Silvia Martini

Prevention of hepatitis C recurrence by bridging sofosbuvir/ribavirin from pre to post liver transplant: a real life strategy

Hepatitis C virus (HCV) re‐infection following liver transplant (LT) is associated with reduced graft and patient survival. Before transplant, Sofosbuvir/Ribavirin (SOF/R) treatment prevents recurrent HCV in 96% of those patients achieving viral suppression for at least 4 weeks before transplant. We evaluated whether a bridging SOF‐regimen from pre‐ to post‐transplant is safe and effective to prevent HCV recurrence in those patients with less than 4 weeks of HCV‐RNA undetectability at the time of transplant.

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.

Transcatheter arterial chemoembolization for hepatocellular carcinoma in cirrhosis: influence on portal hypertension.

Background Transcatheter arterial chemoembolization (TACE) is a routine treatment for hepatocellular carcinoma in cirrhotic patients. Whether TACE influences the degree of portal hypertension remains uncertain. Aim and Patients We retrospectively analyzed the clinical course of 283 TACE to investigate the incidence of variceal bleeding and ascites after the procedure. We also prospectively evaluated portal pressure by hepatic venous portal gradient (HVPG) before and within 3 days by TACE in a group of 15 patients. Results Before TACE, esophageal varices were present in 125 patients. Variceal bleeding occurred in three (1.5%) and ascites in two (1%) patients during the follow-up post-TACE. Patients with variceal bleeding were significantly older (P=0.019). In 15 patients who underwent portal pressure measurement before and within 3 days by TACE, HVPG was unchanged (mean 13.1 vs. 12.8 mmHg, P>0.05). Conclusion In our series portal hypertension-related complications after TACE were rare and did not result in higher mortality. As TACE did not influence HVPG, the preventive ligation of esophageal varices before TACE does not seem justified.

The Italian compassionate use of sofosbuvir in HCV patients waitlisted for liver transplantation: A national real-life experience

This study aimed to assess the real‐life clinical and virological outcomes of HCV waitlisted patients for liver transplantation (LT) who received sofosbuvir/ribavirin (SOF/R) within the Italian compassionate use program.

Delisting HCV-infected liver transplant candidates who improved after viral eradication: Outcome 2 years after delisting

Treating patients with decompensated cirrhosis with direct‐acting antiviral (DAA) therapy while on the waiting list for liver transplantation results in substantial improvement of liver function allowing 1 in 4 patients to be removed from the waiting list or delisted, as reported in a previous study promoted by the European Liver and Intestine Transplant Association (ELITA). The aim of this study was to report on clinical outcomes of delisted patients, including mortality risk, hepatocellular carcinoma development and clinical decompensation requiring relisting.

Are immunoglobulins against the HBsAg still needed in liver transplantation for hepatitis D

In the October issue of the Journal, Dr. Fung and colleagues have reported excellent results with entecavir alone in the post–liver transplant prophylaxis of hepatitis B virus (HBV) reinfection, prompting Dr. Gane to conclude in his Editorial that entecavir monotherapy should be generally adopted as hepatitis B immunoglobulins (HBIG)-free antiviral prophylaxis to prevent HBV recurrence. A proportion of the hepatitis B surface antigen (HBsAg)-positive transplants have disease caused by the hepatitis D virus (HDV), not by the HBV; the latter provides to the former biological support to thrive, but remains a bystander with no pathogenic impact throughout most HDV infections. Given that there is no therapy against HDV, the combination of HBIG with HBV antivirals has been adopted by default as prophylaxis against HDV reinfection, with excellent results. The paper by Fung raises nevertheless the issue whether monotherapy with HBV antivirals could be equally efficacious after liver transplantation, dispensing with the cost and inconvenience of the administration of the HBIG. In principle, this approach would seem dangerous as the HDV is thought to require only HBsAg to coat its virion. Entecavir and other HBV antivirals do not interfere with HBsAg, and in Fung’s study the HBsAg antigen persisted in serum of around 15% of the recipients. However, in contrast to this theoretical concern, 81 HDV transplants were given in recent years’ longterm prophylaxis with antivirals only, in monotherapy or in various combinations, right from surgery or after a short course of concomitant HBIG (Table 1). The patients were followed up to 20 years. Remarkably, only 1 of the 81 (1.2%) recipients experienced a relapse of HBV/HDV disease; and in the report by } Ocal (Table 1), HBs antigenemia became detectable in the blood of 6 patients, none of whom had a disease relapse. These data would suggest that, to recur in the liver graft, the HDV must be rescued by a reactivation of the HBV infection, an event which is of course preventable with HBV antivirals. Interestingly, in a recent case report from Japan, HDV infection recurred in association with an HBV flare several years after grafting, at a time when HBV antiviral therapy had been discontinued. This evidence calls for the consideration of monotherapy with HBV antivirals as an equally efficacious, but cheaper, prophylaxis also against HDV reinfection.