No abstract

Long-term immunoprophylaxis with hepatitis B immune globulin (HBIG) is widely accepted for the prevention of recurrent hepatitis B virus (HBV) infection after liver transplantation in HBV-V iral reinfection is the main problem after liver transplantation for hepatitis B virus (HBV)-related liver disease. 1,2 Long-term antibody to hepatitis B surface antigen (anti-HBs) immunoprophylaxis (hepatitis B immune globulin [HBIG]) is an efficient way of preventing HBV reinfection in HBV DNA-negative patients. [3][4][5][6] There is no consensus on the optimal duration of HBIG administration. Attempts have been made to stop HBIG administration and to replace it with HBV vaccination 7,8 or lamivudine. 9,10 Active HBV replication before transplantation is the main factor predictive of failure of HBIG prophylaxis. Attempts to improve the results of prophylaxis in patients with active HBV replication include maintenance of anti-HBs antibody titers over 500 IU/L 11,12 and antiviral therapy before and after transplantation. 13 Lamivudine administration before and after transplantation, without HBIG, is hindered by the occurrence of drug-resistant mutants. [13][14][15] However, combined prophylaxis with lamivudine and HBIG has shown promising results. [16][17][18][19][20][21] This article reports the long-term results of HBIG administration in 284 hepatitis B surface antigen (HBsAg)-positive liver transplantation patients and of combination prophylaxis with HBIG and antiviral therapy before and after transplantation in a subgroup of 25 HBV DNA-

Differences in hepatitis C virus (HCV) variants of the highly conserved 5 untranslated region (UTR) have been observed between plasma and peripheral blood mononuclear cells (PBMC). The prevalence and the mechanisms of this compartmentalization are unknown. Plasma and PBMC HCV variants were compared by single-strand conformation polymorphism (SSCP) and by cloning or by genotyping with a line probe assay (LiPA) in 116 chronically infected patients, including 44 liver transplant recipients. SSCP patterns differed between compartments in 43/109 analyzable patients (39%). Differences were significantly more frequent in patients with transplants (21/38 [55%] versus 22/71 [31%]; P < 0.01) and in those who acquired HCV through multiple transfusions before 1991 (15/20; 75%) or through drug injection (16/31; 52%) than in those infected through an unknown route (7/29; 24%) or through a single transfusion (5/29; 17%; P < 0.001). Cloning of the 5 UTR, LiPA analysis, and nonstructural region 5B sequencing revealed different genotypes in the two compartments from 10 patients (9%). In nine patients, the genotype detected in PBMC was not detected in plasma and was weak or undetectable in the liver in three cases. This genotypic compartmentalization persisted for years in three patients and after liver transplantation in two. The present study shows that a significant proportion of HCV-infected subjects harbor in their PBMC highly divergent variants which were likely acquired through superinfections.Hepatitis C virus (HCV) frequently leads to chronic infection contributing to liver cirrhosis and hepatocellular carcinoma. HCV is an enveloped, positive-stranded RNA virus that circulates in vivo as a population of closely related variants collectively referred to as a quasispecies. This quasispecies nature may be involved in viral persistence at the early stages of infection (12), allowing the emergence of immune escape mutants (11, 13). The infection of immune cells could be another viral mechanism of evasion contributing to host failure in eradicating the virus (32). The issue of extrahepatic replication of HCV is still debated. Detection of HCV RNA in extrahepatic compartments can be due to the adsorption of plasma variants (17, 31). However, the minus-stranded HCV RNA, the replicative intermediate, which is not detected in plasma, has been detected in peripheral blood mononuclear cells (PBMC) in many studies (4,8,10,15,18,21,22,23,25,28,37), but this is not sufficient to demonstrate that a complete and productive replication of HCV really occurs in these cells.Another point supporting autonomous HCV replication in PBMC is the common finding in these cells of HCV variants differing from those circulating in serum (26, 31). The study of different blood cell subsets also revealed that quasispecies compositions can differ significantly between peripheral B and T lymphocytes, monocytes, and plasma (1). We have recently shown that this compartmentalization is a frequent phenomenon (10).Compartmentalization of HCV variants has been mai...

The aim of this open trial was to assess the efficacy and the safety of interferon (IFN) alfa therapy in liver transplant recipients with chronic active hepatitis caused by hepatitis C virus. In July 1991, among 447 liver recipients regularly observed at our institution, 46 had developed HCV-related chronic active hepatitis defined by piece meal necrosis. Fourteen of these 46 patients received IFN alfa 3 mIU three times weekly for a planned duration of 6 months and were compared to the 32 untreated patients. Genotyping and quantification of viremia were performed using type-specific amplification and branched DNA assay. Histological follow-up was available in all patients and routinely before and after IFN therapy. Treated and untreated patients did not differ regarding gender, age, length of follow-up, maximum histological score, and genotypes (41 of 46 were of type lb). Induction of chronic rejection was observed in 5 of 14 treated patients leading to retransplantation in 3. In contrast, chronic rejection occurred in 1 of 32 untreated patients (P < .005) during the posttransplantation follow-up. Among the 9 treated patients without rejection, a decrease of transaminases or of HCV RNA levels of more than 50% were observed in 8 and 4, respectively; 2 patients had a complete response, and 1 did not relapse after discontinuation of IFN. Histological improvement occurred in 2 of the treated patients and in none of the untreated patients. IFN therapy in liver transplant recipients has poor antiviral effect and can induce chronic rejection. Its use in this setting should be cautious. (HEP-

No abstract