摘要:

AbstractThe presence of unique hepatitis B virus (HBV) variants has been investigated in two Chinese patients with chronic liver disease, whose sera were positive for HBV‐DNA by dot blot hybridization or polymerase chain reaction (PCR) but hepatitis B surface antigen (HBsAg)–negative by conventional polyclonal antibody based immunoassays. PCR amplification of HBV‐DNA followed by direct sequencing showed an insertion of six nucleotides, which introduced two additional amino acids between codons 122 and 123 in one patient (Isolate 1), whereas a nine nucleotide insertion in the other patient (Isolate 2) gave rise to three amino‐acids between codons 123 and 124 immediately upstream from the ‘a’ determinant in the S gene. These insertions have not been described previously in any published sequences of the known subtypes and were absent from sequences of 30 HBsAg‐positive Chinese patients from the same region. In the cases under study, the insertion is associated with four consecutive adenine molecules from nucleotides 516 to 519. It seems likely that this area is a hot spot for insertions in HBV. We found none of the previously described amino‐acid deletions or substitutions in thepre‐S1,pre‐S2andSgenes, which are involved in unusual antigenic profiles. This finding suggests that genetic mutations in theSgene outside the ‘a’ determinant may be responsible for failure to detect HBsAg in some Chinese patients with chronic hepatitis caused by HBV infection. (HEP

ISSN:0270-9139    

DOI:10.1002/hep.1840210202

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractBased on the knowledge that patients with porphyria cutanea tarda (PCT) usually have chronic liver disease, several authors studied a possible relationship to hepatotropic virus infections. However, the prevalence of hepatitis B virus (HBV)‐DNA by polymerase chain reaction (PCR) in serum of these patients, as well as the presence of hepatitis C virus (HCV)‐RNA in paired liver, peripheral blood mononuclear cells (PBMCs), and serum samples in these patients has not been reported. We have studied 34 patients with sporadic PCT. Antibodies against HBV were detected in 91% of the patients, but in only 41% of the patients against HBV (P<.01). Viral genomes of HCV and HBV were detected in 65% and 40% of our patients, respectively (P<.05). Genomic and antigenomic HCV strands were found in liver biopsy specimens (100% and 54%), mononuclear cells (100% and 54%), and serum (45% and 0%) from 11 patients. Twelve patients were retrospectively studied, and no correlation was observed between the appearance or disappearance of viral genomes and the simultaneous presence of both genomes with the course of porphyria. In our patients with PCT, detection of viral genomes did not correlate with phlebotomy or length of time since PCT was diagnosed. Our findings demonstrate that HCV infection may be underestimated when detection is performed only in serum of PCT patients, and that HBV infection might also be increased in PCT. (HEPATOLOGY1995;21:279

ISSN:0270-9139    

DOI:10.1002/hep.1840210203

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractHepatitis C virus (HCV) infection persists for an indefinite length of time in a major proportion of patients, inducing chronic liver lesions that evolve to cirrhosis and hepatocellular carcinoma (HCC) in approximately 20% of cases. We studied HCV viremia and genotypes by reverse transcription–polymerase chain reaction (RT‐PCR) in 341 consecutive anti‐HCV–positive patients. Of these, 167 patients had persistently normal or near normal alanine aminotransferase (ALT) levels (fluctuations ≤5 IU above the upper limit of normal); the remaining 174 patients presented with elevated ALT and histological evidence of chronic liver disease. Seventy percent of patients with normal ALT values had circulating HCV RNA despite the absence of biochemical indicators of liver damage and mild histological forms of chronic hepatitis were detected in most patients who underwent liver biopsy. Isolated genotype III infection was significantly more prevalent in this patient group with respect to control patients with abnormal ALT values (70% vs. 39%;P<.001). Conversely, isolated genotype II was more frequently found in patients with elevated ALT values and evidence of chronic liver disease (45% vs. 23%;P<.01) and it was progressively more represented in advanced liver disease, such as cirrhosis and HCC. Virological features of HCV infection might be associated with different clinical manifestations, suggesting a potential prognostic significance on disease outcome. (HEPATOLOGY1995;21

ISSN:0270-9139    

DOI:10.1002/hep.1840210204

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractThe aim of this study was to determine whether 12 months course of interferon alfa (IFN‐α) therapy could improve the beneficial effect of IFN in chronic hepatitis C. Eighty‐eight patients were treated with natural IFN‐α for either 28 weeks (45 cases) or 52 weeks (43 cases). Sustained response was achieved in 15 (33.3%) of 45 cases treated for 28 weeks and in 23 (53.5%) of 43 cases treated for 52 weeks. Transient response with relapse of alanine transaminase (ALT) after completion of therapy was observed in 13 cases (28.9%) treated for 28 weeks and in 4 cases (9.3%) treated for 52 weeks. Thus, ALT relapse was suppressed by prolonged IFN treatment. No response was found in 17 cases (37.8%) treated for 28 weeks and in 16 cases (37.2%) treated for 52 weeks, indicating that approximately 38% of the patients with chronic hepatitis C were resistant to IFN therapy even with prolonged treatment. The rate of sustained response was significantly higher in patients with type 2a or 2b than in those with type 1b. Even in type 1b cases, it was higher in the 52‐week treatment group than in the 28‐week treatment group, and the rate of transient response was lower in the 52‐week treatment group, indicating that relapse in type 1b cases was suppressed by prolonged IFN therapy. IFN therapy was not effective for patients with advanced liver fibrosis. In multivariate regression analysis viral genotype and pretreatment level of serum hepatitis C virus (HCV) RNA were correlated independently with sustained response. Periportal necrosis, intralobular inflammation, and hepatic fibrosis scores were significantly improved in the sustained response group by IFN therapy. In the transient response group, a significant decrease in scores for intralobular inflammation and portal inflammation was observed, whereas all four histological scores were not improved in the no response group. In conclusion, prolonged IFN therapy can suppress relapse of chronic hepatitis C, even in type 1b patients. However, approximately 38% of the patients are resistant to prolonged IFN therapy, suggesting the need to develop a new therapy. (HEPATOLOGY199

ISSN:0270-9139    

DOI:10.1002/hep.1840210205

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractTransforming growth factor β1 (TGFβ1) is a cytokine involved in liver fibrogenesis. Previous semiquantitative studies of patients with chronic viral hepatitis showed that liver TGFβ1 messenger RNA (mRNA) was increased, compared with normal controls and with patients with chronic hepatitis C virus (HCV) infection who responded favorably to interferon alfa (IFNα) treatment. To evaluate its potential prognostic significance, we measured liver TGFβ1 mRNA, using a new competitive reverse gene amplification assay, in a total of 35 patients with chronic HCV. This technique was reproducible and sensitive; we could measure as few as 5,000 molecules of TGFβ1 mRNA per microgram of total liver RNA. In patients with chronic HCV, the mean level of TGFβ1 mRNA was 200‐fold higher than in controls. However, no correlation could be found between TGFβ1 mRNA and either the biological (serum amino‐terminal peptide of type III procollagen) and histological (Knodell scores) indices of liver fibrosis or a favorable response to IFNα therapy. In 9 patients, second liver specimens were obtained after treatment; in most cases, TGFβ1 mRNA levels and hepatic histological findings varied in parallel. These data are consistent with the hypothesis that TGFβ1 plays a role in stimulating liver fibrogenesis during chronic HCV, despite the lack of prognostic value of TGFβ1 mRNA levels measured before treatment. Additional biological parameters, such as the processing of the TGFβ1 precursor to its active form or the respective levels of the three TGFβ receptor subtypes within the liver, could explain the lack of correlation between TGFβ1 mRNA and indices of liver fibrogenesis. (HEPATOLO

