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)

CROSS SECTIONAL STUDY OF PREVALENCE AND RISK FACTORS OF HEPATITIS B AND HEPATITIS C INFECTION IN A RURAL VILLAGE OF INDIA

Background - Hepatitis B virus and hepatitis C virus are among the principal causes of severe liver disease. There is limited data of epidemiology of Hepatitis B in community, more so in rural population. Objective - To find the prevalence of hepatitis B and C infection in community and study the risk factors for their transmission. Methods - This was a community based cross sectional study. A total of 1833 randomly selected subjects from a rural area were interviewed for risk factors for transmission and tested for markers of hepatitis B and hepatitis C infection. All the positive card tests were confirmed by ELISA. Results - Out of 2400 subjects, rate for participation was 76.38%. None of the subjects was positive for anti hepatitis C virus antibody. Point prevalence for HBsAg positivity was 0.92. Being healthcare worker and having tattoo were significantly associated with HBsAg positive results. Nose and ear piercing was reported by almost. History of blood or blood product transfusion, I/V drug abuse, multiple sexual partners, unsafe Injections, hemodialysis and any h/o surgery was not associated with HBsAg positivity. Conclusion - Health care workers are at high risk for transmission of hepatitis B. Educating common people regarding mode of transmission of Hepatitis B and C will help to reduce their transmission.

Contexto - O vírus da hepatite B e o vírus da hepatite C estão entre as principais causas de doença grave do fígado. Há dados limitados de epidemiologia da hepatite B na comunidade observada, mais ainda na população rural. Objetivo - Encontrar a prevalência de infecção de hepatite B e C em uma comunidade da India e pesquisar os fatores de risco para sua transmissão. Métodos - Feito estudo de corte transversal em uma comunidade. Um total de 1833 sujeitos selecionados aleatoriamente em uma área rural foram entrevistados para fatores de risco para transmissão e testados para marcadores da infecção por hepatite B e C. Todos os testes positivos de cartão foram confirmados por ELISA. Resultados - Dos 2400 pacientes objetivados houve uma taxa de participação de 76.38%. Nenhum dos indivíduos foi positivo para anticorpo anti vírus da hepatite C. A prevalência pontual para a positividade do HBsAg foi de 0,92. Ser trabalhador na área de saúde e ter tatuagem foram significativamente associados com resultados positivos de HBsAg. "Piercing" em nariz e orelha foram relatados por quase todos. História de transfusão de sangue ou uso de hemoderivados, abuso de drogas via endovenosa, múltiplos parceiros sexuais, injeções inseguras, hemodiálise e história prévia de cirurgia, não estiveram associadas à positividade do HBsAg. Conclusão - Os trabalhadores de saúde estão em alto risco para a transmissão de hepatite B. Educar pessoas comuns sobre o modo de transmissão de hepatite B e C ajudará a reduzir a sua transmissão.

Cinitapride Extended-Release Tablets Versus Cinitapride Immediate-Release Tablets in the Treatment of Functional Dyspepsia and Gastroesophageal Reflux Disease : A Randomized Clinical Trial.

Prokinetics are commonly used for Functional Dyspepsia (FD) and GastroEsophageal Reflux Disease (GERD). Aims and Objectives: To evaluate the safety and efficacy of cinitapride Extended-Release (ER) tablets versus conventional cinitapride Immediate-Release (IR) tablets for the treatment of FD and GERD. Materials and Methods: Patients with FD and GERD received either cinitapride ER 3 mg tablets OD or cinitapride IR 1 mg tablets TID for 4 weeks in this randomized, multicentre study. Change in the mean intensity score of gastrointestinal (GI) symptoms (overall and individual) at the end of the study and at each weekly follow up visit as compared to baseline, patients with complete resolution of GI symptoms, patients with > 50% reduction from baseline in overall intensity score, rescue medication use and overall efficacy were recorded. The safety variables were reported adverse events (AEs), laboratory parameters, electrocardiogram, and overall tolerability. Unpaired t test, chi square test or Fisher’s exact test were used for analysis. p < 0.05 was considered significant. Results: Total 218 patients were enrolled Cinitapride ER tablets were non-inferior (non-inferiority margin -2.5) to cinitapride IR tablets for the change in the mean overall GI symptom intensity score at the end of the study as compared to the baseline (treatment difference - 0.2 (95% CI: -2.2, 1.7)); also, no significant difference was found for other efficacy variables (p > 0.05). Eight AEs of mild-to-moderate intensity were reported. There was also no difference in the overall tolerability between the study groups (p = 0.875). Conclusions : Both the study treatments were comparable in terms of safety and efficacy for the treatment of FD and GERD.

Rabeprazole plus domperidone: the answer for gastro-oesophageal reflux disease.

