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We conducted a study to evaluate the efficacy of pegylated interferon/ribavirin in patients who did not respond to previous posttransplant recurrent HCV treatment with IFN/ribavirin combination. Twenty-seven patients were consecutively included in this study and retreated with pegylated interferon alfa-2b (1.5 microg/kg/week) with ribavirin (800-1000 mg daily) for 48 weeks for genotype 1 and 4 and 24 weeks for other genotypes. We compared them with 21 untreated patients enrolled during the same period. Primary endpoint was the SVR and secondary endpoint was histological evaluation 24 weeks after ending therapy. Twenty-seven patients started therapy but 2 (7%) stopped because of side effects. On an intent-to-treat basis, eight patients (30%) had an SVR. Cyclosporine as immunosuppressive therapy during antiviral therapy (p = 0.03) and EVR (p = 0.02) were significantly associated with viral clearance. In 46 patients in whom paired graft biopsies were available, fibrosis score was improved in 76% of treated patients versus 5% in untreated patients. Among treated patients, improvement of fibrosis was not correlated to SVR. Our data show that 30% of patients who have failed prior posttransplantation treatment achieved an SVR when retreated with pegylated interferon alfa-2b/ribavirin. More interesting is that fibrosis score was improved in 65% of treated patients despite failure of HCV eradication.

Recurrent hepatitis C infection is an important cause of progressive fibrosis, cirrhosis and graft loss after liver transplantation. Treatment for post-transplant recurrence results in sustained virological response (SVR) in up to 30% of cases. The aim of this study was to evaluate the impact of SVR on patients and graft survival. Thirty-four patients with an SVR to IFN-ribavirin were included. Forty-six nonresponders to the combination formed the control group. Follow-up data were recorded every 6 months and included HCV RNA, and the occurrence of clinical problems (cirrhosis, decompensation, hepatocellular carcinoma, death). A graft biopsy was performed every year. The mean follow-up duration was 52 months in responders and 57 months in nonresponders. Two patients died in each group of patients. Two patients with SVR developed late virological relapse. Fibrosis decreased in 38% of patients with SVR, remained stable in 44% and worsened in 18%. In contrast, fibrosis increased in the majority of nonresponder patients (74%, p<0.001). At the end of follow-up, no patient without cirrhosis at inclusion developed cirrhosis of the graft versus 9 among nonresponder patients (p=0.009). No difference in patient survival was observed in the two groups. In conclusion, this study shows that HCV eradication has a positive impact on graft survival.

Background/aims: Hepatitis G virus (HGV), a new RNA virus that is parenterally transmitted, has frequently been found in patients with chronic hepatitis C (HCV) infection but its role in chronic liver disease is unknown. The purpose of this study was to determine the prevalence of HGV infection in transplantation patients infected with hepatitis C and to assess the impact of HGV co-infection on the course of HCV infection after liver transplantation., Methods: Eighty-nine liver transplantation recipients with persistent hepatitis C viremia detected by polymerase chain reaction (PCR) were evaluated. Serum samples were tested before and after liver transplantation for HGV RNA by two different PCR methods: LC assay (Abbott Laboratories) and an RT-PCR procedure which we developed using the silica gel technique for extraction of the HGV RNA. E2 antibodies were detected before orthotopic liver transplantation by an EIA-test. HCV RNA was quantified by branched DNA assay, and HCV genotype was determined. A mean of nine liver biopsy specimens were examined for each patient and the severity of the lesions was compared in HCV-positive patients with or without HGV co-infection., Results: The concordance between the two HGV RNA detection methods was excellent and the reproducibility of our RT-PCR procedure was confirmed. The prevalence of pretransplantation and posttransplantation HGV infection was 11% and 19%, respectively. Pretransplantation HGV infection was positively correlated with posttransplantation HGV infection (p<0.001). Before transplantation the E2 antibodies seroprevalence was 34%. Seven patients became HGV RNA positive after transplantation, but all of them were negative for E2 antibodies. Among the patients who remained RNA negative after liver transplantation, 40% were positive for E2 antibodies (p=0.04). Pretransplantation clinical features (except AST mean value) were not different in patients with HCV and HGV co-infection and those with HCV only. After a mean follow-up of 34 months (range: 6 to 70), 67/89 (75%) patients developed histological features of recurrent hepatitis but the frequency of the occurrence of graft hepatitis was not different between HGV/HCV co-infected patients and those with HCV alone (p=0.89). The mean interval from orthotopic liver transplantation to recurrence was 12.2 months (range: 3-63), which was not different for HVG/HVC-co-infected patients and HCV-infected patients. The histological severity of posttransplantation liver disease, and the graft and patient survival were not different for patients with and without HGV co-infection., Conclusions: Our results suggest the general persistence of HGV infection after liver transplantation, but HGV co-infection did not appear to influence the posttransplantation course of HCV infection. Before transplantation the prevalence of E2 antibodies was 34%, and our data clearly indicate that E2 antibodies were protective against HGV infection.