ISSN:0270-9139    

DOI:10.1002/hep.1840210206

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractSkin and/or liver biopsy specimens were obtained from the following patients: 15 anti–hepatitis C virus (HCV), HCV RNA–positive patients and 3 anti‐HCV, HCV RNA–negative patients with type II mixed cryoglobulinemia (MC); 7 anti‐HCV, HCV RNA–positive patients with chronic active liver disease (CALD); 5 anti‐HCV, HCV RNA–negative patients with noncryoglobulinemic vasculitis; and 7 anti‐HCV, HCV RNA–negative patients with lichen ruber planus. A pool of murine monoclonal antibodies (MAbs) developed against c22‐3, c33c, and c100‐3 proteins was used to detect HCV‐related antigens (Ags) by indirect immunohistochemistry. Acid electroelution (AEE) of tissue sections was performed to enhance the sensitivity of the immunohistochemical method. In anti‐HCV–positive MC patients, specific HCV‐related Ags were detected in the small vessels of the skin and in the cytoplasm of hepatocytes. Prior AEE of biopsy sections allowed detection of HCV Age in 6 of 15 (40%) skin biopsy and in 9 of 14 (64.3%) liver biopsy specimens. HCV immunoreactive deposits in the skin displayed two immunohistochemical patterns: (1) coarse intraluminal material associated with dermal inflammatory infiltrates and intravascular deposition of eosinophilic hyaline material; and (2) reactivity confined to the vessel wall in the context of an apparently normal tissue. Immunoglobulin (Ig) G and IgM deposition in the skin showed immunohistochemical features comparable with those found for HCV Ag deposits. In addition, tissue complement reactivity was detected in 6 (40%) of them and was strictly associated with histological and clinical signs of active vasculities. Five of 7 (71.4%) liver biopsy specimens, but none of 7 skin biopsy specimens, from anti‐HCV, HCV RNA–positive patients without circulating cryoglobulins displayed immune reactivity after AEE procedure. Consistently negative results were obtained with skin and liver sections from all anti‐HCV, HCV RNA–negative patients. These findings indicate that, under the experimental conditions used, in 40% of anti‐HCV, HCV RNA–positive patients with MC, skin tissue deposits consist of HCV‐containing immune complexes. In addition, the occurrence of HCV reactivity in apparently normal blood vessels suggests that deposition of viral Ags precedes and possibly initiates tissue damage. Whether in the remaining patients HCV Ags cannot be detected because of the insufficient sensitivity of the method or the involvement of Ags other than those assayed, remains

ISSN:0270-9139    

DOI:10.1002/hep.1840210207

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractIn HBsAg‐negitive patients with hepatocellular carcinoma (HCC), hepatitis B virus (HBV) genomes are present at a low copy number per cell, and the role of HBV in liver transformation is still unclear. We have mapped by polymerase chain reaction (PCR) the HBV genome in 19 HBsAg‐negative tumorous and 9 corresponding nontumorous tissues and evaluated, by RT‐PCR, the presence of HBV S, X, and C transcripts in the tumorous and nontumorous tissue of nine HBsAg‐negative and, for comparison, six HBsAg‐positive patients. Disrupted, presumably integrated, HBV genomes were detected by PCR in 10 of 19 tumorous tissues and in only one of nine nontumorous tissues. Significant accumulation of viral RNAs containing X but not C or S sequences was shown in 7/9 tumors and 7/8 nontumorous tissues from HBsAg‐negative patients. In contrast, viral RNAs revealed by X‐as well as by S‐ and C‐specific primers were detected in five of six tumors and in six of six nontumorous tissues from HBsAg‐positive patients. In conclusion, our results suggest the frequent integration of the HBV genome and the accumulation of X‐related RNAs in HCCs developing in HBsAg‐negative patients. This finding is consistent with a role, in these cases, for the potentially transforming X protein. (HEP

ISSN:0270-9139    

DOI:10.1002/hep.1840210208

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractBecause 70% to 75% of patients with chronic hepatitis C either do not respond to or relapse after interferon (IFN) therapy, and because ursodeoxycholic acid (UDCA) has been shown to reduce aminotransferase levels in patients with chronic hepatitis, we undertook a prospective controlled randomized trial of IFN (group I) versus IFN plus UDCA (group II) in 80 patients with chronic hepatitis C. IFN was administered in both groups for 6 months (3 to 5 million units [MU] three times a week), and in group II UDCA (10 mg/kg/d) was administered with IFN and then alone for 3 additional months. Response to therapy was defined as the normalization of alanine transaminase (ALT) levels. The results showed that 6 months after cessation of IFN, 59% of responders had relapsed in group I but only 27% had relapsed in group II (P= .03). There was no difference between the two groups for the initial (month 6) and the late (months 15 and 18) response rates to IFN. There was no virological effect or significant histological improvement attributable to the addition of UDCA to IFN treatment. In conclusion, the results of this study show that the addition of UDCA to IFN therapy significantly prolongs the period for which serum ALT remain, within the normal range after discontinuation of IFN. Further studies would be required to determine whether UDCA has any potential for long‐term amelioration of the histological severity of liver disease caused by hepatitis C virus (HCV) infection, and therefore, whether it could be advocated as an adjunct to antiviral therapy. (HEPATOLOGY1995;21:322–3

