摘要:

AbstractWe report a prospective clinical and virological study of 18 patients undergoing orthotopic liver transplantation, selected because of hepatitis C virus (HCV) RNA positivity before transplantation. Nine of the 18 patients (50%) developed chronic active hepatitis (CAH) in liver allografts during the first year posttransplantation; hepatitis was first observed between 6 and 25 weeks post‐transplantation. HCV viremia was measured for all patients before transplantation and on posttransplantation days 3, 7, and 14, and months 1, 6, 12, and 24 to 41, by quantitative competitive RNA polymerase chain reaction (QC‐PCR). HCV RNA levels on posttransplantation days 3, 7, and 14 were significantly higher among patients who subsequently developed CAH versus those who did not (P<.02 byt‐test and Mann‐Whitney test on all three dates). However, HCV RNA levels in sera obtained at 1, 6, and 12 months posttransplantation did not correlate with CAH at 1 year or with HCV genotype determined in posttransplantation sera. At least two serial liver biopsy specimens from each patient were stained for HCV nonstructural 4 (NS4) antigen by immunohistochemistry. The intensity of cytoplasmic staining of NS4 antigen was significantly higher for specimens with CAH versus those without CAH (P= .028 by λ). Three patients developed bridging fibrosis in liver allografts during the first year after transplantation; all three patients had intense (3+) immunostaining for NS4 antigen, and the infecting genotypes were 1a, 1b, and 1a plus 1b, respectively. In summary, the 18 patients all developed high‐titer viremia by 1 month after liver transplantation, whereas CAH developed in 50% of allografts during the first year after transplantation. Patients with recurrent CAH were characterized by higher HCV RNA titers during the first 2 weeks posttransplantation and increased staining of HCV NS4 antigen in diseased liver biopsy specimens; however, the role of virological factors in the recurrence of CAH after liver transplantation remains uncertain. (HEPATOLOGY199

ISSN:0270-9139    

DOI:10.1002/hep.1840220102

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractThe mechanisms involved in hepatitis B virus (HBV) persistence are still poorly understood. We have previously shown that the encapsidation of the singly spliced 2.2 kb‐HBV RNA leads to the secretion of circulating HBV defective particles in patients with chronic hepatitis. We have now investigated the presence of the HBV defective particles in sera from patients with acute and chronic hepatitis, using polymerase chain reaction. These defective particles were detected in a larger amount in sera of patients with acute hepatitis that progressed to chronic hepatitis, or had already developed chronic hepatitis, as compared with those who recovered from acute hepatitis (the increase was estimated to be an average of 50‐fold). In addition, we showed that the presence of these defective HBV particles is closely associated with the chronic course of hepatitis B virus infection and with viral multiplication. We also analyzed viral RNAs and proteins synthetized afterin vitrotransfection of Huh7 cell line with the corresponding defective hepatitis B virus DNA molecule. We showed that expression of the defective hepatitis B virus DNA alone leads to a marked intracellular accumulation of the major core protein (HBcAg) and to an increased secretion of hepatitis B e antigen (HBeAg). These observations may be consistent with a role of these defective hepatitis B virus (HBV) particles in viral persistence. (HEPATOLOGY1995;21:10

