Clinical and Liver Biochemistry Phenotypes, and Outcome in 133 Patients with Anti-seizure Drug-Induced Liver Injury.

AIMS AND OBJECTIVE: Anti-seizure drugs that cause idiosyncratic drug-induced liver injury (DILI) are an important cause of morbidity and mortality in individuals exposed to these drugs. The clinical and demographic characteristics, the liver injury pattern, the outcome, and the agents responsible for hepatotoxicity have not been thoroughly studied. We investigated the aforementioned characteristics in a large cohort of DILI registry patients. METHODS: Patients with anti-seizure DILI were studied from a large single-center DILI registry between 1998 and 2021. DILI was defined by international working group criteria with at least a probable relation with RUCAM. Immunoallergic features and organ-specific contribution to outcome were investigated. RESULTS: Anti-seizure drugs accounted for 133 patients (12.5%) among 1067 patients with idiosyncratic DILI. Compared to other agents, patients with anti-seizure DILI were younger (31 vs 41 years; p = 0.31), were more often females (52% vs 46%; p = 0.19) and had a lower frequency of jaundice (41% vs 59%, p = 0.001), MELD score (14.5 vs 16.5; p = 0.02) and mortality (9.8% vs 15.7%, p = 0.03). Anti-seizure DILI exhibited a greater frequency of hypersensitivity skin rashes (75% vs 22%, p < 0.001), including DRESS (51% vs 13%, p < 0.001) and SJS/TEN (19% vs1%, p < 0.001). A total of 18 different anti-seizure agents were responsible for DILI, largely contributed by carbamazepine (n = 36), phenytoin (n = 71), phenobarbitone (n = 8) and valproate (n = 14) which accounted for 89% of cases and 85% of 13 deaths. CONCLUSIONS: Anti-seizure DILI are caused predominantly by first generation drugs. Newer agents account for < 10% of cases. Hypersensitivity reaction is the most common phenotypic presentation. Both severity and mortality are lower with anti-seizure DILI.

Idiosyncratic Drug-Induced Liver Injury Associated With and Without Drug Reaction With Eosinophilia and Systemic Symptoms.

INTRODUCTION: Immunoallergic drug-induced liver injury (DILI) presenting with features of drug reaction with eosinophilia and systemic symptoms (DRESS) is a distinct phenotype. We describe the clinical characteristics, hepatitis pattern, severity, complications, and implicated medications in DILI patients with and without DRESS. METHODS: Using established criteria, we analyzed DILI registry patients with and without DRESS from 1998 to 2021. RESULTS: DILI associated with DRESS (DwD) comprised 179 among 943 cases (19%) of DILI. Compared with the cohort without DRESS, patients with DwD are more often women and have shorter latency, lesser degrees of injury ( P < 0.01), and lower mortality (7.8%) than those without DRESS (16%). Antiepileptic drugs (36%), sulfonamides (19%), antituberculosis drugs (14%), antibiotics (10%), and antiretroviral drugs (8%) account for 87% of the cases of DwD. DISCUSSION: A limited number of drugs cause DwD, representing a fifth of patients with DILI. DwD is characterized by lesser degrees of liver injury and mortality likely because of earlier presentation.

Dengue hepatitis with acute liver failure: Clinical, biochemical, histopathological characteristics and predictors of outcome.

BACKGROUND: Hepatitis infection from non-hepatotropic viruses such as dengue virus (DENV) is increasing worldwide. There is increasing recognition of the changing epidemiology and atypical presentations of DENV infection including acute liver failure (ALF). There is paucity of data regarding incidence, disease characteristics, and markers of prognosis in patients who develop DENV-related ALF. METHODS: We aimed to study the incidence, clinical features, laboratory characteristics, and determinants of outcome in patients of DENV presenting with ALF. We reviewed all patients with DENV infection and focused on DENV-related ALF from 2014 to 2017. Diagnosis of DENV and ALF was confirmed by serological tests and standard criteria, respectively. RESULTS: Thirty-six patients (20 men, mean age 32.3) developed ALF among 10 108 patients with DENV infection (0.35%). Twenty-one patients died (58.3%). Although bilirubin, aspartate and alanine aminotransferase, and international normalized ratio were markedly elevated in all patients with DENV ALF, there was no statistically significant difference between survivors and non-survivors. Lactate levels, pH at admission, and model for end-stage liver disease (MELD) score were the only predictors of mortality. Lactate levels were significantly higher in non-survivors (11.5 ± 4.2 mmol/L) than survivors (6.3 ± 3.6 mmol/L) (P < 0.001). MELD score in non-survivors (26.7 ± 10.2) was significantly higher than in survivors (20 ± 7.2) (P = 0.039). Receiver operator characteristic curve showed lactate or pH to be a superior prognostic marker than MELD with an area under the curve of 0.80, 0.79, and 0.70, respectively. CONCLUSION: Dengue hepatitis progressed to ALF in 0.35%. Development of ALF was associated with a high mortality (> 50%). Lactate level, pH, and MELD score at admission were significant determinants of outcome.

Lessons of the month: Massive gastrointestinal bleeding in a young woman with idiopathic thrombocytopenic purpura (ITP).

Cytomegalovirus (CMV) is a ubiquitous pathogen, belongs to the herpes virus family and can infect the gastrointestinal (GI) system. The disease is usually noted in immunocompromised patients such as solid organ transplant recipients on immunosuppressive drugs, patients with malignancy receiving chemotherapy, patients with AIDS, patients on steroids for autoimmune disorders, and is rarely seen in immunocompetent individuals. In the GI system, CMV most commonly involves the colon, followed by oesophagus, stomach and, rarely, the small intestine. The GI manifestation of CMV infection is usually anorexia, diarrhoea, and blood in stools, abdominal pain and fever. Very rarely, CMV infection may present with a massive GI bleed. We report a case of 36-year-old pregnant woman with idiopathic thrombocytopenic purpura (ITP) who presented with massive GI bleeding following delivery, attributed to isolated CMV enteritis.