ISSN:0270-9139    

DOI:10.1002/hep.1840210209

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractTo determine the rate of vertical transmission of hepatitis C virus (HCV), we prospectively studied 45 babies born to anti‐HCV–positive women with or without con‐comitant infection with the human immunodeficiency virus (HIV). We performed a second‐generation recombinant immunoblotting assay, alanine transaminase (ALT) evaluation, and HCV‐RNA testing on sera from 27 infants of HCV+, HIV– mothers and 18 babies of HCV+, HIV+ women, at birth and thereafter. After birth, HCV antibodies progressively disappeared within 12 months in all children but one, whose mother was HCV+, HIV+; this child was the only one who showed detectable levels of HCV‐RNA and abnormal ALT values throughout the follow‐up (range, 12 to 27 months). Viremia was persistently negative, and ALT levels were continuously normal in the remaining infants, showing that “seronegative” infection with HCV was absent in both groups. Clearance of passively acquired anti‐HCV antibodies was found to be slower among babies born to HIV+ mothers (22.3% vs. 3.8% at 12 months,P= .03) and children whose mothers showed three of four anti‐HCV reactivities by immunoblotting maintained anti‐HCV for longer periods compared with babies born to mothers with one or two anti‐HCV reactivities (P= .0001). Seventeen of 27 babies born to HCV+, HIV– mothers were breast‐fed, and none of them was infected, confirming the apparent safety for HCV of breast milk. In summary, according to our study, vertical transmission of HCV is an infrequent event, and the presence of HIV in the mother is not an important co‐factor for transmission of HCV infec

ISSN:0270-9139    

DOI:10.1002/hep.1840210210

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractLiver transplantation for liver diseases related to hepatitis B virus (HBV) and hepatitis delta virus (HDV) remains problematic because of the risk of viral recurrence. We report here the long‐term virological outcome of patients transplanted for HDV‐related liver cirrhosis (HDV cirrhosis). From December 1984 to December 1990, 76 patients with HDV cirrhosis underwent liver transplantation. Before transplantation, all the patients were HBsAg‐positive/anti‐HDV positive, and all but one were HBV DNA‐negative by dot blot hybridization. HDV RNA was detected by HDV RT‐PCR and liver HDAg by fluorescent HDV Ab. After transplantation, all the patients except four received continuous long‐term anti‐HBs passive immunoprophylaxis. The actuarial 5‐year survival was 88%. All patients who did not receive anti‐HBs immunoprophylaxis remained HBsAg‐positive and developed hepatitis. Among the 68 patients receiving anti‐HBs immunoprophylaxis with a minimum follow‐up of 2 months, HBsAg reappeared in 7 (10.3%) after a mean of 17 months. These seven patients developed hepatitis, with simultaneous HBV and HDV replication; and four cleared later HBsAg. Patients without HBV reinfection were studied for HDV reinfection: liver HD Ag or serum HDV RNA were present in 88% of the patients during the first year, without developing hepatitis; however, they were no longer detectable after 2 years in 95% of the patients. In conclusion, liver transplantation for HDV cirrhosis gives good results, with a 5‐year actuarial survival of 88%. Reappearance of HBsAg occurred in 13.2% and was associated with HBV and HDV reactivation and hepatitis. Among patients who remained HBsAg negative, HDV markers were detectable during the first year, without the development of hepatitis, but disappeared in the long term in most cases.

ISSN:0270-9139    

DOI:10.1002/hep.1840210211

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY