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Biomedical subjects

U Hopf

Publications and source records attributed to U Hopf.

At least 55 records · Page 3Linked to original sources
PubMed1997

Intravenous or intramuscular anti-HBs immunoglobulin for the prevention of hepatitis B reinfection after orthotopic liver transplantation.

To prevent reinfection with hepatitis B virus after orthotopic liver transplantation, patients receive long-term intravenous anti-HBs immunoprophylaxis. We compared the pharmacokinetics of intravenously and intramuscularly administered commercially available hepatitis B virus immunoglobulins. The study group consisted of 12 patients on immunoprophylaxis after orthotopic liver transplantation, who were Hbs antigen negative; 11 were anti-HBe positive and one was HBe positive. The patients first received intravenous immunoglobulin, and six of them were then transferred to intramuscular immunoglobulin. Our findings show that with fortnightly intramuscular application of 1000 IU of anti-HBs, reproducible and stable antibody titers above 100 IU of anti-HBs can be achieved. Side effects of intramuscular immunoprophylaxis are minimal and the method is safe. The switch from intravenous (1500 IU of anti-HBs) to intramuscular (1000 IU of anti-HBs) reduced the cost of immunoprophylaxis by more than 50%.

Adult↗
PubMed1997

A pretransplant infection with precore mutants of hepatitis B virus does not influence the outcome of orthotopic liver transplantation in patients on high dose anti-hepatitis B virus surface antigen immunoprophylaxis.

Hepatitis B virus (HBV) infection of the liver graft is a major complication after orthotopic liver transplantation (OLT) for HBV-related cirrhosis. A high viral load before OLT is a known risk factor, whereas the relevance of precore mutants of HBV is a subject of controversy. The aim of this study was to correlate the pretransplantation viral load and a pretransplantation infection with precore mutant HBV (pmHBV) or wildtype HBV (wtHBV) with allograft damage, graft failure, and survival after OLT. Sixty-nine patients with HBV cirrhosis underwent OLT under high dose immunoprophylaxis with anti-hepatitis B surface (HBs) hyperimmunoglobulins (HBIg). A pretransplantation infection with pmHBV and wtHBV was detected by polymerase chain reaction (PCR) and direct sequencing in 30 patients each (pmHBV and wtHBV group). Nine of 69 patients were PCR-negative (noHBV group). Median pretransplantation levels of HBV DNA assessed by hybridization assay were 42 pg/mL for pmHBV and 54 pg/mL for wtHBV patients. HBV recurred in 17 of 30 (57%) of pmHBV and in 14 of 30 (47%) of wtHBV patients and graft failure occurred in 6 of 30 (20%) of pmHBV and 7 of 30 (23%) of wtHBV patients. Neither HBV recurrence nor graft failure occurred in patients in whom no HBV DNA could be detected by PCR using primers flanking the HBV precore region (noHBV) patients. Allograft damage assessed by histology activity index (HAI) scoring was median 6 for pmHBV and 7 for wtHBV patients. Cumulative survival after 5 years was 72% for pmHBV, 74% for wtHBV, and 100% for noHBV patients. In this study, we provide evidence that pretransplantation viral load, but not infection with pmHBV, determines the outcome after OLT in patients on high dose HBIg prophylaxis.

Adult↗
PubMed1997

Distribution of hepatitis C virus genotypes in German patients with chronic hepatitis C: correlation with clinical and virological parameters.

