Bruna Lavezzo

Treatment of recurrent hepatitis C in liver transplants: efficacy of a six versus a twelve month course of interferon alfa 2b with ribavirin ☆

BACKGROUND/AIMS Interferon (IFN) with ribavirin combination therapy (CT) was proposed for the treatment of hepatitis C recurring in liver transplants. We assessed the efficacy of two protocols of CT in transplanted patients with recurrent severe hepatitis C virus (HCV) hepatitis. METHODS Fifty-seven patients (68% genotype 1b) were treated with IFN alfa-2b 3 million units three times weekly and oral ribavirin 800mg/die for 6 or 12 months. Study end-points were the end of treatment (ETVR) and the 12-month post-therapy sustained virologic response (SVR; negative HCV-RNA). RESULTS ETVR was induced in 9/27 (33%) and in 7/30 patients (23%) treated, respectively, for 6 and 12 months (P=0.4); a SVR was induced in six (22%) of the former and five (17%) of the latter (P=0.4). HCV genotype non-1 patients responded better than genotype 1 (SVR: 43% in genotype non-1 versus 12% in genotype 1, P: 0.02). In ETV responders the hepatitis activity index improved by >2 points in biopsies taken after therapy compared to pre-therapy biopsies. Anemia and leukopenia required reduction of therapy in 51% of the patients. CONCLUSIONS CT is efficacious in controlling HCV disease in about 20% of transplants with recurrent hepatitis C. Six months of therapy are as efficacious as 12 months.

Effect of macrovescicular steatosis and other donor and recipient characteristics on the outcome of liver transplantation

The influence of steatosis and of other donor and recipient characteristics in affecting liver performance post‐orthotopic liver transplantation (OLT) was evaluated in 311 consecutive liver transplantations made in 278 patients. Donor variables considered were age, sex, blood group, cause of death, intensive care unit (ICU) days, need for vasopressors, hepatic enzymes and bilirubin, total and warm ischemia time, and macro‐ and microvescicular steatosis. Recipient variables considered were age, sex, blood group, biliary output, and post‐OLT peak levels of hepatic enzymes. Patient and graft survival were the main outcome indicators. 
In the multivariate analysis, macrovescicular steatosis involving 25% or more of the hepatocytes was the only variable independently associated with shorter patient survival (p<0.05). Five (62.5%) of the eight livers with macrovescicular steatosis involving 25% or more of the hepatocytes incurred in a delayed non‐function (DNF) and one (12.5%) in a primary non‐function (PRNF). The incidence of DNF and PRNF in the group with macrovescicular steatosis involving less than 25% of the liver cells was 1.6% (p<0.001) and 2.3%, respectively. Microvescicular steatosis of any degree was not associated with a worse prognosis. 
Macrovescicular steatosis involving 25% or more of the hepatocytes identifies marginal livers, the use of which significantly increases the risk of graft non‐function post‐OLT.

The first one thousand liver transplants in Turin: a single-center experience in Italy

The first Italian liver transplant center to reach the goal of 1000 procedures was Turin. The paper reports this single‐center experience, highlighting the main changes that have occurred over time. From 1990 to 2002, 1000 consecutive liver transplants were performed in 910 patients, mainly cirrhotics. Surgical technique was based on the preservation of the retrohepatic vena cava of the recipient. The veno‐venous bypass was used in 30 cases only and abandoned since 1997. Operating time, warm ischemia time and length of hospital stay significantly decreased over the years, while operating room extubation became routine. Immunosuppression pivoted on cyclosporine A. Management of retransplantations, marginal grafts, and of HCV‐positive, HBV‐positive and hepatocellular carcinoma recipients were optimized. Median follow‐up of the patients was 41 months. Overall survival rates at 1, 5 and 10 years were 87%, 78% and 72% respectively. Survival rates obtained in the second half of the cases (1999–2002 period) were significantly better than those obtained in the first half (1990–1998 period) (90% vs. 83% at 1 year and 81% vs. 76% at 5 years respectively). Increasing experience in liver transplant surgery and postoperative care allowed standardization of the procedure and expansion of the activity, with parallel improvement of the results.

Treatment of recurrent hepatitis C virus infection after liver transplantation.

Therapeutic strategies were designed based on experience from the treatment options of the last 10 years in the ordinary clinical setting. Interferon was the first treatment used. This monotherapy was discontinued with the arrival of ribavirin. Ribavirin monotherapy has also been shown to have a limited effect and in recent years the combination of interferon and ribavirin has become the first line therapy.

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.

Hypothermic oxygenated machine perfusion for liver transplantation: An initial experience

OBJECTIVES Due to widespread exploitation of extended criteria donors, machine perfusion is emerging as an alternative to static cold storage for organ preservation. Hypothermic oxygenated machine perfusion has been associated with improved outcomes after liver transplant, both in laboratory and clinical settings. Here, we present our initial experience with hypothermic oxygenated machine perfusion, evaluating incidence of postreperfusion syndrome, early allograft dysfunction, and long-term biliary complications. MATERIALS AND METHODS End-ischemic dual (hepatic artery and portal vein) hypothermic oxygenated machine perfusion was carried out for 150 to 200 minutes before organ implantation in 4 liver transplants considered at increased risk due to donor, recipient, or matching issues. RESULTS No device malfunction occurred. Theatre logistics were minimally affected. Incidences of post-reperfusion syndrome and early allograft dysfunction were 25% and 50%. At 6-month follow-up, all patients were alive with normal hepatic function and no evidence of ischemic cholangiopathy. CONCLUSIONS In our experience, hypothermic oxygenated machine perfusion appeared safe and logistically simple. Further studies are needed to assess the real value of this technique and to identify which subset of patients would benefit from its implementation.