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Biomedical subjects

H Liehr

Publications and source records attributed to H Liehr.

At least 19 recordsLinked to original sources

Combination therapy with interferon-alpha 2b and ribavirin for the treatment of relapse patients and non-responders with chronic HCV infection.

BACKGROUND: Treatment of patients with chronic hepatitis C after failure of an interferon monotherapy remains controversial. While relapse patients have a sustained response after a combination therapy with interferon-alpha 2b 3 x 3 MU/week plus ribavirin 1,000/1,200 mg daily for 24 weeks in up to 49%, the standard therapy for initial non-responders remains to be determined. METHODS: We therefore conducted a large multicenter trial to compare efficacy and safety of a combined interferon/ribavirin therapy in 327 non-responders and 181 relapse patients with chronic HCV infection outside of highly specialized institutions. RESULTS: After 6 months therapy with interferon-alpha-2b 3 MU thrice a week plus ribavirin 1,000/1,200 mg daily for 24 weeks 31% of relapse patients and 11% of initial non-responders achieved a sustained response according to an intent to treat analysis. CONCLUSIONS: These data could not confirm the high rate of sustained responders in relapse patients. In addition we were only able to induce a sustained response in every tenth non-responder. These results might reflect the realistic sustained response rates in a non-biased European population of HCV-infected patients.

Administration, Oral↗

Treatment of posttransplant lymphoproliferative disorder with the anti-CD20 monoclonal antibody rituximab alone in an adult after liver transplantation: a new drug in therapy of patients with posttransplant lymphoproliferative disorder after solid organ transplantation?

BACKGROUND: Posttransplant lymphoproliferative (PT-LPD) disorder is a life-threatening complication with an incidence of 1-10%. Uniform treatment, so far, does not exist. METHODS: In December 1996, 5 months after a liver transplant, a 43-year-old patient developed a PT-LPD with para-aortal lymphomas and splenomegaly. Histological investigations revealed a PT-LPD of a diffuse large B-cell type of the centroblastic variant. The patient received three cycles of a modified cyclophosphamide, doxorubicin, vincristine, and prednisone-regimen, resulting in complete remission but the patient withdrew from further treatment. In February 1998, the patient had a recurrence of PT-LPD with gastric involvement and parasplenic lymphomas. The patient rejected cytotoxic treatment because of her fear of drug-induced progressive myopathy, so we conducted treatment with the monoclonal antibody--directed against CD20-rituximab. RESULTS AND CONCLUSIONS: After 2 doses of rituximab, clinical symptoms had disappeared and after 6 doses, gastroscopy revealed no residual disease. At this time, the patient remains in remission, with a follow up of > or =6 months. Anti-CD20 monoclonal antibody rituximab is a new, well-tolerated drug for the treatment of lymphomas. In addition, this drug may offer an additional treatment option for patients with PT-LPDs.

Adult↗

A German drug-monitoring study in general practice patients receiving cisapride for functional dyspepsia.

An open prospective drug monitoring study was undertaken to assess the efficacy and tolerability of 5 mg cisapride three times daily in 37,925 general practice patients with functional dyspepsia. Short-term (mean, 4 weeks) cisapride treatment was associated with a significant reduction in overall dyspeptic symptom scores and improvements in scores of all eight individual dyspeptic symptoms (epigastric discomfort, fullness, nausea, bloating, heartburn, acid regurgitation, loss of appetite, and vomiting). Physician's and patient's subjective global evaluations of antidyspeptic efficacy were good or very good in 80% to 90% of cases. The tolerability of cisapride was judged to be satisfactory, good or very good in approximately 95% of patients, with adverse drug reactions being documented in 4.8% of patients. Of these, diarrhea/loose stools (2.5% of all patients) and headache (0.7%) were most frequent. Premature treatment withdrawal due to poor tolerability was necessary in only 0.35% of patients.

Adolescent↗

[Clinical studies of the specificity of detecting viral DNA in non-A, non-B hepatitis in liver tissue and lymphocytes].

