Risk Factors for Liver Decompensation and HCC in HCV-Cirrhotic Patients after DAAs: A Multicenter Prospective Study

Background: Prospective studies on predictors of liver-related events in cirrhotic subjects achieving SVR after DAAs are lacking. Methods: We prospectively enrolled HCV cirrhotic patients in four Italian centers between November 2015 and October 2017. SVR and no-SVR cases were compared according to the presence or absence of liver-related events during a 24-month follow-up. Independent predictors of liver-related events were evaluated by Cox regression analysis. Results: A total of 706 subjects started DAAs therapy. SVR was confirmed in 687 (97.3%). A total of 61 subjects (8.9%) in the SVR group and 5 (26.3%) in the no-SVR group had liver-related events (p 20 KPa (HR 7.2; 95% CI 1.9-26.7) was the sole independent predictor of HCC. A decrease in liver stiffness (Delta LSM) by at least 20% at the end of follow-up was not associated with a decreased risk of liver-related events. Conclusion: Baseline LSM ≥ 20 kPa identifies HCV cirrhotic subjects at higher risk of liver-related events after SVR

The clinicopathological spectrum of COVID-19-associated cutaneous manifestations: an Italian multicenter study of 197 adult patients

Background: COronaVIrus Disease 19 (COVID-19) is associated with a wide spectrum of skin manifestations. Objective: To describe clinical and histopathological findings of COVID-19-associated cutaneous manifestations and to explore the relationship between cutaneous phenotypes and systemic findings of COVID-19. Methods: Twenty Italian Dermatology Units were asked to gather demographic, clinical and histopathological data of patients with COVID-19-associated skin manifestations. Results: Data of 197 patients with COVID-19-related dermatologic manifestations were collected. The most frequent cutaneous phenotypes were the confluent erythematous/maculo-papular/morbilliform rash (n=54; 27.4%) and chilblain-like acral pattern (n=50; 25.4%). Chilblain-like acral pattern, which were more frequent in young patients, was positively associated with the asymptomatic status (φ= 0.55; p< 0.0001) and negatively associated with disease severity (φ= -0.33; p< 0.0001). On histopathology, microthrombi were a hallmark of the vasculopathic/vasculitic pattern, including chilblain-like acral pattern, purpuric "vasculitic" pattern and livedo reticularis/racemosa-like pattern. Limitations: The retrospective nature of the study made it difficult to collect histopathological data in all cases. Laboratory confirmation of COVID-19 was not possible in every patient. Conclusions: Six main clinicopathological phenotypes of COVID-19-associated skin manifestations have been identified. Further studies are needed to better characterize the pathomechanisms underlying these cutaneous phenotypes and their relationship with the extracutaneous manifestations.

Predictors of serious adverse events and non-response in cirrhotic patients with primary biliary cholangitis treated with obeticholic acid

Background & Aims Obeticholic acid (OCA) has recently been restricted in patients with primary biliary cholangitis (PBC) with "advanced cirrhosis" because of its narrow therapeutic index. We aimed to better define the predicting factors of hepatic serious adverse events (SAEs) and non-response in cirrhotic patients undergoing OCA therapy. Methods Safety and efficacy of treatment were evaluated in a cohort of consecutive PBC cirrhotic patients started with OCA. OCA response was evaluated according to the Poise criteria. Risk factors for hepatic SAEs and non-response were reported as risk ratios (RR) with 95% confidence intervals (CIs). Results One hundred PBC cirrhotics were included, 97 Child-Pugh class A and 3 class B. Thirty-one had oesophageal varices and 5 had a history of ascites. Thirty-three per cent and 32% of patients achieved a biochemical response at 6 and 12 months respectively. Male sex (adjusted-RR 1.75, 95%CI 1.42-2.12), INR (1.37, 1.00-1.87), Child-Pugh score (1.79, 1.28-2.50), MELD (1.17, 1.04-1.30) and bilirubin (1.83, 1.11-3.01) were independently associated with non-response to OCA. Twenty-two patients discontinued OCA within 12 months: 10 for pruritus, 9 for hepatic SAEs (5 for jaundice and/or ascitic decompensation; 4 for upper digestive bleeding). INR (adjusted-RR 1.91, 95%CI 1.10-3.36), lower albumin levels (0.18, 0.06-0.51), Child-Pugh score (2.43, 1.50-4.04), history of ascites (3.5, 1.85-6.5) and bilirubin (1.30, 1.05-1.56), were associated with hepatic SAEs. A total bilirubin >= 1.4 mg/dl at baseline was the most accurate biochemical predictor of hepatic SAEs under OCA. Conclusions An accurate baseline assessment is crucial to select cirrhotic patients who can benefit from OCA. Although OCA is effective in one third of cirrhotics, bilirubin level >= 1.4 mg/dl should discourage from its use