Biomedical subjects

B C Portmann

Publications and source records attributed to B C Portmann.

At least 37 records · Page 2Linked to original sources

PubMed1995

Ribavirin therapy for hepatitis C infection following liver transplantation.

Hepatitis C infection following orthotopic liver transplantation may lead to progressive chronic graft dysfunction. In this study, seven liver transplant recipients with chronic allograft dysfunction due to hepatitis C infection (one acquired and six recurrent infections) were treated with oral ribavirin for 6 months. Symptoms of lethargy, nausea and anorexia improved in all patients within 2 weeks of starting the drug, with a fall in serum AST of at least 40% by this time. Ribavirin-induced haemolysis was clinically significant in three patients, necessitating a reduction in the daily dose of ribavirin from 1.2 g to 0.2 g. Comparison of the pre- and post-treatment biopsy specimens in the four patients who tolerated the full dose of ribavirin and who had normal AST levels at the end of 6 months of treatment showed significant histological improvement with reduction in either lobular or periportal inflammation in all of the patients and a reduction in periportal fibrosis in one patient. HCV RNA remained detectable in serum in all of the patients at the end of the study.

Female↗

PubMed1995

Detection of hepatitis E virus genome and gene products in two patients with fulminant hepatitis E.

Non-isotopic in situ hybridization (digoxigenin-labeled probe directed towards hepatitis E virus ORF1) and immunohistochemistry (against hepatitis E virus ORF2 and ORF3) were applied to detect hepatitis E virus genome and gene product in the liver tissue of two patients with fulminant hepatitis E seropositive for hepatitis E virus RNA. Both hepatitis E virus RNA and hepatitis E virus antigens were detected exclusively in the cytoplasm of hepatocytes and not detected in other cell types. In both patients, more than 50% of the hepatocytes were positive for both hepatitis E virus RNA and hepatitis E virus antigens, most of which showed degenerative changes. This is consistent with the histological appearance of marked loss of hepatocytes with acinar collapse. Interestingly, denaturation of the RNA before in situ hybridization was found to enhance hepatitis E virus RNA detection. We conclude that: (1) hepatitis E virus RNA and hepatitis E virus antigens can be demonstrated in the liver in hepatitis E virus-related fulminant hepatitic failure, (2) hepatitis E virus is hepatocyte-tropic within the liver, (3) cytoplasmic localization of hepatitis E virus RNA and hepatitis E virus antigens is consistent with cytoplasmic replication, and (4) the presence of degenerative changes in hepatitis E virus positive cells, together with the histological appearance of hepatocyte loss in the absence of significant inflammatory infiltrate, suggests that hepatitis E virus-related fulminant hepatitic failure is mediated by a cytopathic mechanism.

Acute Disease↗

PubMed1995

Serum intercellular adhesion molecule-1 levels in chronic hepatitis C: association with disease activity and response to interferon alpha.

Soluble intercellular adhesion molecule-1 (sICAM-1) is probably released from a variety of cells, including leukocytes and endothelial cells at sites of inflammation or in the circulation, and serum levels may therefore be used to give an indication of immune activation and inflammatory processes. In the present study, an ELISA was used to measure serum ICAM-1 levels in 43 patients with chronic hepatitis C and these were correlated with histological changes in the liver and the response to interferon alpha treatment. Serum ICAM-1 levels were significantly higher in patients with chronic hepatitis C infection than in normal subjects and correlated positively with the grade of histological activity, in particular the degree of portal, periportal, and lobular inflammation, but not with the presence of lymphoid aggregates. There was also a weak but significant positive correlation between sICAM-1 and serum aspartate aminotransferase activities, and sICAM-1 levels were substantially greater in patients with than those without cirrhosis. Serum ICAM-1 levels fell significantly in 11 responders out of 19 patients treated with interferon alpha, whereas levels remained unchanged in the non-responder group. sICAM-1 levels correlate with the clinical status of patients with chronic hepatitis C infection and fall with successful interferon treatment.

