Meghraj Ingle

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.

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.

An open-label randomized control study to compare the efficacy of vitamin e versus ursodeoxycholic acid in nondiabetic and noncirrhotic Indian NAFLD patients.

Background/Aim: The study was carried out to compare the efficacy of Vitamin E versus Ursodeoxycholic acid (UDCA) in nondiabetic nonalcoholic fatty liver disease (NAFLD) patients. Patients and Methods: We randomized 250 non cirrhotic and non diabetic NAFLD patients diagnosed on ultrasound, with raised alanine aminotransferase (ALT) level. (>40 IU/L), to receive Vitamin E 400 mg twice a day (Group A) or UDCA 300 mg twice a day (Group B) for 52 weeks. Lifestyle modification to achieve at least 5% weight reduction and subsequent weight control and regular exercise was advised to both groups. The primary study endpoint was normalization of ALT. Secondary endpoints were the proportion of patients with reduction in ALT, relative reduction in the NAFLD Fibrosis score (NFS), symptomatic improvement and tolerability. Results: One hundred and fifty patients received UDCA as compared to 100 patients receiving Vitamin E. The treatment groups were comparable at entry with regard to age (44.1 vs 42.4 years), gender (67% vs 63% female), risk factors for nonalcoholic steatohepatitis, hypochondriac pain, serum liver biochemistries, and NAFLD Fibrosis score. The primary endpoint was achieved in 21 (14%) and 19 (19%) of patients in Group A and Group B, respectively (P = 0.2). The proportion of patients with reduction in ALT (56% vs 63%, P = 0.2), symptomatic improvement (78% vs 67%, P= 0.058), reduction in the NFS (44% vs 47%, P= 0.69), and tolerability (98% vs 95%, P= 0.2) were similar between Group A and Group B, respectively. Conclusion: UDCA is an effective and safe alternative to Vitamin E in nondiabetic–noncirrhotic Indian NAFLD patients.

The role of capsule endoscopy in etiological diagnosis and management of obscure gastrointestinal bleeding

Background/Aims To investigate the various etiologies, yields, and effects of capsule endoscopy (CE) on management and complications, along with follow up of patients with obscure gastrointestinal (GI) bleeding. Methods The study group of patients included those having obscure, overt, or occult GI bleeding. The findings were categorized as (A) obvious/definitive, (B) equivocal, or (C) negative. Any significant alteration in patient management post CE in the form of drug or surgical intervention was noted. Results Total patients included in the study were 68 (48 males and 20 females). The ratio of male:female was 2.4:1. The age ranged between 16 years to 77 years. Mean age for males was 62±14 years, for females 58±16 years. The total yield of CE with definitive lesions was in 44/68 (65.0%) of patients. In descending order (A) angiodysplasia 16/68 (23.53%), (B) Crohns disease 10/68 (14.70%), (C) non-steroidal anti-inflammatory drug enteropathy 8/68 (11.76%), (D) small bowel ulcers 4/68 (5.88%), (E) jejunal and ileal polyps 2/68 (2.94%), (F) intestinal lymphangiectasis 2/68 (2.94%), and (G) ileal hemangiomas 2/68 (2.94%) were followed. Equivocal findings 12/68 (17.65%) and negative study 12/68 (17.65%) was found. Complications in the form of capsule retention in the distal ileum were noted in 2/68 (2.94%) subjects. Statistically, there was a higher probability of finding the etiology if the CE was done during an episode of bleeding. Conclusions CE plays an important role in diagnosing etiologies of obscure GI bleeding. Its role in influencing the management outcome is vital.

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%), Crohns 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 Burkitts 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.

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.

