摘要:

AbstractThe advent of specific antiviral therapy for chronic hepatitis C has increased the importance of establishing the correct etiology of chronic hepatitis in patients, especially because interferon alfa (IFN‐α) has been reported to exacerbate autoimmune hepatitis (AIH), whereas corticosteroids increase viral replication in chronic hepatitis C. In our medical center, we have treated many patients with apparent chronic hepatitis C and serological or clinical evidence of autoimmunity. Our aim was to estimate the prevalence of this association and to learn whether demographic or clinical features distinguished between patients with or without autoimmune markers. We performed a retrospective review of the records of 244 unselected patients seen at the Clinics and Hospital of the University of Massachusetts between May 1991 and November 1993, who had elevated serum aminotransferases. One hundred seventeen patients had chronic hepatitis C defined by elevations of serum alanine transaminase (ALT) for at least 6 months, positive serum antibodies to hepatitis C virus (HCV; second‐generation enzyme immunoassay [EIA2] or recombinant immunoblot assay [RIBA]), and absence of hepatitis B surface antigen in the serum. Records were reviewed for results of autoimmune markers in sera, including anti‐nuclear antibodies (ANAs), anti—smooth muscle antibodies (SMAs), rheumatoid factor (RF), anti‐mitochondrial antibodies (AMAs), anti—liver and kidney microsomal (LKM) antibodies, and cryoglobulins. We found a high prevalence of positivity, particularly for anti‐SMAs (66%) and RF (76%) in both men and women. Forty of 41 patients tested negative for anti‐LKM antibodies. There were no significant differences in age, gender, severity of hepatitis, or response to IFN between those who were positive for autoimmune markers and those who were not. None of the patients treated with IFN developed clinical manifestations of autoimmune disease. We conclude that markers of autoimmunity occur with high and equal frequency in men and women with chronic hepatitis C. Their presence should not preclude therapy with IFN, which often improves hepatitis and features of autoimmune disease in pa

ISSN:0270-9139    

DOI:10.1002/hep.1840210302

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractHepatocyte turnover rates were studied in two lineages of transgenic mice that overproduce the hepatitis B virus (HBV) large envelope protein and retain filamentous hepatitis B surface antigen (HBsAg) particles in the endoplasmic reticulum, resulting in the formation of ground glass hepatocytes. The high producer lineage (50‐4) develops a necroinflammatory liver disease that progresses to hepatocellular carcinoma (HCC), whereas the low producer lineage (107‐5) displays no histopathologic changes other than ground glass hepatocytes. Bromodeoxyuridine (BrdU)‐labeling studies of S‐phase hepatocytes provide quantitative evidence for a strong, sustained proliferative response in the hepatocytes in lineage 50‐4 that occurs after the onset of hepatocellular injury but long before the development of liver cell tumors. In contrast, the level of hepatocellular proliferation in lineage 107‐5 is the same as nontransgenic controls. The findings support the concept that sustained hepatocellular proliferation plays an important role in the development of hepatocellular carc

ISSN:0270-9139    

DOI:10.1002/hep.1840210303

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractThe objective of this study was to evaluate the role of hepatitis B virus (HBV) precore mutations in patients with anti‐HBe—positive chronic hepatitis B with or without previous known HBe antigen (HBeAg) viremic phase, and to assess the potential implication of precore mutants in HBeAg—negative reactivation after loss of HBeAg. Nineteen patients were studied: 7 had a previous HBeAg‐positive phase and had spontaneous or therapeutically induced loss of HBeAg (group A); 12 had no previous HBeAg‐positive phase (group B). Direct sequencing of PCR products was performed on serum collected during the anti‐HBe—positive phase in the two groups. In group A, precore sequencing showed that 5 patients were infected by wild‐type virus, 1 patient was infected with a precore mutant, and 1 patient was found to be infected by a mixture of wild‐type and precore mutant viruses. In group B, precore sequencing showed that only 1 patient was infected with wild‐type virus and that 11 were infected with precore mutants. In a few patients, the presence of HBeAg within immune complexes may explain HBeAg negativity. In conclusion, our results show that, in patients with anti‐HBe—positive chronic hepatitis B: (1) precore mutations creating a stop codon are more frequently found in those without known previous HBeAg positivity; (2) after loss of HBeAg, the patients who have anti‐HBe—positive reactivation are infected by wild‐type virus, which suggests that reactivation is not related to precore mutations; (3) HBeAg negativity may be caused