Adult↗

PubMed1995

Prevalence and pattern of familial disease in primary biliary cirrhosis.

Susceptibility to primary biliary cirrhosis (PBC) may be partly inherited although instances of PBC within families are only infrequently described. The records of 736 patients with PBC seen over a 25 year period were examined to identify those with a positive family history. Ten patients originating from eight families were identified, giving a frequency of 1.33%. They comprised mother and daughter pairs; in two families both mother and daughter had been seen at our clinic. The daughters presented at an earlier age, median 36 years (range 24-54), than the mothers, 52 years (50-81). During follow up one daughter (45 years) and six mothers have died (range 53-81 years) and two mothers and one daughter have had a transplant aged 57, 57, and 30 years respectively. It is concluded that familial PBC is not rare, that it is related to maternally inherited factors, and that disease tends to present earlier in the second generation.

Age Factors↗

PubMed1995

Hepatocellular carcinoma complicating autoimmune hepatitis: role of hepatitis C virus.

The risk of hepatocellular carcinoma in autoimmune hepatitis is low, even in patients with long-standing cirrhosis. Because of the increasing recognition of an association of hepatitis C virus (HCV) with autoimmune hepatitis, at least in some geographical areas, and with hepatocellular carcinoma (HCC) (hepatoma), we have examined eight cases (4 male, 4 female) who presented between 1985 and 1993 with hepatoma complicating autoimmune hepatitis. All had steroid-responsive autoimmune hepatitis with serum anti-smooth muscle and anti-nuclear autoantibodies. Median duration of disease was 17.1 years, and all patients had biopsy-proven cirrhosis. One patient had a history of intravenous drug abuse, and four had previously received blood transfusions. Serum samples (stored at -20 degrees C from up to 9 years before diagnosis of hepatoma) were tested for anti-hepatitis C virus antibodies by a second-third-generation assay and for HCV RNA by the polymerase chain reaction method using primers from the 5'noncoding region. Tissue from liver adjacent to tumor areas was subjected to polymerase chain reaction along with tissue from previous liver biopsy specimens (taken up to 19 years before diagnosis of hepatoma) in all patients. Six patients had evidence of HCV infection: four seropositive for HCV RNA (two of whom were also anti-HCV positive) and two seronegative for HCV RNA and anti-HCV but with HCV RNA in liver tissue at presentation with hepatoma. Retrospective testing showed probable acquisition of HCV through blood transfusion in the four transfused patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1994

Hepatic and extrahepatic hepatitis C virus replication in relation to response to interferon therapy.

Response to a 1-yr course of interferon-alpha 2b was assessed in 18 patients with chronic hepatitis C virus infection in relation to clinical, biochemical and histological parameters and to the presence or absence of hepatitis C virus RNA and the presumed replicative form of the virus (negative-strand hepatitis C virus RNA) in serum, liver and peripheral blood mononuclear cells. The findings were compared with those in seven untreated patients studied over the same period. At the start of the study, positive-strand hepatitis C virus RNA was found in sera of all 25 patients, in livers of 24 and in peripheral-blood mononuclear cells of 19 of 22 tested; negative strand was found in livers of 11 and in peripheral-blood mononuclear cells of 15 of 22. Negative-strand hepatitis C virus RNA was not found in the serum of any patient at any stage. All of the five treated patients considered to show complete response during the study period cleared hepatic hepatitis C virus RNA, and four also became seronegative, but three had evidence suggestive of viral replication in their peripheral-blood mononuclear cells; two of these last patients subsequently relapsed. Loss of hepatic hepatitis C virus RNA was the only significant difference between these five and the seven partial and six nonresponders, but it is uncertain whether the observed changes were due specifically to interferon-induced modulation of virus expression because similar (apparently spontaneous) changes were seen in four of the untreated patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Recurrence of hepatitis C following orthotopic liver transplantation: a polymerase chain reaction and histological study.