Endoscopic Ultrasonography Can Prevent Unnecessary Diagnostic Endoscopic Retrograde Cholangiopancreatography Even in Patients with High Likelihood of Choledocholithiasis and Inconclusive Ultrasonography: Results of a Prospective Study

Background/Aims Endoscopic retrograde cholangiopancreatography (ERCP) is the initial therapy recommended for patients with high likelihood of choledocholithiasis. To determine whether endoscopic ultrasonography (EUS) can prevent diagnostic ERCPs in patients with high probability of choledocholithiasis and inconclusive ultrasonography (US). Methods All patients with high likelihood of choledocholithiasis and negative US underwent EUS. ERCP was performed for the patients who showed a definite stone/sludge on EUS. Patients without choledocholithiasis were followed up for 3 months. The primary outcome was avoidance of diagnostic ERCP. Results We included 78 patients (51 women; 27 men). Of these, 25 and 7 (total 41%) were diagnosed with choledocholithiasis and sludge, respectively; stone/sludge was removed in 96.9% of the patients. EUS ruled out choledocholithiasis in 38 patients (48.7%). Two of them were found to have choledocholithiasis on follow-up. The sensitivity, specificity, positive and negative predictive value of EUS for detecting choledocholithiasis were 93.9%, 97.3%, 96.9%, and 94.7%, respectively. Unnecessary ERCP was avoided in 57.7% of the patients by using the EUS-first approach. Conclusions EUS is a highly accurate and safe procedure. EUS can replace ERCP as the initial investigation in patients with a high probability of choledocholithiasis. It avoids unnecessary ERCP; hence, decreasing related costs and complications.

Role of Rectal Diclofenac Suppository for Prevention and Its Impact on Severity of Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis in High-Risk Patients

Background The aim was to study the role of rectal diclofenac in prevention of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis and its impact on severity of post-ERCP pancreatitis. Methods We conducted a single-center, prospective, open-labeled, randomized trial for evaluating the use of rectal diclofenac in prevention of post-ERCP pancreatitis in high-risk patients. We assessed 526 patients coming for ERCP for different indications. Four hundred patients were eligible for the study. Those not fitting the high-risk criteria and with acute pancreatitis were excluded. These patients were randomized in two groups: 200 patients received rectal diclofenac prior to or during the procedure, while 200 patients received placebos. Serum amylase was measured at 2 and 36 hours. Post-ERCP pancreatitis was defined as serum amylase > 3 times upper limit of normal with associated severe abdominal pain. Severity was graded according to days of hospitalization and complications. Results Twenty-nine out of 400 (7.2%) patients developed post-ERCP pancreatitis. Six out of 200 (3%) patients in rectal diclofenac group developed post-ERCP pancreatitis compared to 23 out of 200 (11.5%) patients in placebo group. The difference was statistically significant (P = 0.001). All patients (six) in rectal diclofenac group developed mild pancreatitis as compared to severe pancreatitis in four and moderate pancreatitis in five patients in the placebo group. Conclusion Rectal diclofenac prior to or during ERCP in high-risk patients reduces the incidence as well as severity of post-ERCP pancreatitis compared to placebo.

Prospective comparative study of inhibitory control test and psychometric hepatic encephalopathy score for diagnosis and prognosis of minimal hepatic encephalopathy in cirrhotic patients in the Indian subcontinent.

This study aimed to determine the usefulness of inhibitory control test (ICT) for diagnosing minimal hepatic encephalopathy (MHE) in the Indian subcontinent and its correlation with the severity of liver disease and to determine its prognostic significance.

Difficult colonoscopy: air, carbon dioxide, or water insufflation?

Background/Aims This study aimed to compare tolerance to air, carbon dioxide, or water insufflation in patients with anticipated difficult colonoscopy (young, thin, obese individuals, and patients with prior abdominal surgery or irradiation). Methods Patients with body mass index (BMI) less than 18 kg/m2 or more than 30 kg/m2, or who had undergone previous abdominal or pelvic surgeries were randomized to air, carbon dioxide, or water insufflation during colonoscopy. The primary endpoint was cecal intubation with mild pain (less than 5 on visual analogue scale [VAS]), without use of sedation. Results The primary end point was achieved in 32.7%, 43.8%, and 84.9% of cases with air, carbon dioxide and water insufflation (P<0.001). The mean pain scores were 5.17, 4.72, and 3.93 on the VAS for air, carbon dioxide, and water insufflation (P<0.001). The cecal intubation rate or procedure time did not differ significantly between the 3 groups. Conclusions Water insufflation was superior to air or carbon dioxide for pain tolerance. This was seen in the subgroups with BMI <18 kg/m2 and the post-surgical group, but not in the group with BMI >30 kg/m2.