ISSN:0270-9139    

DOI:10.1002/hep.1840210304

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractIn acute and chronic viral disease the specific response of CD4+T lymphocytes to certain viral proteins is an essential part of antiviral effector mechanisms. In hepatitis C virus infection, the contribution of the immune system and particularly of CD4+T lymphocytes to the pathogenesis of disease is unknown. We serially determined the peripheral blood CD4+T lymphocyte response to several recombinant hepatitis C virus proteins (core, NS3, NS4, NS5) and 17 overlapping synthetic peptides derived from the core sequence over up to 48 months in 43 patients with chronic hepatitis C; of these, 16 had been treated with interferon alfa (IFN). Twelve of 27 untreated patients, 4 of 4 sustained responders to IFN, 7 of 8 patients with a transient response, and 1 of 4 nonresponders showed a proliferative response to hepatitis C virus proteins. The hepatitis C virus core protein was the most immunogenic protein, and fine analysis with peptides indicated amino acids 23 to 42, 66 to 85, and 131 to 150 as immunodominant regions. In a subgroup of nine patients, proliferation assays were performed before or during IFN. In this subgroup, sustained responders but not those with a transient or no response to IFN showed a specific CD4+immune reaction to hepatitis C viral antigens (P<.05). Infection with hepatitis C virus genotype 3a was significantly associated with a sustained response to IFN (P<.05). In general, a CD4+T lymphocyte response was more common in patients with chronic hepatitis C who responded to interferon‐alpha as compared with nonresponders. Thus a strong CD4+reaction before and during IFN therapy may be a predictor of sustained respons

ISSN:0270-9139    

DOI:10.1002/hep.1840210305

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractPersistent viremia after clinical or subclinical hepatitis C virus (HCV) infection is believed to occur in patients with chronic hepatitis C, but little is known about the duration of HCV replication in patients with acute hepatitis who have recovered or the relation of HCV viremia with the kinetics of antibodies to HCV (anti‐HCV). We tested HCV‐RNA and anti‐HCV in serial serum samples from 41 patients with posttransfusion non‐A, non‐B hepatitis, followed for an average of 6 years after transfusion. Serum HCV‐RNA was measured by nested polymerase chain reaction, which used primers from the 5′ untranslated region of the HCV genome. Anti‐HCV were tested with first‐ and second‐generation enzyme‐linked immunosorbent assays (ELISA 1 and ELISA 2), and with a second‐generation recombinant immunoblot assay. Of the 41 patients, 10 recovered and 31 progressed to chronic liver disease. HCV‐RNA was detected in serum before or simultaneously with the onset of hepatitis in all cases, and lasted between 2 and 6 weeks in 5 of the 10 patients who recovered, whereas it persisted for the entire follow‐up period in every case with chronic hepatitis and in the remaining 5 patients with self‐limiting hepatitis. Anti‐HCV were detected with ELISA 2 in the first serum sample, with raised serum transaminases in 57% of patients, but in only 6% with ELISA 1. In the sample obtained 1 month after the onset of hepatitis, anti‐HCV were detected with ELISA 2 in 94% of patients, but in 34% with the ELISA 1. Anti‐HCV (anti C‐33 and anti‐c22) were cleared in the five patients with transient hepatitis C viremia, but remained detectable in those with chronic viremia. In conclusion, serum HCV‐RNA is detected at the onset of acute posttransfusion hepatitis C and persists in patients progressing to chronic hepatitis. Some patients with self‐limiting hepatitis become HCV‐RNA negative soon after the onset of hepatitis, whereas in others it persists throughout follow‐up, sugge

ISSN:0270-9139    

DOI:10.1002/hep.1840210306

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractRecombinant interferon alfa (r‐IFNα2) has been shown to normalize the aminotransferase levels in approximately 50% of patients with chronic hepatitis C virus (HCV). Few patients experience a relapse during the treatment, in spite of a complete initial response (breakthrough). We studied 191 HCV Ab‐positive patients with histologically proven chronic hepatitis. All of them were treated with r‐IFNα2 (3 MU three times a week). A complete response was seen in 54.4%. However, 12 of 104 responders experienced a breakthrough. At the time of breakthrough, neutralizing IFN antibodies were positive in 6 of 12 patients. Binding IFN antibodies were positive in all of these 12 patients. Continued treatment with r‐IFNα2, even at higher doses, did not restore the previous response in any patient. All of them were then switched to natural lymphoblastoid IFN, and this rapidly restored a complete response in all of th

ISSN:0270-9139    

DOI:10.1002/hep.1840210307

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractThe incidence of hepatocellular carcinoma (HCC) was prospectively studied in 251 chronic hepatitis patients, and was compared between the 127 cases of hepatitis B and 124 cases of hepatitis C. All patients were diagnosed by needle biopsy on entering the study, and the cases consisted of chronic persistent hepatitis (CPH), chronic active hepatitis (CAH)2a, and CAH2b (cirrhosis was not included). Of the cases of chronic hepatitis B, 5 cases of HCC (3.9%) were detected; among the chronic hepatitis C cases, 13 cases (10.4%) were detected. Thus, although the mean follow‐up periods were in the same range, the incidence of hepatocellular carcinoma was 2.7 times higher in hepatitis C than in hepatitis B (χ2= 3.116,P<.05). Using the Kaplan‐Meier method, the incidence of HCC was significantly higher in chronic hepatitis C (P= .0194, generalized Wilcoxon test). In hepatitis C, the incubation period until HCC was detected was shorter when the liver disease was more advanced. Such a tendency was not observed in hepatitis B. In the 13 cases of HCC occurring in chronic hepatitis C, noncirrhotic liver was seen in only 1 case (7.7%), whereas 2 of the 5 cases of HCC (40%) in chronic hepatitis B were noncirrhotic. The prevalence of hepatitis C virus (HCV) genotypes II and III was the same in the total followed cases and HCC c