Hepatitis C virus was sought by nested polymerase chain reaction in the preoperative biopsy or the explanted liver of 100 consecutive adult patients undergoing orthotopic liver transplantation. In those found to be positive preoperatively, polymerase chain reaction was performed on subsequent biopsies. Of the 12 patients in whom HCV-RNA was identified in the liver by polymerase chain reaction preoperatively, viral recurrence was documented in ten of the 11 with posttransplant liver tissues available for study. In the one exception, hepatitis C virus was undetectable in the liver graft despite repeated co-amplification of albumin mRNA as an internal control, which may indicate viral clearance. In eight of the ten positive cases, HCV-RNA was also detectable in serum postoperatively, while HCV-RNA was undetectable in serum in both the cases in whom HCV-RNA was undetectable in tissue and in the patient who declined post-transplant biopsy. Two of the 12 patients infected with hepatitis C virus preoperatively have died during the follow-up period from causes unrelated to hepatitis C virus infection. While biochemical liver function in seven of those remaining has been excellent, histological evidence of at least mild chronic active hepatitis has been present in all ten cases for whom long-term biopsies are available. Three cases have progressed to severe, symptomatic chronic active hepatitis within 2 years of transplantation. Recurrent hepatitis C is associated with progressive liver disease and appreciable morbidity in a significant proportion of patients.

Adult↗

PubMed1994

Fulminant hepatic failure secondary to hydroxychloroquine.

Hydroxychloroquine is widely used in rheumatological disease but hepatic side effects have not been reported previously. Two cases are described of fulminant hepatic failure developing after the start of hydroxychloroquine treatment for a chronic rheumatological disorder. In both cases the symptoms of liver disease developed within two weeks of starting hydroxychloroquine and rapidly progressed to fulminant hepatic failure and in neither case was there any pre-existing liver disease. One patient had emergency orthotopic liver transplantation and the other died before a donor organ became available.

Adolescent↗

PubMed1993

Loss of HBsAg with interferon-alpha therapy in chronic hepatitis D virus infection.

Eleven patients with chronic hepatitis D virus (HDV) infection who had chronic active hepatitis and HDV antigen on liver biopsy were randomised in a crossover therapeutic trial of interferon-alpha 2b vs. no therapy. Nine patients had a history of intravenous drug use (drug free > 6 months before therapy), 8 had histological evidence of cirrhosis, and 7 out of 10 tested were found to be seropositive for antibody to hepatitis C virus (HCV). Six patients were randomised to receive interferon-alpha 2b therapy for 1 year, and 5 patients received no therapy for 1 year followed by the same regime of interferon-alpha 2b treatment. All patients with a history of intravenous drug use found self-injection stressful, 3 patients restarted using illicit drugs, and 2 patients with active cirrhosis developed severe thrombocytopenia during therapy and treatment was stopped in these patients. Of the 6 patients who completed at least 11 months of treatment, 4 lost serum hepatitis B surface antigen (HBsAg) with 3 developing antibody to HBsAg and one patient completing treatment. Among the 6 patients who had posttreatment liver biopsy, 5 showed an improvement in liver histology (3 of them lost serum HBsAg). These results provide further evidence that interferon-alpha is beneficial in chronic HDV infection although the psychological stress associated with the treatment, especially in patients with a previous history of intravenous drug use, is not inconceivable.

Adult↗

PubMed1993

Hepatic alpha-interferon expression in cytomegalovirus-infected liver allograft recipients with and without vanishing bile duct syndrome.

In previous studies cytomegalovirus (CMV) infection was identified as one risk factor in the development of vanishing bile duct syndrome (VBDS) after orthotopic liver transplantation (OLT), but its precise role in relation to the pathogenesis of tissue damage is uncertain. In the present study alpha-interferon (alpha-IFN) expression in the liver was studied as an indirect marker of viral infection in serial liver biopsies from 42 patients following OLT. alpha-IFN was identified more frequently in the bile duct cytoplasm of patients developing VBDS, with or without evidence of preceding CMV infection (7/8 and 4/5 cases, respectively), when compared with patients with acute CMV but without evidence of VBDS (6/19 cases; P < 0.05) or those with neither complication (2/10 cases; P < 0.01). alpha-IFN was detectable in bile duct cytoplasm for a longer period in patients developing VBDS than in those with acute CMV infection alone (median 14 weeks and range 9-19, median 6 weeks and range 1-11 weeks, respectively; P < 0.025). These data indicate that persistent CMV infection of bile duct cells is a likely co-factor linked to progression to VBDS, but the processes that allow persistent viral infection and bile duct destruction remain to be determined.