To study and document the efficacy and tolerability of rabeprazole and domperidone in the treatment of patients suffering from gastro-oesophageal reflux disease (GERD), an open, prospective, non-comparative study was carried out among 50 adult patients of either sex attending gastroenterology OPD of a leading, tertiary-care teaching hospital in Mumbai with the clinical diagnosis of GERD. One capsule of rabeprazole and domperidone was swallowed in empty stomach each day for up to 4 weeks by the patients. Rabeprazole and domperidone provided significant and remarkable improvement in symptoms of GERD. Although, the improvement was observed at first follow-up visit (within 2 weeks), continuing treatment for 4 weeks provided additional gains. Almost all patients tolerated the drug well. Most patients (94%) had excellent or good relief as assessed by their physician whilst 86% of patients rated treatment with rabeprazole and domperidone as good or excellent. Rabeprazole and domperidone not only provided desired relief of symptoms of GERD but also is very well tolerated. This combination may also improve the quality of life of patients suffering from GERD.

Profile of chronic small-bowel diarrhea in adults in Western India: a hospital-based study.

BACKGROUND: Small-bowel diarrhea is reported to account for 10% of all cases of chronic diarrhea. Data on the etiology and clinical presentation of chronic small-bowel diarrhea in adult Indians is scarce. METHODS: 50 patients (mean age 32.8 years; 26 men) with chronic small bowel diarrhea were evaluated clinically, and investigated to determine etiology. The diagnosis of small-bowel diarrhea was based on history, stool volume and associated symptoms. RESULTS: Abdominal pain (n=22, 44%) and weight loss (n=37, 74%) were the most common symptoms, apart from diarrhea. Anemia (70%) and hypoalbuminemia (48%) were other important biochemical abnormalities. Intestinal tuberculosis (26%) and celiac disease (26%) were the most common causes of chronic small-bowel diarrhea. CONCLUSION: Tuberculosis of intestine and celiac disease are common causes of small-bowel diarrhea in our population. Tropical sprue seems to be a rare cause.

Intestinal amyloidosis presenting as malabsorption syndrome.

Intestinal amyloidosis presenting with small bowel diarrhoea with malabsorption is an infrequent clinical entity. The present case report includes such a case and discusses the diagnostic approach in such a case.

Hepatic granuloma in chronic hepatitis C.

We report the findings in a 54-year-old male with chronic hepatitis C with granulomas liver biopsy. Unfortunately, this patient died before treatment could be started.

Comparative evaluation of the efficacy and tolerability of itopride hydrochloride and domperidone in patients with non-ulcer dyspepsia.

BACKGROUND: Prokinetic drugs are widely used for treatment of non-ulcer dyspepsia (NUD). AIMS AND OBJECTIVES: To assess the efficacy and tolerability of a new prokinetic agent, itopride hydrochloride in patients of NUD and compare it with domperidone. METHODS: Fifty-six patients who fulfilled the inclusion and exclusion criteria were enrolled in the study. Patients underwent upper gastrointestinal endoscopy to rule out organic pathology as a cause for their symptoms. The patient's symptoms were graded on a 4-point scale (0 to 3) at the beginning of treatment and at the end of Week-one and Week-two Patients were randomly allocated to receive either one tablet of itopride hydrochloride 50mg three times daily or one tablet of domperidone 10mg three times daily for two weeks. Pre-treatment and post-treatment hemogram, liver function and renal function tests, prolactin level and ECG were done in all patients. The response to therapy was evaluated by assessing the relief of symptoms at the end of two weeks on a 5-point scale. Statistical analysis was done using two-tailed paired t-test; Wilcoxon matched pairs ranks sum test, Mann-Whitney-U test and chi-square test as applicable. RESULTS: Of the fifty-five patients enrolled in the study (age range of 18-60 yrs, median age of 35yrs), 26 were males and twenty nine were females. They had a median duration of symptoms for 4 weeks. Twenty-seven patients received itopride and 28 received domperidone. One patient did not follow up in the domperidone group, thus 54 patients were evaluable for analysis. Moderate to complete symptomatic relief was observed in 22 (81%) patients in the itopride group and 19 patients (70%) in the domperidone group (p > 0.05, NS). Both the drugs were well tolerated and neither caused prolongation of QT interval nor any abnormality in any serum biochemistry values. CONCLUSION: Therapy with itopride resulted in good symptomatic relief, was safe, well tolerated and comparable in efficacy to domperidone in relieving the symptoms of NUD. By virtue of its efficacy and tolerability, it could be an ideal choice for providing symptomatic relief to patients suffering from non-ulcer dyspepsia.

Type 1 diabetes mellitus and extrahepatic portal vein obstruction: a causal association?

So far, no association has been described between multifactiorial disorders such as insulin- dependent diabetes mellitus and extrahepatic portal vein obstruction (EHPVO), which is the most common cause of extra-hepatic portal hypertension in children. We describe 3 cases of EHPVO who developed type 1 diabetes mellitus.

Portal hypertensive jejunopathy: a case control study.