BACKGROUND/AIMS: The hepatitis C virus genotypes have been shown to be differently distributed between distinct geographical areas and to be associated with different clinical presentations. In the present study we investigated the distribution of HCV genotypes in 379 German patients with chronic hepatitis C in relation to age, sex, route of infection, liver histology and viremia. METHODS: Typing of HCV was done using restriction fragment length polymorphism analysis as well as a DNA enzyme immunoassay. HCV RNA concentrations were determined by quantitative polymerase chain reaction. Liver biopsies were performed in 187 patients and the histological activity was graded by the Knodell score. RESULTS: Seventy percent were infected with genotype 1 (20% subtype 1a, 80% subtype 1b), 4% with genotype 2 and 26% with genotype 3 (all subtype 3a). Genotype 3a and 1a infection was significantly associated with intravenous drug abuse. In contrast, genotype 1 predominated in patients with post-transfusion hepatitis and infection of unknown origin. A changing relative prevalence of HCV genotypes in relation to age was also observed. Patients with genotype 3 infection showed significantly lower HCV RNA levels and a lower mean histological activity score as compared to patients with genotype 1 and genotype 2. However, using multivariate analysis, only age and mode of transmission but not histological activitiy score were shown to be independent variables. CONCLUSIONS: Our study confirms previous reports from other countries that HCV variants can be classified into a relatively small number of discrete genotypes, and that the subtype 1b clearly predominates. However, we found evidence that there is a changing relative prevalence of HCV genotypes in relation to age, and that the mode of transmission is reflected in the predominance of certain genotypes.

Adolescent↗
PubMed1996

GB virus C infection in patients with chronic hepatitis B and C before and after liver transplantation.

Recently, a novel virus, tentatively designated GB virus (GBV-C) was identified in patients with hepatitis. The frequency of this novel virus infection was therefore investigated in 58 patients with chronic hepatitis B virus (HBV) infection and in 74 patients with chronic hepatitis C virus (HCV) infection who had received orthotopic liver transplantation (OLT) because of decompensated liver cirrhosis. Before OLT, GBV-C sequences were found by reverse transcription nested polymerase chain reaction with primers derived from the helicase-like region in six (10%) of the HBV- and in six (8%) of the HCV-infected patients. Specificity of the polymerase chain reaction products was confirmed in eight of them by direct sequencing. Pretransplant GBV-6 viremia was associated with posttransplant viremia in 75% of patients. The comparison of GBV-C nucleotide and amino acid sequences within the helicase-like region revealed that pre- and posttransplant sequences differed only in 0-7 nucleotide exchanges, and with the exception of one, all of them were silent mutations. After OLT, 29% of the HBV- infected and 12% of the HCV-infected patients became GBV-C positive,indicating a high rate of "de novo" GBV-C infection. By correlating the GBV-C status with the frequency of the occurrence of graft hepatitis in both groups of patients, it became evident that posttransplant GBV-C viremia did not increase the risk for this clinical condition. However, we found a significantly higher percentage of hepatocellular carcinoma in patients with pre-OLT GBV-C/HCV coinfection compared with patients with HCV infection alone (5/6 vs. 16/68;P<0.01).

Adult↗
PubMed1996

Pre-core mutants of hepatitis B virus in patients receiving immunosuppressive treatment after orthotopic liver transplantation.

Orthotopic liver transplantation (OLT) is a possible treatment for acute or chronic liver failure due to hepatitis B virus (HBV) infection, but reinfection of the graft can be a serious complication. The aim of this study was to monitor HBV markers, to analyse pre-core-/core-mutations as well as to identify the viral population causing reinfection after OLT, and to investigate the emergence or disappearance of these mutants in patients receiving immunosuppressive treatment. Fifty-four pre-and posttransplant serum samples of 17 patients were analysed. All patients underwent OLT for HBV-related liver disease and had HBV-DNA before and after OLT. Total DNA was extracted from all sera and a 240 bp fragment comprising the pre-core region of HBV was amplified by polymerase chain reaction (PCR). Pre-core mutants of HBV were determined by direct sequencing of these PCR products and by sequencing of PCR clones. Eight of 17 patients were infected with pre-core wildtype HBV before OLT (group A). Seven of eight patients of group A were reinfected by pre-core wildtype HBV after OLT. In one of eight patients in addition to wildtype HBV a mutant strain (nt. 1899 G-->A) was detected. Nine of 17 patients were infected with pre-core mutant HBV before OLT (group B). Six of nine patients of group B were reinfected with the same mutant population; in one, an additional pre-core mutation emerged; two patients lost pre-core mutant HBV (nt. 1896 and 1899 G-->A). In one of the latter two, a pre-core start-codon mutant (nt. 1816 G-->T), not detectable before OLT, emerged, in the other a nt. 1897 G-->A stop-codon mutant persisted. Five patients of each group were followed-up for more than 24 (25 to 58) months on immunosuppressive therapy. In all five patients of group A, pre-core wildtype of HBV persisted during long-term follow up. Two of five patients of group B were infected stably with a stop-codon HBV-mutant nt. 1896. In three patients, the nt. 1896 stop-codon mutant disappeared during immunosuppressive therapy. However, in one of the latter three, an HBV stop-codon mutant nt. 1897 persisted. In conclusion, most patients who underwent OLT for HBV-related disease were reinfected with the same virus population that existed before OLT. In rare cases, new mutants emerged after OLT or preexisting mutants were lost. During long-term follow-up on immunosuppressive therapy, in the majority of patients pre-core mutants disappeared and wildtype HBV became the predominant virus strain.

Antiviral Agents↗
PubMed1996

Viral dynamics of hepatitis C early after orthotopic liver transplantation: evidence for rapid turnover of serum virions.

The pathogenesis of hepatitis C virus (HCV) infection is likely to be associated with viral replication in vivo, but little is known concerning the dynamics of HCV turnover. We performed serial measurements of serum HCV-RNA levels following orthotopic liver transplantation (OLT) in nine patients with HCV-positive cirrhosis. Serum HCV-RNA levels were determined by quantitative polymerase chain reaction before, immediately after, and for up to 1 month after OLT. There was a rapid decline in HCV-RNA levels from 3.1 +/- 1.3 x 10(5) copies/ mL (mean +/- SEM) preoperatively to 0.15 +/- 0.6 x 10(5) copies/mL on the first and 0.16 +/- 0.6 x 10(5) copies/mL on the second postoperative day (mean viral half-life, 4.0 +/- 0.5 h). Thereafter, HCV-RNA levels increased in all but one patient, and by postoperative day 8 reached 3.6 +/- 1.3 x 10(5) copies/mL, exceeding the preoperative levels irrespective of the use or not of rescue immunosuppressive therapy including steroid bolus administration. In most patients, serum virions continued to increase averaging 11.6 +/- 2.8 x 10(5) copies/mL on the 30th postoperative day. These findings indicate that the half-life of HCV is quite short, and that extrahepatic viral replication contributes little to the total virus pool in serum. Furthermore, the marked HCV replication beginning as early as the third postoperative day strongly suggests that the liver graft is rapidly reinfected by HCV after OLT.

Adult↗
PubMed1996

Clinical significance of recurrent primary biliary cirrhosis after liver transplantation.

Primary biliary cirrhosis (PBC) represents a classic indication for orthotopic liver transplantation (OLT); as an autoimmune disease, however, the existence and incidence of recurrent PBC is a matter of significant controversy. Between September 1988 and September 1994 a total of 544 OLTs was performed at our institution. Forty-nine patients (40 female) with a median age of 50.5 years and previous surgery in 36.4%, received a liver graft for PBC. The mean serum bilirubin level was 8.9 mg/dl (range 0.7-29.7). Immunosuppression was commenced as a cyclosporine A-based quadruple therapy or with FK 506 and prednisolone. Protocol liver biopsies were taken at defined intervals posttransplant. Two patients died due to Legionella pneumonia and hypoxic brain damage 2 and 8 weeks after OLT, resulting in an actuarial 5-year survival rate of 95% with 47/49 patients being alive compared to 83.5% of all other liver recipients. Evidence of recurrence of PBC, as defined by elevated cholestatic parameters and histological features of PBC, was found in four patients, another five patients showed only histological signs. Recurrence of PBC, which might compromise the long-term outcome after OLT, was suspected in 4/47 patients (8.5%). This evidence of recurrent PBC is in conflict with findings of other groups that did not report recurrent PBC. OLT is still the optimal therapy for advanced PBC, with an excellent prognosis.

Female↗
PubMed1996

Hepatitis C: indication for anti-viral therapy?