ISSN:0270-9139    

DOI:10.1002/hep.1840210308

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractDuring the cross‐sectional studies (February 1981 to July 1984) performed by the Group for Epidemiology and Prevention of Cholelithiasis (GREPCO) in Rome, Italy, 161 subjects were identified as having gallstones. Ten subjects did not participate in the prospective follow‐up. At entry, 33 of the 151 remaining subjects were symptomatic, and 118 were asymptomatic. Data on incidence of biliary colics, complications, cholecystectomy, and death were collected at least every 2 years. In the initially asymptomatic group, the cumulative probability (% ± SE) of developing biliary colic was 11.9 ± 3.0 at 2 years, 16.5 ± 3.5 at 4 years, and 25.8 ± 4.6 at 10 years. None of the variables considered as possible modifiers of the natural history were found to be associated with an increased risk of developing biliary colic. The cumulative probability (% ± SE) of developing complications after 10 years was 3.0 ± 1.8 in the initially asymptomatic group and 6.5 ± 4.4 in the symptomatic group (P= NS). Incidence of cholecystectomy was higher in the initially symptomatic than in the asymptomatic group (log‐rank test = 2.27;P= .02). Fifteen (53.6%) of the 28 operated in the initially asymptomatic group were submitted to cholecystectomy, although specific symptoms did not occur. Twelve (10.2%) and 2 (6.1%) of the initially asymptomatic and symptomatic subjects died during the follow‐up. One patient in the former group died at age 64 of a histologically proven adenocarcinoma of the gallbladder. In conclusion, this study demonstrates that the natural history of gallstones is less benign than is genera

ISSN:0270-9139    

DOI:10.1002/hep.1840210309

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractThe efficacy of endoscopic treatment in primary sclerosing cholangitis has not been clearly established. This report presents endoscopic intervention in 53 consecutive patients with this disorder. Pertinent data were abstracted from the GI‐TRAC database, medical records, and cholangiograms, and clinical follow‐up was obtained by telephone interview of the subjects. Assessed treatment outcomes were clinical symptom, liver function test, and cholangiographic appearance. Between 1986 and 1993, 85 patients with primary sclerosing cholangitis underwent successful ERCP, of which 36 men and 17 women underwent 100 therapeutic endoscopic procedures. Forty‐three of 50 dilations, 37 of 38 stentings, 8 of 8 nasobiliary tube placements, and 11 of 17 stone extractions were technically successful. These treatments were complicated by cholangitis or pancreatitis in 15 patients. Clinical follow‐up was obtained in 50 of 53 patients who had undergone 85 procedures (median follow‐up of 31 months): 28 patients felt better, 21 felt the same, and 1 felt worse. Liver function tests obtained within 3 months of the endoscopic treatment were significantly improved compared with pretreatment values (P<.001). Cholangiograms showed improvement in 36% of the patients, no change in 51%, and the effect of therapy could not be assessed in 13%. Overall, 41 of 53 patients (77%) had improvements of their clinical symptoms, liver function tests, or chola

ISSN:0270-9139    

DOI:10.1002/hep.1840210310

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY

摘要:

AbstractSpontaneous bacterial peritonitis (SBP) is a frequent and severe complication of cirrhosis.Escherichia coliis the most frequent bacterium isolated in this condition. The presence of capsular antigens, mainly the K1 capsular polysaccharide, has been associated with invasiveness inE coliinfections. Capsular serotypes ofE colicausing SBP were determined in 37 cirrhotic patients. Twenty‐seven strains were encapsulated (72.9%), 9 of them (24.3%) with K1 capsular polysaccharide, and 10 were nonencapsulated. Patients with encapsulatedE colishowed a significantly higher incidence (92.5% vs. 50%;P<.01) and number of complications per patient (1.9 ± 1.1 vs. 0.8 ± 1.0;P<.01) than patients with nonencapsulated strains. Although mortality was higher in patients with encapsulated strains (44.4% vs. 20%), the difference did not reach statistical significance. Considering patients infected by encapsulated strains, the incidence of complications and mortality were similar in patients with or without K1 strains. These data suggest that the presence of encapsulated strains could have a prognostic significance in SBP caused byE coliin cirrhotic patie

ISSN:0270-9139    

DOI:10.1002/hep.1840210311

出版商:W.B. Saunders    

年代:1995

数据来源: WILEY