Jérôme Dumortier

Long‐term outcome of patients with hereditary hemorrhagic telangiectasia and severe hepatic involvement after orthotopic liver transplantation: A single‐center study

Hepatic involvement occurs in up to 74% of patients with hereditary hemorrhagic telangiectasia (HHT) and is characterized by a spectrum of arteriovenous malformations. Three different types of intrahepatic shunting may be present: hepatic artery to hepatic veins, hepatic artery to portal vein, and portal vein to hepatic vein. Hepatic involvement in HHT may lead to biliary ischemia, portal hypertension, or high‐output cardiac failure (HOCF). Orthotopic liver transplantation (OLT) has been proposed as the only definitive curative treatment. The aim of this study was to evaluate the long‐term outcome of patients with hepatic involvement due to HHT after OLT with respect to mortality, cardiac and hepatic status, epistaxis, and quality of life. Patients with HHT and severe hepatic vascular malformations who underwent OLT in the Lyon Liver Transplant Unit (LLTU) from 1993 to 2007 were followed at the LLTU and the French Reference Center for HHT. Quality of life was evaluated with the Short Form 36 questionnaire. There were 13 patients who fulfilled the entry criteria of the study (12 women and 1 man). The mean age at the time of OLT was 51.8 years (range = 33‐65 years). Indications for OLT were cardiac failure (n = 9), biliary necrosis (n = 2), both cardiac failure and biliary necrosis (n = 1), and hemobilia (n = 1). The mean duration of follow‐up was 109 months (range = 1‐200 months). Twelve patients (92.3%) are still alive. For the 9 patients with HOCF, the mean cardiac index decreased from 5.4 L/minute/m2 before OLT to 3.0 L/minute/m2 after OLT. No severe hepatic complications were observed after OLT. Nine of the surviving patients (75%) experienced dramatic improvements in epistaxis and quality of life, including an ability to undertake more physical activity. In conclusion, OLT is an important therapeutic option for patients with HHT who have severe hepatic involvement. In the reported cohort, the mortality after OLT for this indication was low. Liver Transpl 16:340–347, 2010.

What is the best alternative to inulin clearance to estimate GFR in patients with decompensated alcoholic cirrhosis

BACKGROUNDnAccurate evaluation of the glomerular filtration rate (GFR) in patients awaiting liver transplantation is important because they have a greater risk of impaired renal function. A major percentage of these patients have alcoholic cirrhosis, and the accuracy of bedside used GFR estimates have not been specifically evaluated in this group. The aim of this study was to evaluate the validity of the simplified Modification of Diet in Renal Diseases (MDRD) and Cockcroft and Gault (CG) formulas in patients with decompensated alcoholic cirrhosis in comparison to inulin clearance as the reference method.nnnMETHODSnGFR estimated by the simplified MDRD and CG formulas were retrospectively compared to the true GFR measured by inulin clearance in a single-centre cohort of 148 patients with decompensated alcoholic cirrhosis.nnnRESULTSnMean ± standard deviation of age, body mass index, inulin clearance and MDRD and CG estimates were 54.4 ± 6.9 years, 26.5 ± 4.7 kg/m(2), 76.9 ± 28.0 mL/min per 1.73 m(2), 99.4 ± 34.0 mL/min per 1.73 m(2) and 98.7 ± 32.0 mL/min per 1.73 m(2), respectively; 70% of the patients had a GFR, measured by inulin clearance, below 90 mL/min per 1.73 m(2). The difference between estimated GFR and true GFR were 23 ± 23 mL/min per 1.73 m(2) for MDRD and 22 ± 20 mL/min per 1.73 m(2) for Cockcroft and Gault.nnnCONCLUSIONSnThe simplified MDRD and CG formulas largely overestimated GFR in patients with decompensated alcoholic cirrhosis. Results of such bedside formulas should be interpreted with caution in these patients.

Sofosbuvir-based antiviral therapy in hepatitis C virus patients with severe renal failure.