Hepatitis C infection is a frequent indication for liver transplantation. In general, recurrent graft hepatitis is assumed to be mild, but may be the cause of lethal postoperative complications in a small patient population. Out of 500 transplants in 458 patients, 123 patients were transplanted due to hepatitis C infection (26.7%) between September 1988 and April 1994. Cumulative 1- to 6-year patient survival was similar for patients transplanted due to hepatitis C (87.0%) and those transplanted for other indications (86.0%). In patients with hepatitis C virus (HCV), death, in 50% of the cases, was related to HCV recurrence and chronic rejection. Four patients (25.0%) died because of severe infection and multiple organ failure syndrome unrelated to HCV recurrence and chronic rejection. The incidence of retransplantation was similar in HCV (9.8%) and other patients (8.4%). In HCV patients, 6 of 12 retransplantations (50.0%) were performed due to HCV recurrence and chronic rejection. Of 123 HCV patients, 45 experienced histologically proven recurrent graft hepatitis between 2 weeks and 5.5 years after transplantation. The incidence of acute rejection was similar in both groups. The incidence of steroid-resistant rejection was, however, higher in HCV patients (29.3%) than in those transplanted for other indications (14.5%; P < or = 0.05). Furthermore, there was a significant association between acute rejection and the development of recurrent graft hepatitis. In conclusion, patients with hepatitis C may be transplanted with as good patient and graft survival rates as patients transplanted for other indications. However, the combination of recurrent graft hepatitis and chronic rejection remains the most limiting factor for some of these patients, which strengthens the necessity for a specific anti-viral therapy.

Graft Rejection↗
PubMed1996

Famciclovir therapy for recurrent hepatitis B virus infection after liver transplantation.

Between November 1993 and June 1995 18 patients received oral famciclovir (3 x 500 mg) for treatment of hepatitis B virus (HBV) reinfection after liver transplantation. Reinfection was defined as the reoccurrence of HBsAg in the serum. In the first 15 patients, famciclovir therapy was initiated after clinical signs of graft hepatitis, whereas the last 3 patients received treatment immediately after HBV-DNA was detected. Famciclovir was well-tolerated in all patients. HBV-DNA values were decreased to undetectable levels in 8 out of 18 patients. Clinical status improved in 7 patients, whereas 5 patients remained unchanged and 6 patients progressed to deteriorating graft function and death. When famciclovir was initiated early after reinfection, a response rate of approximately 66% was observed. Late onset of therapy in patients with fulminant hepatitis generally failed to provide any clinical benefit.

2-Aminopurine↗
PubMed1996

Hepatitis GBV-C sequences in patients infected with HCV contaminated anti-D immunoglobulin and among i.v. drug users in Germany.

BACKGROUND/AIMS: A novel virus, GB virus-C (GBV-C), with a genome organization similar to those of the Flaviviridae family was identified in sera of patients diagnosed with hepatitis. Up to now little has been known about the prevalence of GBV-C sequences in German hepatitis C virus infected patients. METHODS: We investigated two groups of patients chronically infected with hepatitis C virus: (i) Women infected in 1978/79 with HCV-contaminated anti-D immunoglobulin batches in former Eastern Germany, and (ii) i.v. drug users infected with different HCV subtypes. Nested polymerase chain reaction products amplified with GBV-C specific primer pairs within the helicase region were sequenced directly and compared with the GBV-C sequences reported recently. RESULTS: GBV-C sequences of the putative NS 3 gene region were shown to occur in two randomly selected anti-D immunoglobulin batches of 1978 (GI and GII) and two sera of HCV-infected women drawn in 1979. In patient 3, the HCV-infected erythrocyte donor in 1978, specific GBV-C sequences were also evident in serum drawn in 1990. In the high-risk group of i.v. drug users, 49% were GBV-C RNA positive. Among the 21 GBV-C positive samples, 11 were coinfected with HCV subtype 3a and 10 with subtype 1 b. All isolates showed an overall homology to the GBV-C sequence reported by Simons of 75-81% at the nucleotide level and 94-100% at the amino acid level. CONCLUSION: GBV-C sequences are detectable in the anti-D immunoglobulin batches which caused a hepatitis C virus outbreak in 1979, and a first hint of its transmission to recipients was shown. The detection of GBV-C in patient serum drawn 12 years after the onset of chronic liver disease confirms the persistence of the novel virus described here. In the group of i.v. drug users a high frequency of GBV-C sequences (49%) was shown, and the considerable variability of the nucleotide sequences indicates the existence of different GBV-C genotypes/subtypes.