Bile Duct Diseases↗

PubMed1993

Hepatic 60-kD heat-shock protein responses in alcoholic hepatitis.

The precise mechanism of the pathogenesis of alcoholic hepatitis is unknown, but immune involvement may perpetuate and exacerbate the process. Heat-shock proteins, normally protective, may be immunogenic and have been shown to induce antibody formation in some inflammatory conditions. Alcohol, cellular hypoxia and tumor necrosis factor, all involved in alcoholic hepatitis, are potent inducers of heat-shock protein. In this study, we sought 60-kD heat-shock protein in liver tissue with a murine monoclonal antibody and measured circulating antibody to 60-kD heat-shock protein on ELISA. Fourteen of 20 livers from patients with acute alcoholic hepatitis expressed 60-kD heat-shock protein in hepatocyte cytoplasm in a diffuse pattern with superimposed clusters; other cell types were occasionally positive. Twelve of these patients had high-titer IgA 60-kD heat-shock protein antibody in serum. In contrast, 60-kD heat-shock protein was identified in only 2 of the 10 patients with alcoholic cirrhosis without hepatitis (p = 0.013). These two patients had severe liver disease, and one patient in this group was seropositive for IgA 60-kD heat-shock protein antibody. Eight alcoholic patients with fatty liver alone were negative for antigen, and all but one were negative for antibody. The 10 patients without liver damage were negative for antigen and antibody. The findings that 60-kD heat-shock protein is present in liver tissue of patients with acute alcoholic liver damage and that circulating IgA 60-kD heat-shock protein antibody levels are increased may point to one pathogenetic mechanism underlying development and progression of liver damage in alcoholic hepatitis.

Adult↗

PubMed1992

Cytomegalovirus infection persists in the liver graft in the vanishing bile duct syndrome.

Cytomegalovirus infection is one factor implicated in the cause of the vanishing bile duct syndrome complicating liver transplantation. To further investigate the role of cytomegalovirus in this syndrome, we studied serial liver biopsy material by in situ hybridization for cytomegalovirus DNA using a highly sensitive technique that allows the localization of viral replication. Cytomegalovirus DNA was identified in hepatocytes in 10 of 12 patients with the vanishing bile duct syndrome, 1 of whom had no serological evidence of cytomegalovirus infection. It was also present in all 18 patients with uncomplicated cytomegalovirus infection but was not identified in any of 10 subjects with transplants who had neither complication. Nine of the patients in this series underwent a diagnostic liver biopsy at 1 wk and subsequently had cytomegalovirus infection develop; cytomegalovirus DNA was identified in liver tissue of all nine patients, indicating that cytomegalovirus replication commences at an early stage. In those with uncomplicated cytomegalovirus, infection occurred earlier (p less than 0.05) but was eliminated more quickly (p less than 0.0005), and the number of infected hepatocytes was greater (p less than 0.05) when compared with those with the vanishing bile duct syndrome; in these, cytomegalovirus DNA was detectable until death or retransplantation. Cytomegalovirus DNA was never identified in either biliary or endothelial tissue. These data indicate that the vanishing bile duct syndrome is associated with persistent cytomegalovirus replication within hepatocytes.

Cholestasis↗

PubMed1992

Syncytial giant-cell hepatitis--a specific disease entity?

