M. Sacco

Impact of viral eradication with sofosbuvir-based therapy on the outcome of post-transplant hepatitis C with severe fibrosis

Several studies have shown that new direct‐acting antivirals maintain their efficacy in liver transplant (LT) recipients with severe hepatitis C virus (HCV) recurrence. We determined the clinical impact of sofosbuvir/ribavirin in LT through the changes in liver function and fibrosis state at 24 and 48 weeks after treatment.

Type 2 diabetes mellitus and chronic hepatitis C: Which is worse? Results of a long-term retrospective cohort study.

BACKGROUND The long-term outcome in patients with chronic hepatitis C and type 2 diabetes mellitus treated with interferon and ribavirin is unclear. We compared incidence of liver-related events and mortality rates between hepatitis C virus-positive patients with or without diabetes mellitus, and the incidence of diabetes-related events between diabetic patients with and without hepatitis C. METHODS Retrospective study of 309 patients with chronic hepatitis C. Incidence of liver-related events, diabetes-related events and mortality rates were assessed over a mean follow-up of 11.02±4.9 years. RESULTS 50 (16%) chronic hepatitis C patients had diabetes mellitus. Diabetics showed a higher number of diabetes- and liver-related events than non-diabetics (10% vs 1.5%, p=0.006; 18% vs 5.7%, p=0.007, respectively) with a mortality of 14% vs 1.5% (p=0.0003). Baseline cirrhosis (p=0.002) and non-sustained virological response (p=0.01) were independent risk factors for liver events; diabetes mellitus (p=0.01) and hypertension (p=0.0017) were independent factors for diabetes-related events. CONCLUSIONS In patients with chronic hepatitis C, comorbidity with diabetes mellitus was associated with a higher mortality rate and incidence of liver/diabetes-related events. Independent risk factors for liver-related events were the non-response to antiviral therapy and cirrhosis at baseline.

Significant improvement of glycemic control in diabetic patients with HCV infection responding to direct-acting antiviral agents

Many studies showed insulin resistance amelioration in HCV‐patients achieving Sustained Virologic Response (SVR) but results on glycemic control in diabetic patients are unclear. This study aimed to assess fasting glucose (FG) and glycated hemoglobin (HbA1c) values before and after therapy with direct‐acting antivirals (DAAs) in HCV‐patients with type 2 diabetes mellitus (T2DM). Of the 122 consecutively recruited patients with chronic hepatitis C and T2DM, 110 patients were treated with DAAs and 12 remained untreated. Clinical, biochemical, virological, and metabolic features were collected both at baseline and at 12 weeks after the end of therapy (EOT) or after a comparable period of time in untreated patients. A total of 101 patients obtained a SVR (Group 1), while nine were relapsers. Group 2 (21 patients) was composed by the nine relapsers and the 12 untreated patients. A significant reduction of mean FG (134.3 ± 41.32 mg/dL vs 152.4 ± 56.40 mg/dL, P = 0.002) and HbA1c values (46.51 ± 16.15 mmoL/moL vs 52.15 ± 15.43 mmoL/moL, P <  0.001) was found in Group 1 but not in Group 2 (140.6 ± 47.87 mg/dL vs. 145.31 ± 30.18 mg/dL, P = 0.707, and 55.31 ± 20.58 mmoL/moL vs. 53.38 ± 9.49 mmoL/moL, P = 0.780). In Group 1, 20.7% of patients could reduce or suspend their antidiabetic therapy compared to none in Group 2 (P = 0.03), despite the significant weight increase observed in Group 1. SVR induced a significant amelioration of glycemic control in diabetic HCV‐patients, despite a significant weight increase; larger prospective studies are needed to verify whether these results are maintained over the long‐term.

Negativization of viremia prior to liver transplant reduces early allograft dysfunction in hepatitis C–positive recipients

Although early allograft dysfunction (EAD) negatively impacts survival from the first months following liver transplantation (LT), direct‐acting antiviral agents (DAAs) have revolutionized hepatitis C virus (HCV) therapy. We investigated the EAD definition best predicting 90‐day graft loss and identified EAD risk factors in HCV‐positive recipients. From November 2002 to June 2016, 603 HCV‐positive patients (hepatocellular carcinoma, 53.4%) underwent a first LT with HCV‐negative donors. The median recipient Model for End‐Stage Liver Disease (MELD) score was 15, and the median donor age was 63 years. At LT, 77 (12.8%) patients were HCV RNA negative; negativization was achieved and maintained by pre‐LT antiviral therapy (61 patients) or pre‐LT plus a pre‐emptive post‐LT course (16 patients); 60 (77.9%) patients received DAAs and 17 (22.1%) interferon. We compared 3 different EAD definitions: (1) bilirubin ≥ 10 mg/dL or international normalized ratio ≥ 1.6 on day 7 after LT or aspartate aminotransferase or alanine aminotransferase > 2000 IU/L within 7 days of LT; (2) bilirubin > 10 mg/dL on days 2‐7 after LT; and (3) MELD ≥ 19 on day 5 after LT. EAD defined by MELD ≥ 19 on day 5 after LT had the lowest negative (0.1) and the highest positive (1.9) likelihood ratio to predict 90‐day graft loss. At 90 days after LT, 9.2% of recipients with EAD lost their graft as opposed to 0.7% of those without EAD (P < 0.001). At multivariate analysis, considering variables available at LT, MELD at LT of >25 (OR = 7.4) or 15‐25 (OR = 3.2), graft macrovesicular steatosis ≥ 30% (OR = 6.7), HCV RNA positive at LT (OR = 2.7), donor age > 70 years (OR = 2.0), earlier LT era (OR = 1.8), and cold ischemia time ≥ 8 hours (OR = 1.8) were significant risk factors for EAD. In conclusion, in HCV‐positive patients, MELD ≥ 19 on day 5 after LT best predicts 90‐day graft loss. Preventing graft infection by pre‐/peri‐LT antiviral therapy reduces EAD incidence and could be most beneficial in high‐MELD patients and recipients of suboptimal grafts. Liver Transplantation 23 915–924 2017 AASLD.