Adolescent↗
PubMed1996

Responsiveness to interferon alpha treatment in patients with chronic hepatitis C coinfected with hepatitis G virus.

BACKGROUND/AIMS: Patients with chronic hepatitis C are often coinfected with the new identified Flaviviridae-like agent, termed hepatitis G virus (HGV). The aim of the study was to investigate the responsiveness of hepatitis G virus to interferon alpha and to evaluate whether a hepatitis G virus coinfection negatively influences the outcome of treatment in chronic hepatitis C. METHODS: One hundred and fifteen patients with histologically proven chronic hepatitis C were treated with interferon alpha and investigated for the presence of hepatitis G virus coinfection by nested polymerase chain reaction with primers from the helicase region of hepatitis G virus. All patients received at least 3 MU (range 3-6) interferon alpha thrice weekly for at least 6 months (mean 8, range 6-12). Polymerase chain reaction products of seven pre- and post-treatment hepatitis G virus positive patients were directly sequenced for identification of sequence variability during the follow-up. RESULTS: Eighteen (16%) patients were coinfected with hepatitis G virus. Although nine (50%) of these patients became HGV RNA negative during interferon alpha therapy, only three patients (17%) remained HGV RNA negative at the end of follow-up (mean 24 months). The rate of sustained response of chronic hepatitis C was not significantly different between patients with hepatitis C virus infection and HCV/HGV coinfection (19% vs 28%). Severity of liver disease as determined by alanine aminotransferase levels, histology and hepatitis C virus viremia was not significantly different in patients with hepatitis C virus or HCV/HGV coinfection. Sequence analysis of the helicase region revealed that our isolates all belonged to the hepatitis G virus and not to the GBV-C like genotype. No amino acid exchanges during the observation period of up to 48 months were observed, indicating that this region is highly conserved. CONCLUSIONS: The responsiveness of hepatitis G virus to interferon alpha in chronic HCV/HGV coinfected patients is similar to that observed in chronic hepatitis C. Hepatitis G virus coinfection seems not to interfere with the efficacy of interferon alpha treatment in patients with chronic hepatitis C.

Adult↗
PubMed1996

Treatment of chronic hepatitis C with interferon alpha: long-term follow-up and prognostic relevance of HCV genotypes.

To evaluate the importance of hepatitis C virus (HCV) genotypes for the long-term response to interferon alpha (IFN alpha) therapy, we retrospectively investigated 81 patients with chronic hepatitis C treated within two randomized multicenter studies with comparable inclusion criteria. Forty patients received recombinant IFN alpha 3 MU three times a week for 12 months and 41 patients lymphoblastoid IFN alpha 3 or 5 MU three times a week for 6 or 12 months (total dosage 216-720 MU). The patients were followed up for up to 4 yr (2-4 yr, mean 3.2 yr). A sustained remission defined as normalization of aminotransferases and negative PCR for HCV-RNA was achieved in 23% of patients treated with recombinant IFN alpha and in 25% of the group with lymphoblastoid IFN alpha therapy. All patients with sustained remission showed a normalization of aminotransferases during the first 3 months of therapy. Determination of HCV genotypes revealed a major prevalence of type 1 (77%) versus type 2 (5%) and type 3 (18%). The response rate was significantly higher in patients with type 2 and 3 infections (75 and 73%) than in patients infected with genotype 1 (37%) (p = 0.005). Sustained remission was observed in 13% for genotype 1, in 75% for genotype 2, and in 33% for genotype 3 (differences between type 2/3 versus type 1, p = 0.03). There were no significant differences between responders and non-responders concerning age, level of aminotransferases before therapy or the dosage and type of IFN alpha administered. The data indicate that the determination of HCV genotypes may have prognostic relevance in the responsiveness to IFN alpha therapy.

Adult↗