BACKGROUND: Small bowel mucosa is a recognized potential source of bleeding in portal hypertension. However, the frequency of its involvement is not known. AIMS: To document the nature, severity and frequency of endoscopic and histologic changes in the jejunum in patients with portal hypertension. METHODS: Forty consecutive patients with portal hypertension and 43 patients with non-ulcer dyspepsia (controls) underwent push enteroscopy and jejunal, duodenal and gastric biopsies. Biopsies were randomized and examined by a blinded pathologist for inflammation and vascular dilatation, which was quantified by morphometry. RESULTS: Endoscopic jejunopathy was observed in 6 patients and none of the control subjects. All patients with jejunopathy had portal hypertensive gastropathy (PHG) and 5 had duodenopathy. Vascular dilatation was observed in 15 patients and 25 control subjects (p = ns). The degree of vascular dilatation was similar in both groups. Inflammatory changes were observed in 24 patients and 25 control subjects (p = 0.05). CONCLUSIONS: Endoscopic jejunopathy was present in 15% of patients with portal hypertension. These changes were mild in 83% of them. All patients with jejunopathy also had PHG. Histologic changes were similar in patients and control subjects.

Giant mesenteric cyst of abdomen herniating into scrotum.

Cystic mesenteric tumors are rare abdominal neoplasms. We report a 55-year-old man with recurrent benign mesothelioma arising from the left colonic mesentery and extending into the scrotal sac. He recovered well after excision of the abdominal and scrotal mass.

Abdominal wall abscess secondary to subcapsular tubercular liver abscess.

We report a 22-year-old woman who presented with an abdominal wall lump in the right upper quadrant 15 days after starting antitubercular treatment for right pleural effusion. CT scan revealed a right liver lobe subcapsular abscess communicating vith subcutaneous tissue. Aspiration of pus revealed acid-fast bacilli. She responded to 9 months of antitubercular treatment.

Assessment of renal and hepatic hemodynamics in cirrhosis of liver.

BACKGROUND AND OBJECTIVE: Investigators have documented an increase in renal artery resistance in cirrhotic patients. We studied the hepatic and renal hemodynamics by color Doppler in patients with liver cirrhosis in relation to the presence and severity of ascites. METHODS: A prospective study was carried out in a large public hospital on 33 patients with cirrhosis of liver and 11 healthy control subjects. Eleven patients had no ascites, 12 had diuretic-responsive ascites and 10 had refractory ascites. The resistance index (RI) of the hepatic artery was measured by color Doppler on its main branch and renal artery RI was measured on the main renal, interlobar and cortical arteries of the right kidney. RESULTS: Considering intraobserver variabilities, coefficient of variation for RI was 2.3%-7.8% (mean [SD] 4.2% [1.8%]). Hepatic artery RI were 0.68 (0.07), 0.68 (0.1), 0.81 (0.04), 1.0 (0.12) in control subjects and cirhotics with no ascites, responsive ascites and refractory ascites, respectively. Renal RI was significantly higher than in control subjects at all three levels in patients with responsive and refractory ascites, being higher in those with refractory than responsive ascites. Renal RI decreased from hilum towards the outer parenchyma, in cirrhotics with no ascites and responsive ascites but not in refractory ascites. CONCLUSION: Hepatic artery RI is higher in cirrhotics and is related to presence and severity of ascites. In control subjects and patients with no ascites or responsive ascites the renal RI decreased from hilum to the outer parenchyma.

Assessment of portal hemodynamics by ultrasound color Doppler and laser Doppler velocimetry in liver cirrhosis.

BACKGROUND: Color Doppler is a noninvasive method for assessing portal hemodynamics. Laser Doppler velocimetry is useful in assessment of microcirculatory abnormalities in portal hypertensive gastropathy (PHG). AIMS: To study portal hemodynamics by color Doppler and gastric mucosal blood flow (GMBF) by laser Doppler velocimetry in patients with cirrhosis. METHODS: Twenty-eight patients with cirrhosis of liver (24 men) and 10 healthy subjects (7 men) were studied. Portal venous blood flow (PVBF) and portal flow velocity (PFV) were assessed by color Doppler at the level where the hepatic artery crosses the portal vein, and GMBF was measured by laser Doppler velocimetry. RESULTS: PVBF (379.5 [102.9] mL/min), PFV (5.3 [1.1] cm/sec) and GMBF (3.5 [0.8] volts) were significantly lower in patients with cirrhosis than in controls. PVBF and PFV were significantly lower in patients in Child class B and C than those in class A. Patients with ascites had significantly lower PVBF, PFV and GMBF than those without; values were also lower in patients with PHG than in those without. History of bleeding had no relation with PVBF and PFV. GMBF showed good correlation with PVBF (r=0.58, p<0.001) and with PFV (r=0.48, p<0.01). CONCLUSIONS: In cirrhosis of liver, PVBF, PFV and GMBF are significantly lower, and the changes increase with increasing severity of liver disease.