephalopathy, MELD score and alkaline phosphatase at one week are independent predictors of mortality.(AU)

Drug Induced Liver Injury at a Tertiary Hospital in India: Etiology, Clinical Features and Predictors of Mortality.

INTRODUCTION AND AIMS: Drug-induced liver injury (DILI) is rare; however, it is one of the important causes of acute liver failure which results in significant morbidity or mortality. MATERIAL AND METHODS: Patients with suspected DILI were enrolled based on predefined criteria and followed up for at least 6 months or until normalization of liver tests. Causality assessment was done by applying the Roussel Uclaf Causality Assessment Method model. RESULTS: We collected data from 82 individuals diagnosed with DILI at our hospital from 2014 through 2015 (41 men; median age, 38 years). The most commonly implicated drugs were antitubercular therapy (ATT) (49%), antiepileptic drugs (12%), complementary and alternative medicine (CAM) in 10%, antiretroviral drugs (9%) and non-steroidal anti-inflammatory drugs (6%). 8 out of 13 deaths were liver related. Also, liver related mortality was significantly higher for ATT DILI (17.5%) vs. those without (2.4%) (P = 0.02). There was no significant difference in overall as well as liver related mortality in hepatocellular, cholestatic or mixed pattern of injury. Laboratory parameters at one week after discontinuation of drug predicted mortality better than those at the time of DILI recognition. On multivariate logistic regression analysis, jaundice, encephalopathy, MELD (Model for end stage liver disease) score and alkaline phosphatase at one week, independently predicted mortality. CONCLUSION: DILI results in significant overall mortality (15.85%). ATT, anti-epileptic drugs, CAM and antiretroviral drugs are leading causes of DILI in India. Presence of jaundice, encephalopathy, MELD score and alkaline phosphatase at one week are independent predictors of mortality.

Comparison of Tissue Elastography With Magnetic Resonance Imaging T2* and Serum Ferritin Quantification in Detecting Liver Iron Overload in Patients With Thalassemia Major.

BACKGROUND & AIMS: We investigated whether tissue elastography (TE) can be used as an alternative to magnetic resonance imaging (MRI) T2* analysis to determine the degree of iron overload in patients with thalassemia major. METHODS: We conducted a prospective study of 154 patients (99 male; mean age, 12 ± 3.6 years) with thalassemia major requiring chronic blood transfusion and on iron chelator therapy. The study was performed at a tertiary hospital in India from January 2015 through June 2015. We performed routine blood sample analyses, measurements of serum levels of ferritin, and TE within 1 month of MRI T2* analysis of the liver. The Spearman correlation test and linear regression analysis were used to evaluate the correlation between TE liver stiffness measurements and R2* MRI results or serum ferritin levels. RESULTS: The subjects' mean total serum levels of bilirubin, alanine aminotransferase, aspartate aminotransferase, and albumin were 1.4 ± 0.6 mg/dL, 65.0 ± 51.8 IU/L, 62.9 ± 44 IU/L, and 4.2 ± 0.2 g/d, respectively. Mean liver stiffness measurement, MRI T2* (3 T), corresponding MRI R2* (3 T), and ferritin values were 8.2 ± 4.4 kPa, 3.18 ± 2.6 milliseconds, 617.3 ± 549 Hz, and 4712 ± 3301 ng/mL, respectively. On the basis of MRI analysis, 67 patients (43.5%) had mild iron overload, 49 patients (31.8%) had moderate iron overload, and 22 patients (14.3%) had severe iron overload. Fibroscan liver stiffness measurements correlated with MRI R2* values (r = 0.85; P < .001). TE results identified the patients with severe, moderate, and mild iron overload with area under the receiver operating characteristic curve values of 94.8%, 84.5%, and 84.7%, respectively. Liver stiffness measurements greater than 13.5, 7.8, and 5.5 kPa identified patients with severe, moderate, and mild iron overload, respectively; the sensitivity and specificity values were 92% and 93% for severe overload, 82% and 82% for moderate overload, and 73% and 75% for mild overload. No correlation was found between TE results and serum level of ferritin (r = 0.19; P = .11). CONCLUSIONS: Results of TE correlate with those from MRI T2* analysis. TE is cheaper and more available than MRI and might be used to estimate hepatic iron overload, especially moderate to severe overload in patients with thalassemia major who require chronic transfusion.

Renal Vein and Inferior Vena Cava Thrombosis: A Rare Extrasplanchnic Complication of Acute Pancreatitis.