Syncytial giant-cell hepatitis was recently reported to be related to a paramyxovirus and carried a poor prognosis. Twelve patients with syncytial giant-cell hepatitis seen in an 8 1/2-year period in our institute were reviewed. Seven patients had an identifiable aetiological cause: two had autoimmune chronic active hepatitis, one had primary sclerosing cholangitis and autoimmune chronic active hepatitis, two presented with prolonged jaundice after acute hepatitis A and B, one had chronic Epstein-Barr virus infection and the remaining patient was seropositive for antibody to hepatitis C virus. One patient with autoimmune chronic active hepatitis who had frequent syncytial giant cells in the liver responded promptly to corticosteroid treatment and a repeated biopsy 3 years later showed histological improvement with a marked decrease in the number of syncytial giant cells. Of the remaining five patients, three ran a clinical course of fulminant hepatic failure and two had severe chronic active hepatitis. These data indicate that syncytial giant-cell hepatitis is unlikely to be related to only one single aetiological agent and that syncytial giant-cell hepatitis does not always carry an ominous prognosis.

Adolescent↗

PubMed1992

Evidence that hepatitis D virus needs hepatitis B virus to cause hepatocellular damage.

Serial liver biopsy specimens from 11 patients who had liver transplants after hepatitis D virus (HDV)-related end-stage liver disease developed were examined, allowing a novel opportunity to study the evolution of HDV infection in relation to hepatitis B virus (HBV) infection from the earliest stages. Hepatitis D virus antigen was detected in liver tissue in the absence of either tissue or serologic evidence of HBV recurrence within 3 months in all eight patients biopsied at that time. After serologic evidence of recurrent HBV infection in nine patients, there was a massive increase in hepatic expression of hepatitis D virus antigen and this was associated with the transient appearance of serum hepatitis D virus antigen in four patients. Coexpression of both HBV and HDV antigens in the liver was associated with the onset of lobular hepatitis, which progressed to chronic hepatitis in five patients. These findings indicate that HDV can survive and synthesize HDAg in the absence of detectable HBV, but when HBV replication increased to a detectable level, HDV replication was enhanced massively. Contrary to current thinking, the data suggest that HDV is not directly cytopathic and that HBV is an essential cofactor in the evolution of hepatocellular damage.

Adult↗

PubMed1992

Differential effect of chronic hepatitis D virus infection on intrahepatic expression of hepatitis B viral antigen.

AIMS: To determine how chronic hepatitis D virus (HDV) infection affects intrahepatic hepatitis B virus (HBV) antigen expression. METHODS: Ninety eight liver biopsy specimens from 68 patients seropositive for total antibody to HDV were studied by immunohistochemistry, and the amount of HBV antigens was also quantified by radioimmunoassay in 12 patients and compared with 30 patients with chronic HBV infection. RESULTS: Forty nine of the 68 patients were positive for intrahepatic HDV antigen and only five were positive for HBV core antigen (HBcAg). HBV surface antigen (HBsAg) was present in 55 (80.9%) patients and was always cytoplasmic in distribution. Hepatic pre-S1 and pre-S2 expressions paralleled that of HBsAg, and were detected in 53 (77.9%) and 54 (79.4%) patients, respectively. There was no relation between the intrahepatic expression of HDV antigen and HBsAg/pre-S1/pre-S2. Follow up biopsy specimens in 25 patients showed either static or deteriorating histology while intrahepatic HDV antigen remained the same or fell. The patients with intrahepatic expression of HBcAg had either absent or noticeably decreased expression of HBcAg in their follow up biopsy specimens (median two years). In contrast, HBsAg/pre-S1/pre-S2 were the same or increased (p less than 0.001). Quantification of intrahepatic HBsAg in patients with chronic HDV infection (0.61 pg/hepatocyte, range: 0.05-1.08, n = 12) showed no difference with patients with chronic HBV infection alone (0.64 pg/hepatocyte, range: 0.02-1.02, n = 30, p = NS). CONCLUSION: These data indicate that chronic HDV infection suppresses intrahepatic expression of HBcAg but not HbsAg and pre-S antigens, suggesting a differential effect of chronic HDV infection on HBV gene expression.

