Vijayan Balan

Treatment of recurrent hepatitis C infection after liver transplantation with combination of pegylated interferon α2b and ribavirin: An open-label series

Background. Hepatitis C virus (HCV) recurrence after orthotopic liver transplantation (OLT) is universal. We aimed to evaluate the efficacy and safety of pegylated interferon (PEG-IFN) and ribavirin (RIB) in the treatment of post-OLT HCV recurrence. Methods. Thirty-seven patients with recurrent HCV after OLT were screened and began treatment. Nineteen patients have completed therapy. PEG-IFN was started at a dose of 0.5 &mgr;g/kg per week and titrated toward a maximum dose of 1.5 &mgr;g/kg per week. RIB was started at a dose of 400 mg per day and titrated toward a maximum of 1000 mg per day, as tolerated. Therapy continued for 1 year after HCV replication was undetectable by reverse transcriptase-polymerase chain reaction and was discontinued if there was no virologic clearance at 48 weeks. Results. Twelve patients (63%) completed the combination regimen. Therapy was discontinued in seven (37%) patients. Seven patients (37%) had undetectable viral load at the end of treatment. Of those, five patients (26%) had sustained viral response 6 months after discontinuation of therapy. Five patients (26%) had no virologic response. Necro-inflammatory score declined from 5.22 to 2.89 (P =0.05) in nonresponders versus 6.8 to 2.6 (P <0.01) in responders. Fibrosis stage did not change in either group. Genotype 1-infected patients had a lower likelihood of attaining end of treatment or sustained viral response (P <0.05 for both). Conclusions. Post-OLT HCV recurrence can be safely treated with PEG-IFN and RIB. Bone marrow toxicity, depression, and rejection are limiting factors that require aggressive management. There was short-term histologic benefit to the use of this regimen, even in those patients without viral clearance.

AUTOIMMUNE LIVER DISEASES: Recurrence After Liver Transplantation

PBC and AIH recur after OLTx. The recurrence of PSC is less clear. Recurrence of these diseases seems to be of relatively little importance in the short term; however, longer follow-up is required to address the significance of recurrent disease. Immunosuppression in these patients may alter the natural history of these entities in the post-transplant setting.

A randomized, double blind, placebo controlled trial of interferon-alfa and amantadine versus interferon-alfa alone in the treatment of chronic hepatitis C

Before the availability of ribavirin, interferon-a was the only approved therapy for chronic hepatitis C but it caused hepatitis C (HCV) clearance in only 10% to 15% of the patients. Aim: to determine if interferon-a and amantadine combination was superior to interferon-a alone in the treatment of chronic hepatitis C. Methods: randomized, double blind, placebo controlled trial of interferon naive patients with HCV. Patients with Childs B/C cirrhosis were excluded. 70 patients were required to detect a response rate of 50% compared to 15% response rate reported with interferon alone (a=0.05, 13=0.1). All patients received interferon-a2a (Roferon, Roche pharmaceuticals) 3 mu 3 times a week and either amantadine 100 mg twice a day or placebo for 24 weeks. Results: The study was terminated when ribavirin became available and therefore only 24 patients were enrolled. Twelve were randomized to interferon-a and amantadine and 12 to interferon-o and placebo. All patients had elevated serum ALT, positive HCV RNA and chronic hepatitis on liver biopsy. One patient had cirrhosis. Two patients in amantadine group and 4 in placebo group withdrew. None had end of treatment biochemical response but one patient in the amantadine group and 2 in the placebo group became HCV RNA negative by PCR (preliminary data). Conclusion: Interferon-a and amantadine combination is similar in efficacy to interferon-a alone in the treatment of patients with chronic hepatitis C. 6730

Increased prevelance of osteoporosis in patients with end-stage liver diseasse secondary to hepatitis C infection and alcohol

Background: Decrease in portal flow are known to be partly compensated by the increase in hepatic arterial flow under various pathological conditions. However, it is unclear whether this phenomenon is also observed when the hemihepatic portal flow is interrupted and whether the arterial flow decreases when the portal flow is increased. Methods:Both portal and hepatic arterial blood flow was measured intraoperatively by transit time 2-channel ultrasonic volume tlowmeter innine donorsof living-related liver transplantations. Simultaneous measurements of right hepatic artery (RHA) and left hepatic artery (LHA), right portal vein (RPV) and left portal vein (LPV) were carried out with and without clamping RPV by vascular forceps. Results: Blond flow of RHA was significantly increased when RPV is clamped by 202 % (141.0}.3 ml/min to 257.3}.5 ml/min, respectively; p=O.02). Blood flow of LPV significantly increased when RPV clamping by 316 % (387.9}.8 ml/min to 217.8}.3 ml/min, respectively; p = 0.01). Blood flow of LHA didnt increase significantly when RPV is clamped (116.5}.9 ml/min to 140.0}.9 ml/min, respeetively; p=0.27). Total portal flow significantly decreased by 62 % when RPV clamping (705.0}.6 ml/min to 387.9}.8 ml/min, respectively; p=O.03). Total hepatic arterial flow with and without clamping RPV were not significantly different (373.8}.1 ml/min vs. 281.0}.5 ml/min, respectively; p = 0.09). RPV flow was compensated with the increase of RHA flow by 13 %. With clamping RPV, total hepatic flow of the left hemiliver significantly increased by 162 % (309.4}.3 ml/min to 418.2}.5 ml/min, respectively; p=O.03). Conclusion: Although RPV clamping ensued in the increased LPV flow, total portal flow decreased at least immediately after RPV clamping. Hemihepatic portal venous occlusion resulted in the increase in the arterial flow of the corresponding hemiliver; whereas, in the contralateral hemiliver, the increase in the portal venous flow was not compensated by the decrease in the hepatic arterial flow.