Clinical Features, Laboratory Characteristics and Outcome from Oral Contraceptives-induced Liver Injury in 43 Consecutive Patients and a Brief Review of Published Reports.

Background: Hormonal oral contraceptive (OC) agents such as estrogen or progesterone, either as single agents or in combination, and a non-hormonal drug like ormeloxifene are used for various conditions. However, estrogen and progesterone-containing OC as well as ormeloxifene are seldom associated with hepatotoxicity. We prospectively studied the clinical, demographic, liver injury pattern, complications, and outcome of the hepatotoxicity from OC and ormeloxifene. Methods: We analyzed and compared the aforementioned characteristics among consecutive patients with OC and ormeloxifene-induced drug-induced liver injury (DILI) from two university hospitals in India. Cases fulfilling established DILI criteria and the Roussel Uclaf causality assessment method were identified and followed up until recovery/death. Results: We identified 43 (3.5%) amongst 1226 patients with DILI; 19 (44%) from estrogen and progesterone combination, 21 (49%) from progesterone monotherapy, and 3 (7%) due to ormeloxifene. Seven cases were identified from 1998 to 2014 and 36 cases from 2015 to 2023. All were due to oral tablets. The mean age was 36 years (range 21-75). Nineteen patients (44%) developed jaundice and 5 (11.6%) developed itching. The liver injury pattern was hepatocellular in 19 (44%), mixed in 13 (30%), and cholestatic in 11 (26%). Four patients (9%) died, three from acute liver failure and one due to acute on chronic liver failure. Liver biochemical tests normalized after a mean of 66 days after stopping the implicated agents. Contrastingly, literature search yielded 24 cases of progesterone DILI reported between 1962 and 2019 with no mortality. Conclusion: In contrast to published literature on oral contraceptives, a majority of oral contraceptive-induced DILI in our series were from progesterone monotherapy and a smaller number with ormeloxifene, that often resulted in clinically significant jaundice or liver test abnormalities and rarely in fatality.

An Open-Label Randomized Controlled Trial Comparing Effectiveness of Aggressive Hydration Versus High-dose Rectal Indomethacin in the Prevention of Postendoscopic Retrograde Cholangiopancreatographic Pancreatitis (AHRI-PEP).

BACKGROUND: Although rectal administration of nonsteroidal anti-inflammatory drugs is recommended as the standard pharmacologic modality to prevent postendoscopic retrograde cholangiopancreatography (ERCP) post-ERCP pancreatitis (PEP), vigorous periprocedural hydration (vHR) with lactated Ringer's solution (LR) is emerging as an effective prophylaxis modality for PEP. There has been no head-to-head comparison between these 2. STUDY: This was a single-center, randomized, open-label, noninferiority, parallel-assigned, equal allocation, controlled clinical trial in a tertiary care hospital. Consecutive adults referred for ERCP, satisfying predefined inclusion criteria, underwent simple randomization and blinded allocation into 2 groups. Those allocated to vHR received intravenous LR at 3 mL/kg/h during procedure, 20 ml/kg bolus immediately afterward, and then at 3 mL/kg/h for another 8 hours. Those randomized to rectal Indomethacin received only per-rectal 100 mg suppository immediately post-ERCP. Assuming PEP of 9% in Indomethacin arm and noninferiority margin of 4%, we calculated sample size of 171 patients in each arm for 80% power and α-error 5%. Primary outcome was incidence of PEP, within 1 week, as defined by Cotton's criteria. All analysis were done by intention-to-treat. RESULTS: Between October, 2017 to February, 2018, 521 patients were assessed. In all, 352 were enrolled, 178 randomized to vHR, and 174 to per-rectal Indomethacin. Baseline details and ERCP outcomes were not different between 2 groups. PEP occurred in 6 (1.7%) overall, with 1 (0.6%) in hydration arm, and 5 (2.9%) in indomethacin arm; an absolute risk reduction of 2.3% (95% confidence interval: 0.9%-3.5%) and odds ratio of 0.19 (95% confidence interval: 0.02-1.65). Three patients developed severe PEP, all receiving indomethacin. CONCLUSIONS: vHR with LR is noninferior to postprocedure per-rectal Indomethacin for PEP prevention (ClinicalTrials.govID:NCT03629600).