Adult↗

PubMed1991

Significance of IgM anti-hepatitis D virus (HDV) in chronic HDV infection.

Intrahepatic hepatitis D virus (HDV) antigen (HDAg) and serum HDV RNA are excellent markers of active HDV replication but the relation of IgM anti-HDV to HDV replication and histological activity is less certain. To further elucidate the significance of serum IgM anti-HDV, 90 paired sera and liver biopsies from 64 patients seropositive for total antibody to HDV were analysed for IgM anti-HDV, intrahepatic HDAg expression, and histological inflammatory activity. IgM anti-HDV was strongly associated with intrahepatic HDAg expression with a sensitivity of 94.1% but the assay lacked specificity since 14 out of 22 cases negative for intrahepatic HDAg were also positive for IgM anti-HDV. In 20 patients in whom follow-up biopsies and paired sera were available, two patients lost intrahepatic HDAg but paired serum remained IgM anti-HDV positive. Although the presence of serum IgM anti-HDV correlated significantly with a higher histological inflammatory activity (P = 0.001), there was a considerable overlap with the group seronegative for IgM anti-HDV, again indicating a poor specificity. This lack of specificity of IgM anti-HDV for both HDV replication and histological activity indicates that this assay provides no additional information over and above assay for total antibody to HDV.

Antigens, Viral↗

PubMed1991

Natural history and prognostic variables in primary sclerosing cholangitis.

The clinical features at the time of presentation and the outcome in 126 patients with primary sclerosing cholangitis were studied to clarify the natural history and prognosis in symptomatic and asymptomatic individuals. The median age of the patients at the time of presentation was 36 years, 62% were male, and 16% were asymptomatic. The median follow-up from time of presentation was 5.8 years. There were more patients who had liver transplants (21%) than patients who died of liver-related disease (16%); the estimated median survival to these end points was 12 years. Cholangiocarcinoma was found in 8 patients and in 23% of those undergoing liver transplantation. Asymptomatic patients had milder disease than symptomatic patients, but in a univariate analysis the presence of symptoms was not prognostically significant. On multivariate analysis, the following independent prognostic factors were found: hepatomegaly, splenomegaly, serum alkaline phosphatase, histological stage, and age. These features were combined to produce a prognostic model that should be valuable in the stratification of patients in clinical trials and in the timing of liver transplantation, particularly in those patients seen soon after presentation.

Adenoma, Bile Duct↗

PubMed1991

Dual association of HLA DR2 and DR3 with primary sclerosing cholangitis.

Human leukocyte antigen typing was performed in 81 patients with primary sclerosing cholangitis to investigate reported associations between human leukocyte antigen type and this disease. The results showed a significant increase in the frequency of the antigens B8 and DR3 compared with controls (53% vs. 23%, p less than 0.0005, and 56% vs. 21%, p less than 0.0005). This was caused by a significant rise in the frequency of the human leukocyte antigen A1 B8 DR3 haplotype (32 of 81 patients, 40% vs. 12 of 100 patients, 12%, p less than 0.0005). By contrast, a significant reduction was seen in the frequency of the antigens B44 and DR4 (12% vs. 31%, p less than 0.005, and 12% vs. 34%, p less than 0.001, pc less than 0.011) because of the complete absence of the B44 DR4 haplotype in the patient group (p = 0.027, Fisher's exact test). When all the DR3-positive individuals (including the DR2/DR3 heterozygotes) were eliminated, a significant secondary association with DR2 was noted, 25 (69%) of 36 remaining patients being DR2-positive compared with 27 (34%) of 79 DR3 negative controls (p less than 0.0005, pc less than 0.006). Only 9% of the patients were DR2-positive and DR3-positive. Kaplan-Meier analysis demonstrated that survival was not influenced by the presence of either haplotype nor by the individual antigens. Patients who were DR3-positive were first seen at a significantly younger age than those who were DR2-positive (mean ages = 33 yr and 44 yr, respectively, p less than 0.002, Student's t test).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