ISSN:0270-9139    

DOI:10.1002/hep.1840220103

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractTo assess the differences in the surgical results between patients with hepatitis B‐ and hepatitis C‐related hepatocellular carcinoma (HCC), the operative outcomes of 30 patients with hepatitis B surface antigen (HBsAg)‐positive (the B‐HCC group) and 96 patients with hepatitis C antibody (HCVAb)‐positive (the C‐HCC group), who had undergone hepatic resection from 1989 to 1993, were compared. The mean age of the patients in the C‐HCC group was higher than that in the B‐HCC group (61.7 years vs. 57.0 years,P<.05). The C‐HCC group demonstrated both a greater decrease in liver function and a larger enhancement of inflammatory changes in the liver under a pathological examination (the current rate of active hepatitis: 69% vs. 27%,P<.001). There was also a higher incidence of total postoperative complications in the C‐HCC group (60% vs. 37%,P<.05); however, regarding each individual complication, the rate was similar between the two groups. Two of the six patients with postoperative hepatic failure in the C‐HCC group died. The mortality rate in the C‐HCC group was 2%, but no operative death was encountered in the B‐HCC group. The crude survival and the disease‐free survival rates at 5 years were similar, 61.8% and 46.2% in the B‐HCC group and 52.8% and 23.2% in the C‐HCC group, respectively. The patterns of recurrence were also similar in both groups. The pathological features of HCC were similar between the two groups. In conclusion, the surgical results between the two groups were almost identical. However, because of the reduced liver function along with the enhancement of inflammatory changes in the liver, surgeons should therefore be more careful when determining operative indications and conducting the follow‐up after surgery, especially for the C‐HCC

ISSN:0270-9139    

DOI:10.1002/hep.1840220104

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractThis study was conducted to determine the rate of detection of serum hepatitis B virus (HBV) DNA in hepatitis B surface antigen (HBsAg)‐negative decompensated cirrhotic patients who had hepatitis B core and/or surface antibodies (anti‐HBc and/or anti‐HBs), and to compare the outcome of HBsAg‐positive cirrhotic patients who did or did not clear HBsAg during follow‐up. Six (5%) of 121 HBsAg‐positive cirrhotic patients lost HBsAg after 0.2 to 17.1 years (mean, 9.1 ± 6.2 yr) of follow‐up. The cumulative rates of loss of HBsAg at 1, 5, 10, and 15 years were, respectively, 1.3%, 1.3%, 7.4%, and 44.5%. Compared with the patients who remained HBsAg‐positive, those who lost HBsAg had milder disease at presentation and significantly longer survival. Of the patients who lost HBsAg, 83% had improvement in liver function after the loss of HBsAg, and all were alive at the time of writing (0.8 to 5.7 years after loss of HBsAg), whereas 27% of those who remained HBsAg‐positive had died and 29% had deterioration in liver function. The rate of detection of serum HBV DNA by polymerase chain reaction (PCR) assay was higher in HBsAg‐positive cirrhotic patients who lost HBsAg: 67% versus cirrhotic patients who had no previous history of chronic HBV infection; 16% (cryptogenic) and 29% (hepatitis C virus and/or alcohol‐induced liver disease). In summary, we found that using PCR, serum HBV DNA can be detected in 28% of HBsAg‐negative cirrhotic patients who were studied, but the pathogenic significance of such small amounts of virus is not clear. Liver function can improve and survival can be prolonged in HBsAg positive decompensated cirrhotic patients who subsequently lost HBsAg. (

ISSN:0270-9139    

DOI:10.1002/hep.1840220105

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractHepatitis C virus (HCV) populations in vivo exist as a mixture of heterogeneous viruses called quasispecies, which have variations in the hypervariable region (HVR). However, the relationship between the diversity of HVR quasispecies, the disease stage, or the interferon (IFN) responsiveness remains to be elucidated. To study these, serum samples were obtained from 42 patients with chronic hepatitis C virus infection;24 with chronic active hepatitis (CAH) treated with IFN, 9 with cirrhosis, 9 with hepatocellular carcinoma (HCC). HCV quasispecies populations were separated by the single‐strand conformation polymorphism (SSCP) method targeted to the HVR. The patients were classified into two groups; a single‐band group (n = 12) in which HVR quasispecies was homogeneous and a multiple‐band group (n = 30) in which HVR quasispecies was heterogeneous. Patients with multiple bands had significantly more advanced liver disease than those with a single‐band group (P = .0082). The percentage of patients with single band were 41% in CAH, 22% in cirrhosis, and 0% in HCC. Multi‐variate analyses showed that viral diversity was independently related to the progression of liver disease and was not correlated with the duration of infection. We also found that in CAH, the patients who had multiple bands (n = 14) were more resistant to IFN therapy than those who had a single band (n = 10) (P = .002). These results indicate that the diversity of HCV quasispecies becomes more complex as the disease stage progresses and that CAH with more complex diversity shows less IFN effectiveness. (HEPATOLOGY1995;

