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Biomedical subjects

U Hopf

Publications and source records attributed to U Hopf.

At least 19 recordsLinked to original sources

[Prognostic relevance of hepatitis C virus genotype for responsiveness to interferon-alpha].

The influence of hepatitis C virus (HCV)-genotypes on the responsiveness to interferon- (IFN-alpha) was studied in 116 patients with proven chronic hepatitis C. 88 of 116 (76%) patients were infected with HCV-genotype 1, 7 (6%) with HCV-genotype 2, and 21 patients (18%) with HCV-genotype 3. All patients received at least 3 MU recombinant IFN-alpha-2a, 2b or lymphoblastoid IFN-alpha tiw for at least 6 month (total IFN-alpha dose per patient 216-720 MU, mean 360; treatment duration 6-12 month, mean 8). The follow-up after cessation of therapy was 9-48 months (mean 25). Sustained normalization of the aminotransferase levels was observed in 20 (17%) of the 116 patients. 10 of the 88 (11%) patients with HCV-genotype 1, 7 of the 21 (33%) patients with HCV-genotype 3 (p < 0.02), and 3 out of the 7 patients with HCV-genotype-2- infection achieved a sustained remission. No response was observed in 58 (66%) and 3 (14%) patients with HCV-genotype 1 and 3 infections, respectively (p < 0.002). All but one of the sustained responders remained HCV-RNA negative during the entire follow-up. There were no significant differences between the sustained responders and the group of non-responders and responders with relapse in relation to age, pretreatment aminotransferase levels, histological activity index, or given IFN-alpha dosage. HCV-genotyping is helpful in evaluating the responsiveness to IFN-alpha and will be of importance considering the indication of therapy.

Adult

The optimal immunosuppressant after liver transplantation according to diagnosis: cyclosporine A or FK506?

Since we may soon be able to choose between primarily CsA- or FK506-based immunosuppression, it is important to establish the superior immunosuppressive agent for the individual patient. In the present study, 121 patients, 61 randomly assigned to FK506- and 60 assigned to CsA-based immunosuppression, were analyzed according to the primary diagnosis for liver transplantation. One-year patient survival was similar in all groups. However, the incidence and severity of acute rejection within the 1st year after transplantation was significantly higher in patients transplanted due to HCV disease who were receiving FK506 (58.8%) compared with those patients receiving CsA (27.8%; p < or = 0.05). Furthermore, the incidence of moderate and severe neurotoxicity was significantly higher during the 1st month after LTX in patients transplanted owing to HCV disease treated with FK506 (35.3%) compared with those patients receiving CsA (16.7%; p < or = 0.05). Irrespective of the immunosuppressive regimen, the incidence of early postoperative neurotoxicity was significantly lower in patients transplanted owing to HBV disease, alcoholic cirrhosis and various other liver diseases summarized than in patients transplanted due to HCV disease receiving FK506 therapy. During the 1st year, the incidence and severity of rejection in patients transplanted due to alcoholic cirrhosis and PBC was significantly lower in patients treated with FK506 (11.1% for both groups) compared with those patients receiving CsA (54.5% and 60.0%, respectively; p < or = 0.05. Furthermore, this was accompanied by a lower incidence of toxicity.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease

Long-term follow-up of hepatitis B virus-infected recipients after orthotopic liver transplantation.

The outcome after OLT was studied in 53 patients with chronic hepatitis B virus (HBV)* infection, 15 of whom had, in addition, evidence of hepatitis delta virus (HDV) superinfection. Nine of 53 patients received short-term immunoprophylaxis with anti-hepatitis B surface (HBs) hyperimmunoglobulin up to 1 week after OLT and 44 of 53 patients received long-term unlimited immunoprophylaxis. Eight of 9 (89%) patients with short-term immunoprophylaxis showed reactivation of replication with HBV DNA in serum > 10 pg/ml independently of the preoperative HBV DNA level and HBsAg reappeared in all cases. Four (44%) patients in this group lost their graft because of fulminant hepatitis or cirrhosis and required retransplantation, and 2 patients (22%) died after reinfection in the second graft. Nineteen of 44 (43%) patients with long-term immunoprophylaxis developed HBV values > 10 pg/ml after transplant and 12 of 44 (27%) became HBsAg+ again. Most of them had quantifiable HBV DNA levels before OLT. Retransplantation was required in 5 of 44 (11%) patients and 4 of them died after HBV recurrence. The frequency of HBV reactivation and the development of viral hepatitis after OLT were associated with the preoperative presence of HBV, as determined by the molecular hybridization assay. With nested polymerase chain reaction, all 53 patients were HBV-DNA+ in the serum before and after OLT. with just one exception, none of the patients with HDV superinfection died, in spite of increased HDV replication after OLT. The data indicate that long-term immunoprophylaxis with anti-HBs hyperimmunoglobulin after OLT improves the prognosis in HBV-infected patients. The preoperative detection of HBV DNA in serum by molecular hybridization assay is correlated with graft infection and represents a prognostic parameter. The presence of HDV may have a protective effect after OLT.

Adult

[Long-term follow-up of chronic hepatitis C after treatment with recombinant interferon alpha-2a].

As part of a multicenter randomized study 40 patients with chronic hepatitis C (HCV)-infection, 28 kryptogenic and 12 posttransfusional, were treated with recombinant interferon alfa (IFN alpha-2a) for 1 year in a dosage of 3 x 3 Mio. units per week versus dosis escalation after 8 and 16 weeks in serological non-responders. 36 of the 40 patients were followed over 3 years. The rate of patients with normalization of aminotransferases was 42% after two months of therapy, 28% at the end of treatment, 28% after 1 year and 23% after 3 years of follow-up. The polymerase chain reaction (PCR) for detection of HCV-RNA became negative after two months of treatment in 73%, at the end of therapy in 63%, after 1 year follow-up in 63% and after 3 years in 35%. All patients with persisting remission maintained HCV-RNA negative. Dosis escalation was realized in 8 patients without increase of responder rate. Antibodies against IFN alpha-2a developed in 4 (10%) patients without remarkable influence on the IFN-effect. Histological improvement at the end of treatment was observed in 61% including all patients with serological remission. The data support the prognostic relevance of the course of aminotransferases. If aminotransferases are not normalized during the first two months the treatment can be terminated. Persisting normalization of aminotransferases during 1 year after therapy and negative HCV-PCR result indicate maintaining remission.

Adult

Systemic lupus erythematosus: neuropsychiatric signs and symptoms related to cerebral MRI findings.

A 76.2% prevalence of abnormalities was found in the cerebral MR scans of 21 patients with systemic lupus erythematosus (SLE). These patients were enrolled in the study consecutively as they presented at an immunological out-patient unit. They were not selected on the basis of neuro/psychiatric findings. Circumscribed non-periventricular brain lesions were found in 12 patients (57.1%), mainly in the frontal white or gray matter. Periventricular lesions directly adjacent to the ventricles were detected in 10 patients (47.6%). Eleven patients (52.4%) showed signs of cerebral atrophy. MRI detected more lesions in patients with clinically focal CNS lupus than in patients with seizures or patients without clinically localized findings. Eleven patients had abnormal neuropsychiatric CNS findings; there was no clear correlation between neuropsychiatric signs and symptoms and brain abnormalities as shown by MRI. Seven patients had asymptomatic lesions. Cerebral MRI proved to be the method of choice for the non-clinical diagnosis of neuropsychiatric SLE.

Adolescent

[Primary sclerosing cholangitis (PSC)--humoral immune phenomena, pathogenetic aspects and therapeutic possibilities].

There are about 80% antibodies in PSC against cytoplasmatic antigens of neutrophilic granulocytes of the perinuclear type (pANCA), inconstantly there are antinuclear antibodies (ANA) too, but no antimitochondrial antibodies. The frequent association of PSC with colitis ulcerosa suggests an enterobacterial aetiopathogenesis. PSC sera show clear bands at 60-90 kD and at about 10 kD in the immunoblot with enterobacterial proteins as antigens. Antibodies against enterobacterial lipopolysaccharides and lipid A are to be found in patients with PSC corresponding to the normal collective. After long-term immunization with enterobacterial antigens PSC-like changes with circulating ANA can be induced in mice and rabbits. PSC, comparable to primary biliary cirrhosis, also reacts to treatment with ursodesoxycholic acid but it scarcely reacts to immunosuppressive therapy. At the final stage of the disease liver transplantation is indicated. In our clinic up to now 16 patients with PSC have undergone a transplantation with a one-year-survival rate of 88%. Confirmed re-manifestations of PSC in the transplant have not been diagnosed up to now.

Animals

Hepatitis C virus reinfection in allografts after orthotopic liver transplantation.

From September 1988 to May 1991, 160 orthotopic liver transplantations were performed in our hospital. Twenty-four patients had end-stage cirrhosis caused by chronic non-A, non-B hepatitis. Antibodies against hepatitis C virus were documented before and after orthotopic liver transplantation in 13 patients. Studies using the polymerase chain reaction demonstrated hepatitis C virus RNA in the serum and liver tissue of 17 patients (10 of whom tested positive for hepatitis C virus antibodies) before orthotopic liver transplantation. Tissue samples taken from liver grafts during the operation were hepatitis C virus RNA negative in every case. Ten of these 17 patients had positive hepatitis C virus RNA findings in serum and liver biopsy specimens within the first month after surgery. One patient died of Mucor sepsis 2 mo after orthotopic liver transplantation. Another patient died of multi-organ failure 3 mo after a retransplantation. Two patients underwent retransplantation for graft rejection at 2 and 3 mo, respectively. One year after orthotopic liver transplantation, hepatitis C virus RNA was demonstrated in allograft biopsy specimens in 13 of 15 patients. Two patients remained hepatitis C virus RNA negative in repeated biopsies up to 12 mo. Mild portal and lobular hepatitis developed within 6 months of orthotopic liver transplantation in four patients and within 1 yr in five additional patients. The data suggest that persistent hepatitis C virus reinfects the allograft in most cases, but the risk of acute organ damage caused by hepatitis C virus reinfection is low.

Adult

Hepatitis A vaccination: schedule for accelerated immunization.

Hepatitis A vaccine, strain HM175, was investigated for immunogenicity and tolerability in a prospective multicentre trial. The following vaccination schedules and antigen contents were evaluated: days 0 and 14 with 720 ELISA units (El.U) of antigen, days 0 and 28 with 720 El.U and days 0 and 28 with 360 El.U. In all study groups, the seroconversion rates following two vaccinations were between 95 and 100%. Higher geometric mean concentrations of antibody to hepatitis A virus (anti-HAV) were reached by the vaccine containing 720 El.U of HAV antigen. The vaccine was equally well tolerated in all groups. In addition, an abbreviated schedule, in which 720 El.U of HAV antigen was given on days 0 and 14, resulted in 100% seroconversion by day 28 and a level of anti-HAV that was substantially higher than that observed after passive immunization. This implies that such a vaccine could replace immune globulin administration if time permits.

Adult

[Examination of a Berlin blood donation branch for antibodies to hepatitis C virus with the anti-HCV test and for circulating HCV-RNA using polymerase chain reaction].

Hepatitis C virus (HCV) is responsible for the majority of cases of transfusion-related hepatitis. We performed a first-generation anti-HCV EIA in 665 repeat and 168 first-time blood donors from Berlin. 4.7 and 4.2%, respectively, showed at least one indeterminate or positive result. We further looked for HCV genome in the plasma of 20 donors with reactive anti-HCV-EIA doing a polymerase chain reaction (nested PCR). The control group consisted of 20 patients with chronic hepatitis C. The PCR was negative in all examined blood donors, but was positive in 17 of 20 controls. These findings raise the question, if a positive anti-HCV test correlates with infectiosity.

Berlin

Antimitochondrial antibodies in patients with chronic graft-versus-host disease.

Chronic graft-versus-host disease (cGVHD) and primary biliary cirrhosis (PBC) have many clinical and laboratory features in common. These include scleroderma or lupus erythematosus-like skin lesions, a Sjögren-like sicca syndrome, cholestatic liver disease and a variety of serological autoimmune phenomena. Furthermore, liver histology in both diseases is characterized by lymphocytic infiltration of the portal fields and destruction of small bile ducts. We investigated whether there were also parallels between both diseases in incidence and characteristics of antimitochondrial (AMA) and other autoantibodies. Sera from patients with cGVHD (n = 11, group 1) were examined by immunofluorescence (IFL) and immunoblot (IBL), and the results were compared with sera from patients without cGVHD (n = 21, group 2) and after autologous BMT (n = 16, group 3). In group 1 AMA was detected by IFL in one and by IBL in nine of 11 (81%) patients. Group 2 and 3 patients were AMA-negative by IFL and AMA positive by IBL in statistically lower incidence of 19% and 6% (p less than 0.001), respectively. cGVHD-associated AMA recognized a spectrum of mitochondrial proteins, the most frequent being molecules of 63/60 kD and 22 kD. Follow-up studies showed a temporal correlation between the emergence of AMA and the clinical occurrence of cGVHD. We conclude that patients with cGVHD have a high incidence of AMA similar to patients with PBC, but the reaction pattern of AMA differs between the diseases. The presence of AMA in cGVHD further emphasizes the concept that both diseases may have a related pathogenetic background.

Adolescent