Hepatitis C virus eradication with direct-acting antiviral improves insulin resistance.

Sustained virological response (SVR) after interferon-based therapy is associated with improvement of insulin resistance (IR) in HCV-infected patients. Few data are available in the direct-acting antivirals (DAAs) era, especially in cirrhotic patients. We prospectively evaluated the long-term effect of DAAs on IR. Patients treated with DAAs between May 2015 and December 2016 in 3 tertiary care centres were recruited. Patients with diabetes were excluded. Biochemical and virological data were collected at baseline, 12/24/48 weeks (W) after the end of therapy (EOT). Presence of IR was defined by a 'homeostasis model assessment index for IR' [HOMA-IR])> 2.5. Liver fibroscan was performed at baseline, at 24/48W after EOT. Hundred and thirty-eight patients were enrolled (mean age 58 years, M/F 85/53, GT1 61%, 68.8% cirrhotic). Sixty-eight patients (94/138) had IR. Patients with IR had significantly higher stiffness than patients without it (23 ± 12 vs 15 ± 8; P < .0001). SVR12 was achieved in 135 (98%) patients, and 124 (90%) patients reached the 48W post-EOT. At this time point, the percentage of patients with IR significantly decreased to 49% (P = 0,01). HOMA-IR was significantly lower than baseline (1.8 vs 3; P < .001), and this was related to a significant reduction of insulin level (11.7 ± 6.3 vs 16.4 ± 8.3). High BMI was associated with a significantly lower probability of achieving a non-IR status at 24W (P = .05) and 48W (P = .03).In conclusion, SVR following DAAs led to a significant reduction of IR, even in patients with cirrhosis. Nevertheless, IR can persist after the achievement of SVR, especially in patients with high BMI.

New Perspectives on Treatment of Hepatitis B Before and After Liver Transplantation.

The hepatitis B virus (HBV) infects more than 260 million people globally, with increasing incidence, especially in developing countries. Despite antiviral therapies, HBV-related end-stage liver disease remains one of the most important indications for liver transplantation worldwide. Although new available treatments have improved the outcome of patients with both compensated and decompensated liver disease in some specific clinical settings as acute-on-chronic liver failure mortality is still high. Moreover, the incidence of HBV-related hepatocellular carcinoma (HCC) seems to be increasing and represents a major challenge for the transplant team. In the post-transplant setting, combination of anti-HBV immunoglobulins and oral nucleos(t)ides provided significant improvement on graft and patient survival. Furthermore, recent data suggested the possibility of personalized therapeutic algorithms based on pre and post-transplant viral and host risk factors. Finally, liver grafts from HBV core antibody (anti-HBc) positive or hepatitis B surface antigen (HBsAg) donors can be safely used in order to expand the donor pool, considering adequate allocation and tailored prophylaxis after LT. In this review we have focused on the evolution of antiviral therapy for HBV, highlighting useful information to aid the transplant hepatologist in clinical practice.

Liver transplantation for viral hepatitis in 2015.

Liver transplantation (LT) is a life-saving treatment for patients with end-stage liver disease and for patients with liver cell cancer related to liver disease. Acute and chronic liver diseases related to hepatitis viruses are between the main indications for liver transplantation. The risk of viral reinfection after transplantation is the main limiting factor in these indications. Before the availability of antiviral prophylaxis, hepatitis B virus (HBV) recurrence was universal in patients who were HBV DNA-positive before transplantation. The natural history of recurrent HBV was accelerated by immunosuppression, and it progressed rapidly to graft failure and death. Introduction of post-transplant prophylaxis with immunoglobulin alone first, and associated to antiviral drugs later, drastically reduced HBV recurrence, resulting in excellent long-term outcomes. On the contrary, recurrence of hepatitis C is the main cause of graft loss in most transplant programs. Overall, patient and graft survival after LT for hepatitis C virus (HCV)-associated cirrhosis is inferior compared with other indications. However, successful pretransplant or post transplant antiviral therapy has been associated with increased graft and overall survival. Until recently, the combination of pegylated interferon and ribavirin was the standard of care for the treatment of patients with chronic hepatitis C. Highly active antiviral compounds have been developed over the past decade, thanks to new in vitro systems to study HCV entry, replication, assembly, and release.

Head and neck and esophageal cancers after liver transplant: results from a multicenter cohort study. Italy, 1997-2010.

This study quantified the risk of head and neck (HN) and esophageal cancers in 2770 Italian liver transplant (LT) recipients. A total of 186 post-transplant cancers were diagnosed-including 32 cases of HN cancers and nine cases of esophageal carcinoma. The 10-year cumulative risk for HN and esophageal carcinoma was 2.59%. Overall, HN cancers were nearly fivefold more frequent in LT recipients than expected (standardized incidence ratios - SIR=4.7, 95% CI: 3.2-6.6), while esophageal carcinoma was ninefold more frequent (SIR=9.1, 95% CI: 4.1-17.2). SIRs ranged from 11.8 in LT with alcoholic liver disease (ALD) to 1.8 for LT without ALD for HN cancers, and from 23.7 to 2.9, respectively, for esophageal carcinoma. Particularly elevated SIRs in LT with ALD were noted for carcinomas of tongue (23.0) or larynx (13.7). Our findings confirmed and quantified the large cancer excess risk in LT recipients with ALD. The risk magnitude and the prevalence of ALD herein documented stress the need of timely and specifically organized programs for the early diagnosis of cancer among LT recipients, particularly for high-risk recipients like those with ALD.