A randomized, controlled study to assess the conversion from calcineurin-inhibitors to everolimus after liver transplantation--PROTECT.

Posttransplant immunosuppression with calcineurin inhibitors (CNIs) is associated with impaired renal function, while mTor inhibitors such as everolimus may provide a renal-sparing alternative. In this randomized 1-year study in patients with liver transplantation (LTx), we sought to assess the effects of everolimus on glomerular filtration rate (GFR) after conversion from CNIs compared to continued CNI treatment. Eligible study patients received basiliximab induction, CNI with/without corticosteroids for 4 weeks post-LTx, and were then randomized (if GFR > 50 mL/min) to continued CNIs (N = 102) or subsequent conversion to EVR (N = 101). Mean calculated GFR 11 months postrandomization (ITT population) revealed no significant difference between treatments using the Cockcroft-Gault formula (-2.9 mL/min in favor of EVR, 95%-CI: [-10.659; 4.814], p = 0.46), whereas use of the MDRD formula showed superiority for EVR (-7.8 mL/min, 95%-CI: [-14.366; -1.191], p = 0.021). Rates of mortality (EVR: 4.2% vs. CNI: 4.1%), biopsy-proven acute rejection (17.7% vs. 15.3%), and efficacy failure (20.8% vs. 20.4%) were similar. Infections, leukocytopenia, hyperlipidemia and treatment discontinuations occurred more frequently in the EVR group. No hepatic artery thrombosis and no excess of wound healing impairment were noted. Conversion from CNI-based to EVR-based immunosuppression proved to be a safe alternative post-LTx that deserves further investigation in terms of nephroprotection.

[Antibiotic prophylaxis in liver cirrhosis]. / Antibioprophylaxie de la péritonite bactérienne spontanée.

Bacterial infections are frequent and severe complications in patients with cirrhosis. Spontaneous bacterial peritonitis (SBP) is the most common infection in such patients. The risk of recurrence at one year after a first episode of SBP is higher than 70% and hospital mortality is estimated between 30-50%. Therefore, there is growing interest in antibiotic prophylaxis (ATP) in these patients. Risk factors for the occurrence of SBP include low protein level in ascitis, a history of previous SBP and an episode of gastrointestinal bleeding. In all three situations, the indication of ATP, reviewed in this paper, is recognized and improves survival.

Pegylated interferon-alpha2a/ribavirin treatment of recurrent hepatitis C after liver transplantation.

Hepatitis C virus (HCV) infection invariably recurs after liver transplantation (LT), leading to significant morbidity and mortality. Although the combination of pegylated interferon-alpha (IFN-alpha)/ribavirin is the preferred treatment for these patients, the optimal schedule remains undetermined. In an uncontrolled trial, 19 patients with HCV infection recurring after LT received pegylated IFN-alpha(2a), 180 mug weekly, and ribavirin, 10 mg/kg body weight daily, for 48 weeks. The proportion of patients with undetectable HCV RNA in their serum after 12 weeks of treatment was 53%. Five patients (26%) dropped out of the study due to intolerance (in 2 cases), depression (in 1), or infectious complications (in 2). A sustained virological response (SVR), defined as undetectable serum HCV RNA 24 weeks after the end of treatment, was observed in 9/19 patients (47%). SVR was associated with an early virological response after 12 weeks of therapy (P<0.001) and a treatment duration >80% (P=0.02), but not with baseline HCV RNA level or a cumulative dose of pegylated IFN-alpha(2a) or ribavirin >80% of the scheduled dose. All 4 patients with genotype 2 or 3 reached SVR, as compared with 33% of patients with genotype 1 or 4 (P=0.03). A 48-week course of pegylated IFN-alpha(2a)/ribavirin therapy is effective in patients with recurrent HCV infection after LT.

[Management of patients after liver transplantation]. / Suivi pratique des patients après transplantation hépatique.

The success of liver transplantation essentially depends on the prevention and treatment of long term complications, which may be due to surgery, opportunistic infections, organ rejection and relapse of the initial liver disease. The side effects of immunosuppressive drugs--arterial hypertension, glucose intolerance and diabetes, dyslipidemia and obesity, renal failure, osteoporosis, malignancy, and anaemia--should be regularly screened and treated without delay. Surgical procedures in transplanted patients are safe and rarely followed by complications. Although pregnancy in this setting is considered at risk, because of prematurity and low birth weight, overall outcomes are favourable. The yearly influenza vaccination is strongly recommended. The survival and the quality of life of liver transplant patients also depend on a good communication between the general practitioner and the transplantation centre.

