Interactions between virus-related factors and post-transplant ascites in patients with hepatitis C and no cirrhosis: role of cryoglobulinemia.

Refractory ascites may appear in liver transplant recipients with recurrence of hepatitis C virus infection, even in the absence of advanced fibrosis. The mechanisms are unclear. The aim was to determine whether post-transplant cryoglobulinemia could be a predisposing factor for ascites in this population. Retrospective data of 82 liver transplant recipients with HCV recurrence surviving more than 1 year were collected. Cryoglobulinemia was systematically tested after transplantation. All patients had 1-year protocol biopsy with assessment of sinusoidal distension, perisinusoidal fibrosis, and centrolobular necrosis. Additional biopsies were performed when needed. Fourteen of 82 patients (17%) developed refractory ascites. When ascites appeared, fibrosis was stage F0-F1 in 36% and F2-F3 in 57%. Factors independently associated with post-transplant ascites were pretransplant refractory ascites (P = 0.001), fibrosis ≥stage 2 at 1 year (P = 0.002), perisinusoidal fibrosis at 1 year (P = 0.02), and positive cryoglobulinemia (P = 0.02). Patients with ascites had a significantly worse prognosis compared to those without ascites. Refractory ascites may occur in liver transplant recipients with HCV recurrence in the absence of advanced fibrosis. The finding that both positive cryoglobulinemia and perisinusoidal fibrosis at 1 year were significantly associated with ascites suggests that liver microangiopathy is involved in the mechanisms of HCV-related ascites.

[Hepatitis C and liver transplantation: fibrosis progression and treatment. Or how to improve management]. / Hépatite C et transplantation hépatique. Histoire naturelle et traitement ou comment améliorer la prise en charge?

Hepatitis C virus-related end-stage liver disease, alone or in combination with alcohol, has become the leading indication for liver transplantation in most transplant programs accounting for approximately half of transplants performed in European centers. Hepatitis C virus infection recurs virtually in every post-transplant patient. The natural history of hepatitis C after liver transplantation is variable. Progression of chronic hepatitis C virus is more aggressive after liver transplantation with a cumulative probability of developing graft cirrhosis estimated to reach 30% at 5 years. Approximately 10% of the patients with recurrent disease will die or require re-transplantation within 5 years post-transplantation. Several factors, including those related to the virus, the host, the environment and the donor, are probably implicated in the outcome. The immune status represents the main significant variable in influencing disease severity in hepatitis C virus-infected patients; with higher HCV viral load and the significant association described between the degree of immunosuppression and disease severity. Interventions to prevent, improve, or halt the recurrence of hepatitis C virus infection have been evaluated by multiple small studies worldwide with similar overall rates of virological clearance of approximately 9-30%. Current consensus recommends combination therapy with pegylated interferon and ribavirin for those patients with histological recurrence of hepatitis C virus infection and fibrosis. Therapy is adjusted to tolerance and rescued with granulocyte colony-stimulating factor and erythropoietin for bone marrow suppression. In this article we present a comprehensive review of post-transplant hepatitis C virus infection; in particular fibrosis progression and the major challenges according to treatment.

Solitary pulmonary metastasis arising thirteen years after liver transplantation for HBV-related hepatocellular carcinoma.

We described a 59-year-old male patient who underwent liver transplantation in 1989 for hepatocellular carcinoma (HCC) complicating hepatitis B virus (HBV) cirrhosis. In 2001 (12 years after liver transplantation), he developed a lung metastasis of HCC without intrahepatic recurrence and the resection was done. In July 2003, he was symptom free without any recurrence. HCC metastasis can develop even after a very long time of liver transplantation. Many HCCs grow slowly, and the growth rate of recurrent tumors in patients receiving immunosuppressive therapy is significantly greater than that of those who do not receive immunosuppressive therapy.

Usefulness of routine analysis of ascitic fluid at the time of therapeutic paracentesis in asymptomatic outpatients. Results of a multicenter prospective study.

AIM: The guidelines of the American Association for the Study of Liver Diseases recommend performing exploratory paracentesis on each patient with cirrhosis and chronic ascites. The aim of the study was to evaluate the prevalence of spontaneous bacterial peritonitis and culture-negative neutrocytic ascites in a large population of consecutive asymptomatic cirrhotic ascitic ambulatory patients. METHODS: Patients with cirrhosis and tense ascites hospitalized from January to September 2000 in 5 hepatogastroenterology units prospectively underwent an exploratory paracentesis with cytobacteriological, biochemical and bedside inoculation into aerobic and anaerobic blood culture bottles. Patients studied were not receiving antibiotics except for norfloxacin and had no obvious sign of infection such as fever or hypothermia, chills, unusual abdominal tenderness, de novo or worsening hepatic encephalopathy, recent gastrointestinal bleeding, acute renal failure or marked arterial hypotension. Clinical and biological findings and ascitic fluid cytological and bacteriological results were evaluated at each exploratory paracentesis. The results are given in mean +/- standards deviations with range. RESULTS: Sixty-seven cirrhotic patients (48M/19F, mean age 59 +/- 9 years) had 270 therapeutic paracenteses, preceded by an exploratory aspiration. Fifty-nine patients (88%) had alcoholic cirrhosis. Twenty-five patients (37.3%) received norfloxacin. At first paracentesis 41 (61.2%) and 26 (38.8%) patients were class B and C respectively according to the Child-Pugh classification; the mean Child-Pugh score was 9 +/- 1.5. None had suspicion of infection. The mean number of paracenteses was 5 +/- 4.3 per patient; 59.6% of the paracenteses (161) were compensated with human albumin. Ascitic protein concentration was 17.5 +/- 8.6 g/l, ascitic fluid cell count and number of neutrophils were 127 +/- 155/mm3 and 5.9 +/- 14/mm3 (0-60), respectively. No patient had spontaneous bacterial peritonitis nor culture-negative neutrocytic ascites; 10 cases of monomicrobial bacterascites were observed, all with commensal germs. CONCLUSIONS: In the absence of obvious signs of infection, the prevalence of spontaneous bacterial peritonitis and culture-negative neutrocytic ascites in asymptomatic cirrhotic outpatients with ascites is near 0%. Moreover, for 100 large volume paracenteses, not performing exploratory paracentesis corresponds to a savings of 5,500 euros, without risk for these patients.