Background/aims: This study aimed to assess the tolerance and the real sensitivity of Lipiodol-computed tomography in the detection of small hepatocellular carcinoma by comparison with pathological examination of the explanted livers., Methods: Seventy-two patients with cirrhosis (Child A=8, B=36, C=28) awaiting orthotopic liver transplantation underwent Lipiodol-computed tomography to determine the presence, number and location of possible hepatocellular carcinoma nodules. Before liver transplantation six patients had a presumed single hepatocellular carcinoma diagnosed by biopsy. Liver transplantation was performed a mean of 6 months after Lipiodol-computed tomography. Explanted livers were sectioned at 0.8- to 1-cm intervals. Lipiodol-computed tomography staging and pathologic findings were compared., Results: Pathologic studies showed 24 hepatocellular carcinoma nodules (diameter, 2-42 mm) not diagnosed before liver transplantation in 14 of the 72 livers. Lipiodol-computed tomography detected 6 of these 24 nodules, but none of the daughter lesions (n=9) in the six patients with a presumed single hepatocellular carcinoma. Lesion-by-lesion analysis revealed a sensitivity of 37%. Lipiodol-computed tomography falsely detected three additional nodules not confirmed by pathologic examination (1 haemangioma, 2 nondysplastic regenerating nodules). One Child C patient developed variceal bleeding within 2 days after injection of Lipiodol., Conclusions: Tolerance of this procedure was satisfactory, even in Child C patients. Lipiodol-computed tomography has a low sensitivity in the detection of small hapatocellular carcinoma. These results must be considered when liver resection or liver transplantation is proposed for the treatment of hepatocellular carcinoma.

Study Objectives: Contrast transthoracic echocardiography (TTE) is currently used to identify intrapulmonary shunt (IPS) in patients with end-stage liver disease. The aim of this study was to compare the use of contrast TTE and transesophageal echocardiography (TEE) in detecting IPS., Design: Thirty-seven consecutive outpatients with severe liver disease awaiting liver transplantation underwent contrast TEE and TTE. The IPS was assessed semiquantitatively in four grades with TEE and as positive or negative with TTE., Setting: ICU., Interventions: Patients underwent contrast TEE after pharyngeal anesthesia alone followed by contrast TTE. Contrast echocardiography was performed with a modified fluid gelatin solution., Results: Overall detection rate of an IPS was 51% with TEE and 32% with TTE (p < 0.001). Four patients had an IPS detected with TEE but not with TTE. Quality of imaging was poor in 22% with TTE and 0% with TEE (p < 0.001). A PaO2 < 80 mm Hg or a dyspnea was associated with an IPS in 56% and 50% of patients with TEE and in 33% and 25% with TTE, respectively., Conclusion: Contrast-enhanced TEE is superior to TTE for detecting an IPS in patients with severe liver disease awaiting liver transplantation. The use of gelatin contrast solution allows an early detection of IPS. Because of the high sensitivity of TEE, all patients suspected of hepatopulmonary syndrome should undergo TEE in search of an IPS if TTE is normal.

Background: Chronic liver failure resulting from hepatitis C virus infection often necessitates orthotopic liver transplantation. Recurrence of hepatitis C virus infection after transplantation is inevitable, and the infection is usually severe. Interferon and ribavirin have both been used to treat hepatitis C virus infection after liver transplantation, but neither interferon nor ribavirin monotherapy has demonstrated sustained biochemical or virologic responses or histologic benefit in transplant recipients with recurrent hepatitis C virus infection. The next logical approach to treatment was combination therapy., Methods: Fourteen patients with recurrent hepatitis C virus infection were treated for 6 months with interferon alfa-2b (3 MU thrice weekly) and oral ribavirin (1000 mg/day). After 6 months, patients were maintained on ribavirin monotherapy until the end of the study. Safety and tolerability were satisfactory, and no patients experienced graft rejection during the study., Results: Alanine aminotransferase levels were normalized in all patients after 6 months of therapy. Serum HCV RNA was negative in nine patients; the other five demonstrated a 50% quantitative reduction of HCV RNA. After a mean follow-up of 18 months, all but one patient maintained normal alanine aminotransferase levels. Twelve out of 14 patients achieved a histologic benefit., Conclusions: The biochemical and virologic responses and the histologic benefit seen after combination therapy are significantly better than those reported with either interferon or ribavirin monotherapy. Combination therapy appears to be effective in preventing the progression of HCV-related graft disease after liver transplantation.