摘要:

Summary.Hepatotrophic viruses are responsible for a substantial proportion of cases of both end‐stage chronic liver disease and of acute liver failure which are treated by liver transplantation. We review here current practice in transplantation for viral‐induced liver disease addressing, in particular, the selection of patients for transplantation and the increasingly recognized problem of recurrent disease in liver gra

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00008.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary.The efficacy and tolerability of 12‐month treatment with titrated doses of recombinant interferon‐α2a (IFN‐α2a) in chronic hepatitis C were studied in 67 consecutively recruited patients randomly assigned either to a starting dose of IFN‐α2a 6 MU, subsequently adjusted to the serum alanine aminotransferase (ALT) response (n= 35), or to no therapy (n= 32; controls). End‐of‐treatment ALT levels were normal and hepatitis C virus (HCV) RNA was negative by nested polymerase chain reaction (PCR) in 17 (49%) treated patients compared to none of the controls (P<0.001). During the 12 months after stopping treatment the number of patients who remained in remission was eight (23%) and one respectively (4%) (P= 0.031). Follow‐up liver biopsy showed reduced hepatic inflammation in 80% of treated patients and in 29% of controls (P<0.001). The eight sustained responders and 2 7 non‐responders or relapsers received similar mean total doses of IFN (565 MUvs545 MU) and had a similar incidence of anti‐IFN neutralizing anti‐bodys (13% vs 19%). Absence of cirrhosis was the only independent pretreatment parameter that predicted a sustained response. In conclusion, a mean cumulative dose of IFN 549 MU, titrated over 12 months, was well tolerated, and resulted in the long‐term clearance of HCV RNA and normal ALT l

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00009.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary.In chronic hepatitis B virus (HBV) infection seroconversion from hepatitis B e antigen (HBeAg) to hepatitis B e antibody (HBeAb) may be followed either by remission of the disease with low‐level viraemia, or by continuing inflammation with high‐level viraemia. In both situations the virus may acquire a mutation in the precore sequence which prevents it from encoding HBeAg. We now show that the number of amino acid substitutions in the HBV core is low in viral sequences from patients with HBeAg positive chronic liver disease and HBeAg negative HBeAb positive patients in remission, but the frequency of substitutions is high in HBeAg, negative HBeAb positive patients with active liver disease. Furthermore we show that these substitutions cluster in the promiscuous CD4+T‐helper‐cell epitope and in HBV core/e antibody binding determinants, but are not found in regions recognized by major histocompatability complex (MHC) restricted cytotoxic T lymphocytes. Sequential viral sequences from patients before and after HBeAg/HbeAb seroconversion shows that core mutations arise either at the same time or after the precore stop mutation which prevents the virus from encoding HBeAg. These results are consistent with the hypothesis that after clearance of HBeAg, mutations in regions of the virus recognized by CD4+helper T cells and B cells allow persistence of the HBe negative virus in HBeAb positive patients with viraemia and active he

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00010.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary.The inhibitory effect of antisense phosphorothioate oligodeoxyribonucleotides (S‐oligos) on the production of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) was studied using Hep G2 cells transfected with hepatitis B virus (HBV). Synthetic antisense oligos (15‐mers) directed against the cap site of mRNA transcribed from the SP II promoter and regions of the translational initiation site of the S gene showed a sequence‐specific, dose‐dependent inhibitory effect on HBV gene expression between concentrations of 1.0 μm‐5.0 μm. Oligos directed against the middle of the S gene had little effect on HBsAg and HBeAg expression, as did non‐complementary random‐sequence control. The cells remained viable throughout the experiments and no morphological abnormalities were observed with antisense S‐oligos at concentrations below 20.0 μm. These results suggest a therapeutic potential for antisense oligonucleotides in the treatment of patients who are chronically

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00011.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary.Three main patterns of response are seen when interferon‐α (IFN‐α) is used for the treatment of chronic hepatitis C:1 sustained response with alanine‐aminotransferase (ALT) normalization that is maintained after cessation of therapy, with or without clearance of serum hepatitis C virus (HCV) RNA;2 transient response with ALT normalization during therapy followed by relapse after its withdrawal, and3 no response with no or only partial reduction in ALT levels.In order to define variables that could predict each of these three types of response we studied 321 cases of chronic hepatitis C treated with IFN‐α in two consecutive trials conducted in our Unit. By univariate analysis, age<45 years (P<0.01), known disease duration<60 months (P<0.01), normal gamma‐glutamyltranspeptidase (γGT) levels (P<0.01) and infection by HCV genotype 2 or HCV genotype 3 (P45 years (P<0.01), body weight (P= 0.05), cirrhosis (P<0.01) and elevated γGT levels (P<0.01) were associated with no response. By multivariate analysis sustained response was predicted by HCV genotype 2 (P<0.01) and HCV genotype 3 (P<0.01), known disease duration (P<0.01), patient's age (P<0.05) and associated with the use of a more aggressive treatment schedule (P<0.05). Transient response with relapse was predicted by known duration of disease (P<0.05), HCV genotype 1 (P<0.05) and female sex (P<0.05). No response was statistically associated with elevated γGT levels (P<0.01), higher body weight (P<0.05) and with the less aggressive regimen of 3 MU of natural IFN‐α given three times weekly for 6 months (P<0.05).These results indicate that the HCV genotype as well as the schedule of treatment greatly affect the pattern of response to IFN in chronic hepatitis C and allow us to define criteria to predict which type of response is more likely in i

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00012.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary.The effectiveness of recombinant interferon‐α2b (rIFN‐α2b) in eradicating hepatitis C virus (HCV) RNA from serum has not been completely assessed. We studied 39 patients with compensated chronic hepatitis C diagnosed by liver biopsy and positive HCV RNA measured by polymerase chain reaction (PCR). Group I consisted of 26 patients treated with 3 MU of rIFN‐α2b for 6 months; group II, 13 control patients observed for six months; and group III, 12 out of 13 patients from group n who subsequently received 5 MU of rIFN‐α2b for 6 months. In group I, 11 out of 23 (47.8%) patients who completed treatment had an immediate response and five (21.7%) had a sustained response to therapy six months after treatment. No response was observed in patients from group II. In group III, 7 out of 12 (58.3%) patients who completed treatment had an immediate response and none had a sustained response. Considering all patients who completed rIFN‐α2b treatment, HCV RNA remained positive at the end of therapy in three of five sustained responders (60%), six of 13 patients who relapsed (46.1%), and in all non‐responders (100%). HCV RNA was positive 6 months after therapy in four (80%), 13 (100%). and 17 (100%) patients respectively. All patients with a sustained response had normal aminotransferase levels 18 months after therapy. We conclude that in chronic hepatitis C rIFN‐α2b causes a significant immediate response but this is not sustained, only 2.8% of treated patients had a sustained loss of HCV RNA. Normal aminotransferase persist in the long term, despite per

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00013.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary.We have conducted a randomized study to compare the efficacy and tolerance of human interferon (IFN) β vs recombinant IFN‐α2b in patients with chronic active hepatitis C. Forty patients were included: 21 received IFN‐α (group A) and 19 IFN‐β (group B). IFN was administered intramuscularly at a dose of 6 MU three times a week (tiw) for 2 months (induction phase), followed by 3 MU tiw for 4 months. Clinical, epidemiological and pathological features were similar in the two groups. Normal alanine aminotransferase (ALT) values at the end of treatment was regarded as a response to therapy and the response rate was 57% (12/21) in group A and 5.2% (1/19) in group B (P<0.01). Both types of IFN induced a significant decrease in mean ALT values by the end of the induction phase (P<0.01). When the dose was reduced to 3 MU, a marked, but not significant increase in ALT, was seen in group B, whereas no increase was seen in group A. IFN‐β was better tolerated and haematological adverse effects (platelet and leucocyte decrease) were less pronounced with IFN‐β. Hence, human IFN‐β was less effective than IFN‐α in treating chronic hepatitis C virus (HCV). Doses of IFN‐β of 3 MU intramuscular (IM) tiw were clearly insufficient and it remains to be established whether higher doses of intramuscul

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00014.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY

摘要:

Summary.Serum hepatitis B virus (HBV) DNA is now the most important and reliable marker for monitoring hepatitis B viral replication. Quantitative detection of HBV DNA in serum is based on commercial standardized molecular hybridization test systems. We compared two hybridization assays, the DigeneHybrid Captureassay (Digene Diagnostics, Beltsville, MD) and the Abbott HBV DNA assay (Abbott Laboratories, North Chicago, EL, USA) with the polymerase chain reaction (PCR) technique, for detection and quantitative measurement of serum HBV DNA. Forty‐two patients with various HBV serological marker profiles were included in this study. The patients were divided into four groups according to their HBV DNA values after HBV DNA determination in the serum by the Abbott assay. For each patient HBV DNA was then determined by the Digene assay and by PCR. In the case of Digene and PCR there was a 97.6% correspondence in the outcome of the two methods, whereas in the Abbott assay and PCR there was only 69% correspondence. The McNemar test of symmetry showed no statistically significant difference between the Digene assay and PCR, whereas there was a significant difference (P<0.01) in the Abbott assay and PCR. For low positive HBV DNA values between 1.5 and 20 pg ml‐1the Abbott assay yields inconclusive results. Differences observed between the two hybridization assays underline the need for standardization of HBV DNA quantitat

ISSN:1352-0504    

DOI:10.1111/j.1365-2893.1995.tb00015.x

出版商:Blackwell Publishing Ltd    

年代:1995

数据来源: WILEY