Surgical Outcome of Brunner's Gland Hamartoma: A Single-Centre Experience.

Introduction Brunner's gland hamartomas (BGH) are rare benign lesions with an incidence of <0.01%, accounting for 5 to 10% of all benign tumors of the duodenum. It requires expeditious management by a multidisciplinary team. The aim of the study is to report our experience with surgery for BGH. Methodology Data of all patients who underwent surgical intervention for duodenal polypoidal mass between August 2007 and March 2020 were retrieved from our prospectively maintained gastrointestinal (GI) surgery database. All patients whose histopathology report of the resected specimen confirmed BGH ( n = 9) were included in the present study. Other pathological diagnosis like duodenal lipoma ( n = 2), ganglioneuroma ( n = 1), adenoma ( n = 10), and adenocarcinoma ( n = 4) were excluded. Results Nine patients had confirmatory histopathological diagnosis of BGH and met our inclusion criteria. Three (33.3%) of them were men with a median age of 45 (range: 24-61) years. The median interval between onset of symptoms and diagnosis of duodenal polyp was 14 (range: 4-180) days. Five patients (55.5%) presented with upper GI hemorrhage. Three (33.3%) patients presented with abdominal pain, and one (11.1%) patient presented with episodes of bilious vomiting. Diagnostic endoscopy could detect the lesion in all (100%) patients. Contrast-enhanced computed tomography detected duodenal polypoidal lesion in five (55.5%) patients. The mean size of tumor was 4.78 ± 1.36 cm. These lesions were symptomatic in all the patients and warranted intervention. In view of failed endoscopic intervention ( n = 7, 77.7%), or extramural extension of the tumor ( n = 2, 22.2%), surgical intervention was considered. Most commonly performed operation was duodenal polypectomy ( n = 6, 66.6%). Three postoperative complications developed in two (22.2%) patients. There was no surgery-related mortality. After a median follow-up of 60 (12 -78) months, no patient developed GI bleed or intestinal obstruction. Conclusion In this study, the clinical profile of BGH was explored from the surgeon's point of view. Although endoscopic management is the first-line treatment, surgery plays an important role, particularly, if this fails or is not feasible. In experienced hand, surgery can be performed with acceptable perioperative morbidity and mortality and long-term satisfactory outcomes.

Effects of atorvastatin on portal hemodynamics and clinical outcomes in patients with cirrhosis with portal hypertension: a proof-of-concept study.

BACKGROUND AND AIM: Statins can modulate portal microvascular dynamics in patients with cirrhosis. We present data from a proof-of-concept study aimed at comparing combination of propranolol and atorvastatin versus propranolol alone in reducing portal pressure in patients with cirrhosis. PATIENTS AND METHODS: In this open-label proof-of-concept study, 23 consecutive patients with cirrhosis were randomized into group A (incremental dose propranolol, n=12) or group B (atorvastatin 20 mg daily with propranolol in incremental dose, n=11). Hepatic venous pressure gradient (HVPG) was estimated at baseline, and after 30 days, clinical outcomes were evaluated after 1 year. RESULTS: The two groups were matched with respect to etiology of cirrhosis; clinical, biochemical, and endoscopic parameters; child status; and baseline HVPG. Decreases of wedged hepatic venous pressure, free hepatic venous pressure, and HVPG in group A and group B after 30 days were 4.67±2.57 versus 6.09±3.56 (P=0.290), 1.83±2.62 versus 1.27±1.67 (P=0.546), and 2.58±1.88 versus 4.81±2.82 mmHg (P=0.041), respectively. The proportion of HVPG responders in group A and group B were 50.00 and 90.91%, respectively. The two groups did not, however, differ significantly in terms of clinical outcomes (variceal bleed, endoscopic variceal ligation sessions, hepatic encephalopathy, requirement of therapeutic paracentesis, spontaneous bacterial peritonitis, and death). CONCLUSION: Decrease of HVPG in patients with cirrhosis treated with atorvastatin and propranolol is significantly more than those treated with only propranolol. Atorvastatin, with its pleiotropic effects, may be useful in portal hypertension in cirrhosis. Larger data sets are required for ratification.

Survey of inflammatory bowel diseases in India.

INTRODUCTION: Inflammatory bowel disease (IBD), both ulcerative colitis (UC) and Crohn's disease (CD), once thought to be uncommon, is now seen commonly in India. The Indian Society of Gastroenterology (ISG) Task Force on IBD decided to collate data on the clinical spectrum of IBD currently prevailing in India. METHODS: An open call to members of ISG was given through publication of a proforma questionnaire in the Indian Journal of Gastroenterology and the web portal of ISG. The proforma contained questions related with demographic features, family history, risk factors, clinical manifestations and characteristics, course of disease, and pattern of treatment of IBD. RESULTS: Of 1,255 filled questionnaires received, 96 were rejected and 1,159 (92.3 %) were analyzed. This comprised data on 745 (64.3 %) patients with UC, 409 (35.3 %) with CD, and 5 with indeterminate colitis. The median duration of illness was longer in patients with CD (48 months) compared to those with UC (24 months) (p = 0.002). More than one half of patients (UC 51.6 %, CD 56.9 %) had one or more extraintestinal symptoms. A definite family history of IBD was present in 2.9 % (UC 2.3 % and CD 4.6 %; p = 0.12). The extent of disease in UC was pancolitis 42.8 %, left-sided colitis 38.8 %, and proctitis alone in 18.3 %. The extent of disease involvement in CD was both small and large intestine in 39.6 %, colon alone in 31.4 % and small intestine alone in 28.9 %. Stricturing and fistulizing disease were noted in 18.8 % and 4.4 % of patients with CD respectively. Chronic continuous and intermittent disease course were present in 35.5 % and 47.2 % of UC patients respectively, and in 23.1 % and 68.8 % of CD patients. Four percent of patients with UC had undergone colectomy, while 15.2 % of patients with CD underwent surgical intervention. CONCLUSIONS: The present survey provides a reasonable picture of the demographic features and clinical manifestations of Indian patients with IBD, their risk factors, course of disease, and the treatment given to them.

"Normal" liver stiffness measure (LSM) values are higher in both lean and obese individuals: a population-based study from a developing country.

UNLABELLED: The liver stiffness measure (LSM) needs to be explored in ethnically and anthropometrically diverse healthy subjects (to derive an acceptable normal range) and also in patients with liver disease. In view of this objective, LSM was performed by transient elastography (TE) using FibroScan in 437 healthy subjects with normal alanine aminotransferase (ALT) levels, recruited from a free-living population of the Birbhum Population Project (BIRPOP; www.shds.in), a Health and Demographic Surveillance System (HDSS), and from 274 patients with liver disease attending the Hepatology Clinic of the School of Digestive and Liver Diseases (SDLD; Institute of Post Graduate Medical Education & Research [IPGME&R], Kolkata, India) including 188 with nonalcoholic fatty liver disease (NAFLD) and 86 with chronic hepatitis of viral and other etiologies. Liver biopsy was performed in 125 patients. The range of normal values for LSM, defined by 5th and 95th percentile values in healthy subjects, was 3.2 and 8.5 kPa, respectively. Healthy subjects with a lower body mass index (BMI; < <18.5 kg/m(2)) had a higher LSM compared with subjects who had a normal BMI; this LSM value was comparable to that of obese subjects (6.05 ± 1.78 versus 5.51 ± 1.59 and 6.60 ± 1.21, P = 0.016 and 0.349, respectively). Liver disease patients without histologic fibrosis had significantly higher LSM values compared with healthy subjects (7.52 ± 5.49 versus 5.63 ± 1.64, P < 0.001). Among the histologic variables, stage of fibrosis was the only predictor for LSM. LSM did not correlate with inflammatory activity and ALT in both NAFLD and chronic hepatitis groups. CONCLUSION: LSM varies between 3.2 and 8.5 kPa in healthy subjects of South Asian origin. Both lean and obese healthy subjects have higher LSM values compared with subjects with normal BMI. Liver stiffness begins to increase even before fibrosis appears in patients with liver disease.

Obscure GI bleeding in the tropics: impact of introduction of double-balloon and capsule endoscopies on outcome.

BACKGROUND: Innovative but costly small-bowel enteroscopies, capsule endoscopy (CE), and double-balloon endoscopy (DBE) have revolutionized the management of obscure GI bleeding (OGIB). OBJECTIVE: To measure the impact of these procedures on outcomes of OGIB in a resource-poor setting. DESIGN: Prospective cohort study and comparison with a historical cohort. SETTING: Tertiary-care center in India. PATIENTS: Fifty-three patients with OGIB, diagnosed by American Gastroenterological Association criteria. INTERVENTIONS: DBE and/or CE were performed. Patients were then offered specific treatment and/or hematinics. MAIN OUTCOME MEASUREMENTS: The etiology of OGIB in a tropical country and yield of DBE and/or CE. The number of investigations required, follow-up hemoglobin, rebleeds, and interventions/transfusions needed were compared between the present and historical cohort. RESULTS: Mean age was 46.4 years with hemoglobin (mean +/- standard deviation) of 8.3 +/- 2.3 g/dL at evaluation. OGIB was overt in 33 and occult in 20. They underwent 173 investigations before referral. DBE and/or CE localized the source of bleeding in 43 (yield 81%). Angiodysplasias, tumors, Crohn's disease, intestinal tuberculosis, and hookworm infestation were predominant etiologies. Compared with the historical cohort, DBE and/or CE have reduced the number of investigations per patient, increased the yield of mid intestinal source of OGIB, and reduced the number of surgeries, especially emergency laparotomies. There was no significant alteration in the overall yield, mortality, and rebleeding rates. LIMITATION: Small cohort without economic analysis. CONCLUSIONS: The demographic profile and etiological spectrum of OGIB in the tropics is different. DBE and/or CE have made a favorable impact on management.

Nonobese population in a developing country has a high prevalence of nonalcoholic fatty liver and significant liver disease.

UNLABELLED: There is a paucity of community-based epidemiological data on nonalcoholic fatty liver (NAFL) among nonaffluent populations in developing countries. Available studies are radiological and/or biochemical and lack histological assessment, limiting their strength. We conducted a prospective epidemiological study comprising a 1:3 subsample of all adult (>18 years) inhabitants of a rural administrative unit of West Bengal, India. Subjects positive for hepatitis B virus and/or hepatitis C virus infection and consuming any amount of alcohol were excluded. Diagnosis of NAFL was by dual radiological screening protocol consisting of ultrasonographic and computed tomographic examination of the liver. Transient elastographic examination and liver biopsy were performed in a subset to identify significant liver disease. The risk factors of having NAFL were analyzed. A total of 1,911 individuals were analyzed, 7% of whom were overweight and 11% of whom had abdominal obesity. The prevalence of NAFL, NAFL with elevated alanine aminotransferase, and cryptogenic cirrhosis was 8.7%, 2.3%, and 0.2%, respectively. Seventy-five percent of NAFL subjects had a body mass index (BMI) <25 kg/m(2), and 54% were neither overweight nor had abdominal obesity. The subjects with the highest risk of having NAFL were those with a BMI >25 kg/m(2) (odds ratio 4.3, 95% confidence interval 1.6-11.5). Abdominal obesity, dysglycemia (fasting plasma glucose >100 mg/dL or elevated homeostatic model assessment of insulin resistance), and higher income were the other risk factors. Even having a normal BMI (18.5-24.9 kg/m(2)) was associated with a 2-fold increased risk of NAFL versus those with a BMI <18.5 kg/m(2). CONCLUSION: There is a significant prevalence of NAFL and potentially significant liver disease, including cryptogenic cirrhosis, in this predominantly nonobese, nonaffluent population in a developing country. NAFL will be a major determinant of future liver disease burden in countries of the developing world.

Crohn's disease in India: a multicenter study from a country where tuberculosis is endemic.

Although Crohn's disease is thought to be rare and intestinal tuberculosis common in India, Crohn's disease is being reported more often. However, there is a lack of systematic study on Crohn's disease from India. In this analysis of data from three inflammatory bowel disease clinics (two in northern India and one in eastern India), criteria for Crohn's disease were applied retrospectively: (1) World Health Organization (WHO) criteria; or (2) compatible histology (European Crohn's and Colitis Organization) or failure of response to 4-8 weeks of anti-tuberculosis therapy (Asia-Pacific guidelines); or (3) compatible macroscopic, radiologic, colonoscopic features (European Crohn's and Colitis Organization). Others were classified as probable Crohn's disease. The Montreal classification was used for disease phenotype. Age at onset and duration of symptoms (182 patients, 117 male) were 34.5 (+/-13.6; 7-73) years and 3.0 (+/-5.8; 0.1-36) years, respectively. Diarrhea (68%), abdominal pain (62%), and weight loss (57%) were common. The common intestinal complications were occult (27%) and overt (40%) gastrointestinal bleeding and obstruction (28%). There were 141 (78%) and 41 (22%) with definite and probable Crohn's disease respectively. Of 147 (81%) available histopathology specimens (endoscopic biopsy in 110; 75%), 31 (21%) had granuloma. Seventy-one out of 166 (43%) had received anti-tuberculosis therapy in the past. Results from the Montreal classification were as follows: age at onset, A1:A2:A3 6%:64%:30%; location of disease, L1:L2:L3:L4 32%:41%:23%:4%, and disease behavior, B1:B2:B3 51%:24%:25%. Twenty-six (15%) and 31 (17%) patients had upper gastrointestinal and perianal modifiers. The drugs used were: aminosalicylates (128, 70%), steroids (76, 42%), azathioprine (53, 29%), methotrexate (4, 2%), and salazopyrine (14, 8%). Sixty-six (36%) patients underwent surgical treatment. We concluded that the phenotype of Crohn's disease in India is very similar to that described in other regions of Asia and the West, except for a delay in diagnosis and a more complicated disease at diagnosis.

Community-based epidemiology of hepatitis B virus infection in West Bengal, India: prevalence of hepatitis B e antigen-negative infection and associated viral variants.

BACKGROUND AND AIMS: There is a paucity of population-based epidemiological information regarding hepatitis B virus (HBV) infection in India. The present study was planned to outline the magnitude and pattern of HBV infection, hepatitis B e antigen (HBeAg)-negative infection and the associated viral mutants in India. METHODS: A community-based epidemiological study of HBV infection was carried out in West Bengal, India. Serological markers of infection and potential risk factors for HBV transmission were determined. Among the infected individuals, HBV-DNA, genotypes and mutations in the precore (PC) stop codon and basal core promoter (BCP) regions were determined by DNA sequencing and polymerase chain reaction (PCR) restriction fragment length polymorphism methods. RESULTS: Of the 7653 people included in the study, 227 (2.97%) tested positive for hepatitis B surface antigen (HBsAg), of whom 204 (90%) were HBeAg-negative and hepatitis B e antibody (anti-HBe)-positive, and 78% had normal alanine aminotransferase (ALT) levels. HBV-DNA could be detected by PCR in only 32% of people. G1896A PC stop codon mutants were present in 12% of people, BCP mutants in 18% and the remainder (70%) of the HBeAg-negative infections were associated with wild type sequences in these regions. CONCLUSIONS: This first general population-based epidemiological study of HBV infection from India suggests that HBV acquisition starts in early childhood and peaks in adulthood. Most infections in the community are e-negative and inactive. The point prevalence of PC stop codon and BCP mutants is low in this primarily inactive and asymptomatic HBV-infected population sample in eastern India.