Acute pancreatitis is an inflammatory disorder often associated with various complications. Approximately one fourth of patients with acute pancreatitis develop vascular complications, of which venous thrombosis forms a major group. Extrasplanchnic venous thrombosis is less common, and simultaneous renal vein and inferior vena cava thrombosis is reported only twice. We report a case of alcohol-related acute pancreatitis complicated by simultaneous renal vein and inferior vena cava thrombosis.

Post Colonoscopy Ischaemic Colitis in a Patient without Risk Factors for Colon Ischemia: A Case Report.

Ischaemic colitis is the most common form of intestinal ischaemia and is more common in the elderly and in the people having risk factors for colonic ischaemia. Colonoscopy procedure itself is a rare cause of ischaemic colitis. Fewer than 20 cases of ischaemic colitis caused by colonoscopy procedure have been reported in the english literature till date. This patient presented to us within hours of routine colonoscopy with rectal bleeding and lower abdominal pain. On repeat colonoscopy, the patient had mucosal oedema and ulcerations in the descending colon and sigmoid colon. Computed tomography of abdomen and biopsy of the involved segment confirmed ischaemic colitis. The patient recovered with conservative management.

Spectrum of chronic small bowel diarrhea with malabsorption in Indian subcontinent: is the trend really changing?

BACKGROUND/AIMS: This study aimed to document the recent etiological spectrum of chronic diarrhea with malabsorption and also to compare features that differentiate tropical sprue from parasitic infections, the two most common etiologies of malabsorption in the tropics. METHODS: We analyzed 203 consecutive patients with malabsorption. The etiological spectrum and factors that differentiated tropical sprue from parasitic infections were analyzed. RESULTS: The most common etiology was tropical sprue (n=98, 48.3%) followed by parasitic infections (n=25, 12.3%) and tuberculosis (n=22, 10.8%). Other causes were immunodeficiency (n=15, 7.3%; 12 with human immunodeficiency virus and 3 with hypogammaglobulinemia), celiac disease (n=11, 5.4%), Crohn's disease (n=11, 5.4%), small intestinal bacterial overgrowth (n=11, 5.4%), hyperthyroidism (n=4, 1.9%), diabetic diarrhea (n=4, 1.9%), systemic lupus erythematosus (n=3, 1.4%), metastatic carcinoid (n=1, 0.5%) and Burkitt's lymphoma (n=1, 0.5%). On multivariate analysis, features that best differentiated tropical sprue from parasitic infections were larger stool volume (P=0.009), severe weight loss (P=0.02), knuckle hyperpigmentation (P=0.008), low serum B12 levels (P=0.05), high mean corpuscular volume (P=0.003), reduced height or scalloping of the duodenal folds on endoscopy (P=0.003) and villous atrophy on histology (P=0.04). Presence of upper gastrointestinal (GI) symptoms like bloating, nausea and vomiting predicted parasitic infections (P=0.01). CONCLUSIONS: Tropical sprue and parasitic infections still dominate the spectrum of malabsorption in India. Severe symptoms and florid malabsorption indicate tropical sprue while the presence of upper GI symptoms indicates parasitic infections.

Esomeprazole induced galactorrhea: a novel side effect.

Proton pump inhibitors (PPIs) are one of the most frequently prescribed medications across the globe. Esomeprazole is the S-isomer of omeprazole, and it is currently the most widely prescribed PPI. The safety profile of esomeprazole is extremely favorable with only minor side effects, like headache and diarrhea, that are encountered in day to day practice. We report a case of a young female with symptoms of gastroesophageal reflux disease who developed galactorrhea after starting esomeprazole therapy. Resolution of galactorrhea after stopping the drug and self-rechallenge by the patient herself with reappearance of galactorrhea confirmed the culprit to be esomeprazole only. We postulate that esomeprazole may have a mild inhibitory effect on CYP3A4, which leads to decreased metabolism of estrogen, thereby increasing serum estrogen levels. Estrogen causes stimulation and production of prolactin release, which results in development of galactorrhea. This is the first case of esomeprazole induced galactorrhea, to the best of our knowledge.

A Rare Case of Hypermobile Mesentery With Segmental Small Bowel Pneumatosis Cystoides Intestinalis.