ISSN:0270-9139    

DOI:10.1002/hep.1840220106

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractHepatitis B virus (HBV) DNA‐transfected hepatoma cells were incubated with the immunosuppressive agents prednisolone, azathioprine, and cyclosporin A (CsA) and the antiviral agents ganciclovir and foscarnet to investigate the effects of these compounds on HBV replication. Prednisolone and azathioprine increased in‐tracellular viral DNA and RNA levels approximately twofold and fourfold, respectively. Treatment with CsA did not alter the levels of viral RNA or DNA. A combination of all three immunosuppressive agents increased the level of intracellular viral DNA eightfold, indicating an additive effect. Incubation of the cells in the presence of foscarnet decreased levels of both single‐stranded and relaxed circular viral DNA, and in the presence of ganciclovir decreased the levels of relaxed circular viral DNA, predictable effects from their known mechanism of action. The stimulatory effect on viral replication induced by the combination of immunosuppressive agents was substantially inhibited by ganciclovir‐foscarnet treatment. These observations could have implications for the management of recurrent HBV infection after liver transplantation. (Hepatology1995 22

ISSN:0270-9139    

DOI:10.1002/hep.1840220107

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractTo examine the extent of hepatitis B virus infection (HBV) in an inner‐city community, we determined the prevalence, incidence, and correlates of HBV seroreactivity in a representative sample of unmarried whites, African‐Americans, and Hispanics living in San Francisco during 1988 to 1989 and again 1 year later in 1989 to 1990. Unmarried men and women aged 20 to 44 years were surveyed in a random household sample drawn from three neighborhoods of varying geographic and cultural characteristics. Hepatitis B infection was determined by testing specimens for antibody to hepatitis B core antigen (anti‐HBc). Of blood samples available from 1,108 participants from the initial survery, 159 (14%) were anti‐HBc positive. There was a strong positive association between anti‐HBc positivity and positive serological tests for human immunodeficiency virus, herpes virus type 2, and syphilis. In women and heterosexual men, after controlling for other variables, anti‐HBc positivity was significantly associated with older age (P<.001), nonwhite ethnicity (P<.01), less education (P<.05), injection drug use (P<.001), being paid for sex (P<.05), and lifetime number of sexual partners (P<.05). Among homosexually active men, after controlling for other variables, anti‐HBc positivity was significantly associated with nonwhite ethnicity (P<.001), injection drug use in a sexual partner (P<.05), and number of lifetime sexual partners (P<.05). There were 19 (3.2%) incident HBV infections. Participants who used injection drugs (relative risk [RR], 8.2; 95% confidence interval [CI]3.9 to 17.4), crack cocaine (RR, 3.5; 95% CI, 1.2 to 9.6), or who were paid for sex (RR, 7.6; 95% CI, 1.4 to 41.1) were more likely to have recently acquired HBV than participants who did not practice these activities. HBV antibodies were found in 14% of an ethnically diverse community based sample, and in general were associated with serological evidence of and risk behaviors for sexually transmitted diseases as well as with injection drug use. Subjects with incident compared with those with prevalent HBV infections were younger, more commonly heterosexual, and more commonly illicit drug users. (HEPATOLOGY1

