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.

Granulomatous Tubercular Hepatitis Presenting as Secondary Hemophagocytic Lymphohistiocytosis: A Case Report and Systematic Review of the Literature.

Hemophagocytic lymphohistiocytosis is a life-threatening disorder characterized by persistent pathologic activation of cytotoxic T lymphocytes, natural killer cells, and macrophages. We present details of a young patient who presented with high-grade fever, jaundice, and breathlessness. On investigations, he had hepatitis, anemia, neutropenia, and coagulopathy. He also had hypertriglyceridemia, hypofibrinogenemia, and hyperferritinemia. Bone marrow aspiration revealed histiocytosis, and transjugular liver biopsy revealed necrotizing granulomas positive for Mycobacterium tuberculosis on acid-fast bacilli staining. He was successfully managed with a combination of immunosuppressants and antitubercular therapy. Tuberculosis associated hemophagocytosis syndrome is rare and should be considered in patients with unexplained hemophagocytosis syndrome, especially in tuberculosis-endemic regions. Prompt recognition and treatment with antitubercular treatment and immunosuppressants are associated with good outcomes.

Maintenance zinc therapy after initial penicillamine chelation to treat symptomatic hepatic Wilson's disease in resource constrained setting.

BACKGROUND: Experience with zinc in treating symptomatic hepatic Wilson's disease (WD) is limited. AIM: To study the efficacy of Penicillamine followed by zinc in treating symptomatic hepatic Wilson's disease. METHODS: We retrospectively analyzed case records of 31 symptomatic hepatic WD patients for whom disease severity scores (Child's, model for end-stage liver disease (MELD), Nazer's, and New Wilson Index (NWI) score) and 24-h urinary copper were compared at 3-time points-baseline at presentation, at transition from penicillamine to zinc and at end of follow up. RESULTS: Thirty-one patients (median age 11 [5-24] years) with symptomatic hepatic WD were studied; ten had associated neuropsychiatric manifestations of WD. Penicillamine was changed to zinc sulfate either due to financial constraints (28 patients) or due to adverse effects of penicillamine (3 patients). At presentation (baseline), six patients belonged to Child's class A, five to Child's B, and 17 to Child's C. Duration of initial penicillamine chelation therapy was 134 (2-320) weeks, and of subsequent zinc therapy was 363 (35-728) weeks. There was a significant improvement in liver function tests and disease severity scores (Child's, MELD, Nazer's, and NWI score) at the transition from penicillamine to zinc compared to baseline. This improvement was maintained until the end of study period with 90% survival at 10 (2-20) years. Fifteen of the 17 Child's C cirrhotic patients showed significant improvement in disease severity scores from baseline until end of follow up. CONCLUSIONS: Penicillamine followed by zinc may be a safe and effective treatment in resource-constrained setting for symptomatic hepatic WD patients in all grades of baseline disease severity. Some patients with decompensated cirrhosis due to WD may be managed with medical treatment, avoiding liver transplantation.

IAGG/IAGG GARN International Survey of End-of-Life Care in Nursing Homes.

This article reports the findings of a survey on end-of-life (EOL) care in nursing homes of 18 long-term care experts across 15 countries. The experts were chosen as a convenience-based sample of known experts in each country. The survey was administered in 2016 and included both open-ended responses for defining hospice care, palliative care, and "end of life," and a series of questions related to the following areas-attitudes toward EOL care, current practice and EOL interventions, structure of care, and routine barriers. Overall experts strongly agreed that hospice and palliative care should be available in long-term care facilities and that both are defined by holistic, interdisciplinary approaches using measures of comfort across domains. However, it appears the experts felt that in most countries the reality fell short of what they believed would be ideal care. As a result, experts call for increased training, communication, and access to specialized EOL services within the nursing home.

Effect of Capparis spinosa Linn. extract on lipopolysaccharide-induced cognitive impairment in rats.

Cognitive disorders in mankind are not uncommon. Apart from neurodegenerative diseases such as Alzheimer's (AD), various stresses also affect cognitive functions. Plants are known to be potential source of compounds that ameliorate several diseases including cognitive impairment. Here, we evaluated effect of aqueous extract of caper (Capparis spinosa) buds on lipopolysaccharide-induced cognitive impairment in rats using two different oral doses i.e. 10 (pre-treatment) and 30 mg/rat(post-treatment) through assessment of behavioural (Morris Water maze test and Y maze test), biochemical (Cholinesterase assay) and histopathological (H&E staining) parameters. Lipopolysaccharide (from E. coli) administration resulted in an increased neurodegeneration and time taken to reach the platform (in Morris water maze). The increased neurodegeneration in CA1 region of hippocampus was significantly reduced in animals which received caper bud extract; they showed marked reduction in time taken to reach the platform at both the dose levels. The experiment demonstrated that caper bud extract exhibits potential protective effect against learning and memory damage induced by chronic administration of lipopolysaccharide (175 µg/kg) for 7 days. The results suggest that the caper bud extract could be explored for its use in the treatment of cognitive disorders.

Design, synthesis, and biological evaluation of substituted-N-(thieno[2,3-b]pyridin-3-yl)-guanidines, N-(1H-pyrrolo[2,3-b]pyridin-3-yl)-guanidines, and N-(1H-indol-3-yl)-guanidines.

Sulfonylureas stimulate insulin secretion independent of the blood glucose concentration and therefore cause hypoglycemia in type 2 diabetic patients. Over the last years, a number of aryl-imidazoline derivatives have been identified that stimulate insulin secretion in a glucose-dependent manner. In the present study, we have developed three series of substituted N-(thieno[2,3-b]pyridin-3-yl)-guanidine (2a-l), N-(1H-pyrrolo[2,3-b]pyridin-3-yl)-guanidine (3a-l), and N-(1H-indol-3-yl)-guanidine (4a-l) as new class of antidiabetic agents. In vitro glucose-dependent insulinotropic activity of test compounds 2a-l, 3a-l, and 4a-l was evaluated using RIN5F (Rat Insulinoma cell) based assay. All the test compounds showed concentration-dependent insulin secretion, only in presence of glucose load (16.7mmol). Some of the test compounds (2c, 3c, and 4c) from each series were found to be equipotent to BL 11282 (standard aryl-imidazoline), which indicated that the guanidine group acts as a bioisostere of imidazoline ring system.