Pneumatosis intestinalis is a rare condition that affects 0.03% of the population. Pneumatosis cystoides intestinalis (PCI) is characterized by the presence of multiple gas-filled cysts in the intestinal wall and the submucosa and/or intestinal subserosa. It is usually a secondary finding caused by a wide variety of underlying gastrointestinal or extragastrointestinal diseases. Here, we present the case of a 47-year-old man who was referred to our gastroenterology department with a history suggestive of intermittent small bowel obstruction associated with abdominal pain. Abdominal computed tomography demonstrated PCI of the small bowel. The mesentery and branches of the superior mesenteric artery and superior mesenteric vein were twisted with minimal pneumoperitoneum. Exploratory laparotomy was performed, and demonstrated segmental small bowel PCI secondary to hypermobile mesentery. The affected segment of the ileum was resected, and jejunoileal anastomosis was performed. Here, we report a rare case of segmental PCI probably due to repeated twisting of hypermobile mesentery. The clinical and imaging features of this disorder may mimic those of visceral perforation or bowel ischemia. PCI can be a cause of severe abdominal pain that may require surgical intervention.

Clinical, endoscopic, and pathologic characteristics of colorectal polyps in Indian children and adolescents.

OBJECTIVES: Colorectal polyps are among the common causes for rectal bleeding in children. We studied the clinical, colonoscopic, and histopathological features of colorectal polyps and polyposis syndrome in Indian children and adolescents. METHODS: Medical records of children and adolescents with colorectal polyps and polyposis syndrome were retrospectively reviewed from 2001 to 2014 at Department of Gastroenterology, in large tertiary care center of Mumbai. RESULTS: A total of 120 patients were found to have colonic polyps during study period. Mean age of presentation in children was 7.31 ± 4.05 years (range 2 to 19 years), with male-to-female ratio of 2.16:1. Rectal bleeding was presenting symptom in 95.8 % with mean duration of 12.6 ± 15 months. Majority of polyps (77.5 %) were juvenile, and 97.2 % were located in left colon. Solitary polyps were seen in 76.6 %, multiple polyps in 11.6 %, juvenile polyposis syndrome in 6.6 %, familial adenomatous polyposis in 4.2 %, and Peutz-Jeghers syndrome in 0.8 % of the children. The polyposis syndrome group had higher age at presentation (p = 0.00006), greater likelihood of anemia, abdominal pain, and diarrhea (p = 0.0001, 0.0002, and 0.0051, respectively). Likelihood of adenomatous change in polyps was higher in polyposis syndrome group (p = 0.0003). Left colonic polyps were more common in non-polyposis group, whereas pan-colonic polyps were more common in polyposis syndrome group (p < 0.00001). CONCLUSION: Presence of anemia, abdominal pain, diarrhea, higher age at presentation (more than 10 years), and history of polypectomy are clinical indicators of polyposis syndrome.

Autoimmune Hepatitis Triggered by Treatment With Pegylated Interferon α-2a and Ribavirin for Chronic Hepatitis C.

Hepatitis flare is rarely observed during treatment with pegylated interferon alpha for hepatitis C virus (HCV) infection. A 49-year-old man receiving pegylated interferon α-2a for HCV infection had icterus and hyperbiliru-binemia in the 14th week of therapy, with HCV RNA undetectable after the 12th dose. Liver biopsy was suggestive of chronic hepatitis with cirrhosis without interface pattern. Pegylated interferon was discontinued; a few weeks later, his aminotransferases and immunoglobulin levels increased significantly. Antibody to cytosolic liver antigen-1 was positive, and liver biopsy revealed lymphoplasmacytic infiltrate with intense interface hepatitis, consistent with autoimmune hepatitis.

A Rare Case of an Intraductal Papillary Mucinous Neoplasm of Pancreas Fistulizing Into Duodenum With Adult Polycystic Kidney Disease.

Intraductal papillary mucinous neoplasm (IPMN) accounts for 20-50% of all cystic neoplasms of the pancreas. Rarely, IPMN, whether benign or malignant, can fistulize into adjacent organs like duodenum, stomach or common bile duct. IPMN can be associated with other diseases like Peutz-Jeghers syndrome and familial adenomatous polyposis. Association with adult polycystic kidney disease (ADPKD) is extremely rare. We report a case of a 60-year-old male with a large IPMN in the head of the pancreas diagnosed by magnetic resonance imaging, endoscopic ultrasound and cyst fluid analysis. It was complicated by fistula formation into the second part of the duodenum. Patient was simultaneously having adult polycystic kidney disease. There is only one case report of uncomplicated IPMN with ADPKD in the literature so far. And even rarer, there is no any case report of fistulizing IPMN with ADPKD reported so far, to the best of our knowledge.