ISSN:0270-9139    

DOI:10.1002/hep.1840220108

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractMutations in the hepatitis B virus (HBV) core gene may influence disease activity by altering immune recognition sites or level of virus replication. Sera from 69 Chinese patients with chronic HBV infection were analyzed by direct sequencing of polymerase chain reaction amplification of HBV DNA to determine the frequency and location of naturally occurring HBV core gene mutations. All but one patient had nucleotide changes, and 44 (64%) patients had at least one amino acid change (mean, 3.7; range, 1‐13) when compared with published sequences. Multiple regression analysis showed that the frequency of core gene mutations was significantly associated with precore stop‐codon mutation, hepatitis B e antigen negativity, and active liver disease, but not patients' age. The mean number of amino acid changes/patient for hepatitis B e antigen (HBeAg)‐positive patients with elevated versus normal aminotransferase levels were, respectively, 2.8 ± 0.4 and 0.6 ± 0.2. The corresponding values for HBeAg‐negative patients were, respectively, 5.0 ± 1.2 and 6.0 ± 1.5. Thirteen patients were serially studied, the mean rates of amino acid substitution in HBeAg‐positive patients who did or did not clear HBeAg during follow‐up were 5.7 ± 0.8 and 0 per codon/yr. Most of the mutations were clustered in the middle of the core gene that harbor several major B‐ and helper T‐cell epitopes. Very few mutations were found in the C‐terminal part of the core gene. In summary, mutations in the core gene can be frequently detected in patients with chronic HBV infection. These mutations occur predominantly around the time of HBeAg clearance when liver disease is most active. (HEP

ISSN:0270-9139    

DOI:10.1002/hep.1840220109

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractTo assess the significance of cell‐mediated immunity, T cells were derived from the peripheral blood and liver tissue of hepatitis B virus (HBV)‐infected patients and controls. The analysis of theH‐thymidine‐uptake in response to a panel of recombinant HBV antigens revealed that peripheral blood mononuclear cells (PBMC) of the 25 viremic patients with inflammatory active, chronic hepatitis B, 16 with wild‐type and nine with HBe‐minus HBV mutant infection, showed stronger proliferative responses to HBc and HBe antigens than 16 asymptomatic nonviremic HBsAg carriers with normal aminotransferase levels (HBc: SI 19.3 ± 3.9 vs. 13.0 ± 3.2 vs. 8.0 ± 1.2;P<.01 and HBe: SI 16.6 ± 4.0 vs. 10.7 ± 3.5 vs. 6.9 ± 1.5;P<.05). In 15 patients with acute self‐limited hepatitis B, however, significantly stronger HBc antigen‐specific T‐cell responses were observed during HBV clearance and HBe/anti‐HBe seroconversion, whereas in nine completely HBV‐immunized patients only minor proliferative responses to HBV antigens were observed. Six HBe/HBcAg‐ and two HBeAg‐specific CD4+T‐cell lines could be expanded from liver tissue and peripheral blood of six viremic patients with chronic hepatitis B. Irrespectively of HBV mutations the HBV‐specific activation of the T‐cell lines was restricted by the presence of HLA‐DR molecules and resulted in the release of Th1‐like cytokine patterns. Follow‐up of interferon (IFN) recipients showed simultaneous short‐term increase of HBc/HBe‐ specific T‐cell reactivities in responder patients during HBV clearance and HBe/anti‐HBe seroconversion, whereas in nonresponders high virus load and HBV‐specific immune responses were in imbalance. In conclusion, HBe/HBc‐specific CD4+helper T cells are related to disease activity. From patients with HBe‐minus HBV mutants HBeAg‐specific T cells could be obtainedin vitro, suggestive of viral escape from the host immune response. We speculate that HBe/HBcAg‐specific T helper cells are required to mount an efficient

ISSN:0270-9139    

DOI:10.1002/hep.1840220110

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractEvidence indicates that the accumulation of glutamine in the brain plays an important role in the pathogenesis and severity of the encephalopathy of acute liver failure (ALF). This study usesin vivoproton magnetic resonance spectroscopy (H MRS) to assess brain glutamine (GLN) in five cases of acute liver failure. The findings are consistent with prior investigations and suggest that the alphaH of the GLN molecule can be used for noninvasive spectroscopic quantitation of brain GLN in patients with ALF. (HEPATOLOGY1995;22:69–74

ISSN:0270-9139    

DOI:10.1002/hep.1840220111

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY