The Indian Network of Drug-Induced Liver Injury: Etiology, Clinical Features, Outcome and Prognostic Markers in 1288 Patients.

BACKGROUND: Etiology of and outcomes following idiosyncratic drug-induced liver injury (DILI) vary geographically. We conducted a prospective study of DILI in India, from 2013 to 2018 and summarize the causes, clinical features, outcomes and predictors of mortality. METHODS: We enrolled patients with DILI using international DILI expert working group criteria and Roussel Uclaf causality assessment method. Follow-up was up to 3 months from onset of DILI or until death. Multivariate logistics regression was carried out to determine predictors of non-survival. RESULTS: Among 1288 patients with idiosyncratic DILI, 51.4% were male, 68% developed jaundice, 68% required hospitalization and 8.2% had co-existing HIV infection. Concomitant features of skin reaction, ascites, and encephalopathy (HE) were seen in 19.5%, 16.4%, and 10% respectively. 32.4% had severe disease. Mean MELD score at presentation was 18.8 ± 8.8. Overall mortality was 12.3%; 65% in those with HE, 17.6% in patients who fulfilled Hy's law, and 16.6% in those that developed jaundice. Combination anti-TB drugs (ATD) 46.4%, complementary and alternative medicines (CAM) 13.9%, anti-epileptic drugs (AED) 8.1%, non-ATD antimicrobials 6.5%, anti-metabolites 3.8%, anti-retroviral drugs (ART)3.5%, NSAID2.6%, hormones 2.5%, and statins 1.4% were the top 9 causes. Univariate analysis identified, ascites, HE, serum albumin, bilirubin, creatinine, INR, MELD score (p < 0.001), transaminases (p < 0.04), and anti-TB drugs (p = 0.02) as predictors of non-survival. Only serum creatinine (p = 0.017), INR (p < 0.001), HE (p < 0.001), and ascites (p = 0.008), were significantly associated with mortality on multivariate analysis. ROC yielded a C-statistic of 0.811 for MELD and 0.892 for combination of serum creatinine, INR, ascites and HE. More than 50 different agents were associated with DILI. Mortality varied by drug class: 15% with ATD, 13.6% with CAM, 15.5% with AED, 5.8% with antibiotics. CONCLUSION: In India, ATD, CAM, AED, anti-metabolites and ART account for the majority of cases of DILI. The 3-month mortality was approximately 12%. Hy's law, presence of jaundice or MELD were predictors of mortality.

Diagnostic utility of alarm features in predicting malignancy in patients with dyspeptic symptoms.

BACKGROUND: Clinical features are of modest benefit in determining the etiology of dyspepsia. Dyspeptic patients with alarm features are suspected to have malignancy; but the proportions of patients and true cutoff values of various quantitative parameters in predicting malignancy are explored to a lesser extent. METHODS: This is a prospective observational study of consecutive patients undergoing esophagogastroduodenoscopy (EGD) for dyspeptic symptoms. Patients' alarm features and clinical details were recorded in a predesigned questionnaire. The diagnostic accuracy of alarm features in predicting malignancy was studied. RESULTS: Nine hundred patients, 678 (75.3%) males, with a mean (standard deviation [SD]) age of 44.6 (13.54) years were enrolled. Commonest indication for EGD was epigastric pain in 614 (68.2%) patients. Dyspepsia was functional in 311 (34.6%) patients. EGD revealed benign lesions in 340 (37.8%) and malignancy in 50 (5.5%) patients. Among the malignant lesions, gastric malignancy was present in 28 (56%) and esophageal malignancy in 20 (40%) patients. Alarm features were present in 206 (22.9%), out of which malignant lesions were seen in 46 (22.3%) patients. Altogether, the alarm features had a sensitivity of 92% and specificity of 81.2% for predicting malignancy. The sensitivity and specificity for weight loss were 76% and 90.8%, while that of abdominal mass were 10% and 99.9% respectively. Based on receiver operating characteristic curve, the optimal age for screening of malignancy was 46.5 years in this population. CONCLUSIONS: Patients of age group 40 to 49 years with dyspeptic alarm symptoms (predominant weight loss) need prompt endoscopy to screen for malignancy. The alarm features are inexpensive screening tools, found to be useful in India, and should be utilized in countries with similar healthcare conditions and disease epidemiology.

Digestive system involvement and clinical outcomes among COVID-19 patients: A retrospective cohort study from Qatar.

BACKGROUND: Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 virus most commonly presents with respiratory symptoms. While gastrointestinal (GI) manifestations either at presentation or during hospitalization are also common, their impact on clinical outcomes is controversial. Some studies have described worse outcomes in COVID-19 patients with GI symptoms, while others have shown either no association or a protective effect. There is a need for consistent standards to describe GI symptoms in COVID-19 patients and to assess their effect on clinical outcomes, including mortality and disease severity. AIM: To investigate the prevalence of GI symptoms in hospitalized COVID-19 patients and their correlation with disease severity and clinical outcomes. METHODS: We retrospectively reviewed 601 consecutive adult COVID-19 patients requiring hospitalization between May 1-15, 2020. GI symptoms were recorded at admission and during hospitalization. Demographic, clinical, laboratory, and treatment data were retrieved. Clinical outcomes included all-cause mortality, disease severity at presentation, need for intensive care unit (ICU) admission, development of acute respiratory distress syndrome, and need for mechanical ventilation. Multivariate logistic regression model was used to identify independent predictors of the adverse outcomes. RESULTS: The prevalence of any GI symptom at admission was 27.1% and during hospitalization was 19.8%. The most common symptoms were nausea (98 patients), diarrhea (76 patients), vomiting (73 patients), and epigastric pain or discomfort (69 patients). There was no difference in the mortality between the two groups (6.21% vs 5.5%, P = 0.7). Patients with GI symptoms were more likely to have severe disease at presentation (33.13% vs 22.5%, P < 0.001) and prolonged hospital stay (15 d vs 14 d, P = 0.04). There was no difference in other clinical outcomes, including ICU admission, development of acute respiratory distress syndrome, or need for mechanical ventilation. Drugs associated with the development of GI symptoms during hospitalization were ribavirin (diarrhea 26.37% P < 0.001, anorexia 17.58%, P = 0.02), hydroxychloroquine (vomiting 28.52%, P = 0.009) and lopinavir/ritonavir (nausea 32.65% P = 0.049, vomiting 31.47% P = 0.004, and epigastric pain 12.65% P = 0.048). In the multivariate regression analysis, age > 65 years was associated with increased mortality risk [odds ratio (OR) 7.53, confidence interval (CI): 3.09-18.29, P < 0.001], ICU admission (OR: 1.79, CI: 1.13-2.83, P = 0.012), and need for mechanical ventilation (OR: 1.89, CI:1.94-2.99, P = 0.007). Hypertension was an independent risk factor for ICU admission (OR: 1.82, CI:1.17-2.84, P = 0.008) and need for mechanical ventilation (OR: 1.66, CI: 1.05-2.62, P = 0.028). CONCLUSION: Patients with GI symptoms are more likely to have severe disease at presentation; however, mortality and disease progression is not different between the two groups.

Hidden Nematode Causing Recurrent Pancreatitis: A Case Report.

Even though hepatobiliary ascariasis has been found to cause pancreatitis, it is rare in Qatar and other countries in the Middle East. In this report, we present a case of biliary duct ascariasis causing recurrent pancreatitis. A 46-year-old woman from the Philippines presented with recurrent clinical and biochemical features of acute pancreatitis and was found to have hepatobiliary ascariasis. She was successfully treated with endoscopic retrograde cholangiopancreatography (ERCP) and antihelminthic medication. Although hepatobiliary ascariasis as a cause of pancreatitis is rare, it should be considered in patients with recurrent pancreatitis without an obvious cause, especially in those from endemic areas or those who have visited endemic areas.

High primary resistance to metronidazole and levofloxacin, and a moderate resistance to clarithromycin in Helicobacter pylori isolated from Karnataka patients.

BACKGROUND: Due to increased prevalence of H. pylori antimicrobial resistance worldwide and more importantly the resistance patterns vary between different geographical regions, it is important to survey local H. pylori antibiotic resistance profile to provide physicians with more informed drug choices to better treat H. pylori infection. To our knowledge, this is the first study to examine the prevalence of antimicrobial resistance of H. pylori in Karnataka state of South India. RESULTS: A total of 113 H. pylori strains were isolated from gastric biopsies and tested: 81.4% were resistant to metronidazole, 54.9% were resistant to levofloxacin, 20.4% were resistant to clarithromycin, 5.3% were resistant to tetracycline and 7.1% were resistant to amoxicillin. Multidrug resistance was detected in 59.3% of total isolated strains, among which 86.6% were resistant to at least both metronidazole and levofloxacin. In this study, 38 out of 113 H. pylori strains had been whole-genome sequenced. Based on the draft genomes, RdxA and/or FrxA inactivation mutations were found to present in 75% of metronidazole-resistant strains. Clarithromycin-resistant strains had mainly A2143G and G2224A mutations in the 23 rRNA gene. While 87.1% levofloxacin-resistant strains had amino acid substitution mutations occurring predominantly at N87 and D91 in GyrA, novel mutations in the same protein including an insertion of five amino acid residues (QDNSV), immediately after the start codon, and a substitution mutation at R295 were identified. CONCLUSION: High primary resistance to metronidazole and levofloxacin, and a modest occurrence of clarithromycin resistance were revealed in H. pylori strains isolated from Karnataka patients. Therefore metronidazole-, levofloxacin- and clarithromycin-based triple therapies are not suitable as first-line treatment in Karnataka. Both amoxicillin and tetracycline can still be used to eradicate H. pylori infection in this region. We also revealed novel mutations in GyrA protein that possibly contribute to H. pylori resistance in levofloxacin, which merit further investigations.

Prevalence of and Factors Associated With Minimal Hepatic Encephalopathy in Patients With Cirrhosis of Liver.

BACKGROUND/OBJECTIVES: Minimal hepatic encephalopathy (MHE), though highly prevalent, is a frequently underdiagnosed complication of cirrhosis of the liver. Because lack of time is reported as the major reason for non-testing, identifying patients at high risk of MHE would help in targeting them for screening. We aimed to determine the factors associated with MHE to help identify patient subgroups with a higher risk of MHE for targeted screening. METHODS: Patients with cirrhosis of liver presenting between April 2015 and November 2016 were included. Those with a Psychometric Hepatic Encephalopathy Score (PHES) of ≤-5 points on psychometric testing were diagnosed to have MHE. Various demographic, clinical and laboratory parameters were included in a univariate and later multiple logistic regression models. RESULTS: Of the 180 (male = 166, 92.2%) patients included 94 (52.2%) had MHE. Though serum albumin, serum total bilirubin, serum aspartate aminotransferase, international normalized ration, Child-Turcotte-Pugh and Model-For-End-Stage-Liver-Disease scores were significant on univariate analysis, only CTP score was found to be significantly associated with MHE (P = 0.002) on multivariate analysis. A higher CTP class was associated with a higher risk of the presence of MHE. The Odds ratio for having MHE was higher with CTP classes of B (P ≤ 0.001) and C (P ≤ 0.001) compared to class A. CONCLUSIONS: MHE is a common complication in patients with cirrhosis of liver and higher CTP scores independently predict the presence of MHE. Patients with CTP class B and C have a higher risk of suffering from MHE than CTP class A. Screening of patients in CTP class B and C is likely to increase the MHE detection rates while saving time, although select CTP class A patients may also need screening in view of public safety or poor quality of life.

Comparative Study of Community Acquired and Nosocomial Spontaneous Bacterial Peritonitis and its Variants in 150 Patients.

BACKGROUND: Nosocomial acquisition of spontaneous bacterial peritonitis (SBP) is debated as having a different microbial etiology and prognosis. Identification of clinical, laboratory predictors of mortality and appropriate empirical antimicrobial selection is necessary to prevent early mortality and morbidity. We aimed to find the clinical and bacteriological profile in nosocomial and community acquired SBP and its variants, and the predictors of mortality. MATERIAL AND METHODS: One hundred and fifty patients with 162 discrete episodes of different types of SBP were analyzed. Relevant clinical and laboratory data were analyzed. SBP was diagnosed according to standard criteria and classified as community acquired if the infection detected within 48 h of admission and as nosocomial after 48 h of admission to the hospital. RESULTS: Eighty seven percent had community acquired SBP (CSBP), 13% had nosocomial SBP (NSBP). Patients of NSBP were older, had more episodes of GI bleed and higher previous episodes of encephalopathy. Patients who died were older, had worse encephalopathy. NSBP had higher one month mortality. Age, serum sodium, encephalopathy and NSBP predicted mortality. Culture positivity was 22.22%. Escherichia coli was the commonest organism isolated. There was no difference in the bacteriological profile between CSBP and NSBP. E. coli showed up to 48% resistance to third generation cephalosporins. Overall sensitivity to aminoglycosides was more than 75%. CONCLUSIONS: Overall mortality was 59%. NSBP had significantly high one month mortality. Age, serum sodium, encephalopathy and NSBP were predictors of mortality. Bacteriological profile was similar between CSBP and NSBP.

Quality of life in dyspepsia and its subgroups using EQ-5D (EuroQol) questionnaire.

BACKGROUND/AIM: Dyspepsia has a significant impact on the quality of life. Health-related quality of life (HRQoL) can be assessed by disease-specific and generic HRQoL instruments. The present study evaluated HRQoL and compared it among dyspepsia subgroups by using EQ (Euro QoL)-5D questionnaire. PATIENTS AND METHODS: Patients with abnormal findings on upper gastrointestinal endoscopy were classified to have organic dyspepsia, whereas those with normal endoscopy were classified as functional dyspepsia if they met the ROME III criteria or as endoscopy negative recent dyspepsia if symptom duration was <6 months. HRQoL was assessed using the EQ-5D questionnaire, and the overall health status on a visual analogue scale (VAS); and the frequency of impairment in each dimension were compared between the dyspepsia subgroups. RESULTS: The overall health status was affected equally in all three dyspepsia subgroups. Impairment in HRQoL was commonly seen in the dimensions of pain (98.4%), usual activities (66.20%), and anxiety/depression (70.60%), however, much less so in mobility (22.70%) and self-care (10.9%). Any impairment in HRQoL was not significantly different between the three subgroups in the dimensions of mobility and usual activities. Self-care was more commonly affected in organic dyspepsia, anxiety/depression was more common with functional dyspepsia, while pain, though significantly different among various subgroups, was very common in all three subgroups. CONCLUSION: HRQoL was equally affected in all three subgroups of dyspepsia but variably so in the different domains of EQ-5D. These differences need to be studied further to improve the management of different etiological subgroups of dyspepsia.

Helicobacter pylori in Dyspepsia: Phenotypic and Genotypic Methods of Diagnosis.