[New aspect in the treatment of chronic hepatis B]. / Traitement de l'hépatite B chronique: ça bouge!

The pegylated interferon is now the first choice of treatment for patients without a counter-indication. The association of this treatment with lamivudine does not increase the effectiveness. For patients non-responders to the PEG-IFN or presenting counter-indications, the long-term administration of lamivudine is limited by the frequent appearance of mutations, so that escape from the treatment requires the use of other antivirals. Adefovir is currently the treatment of choice in the event of resistance to lamivudine. Its effectiveness is confirmed by many studies and the risk of emergence of resistance is very low. Entecavir is a selective inhibitor of polymerase HBV and shows a better efficacy than lamivudine. It is well tolerated and is associated only with a weak risk of resistance, even after a prolonged treatment.

Treatment of hepatocellular carcinoma at the dawn of the third millennium: liver transplantation and its alternatives.

Hepatocellular carcinoma is one of the most frequent tumors worldwide, and its frequency is increasing. The management of hepatocellular carcinoma has changed in recent years, this because screening allows to discover tumors at an earlier stage, and because of effective treatments are available, such as liver transplantation, liver resection, percutaneous ablation and transarterial chemoembolization. Each one of these treatments has its own advantages and drawbacks, and range of application according to the stage of the tumor and of the underlying liver disease. This review summarizes the recent progress in the management of HCC and the practice in our unit.

Adult-to-adult living-donor liver transplantation. A summary of current status and an outline of the program in Geneva.

Living donor liver transplantation is a relatively new procedure in which the right side of the liver is harvested in a healthy donor and transplanted into a recipient. After the first case in 1994, over 3000 cases have been done worldwide. This review summarizes the reasons why the procedure is needed, describes its main technical aspects, highlights the boundaries in which it can be done safely, summarizes the current experience worldwide and describes the main points of the program in our unit. We argue that living-donor transplantation is a viable alternative to a long time on the waiting list for several patients, and it can be performed safely and successfully provided that all precautions are undertaken to minimize the risks in the donor and to increase the chances of a good outcome in the recipients. If these prerequisites are met, and within the framework of a structured multidisciplinary program, we believe that living-donor liver transplantation should be funded by health insurances as a recognized therapeutic option.

Procalcitonin is not an accurate marker of spontaneous bacterial peritonitis in patients with cirrhosis.

BACKGROUND/AIMS: The clinical features of peritonitis are usually absent in cirrhotic patients with an ascitic fluid infection, raising the interest for specific biological markers of inflammation. METHODOLOGY: We prospectively measured the plasma and ascitic fluid levels of procalcitonin, an innovative infection parameter, interleukin-6, and C-reactive protein in 20 cirrhotics with or without spontaneous bacterial peritonitis. The patient's condition was followed-up for 12 weeks after paracentesis. RESULTS: None of the 10 patients with spontaneous bacterial peritonitis presented with severe systemic signs of infection. Procalcitonin level in plasma, but not in ascites, was significantly higher in patients with spontaneous bacterial peritonitis compared to controls (0.74 +/- 0.6 vs. 0.2 +/- 0.1 ng/mL, P < 0.05). Interleukin-6 levels in ascites were similar between groups. C-reactive protein concentrations were higher both in plasma and in ascitic fluid in patients with spontaneous bacterial peritonitis compared to controls (85.3 +/- 63 vs. 18.6 +/- 19 mg/dL, 24.6 +/- 25 vs. 4.5 +/- 4 mg/dL, P < 0.05, respectively). Three patients with spontaneous bacterial peritonitis died, but the outcome was not related to the concentrations of biological markers. CONCLUSIONS: In spontaneous bacterial peritonitis, procalcitonin measurement is not an accurate diagnostic test, possibly due to the absence of systemic inflammatory response syndrome in this condition. In addition, the diagnostic value of C-reactive protein is limited by the wide overlap between values.