Effect of season and sunlight on viral kinetics during hepatitis C virus therapy

HepatiC RegistryBackground and aims] Rapid viral response (RVR) during antiviral treatment for hepatitis C virus (HCV) predicts sustained viral response (SVR). Recently, vitamin D levels have been associated with SVR. As sunlight is the most important source of vitamin D and shows seasonal variation, we evaluated the effect of season on viral kinetics during peginterferon/ribavirin-based therapy for HCV.[Methods] Consecutive HCV patients treated with peginterferon/ribavirin and boceprevir/ telaprevir (June 2011–July 2014) were included. Patients were grouped according to season when therapy was initiated (Season A: May–October and Season B: November–April) depending on hours of daily sunlight. Multiple logistic regression analysis included factors known to influence SVR to treatment. The dependent variables were undetectable viral load (VL) or VL ≤15 UI/mL (VL ≤15) at weeks 4, 8 and 12, end of treatment and SVR.[Results] The study included 930 patients (66.8% men; median 54 years) treated with telaprevir (n=537) or boceprevir, without (n=481) or with lead-in therapy of peginterferon/ribavirin. Baseline characteristics of patients in Season A (45.3%, n=421) and Season B groups were similar. Overall, a higher rate of RVR (23.5% vs 16.1%, p=0.005) and VL ≤15 (51.0% vs 38.6%, p≤0.001) was observed in patients starting treatment during Season A versus Season B. By logistic regression analysis, initiating treatment in Season A proved to be an independent predictor of RVR and VL ≤15.[Conclusions] In our setting, seasonality affects viral kinetics in HCV genotype 1 patients treated with peginterferon/ribavirin-based therapy. Our findings support the hypothesis that vitamin D influences viral response to peginterferon/ribavirin-based therapy.Peer reviewe

Early predictors of corticosteroid response in acute severe autoimmune hepatitis: a nationwide multicenter study

Background and aims: To assess whether corticosteroids improve prognosis in patients with AS-AIH, and to identify factors at therapy initiation and during therapy predictive of the response to corticosteroids. Methods: This was a retrospective cohort study including all patients with AS-AIH admitted to 13 tertiary centres from January 2002 to January 2019. The composite primary outcome was death or liver transplantation within 90 days of admission. Kaplan-Meier and Cox regression methods were used for data analysis. Results: Of 242 consecutive patients enrolled (mean age [SD] 49.7 [16.8] years), 203 received corticosteroids. Overall 90-day transplant-free survival was 61.6% (95% confidence interval [CI] 55.4-67.7). Corticosteroids reduced the risk of a poor outcome (adjusted hazard ratio [HR] 0.25; 95% CI 0.2-0.4), but this treatment failed in 30.5%. An internally validated nomogram composed of older age, MELD, encephalopathy and ascites at the initiation of corticosteroids accurately predicted the response (C-index 0.82; [95% CI 0.8-0.9]). In responders, MELD significantly improved from days 3 to 14 but remained unchanged in non-responders. MELD on day 7 with a cut-off of 25 (sensitivity 62.5%[95% CI: 47.0-75.8]; specificity 95.2% [95% CI: 89.9-97.8]) was the best univariate predictor of the response. Prolonging corticosteroids did not increase the overall infection risk (adjusted HR 0.75; 95% CI 0.3-2.1). Conclusion: Older patients with high MELD, encephalopathy or ascites at steroid therapy initiation and during treatment are unlikely to show a favourable response and so prolonged therapy in these patients, especially if they are transplantation candidates, should be avoided.This study was supported in part by grants from the Spanish Ministry of Science and Innovation, Instituto de Salud Carlos III, number PI20/01302, awarded to Agustín Albillos and number PI 21/01310, awarded to Luis Téllez. CIBEREHD is funded by the Instituto de Salud Carlos III using grants cofinanced by the European Development Regional Fund “A way to achieve Europe” (EDRF). María Carlota Londoño received support from the Plan Nacional de I+D+I co-funded by ISCIII-Subdirección General de Evaluación and Fondo Europeo de Desarrollo Regional (FEDER-"Una manera de Hacer Europa") (PI17/00955). Laura Patricia Llovet received the Resident Award “Clínic-La Pedrera” granted by the Hospital Clínic de Barcelona, Research, Innovation and Education Department

Comprehensive analysis and insights gained from long-term experience of the Spanish DILI Registry

Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER); Agencia Española del Medicamento; Consejería de Salud de Andalucía.Background & Aims: Prospective drug-induced liver injury (DILI) registries are important sources of information on idiosyncratic DILI. We aimed to present a comprehensive analysis of 843 patients with DILI enrolled into the Spanish DILI Registry over a 20-year time period. Methods: Cases were identified, diagnosed and followed prospectively. Clinical features, drug information and outcome data were collected. Results: A total of 843 patients, with a mean age of 54 years (48% females), were enrolled up to 2018. Hepatocellular injury was associated with younger age (adjusted odds ratio [aOR] per year 0.983; 95% CI 0.974-0.991) and lower platelet count (aOR per unit 0.996; 95% CI 0.994-0.998). Anti-infectives were the most common causative drug class (40%). Liver-related mortality was more frequent in patients with hepatocellular damage aged ≥65 years (p = 0.0083) and in patients with underlying liver disease (p = 0.0221). Independent predictors of liver-related death/transplantation included nR-based hepatocellular injury, female sex, higher onset aspartate aminotransferase (AST) and bilirubin values. nR-based hepatocellular injury was not associated with 6-month overall mortality, for which comorbidity burden played a more important role. The prognostic capacity of Hy's law varied between causative agents. Empirical therapy (corticosteroids, ursodeoxycholic acid and MARS) was prescribed to 20% of patients. Drug-induced autoimmune hepatitis patients (26 cases) were mainly females (62%) with hepatocellular damage (92%), who more frequently received immunosuppressive therapy (58%). Conclusions: AST elevation at onset is a strong predictor of poor outcome and should be routinely assessed in DILI evaluation. Mortality is higher in older patients with hepatocellular damage and patients with underlying hepatic conditions. The Spanish DILI Registry is a valuable tool in the identification of causative drugs, clinical signatures and prognostic risk factors in DILI and can aid physicians in DILI characterisation and management. Lay summary: Clinical information on drug-induced liver injury (DILI) collected from enrolled patients in the Spanish DILI Registry can guide physicians in the decision-making process. We have found that older patients with hepatocellular type liver injury and patients with additional liver conditions are at a higher risk of mortality. The type of liver injury, patient sex and analytical values of aspartate aminotransferase and total bilirubin can also help predict clinical outcomes