BACKGROUND: Helicobacter pylori affects almost half of the world's population and therefore is one of the most frequent and persistent bacterial infections worldwide. H. pylori is associated with chronic gastritis, ulcer disease (gastric and duodenal), mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Several diagnostic methods exist to detect infection and the option of one method or another depends on various genes, such as availability, advantages and disadvantages of each method, monetary value, and the age of patients. MATERIALS AND METHODS: Patients with complaints of abdominal pain, discomfort, acidity, and loss of appetite were chosen for endoscopy, detailed history was contained, and a physical examination was conducted before endoscopy. Biopsies (antrum + body) were received from each patient and subjected to rapid urease test (RUT), histopathological examination (HPE), polymerase chain reaction (PCR), and culture. RESULTS: Of the total 223 biopsy specimens obtained from dyspeptic patients, 122 (54.7%) were positive for H. pylori for HPE, 109 (48.9%) by RUT, 65 (29.1%) by culture, and 117 (52.5%) by PCR. The specificity and sensitivity were as follows: RUT (99% and 88.5%), phosphoglucosamine mutase PCR assay (100% and 95.9%), and culture (100% and 53.3%), respectively. CONCLUSION: In this study, we compared the various diagnostic methods used to identify H. pylori infection indicating that, in comparison with histology as gold standard for detection of H. pylori infection, culture and PCR showed 100% specificity whereas RUT and PCR showed 99% and 100% sensitivity, respectively.

Pancreatic Calculus Causing Biliary Obstruction: Endoscopic Therapy for a Rare Initial Presentation of Chronic Pancreatitis.

INTRODUCTION: Biliary obstruction in chronic calcific pancreatitis (CCP) is often caused by inflammatory or fibrotic strictures of the bile duct, carcinoma of head of pancreas or less commonly by compression from pseudocysts. Pancreatic calculi causing ampullary obstruction and leading to obstructive jaundice is extremely rare. METHODS: The medical records of all patients with CCP or biliary obstruction who underwent endoscopic retrograde cholangiopancreatography (ERCP) over 4 years between 2010-2014 at Kasturba Medical College, Manipal were analyzed. RESULTS: Five patients of CCP with impacted pancreatic calculi at the ampulla demonstrated during ERCP were identified. All 5 presented with biliary obstruction and were incidentally detected to have CCP when evaluated for the same; 3 patients had features of cholangitis. All the patients were managed successfully by endoscopic papillotomy and extraction of pancreatic calculi from the ampulla with resolution of biliary obstruction. CONCLUSION: Pancreatic calculus causing ampullary obstruction, though very rare, should be considered as a possibility in patients with CCP complicated by biliary obstruction. Endoscopic therapy is affective in the resolution of biliary obstruction in such patients.

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

BACKGROUND AND AIM: 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. METHODS: Single center analysis of consecutive cases of anti-TB DILI following combination anti-TB drugs exposure from 1997-2011. RESULTS: Of the 269 patients, 191 (71%) experienced jaundice and 69 (25.7%) accounted for ALF. The mean age and treatment duration was 41.3 years and 1.9 months, respectively; males constituted 55.7%. DILI occurred throughout the course of treatment; three-quarters occurred within the first 2 months. HIV infection was present in 21 (7.8%). The 90-day mortality was 22.7%. DILI accompanied by jaundice (n = 191), encephalopathy (n = 69) or ascites (n = 69) resulted in mortality in 30%, 69.6% and 50.7%, respectively (P < 0.001). Age, gender, transaminase levels, HIV or hepatitis B surface antigen (HBsAg) status did not influence survival. Treatment duration, encephalopathy, ascites, bilirubin, serum albumin, international normalized ratio (INR), serum creatinine and leukocyte count were associated with mortality (P < 0.001). Multivariate logistic regression model for mortality, incorporating encephalopathy, albumin, bilirubin, INR, and creatinine yielded a C-statistic of 97%. CONCLUSIONS: Anti-TB DILI occurs throughout treatment duration progressing to ALF in a quarter of patients. The overall mortality is 22.7%, which is higher when accompanied by jaundice, ascites or encephalopathy. An anti-TB DILI model, incorporating bilirubin, INR, encephalopathy, serum creatinine and albumin predicted mortality with C-statistic of 97%.