BackgroundnChronic hepatitis C virus (HCV) infection is the most common chronic liver disease in patients with end-stage renal disease (ESRD). Over the last few years, second-generation direct-acting antivirals have been revolutionary in the treatment of hepatitis C, and sofosbuvir (SOF) is the backbone of most modern treatment strategies. Since SOF is eliminated through the kidney, the aim of this multicentre retrospective study was to assess its antiviral efficacy and safety in HCV-infected patients with severe renal failure [including haemodialysis (HD) patients].nnnMethodsnFifty patients (36 males, mean age ± standard deviation 60.5 ± 7.5 years) with chronic HCV infection (G1: 28/56%, cirrhosis: 27/54%) and severe renal failure [i.e. MDRD estimated glomerular filtration rate (eGFR) <35 mL/min], including 35 on HD, were enrolled. Antiviral treatment consisted of SOF/ribavirin (RBV) (n = 7), SOF/RBV/pegylated interferon (n = 2), SOF/daclatasvir ± RBV (n = 30) or SOF/simeprevir ± RBV (n = 11) for 12 or 24 weeks. A reduced dose of SOF (400 mg three times a week or 400 mg every other day) was given to all HD patients. Initial dose of RBV (n = 12) ranged from 400 to 4200 mg/week.nnnResultsnOn an intent-to-treat-based analysis, sustained virological response rate was 86% at 12 weeks. During therapy, haemoglobin levels were not significantly modified, but recombinant erythropoietin (rEPO) dose significantly increased in patients treated with RBV. Two patients (4%) required blood transfusion. No patient had treatment discontinuation due to side effects. Dose of RBV was reduced in two patients (16.7%) during antiviral therapy. Dose of SOF was reduced in two non-HD patients because of side effects. In non-HD patients, median eGFR was not significantly modified during treatment.nnnConclusionsnOur results strongly suggest that SOF-based antiviral therapy, with a reduced dose of SOF, is safe and effective for the treatment of HCV patients with ESRD, including HD patients.

Adjuvant Intraarterial Lipiodol or 131 I-Lipiodol After Curative Treatment of Hepatocellular Carcinoma: A Prospective Randomized Trial

The prevention of tumor recurrence after curative treatment of hepatocellular carcinoma (HCC) is unresolved. Postoperative intraarterial injection of 131I-labeled lipiodol has been proposed as adjuvant treatment. The aim of this prospective randomized trial was to evaluate if a single dose of postoperative adjuvant intraarterial 131I-lipiodol (vs. unlabeled lipiodol) could reduce the rate of intrahepatic recurrence at 2 y. Methods: Patients who underwent curative treatment for HCC and recovered within 6 wk were randomly assigned to receive a single 2,200-MBq 131I-lipiodol dose or a single unlabeled lipiodol dose on a 1:1 basis. Recurrence-free and overall survival rates were analyzed. Results: Between June 2005 and February 2009, we included 58 patients (median age of 63 y [range, 23–85 y]): 29 received intraarterial 131I-lipiodol and 29 received lipiodol adjuvant treatment. At 2 y after treatment, the rate of patients with intrahepatic recurrence was 28% in the 131I-lipiodol group and 56% in the lipiodol group (P = 0.0449). The Kaplan–Meier analysis confirmed this result, with a 2-y recurrence-free survival in the 131I-lipiodol and lipiodol groups of 73% and 45%, respectively (P = 0.0259). The 5-y recurrence-free survival rates in the 131I-lipiodol and lipiodol groups were 40% and 0%, respectively (P = 0.0184). The overall and specific survivals were not significantly different between groups (P = 0.9378 and P = 0.1339, respectively). 131I-lipiodol had no severe toxic effects. Conclusion: After curative treatment of patients with HCC, one 2,200-MBq dose of intraarterial 131I-lipiodol significantly decreased the rate of intrahepatic recurrence but failed to improve overall or specific survival.