The clinical specifity of an intraparticular virus-DNA of 5001 Bp associated with non-A, non-B hepatitis (HNANB) was evaluated. Investigations were done in liver biopsies and lymphocytes in 173 patients having acute or chronic HNANB (n = 107) or liver diseases of other etiology (n = 66). The sensitivity of the test system (polymerase chain reaction, southern-transfer, DNA-hybridisation with synthetic oligonucleotides) was less than 100 virus particles per probe. In all patients with acute HNANB (n = 5) (parenteral mode of infection) the DNA was found in 100% in liver and lymphocytes, and in 22 of 27 patients with acute sporadic HNANB. HNANB associated substance (HNANB-AS) (1.3 g/ml CsCl) excreted with feces was found in 50%, and 29.6%, respectively. In chronic HNANB the DNA was found in 83.3% in the liver (n = 42) and in 56.7% in lymphocytes (n = 30). The HNANB-AS was found in 45.6% (n = 68). In liver diseases with other etiologies as HNANB-infection (e.g. HBV, HAV, cholestasis, HBsAg pos.-liver cirrhosis) (n = 33) the DNA was found neither in liver biopsies nor in lymphocytes. In liver diseases of uncertain etiology, but with NANB-infection under discussion (e.g. nonspecific reactive hepatitis, fatty liver, HBV neg liver cirrhosis) the DNA was found in the liver in 24% (n = 25) and in lymphocytes in 40% (n = 5). In patients with clinically resolved HNANB no DNA was found in liver and lymphocytes (n = 5). All stools were negative for HNANB-AS in the latter.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Viral↗

[Rapid development of liver cirrhosis following acute non-A, non-B hepatitis].

Four cases of shortly developed liver cirrhosis as consequence of non-A-non-B-hepatitis are described. Liver cirrhosis was diagnosed by liver histology at days 254, 298, 651 and 891 after acute infection, respectively. For the first time a normal liver histology was documented in one case immediately before infection together with follow up biopsies of chronic hepatitis up to liver cirrhosis (day 891) after acute posttransfusion non-A-non-B-hepatitis. Further 20 cases with liver cirrhosis are described in the literature having developed between 90 and 2190 days after acute non-A-non-B-hepatitis. It is concluded that non-A-non-B-hepatitis has to be concerned as a serious etiological factor of liver cirrhosis developing shortly after acute infection.

Acute Disease↗

[Hepatitis non-A, non-B-associated substance in stool from patients with posttransfusion and sporadic hepatitis].

A hepatitis non-A,non-B-associated substance (HNANB-AS) excreted in feces has been detected by means of a sandwich radioimmunoassay using reconvalescent serum and IgG from patients with posttransfusion HNANB. 4380 stool filtrates from 1599 patients were screened with this assay. In patients with posttransfusion or sporadic acute and chronic HNANB the substance was detected with a mean frequency of 34%, in acute posttransfusion HNANB, where samples were screened at the beginning of the clinical symptoms, 71.4% of stool specimens were positive for HNANB-AS. A high frequency of positive results was found in patients undergoing dialysis (31.3%), hemophiliacs (16.6%) and patients with cryptogenic cirrhosis (16%). Positive specimens were seen in hepatitis A (7.1%), acute and chronic HBV-infection (9.6%), various liver diseases (7.8%), outpatients of a physician (3.1%) and clinical or laboratory staff (6%). In these groups, too, anamnestic data speaking in favour for a possible HNANB frequently were obtained. The discovery of a partially double-stranded circular DNA of 5.0 Kb in HNANB-AS which sequence differs from human, bacterial and known viral DNA, argues the presence of a viral particle in stools of patients with sporadic and parenteral HNANB.

Acute Disease↗

[Hepatitis non-A, non-B-associated DNA--demonstration of DNA in proven infectious anti-D-immunoglobulin].

An anti-D-immunoglobulin preparation implicated in a hepatitis non-A,non-B transmission was analyzed for the presence of a DNA, which was originally isolated, cloned and sequenced from feces of a patient with posttransfusion HNANB. The investigation was performed by a DNA polymerase chain reaction using synthetic oligoprimers. Commercially available immunoglobulin preparations served as controls. The demonstration of identical DNA sequences in the infectious material speaks in favour of this up to now unknown circular and partially double-stranded DNA to be a virus genome involved in hepatitis non-A,non-B.

Antibodies, Anti-Idiotypic↗

Cutaneous papulo-vesicular eruptions in non-A, non-B hepatitis.

A relapsing papulo-vesicular rash with or without pruritus was observed in 54 out of 148 patients (36%) with posttransfusion or sporadic, acute or chronic, non-A, non-B (NANB) hepatitis. The predominant location was the trunk and the anterior surfaces of the upper extremities. The face was affected less often. The eruptive phase was accompanied by general symptoms and increases in aminotransferases and gamma-GT values. The nature of the eruption was consistent with cutaneous reactions as frequently seen in enterovirus infections. No predominance was found for special groups of patients when the skin lesions were correlated to either sex, mode of infection or pattern of transaminase elevation (i.e. monophasic or bi-, and multi-phasic).

Acute Disease↗

Virus-binding activity of fibronectin: masking of hepatitis A virus.

Human plasma fibronectin interacts with viruses. When fibronectin-containing human sera negative for antibodies to hepatitis A virus (HAV) were added to suspensions of HAV, radioimmunological detection of HAV was reduced. This masking effect seemed to depend on the fibronectin concentration of the sera: plasma fibronectin purified by cryoprecipitation and affinity chromatography showed a masking effect on purified HAV which was dependent on the concentrations of fibronectin and HAV. Fibronectin peptides were obtained by subtilisin digestion: the non-collagen-binding regions of the fibronectin molecule were involved in the binding of HAV. We conclude that fibronectin has a virus-binding activity which interferes with radioimmunological methods for virus detection, and may contribute to the frequent transmission of hepatitis viruses by blood products enriched in fibronectin.

Adult↗

[Hepatitis non-A, non-B. Retro- and prospective studies on the epidemiology of the acute disease].

The epidemiology was studied in 159 consecutively admitted patients (1981-1983) with acute and chronic parenteral and non-parenteral type non A, non B hepatitis (HNANB). To establish the frequencies of types A (HAV), B (HBV) and HNANB data were collected from the official health statistic of the Federal Republic of Germany (1980-1982). Accordingly, 5 out of 100 000 persons acquired HNANB each year. There was no regional prevalence (i. e. industrial areas, cities) in HNANB as it was present in HAV. The relation of HNANB to HAV and HBV was 1:3:2,4 (health statistic), but was 1:1,1:3 in clinical studies (1979-1983, n = 2027). Of the patients with non-parenteral HNANB (n = 50) most were elder than 20 years of age. Susceptibility for parenteral acquired HNANB was observed in all groups of age. The evaluation of the possible modes of infection revealed 59% of the patients with non-parenteral ("sporadic") type HNANB, other 28,9% had posttransfusion HNANB. When monthly incidence was examined the HNANB infectivity of bloodtransfusions was high during May, June and October. Most cases of sporadic HNANB became clinically ill during summer and October. Difficulties in determination of incubation periods became evident because of the fluctuating increases and decreases of aminotransferases: In posttransfusion HNANB (n = 28) the first increases of aminotransferases were recorded at day 18 +/- 13 whereas peak values happened at day 77 +/- 21. It is concluded, that HNANB is an infection which affects a high proportion of the population, and needs consideration as a common infectious disease.

Adolescent↗

The cyclic behaviour of NANB hepatitis as basis for standardized diagnostic.

Efforts were made to characterize the clinical and biochemical behaviour of NANB hepatitis in 51 patients. 15 patients had posttransfusion NANB hepatitis, 36 a sporadic form of the disease. The patients' complaints predominantly were nausea and vomiting (64%), in about each 25% cardial complaints, lassitude, muscle pain and fever were observed. An eczema in a kind of maculopapular eruptions was frequently seen. The ratio of SGOT/SGPT was almost never less 1.0, Gamma-GT was consistently increased. The biochemical changes relapsed frequently. In posttransfusion NANB hepatitis the relapses were observed to occur predominantly around day 21, 28, 42, 49, 56, 63, 70, 77, and in further weekly intervals.

Alanine Transaminase↗

Detection of a non-A, non-B hepatitis associated substance in stools.

Investigation of stool samples (N = 2223) from 1377 persons revealed an antigen-like substance in the fecess of patients with clinically defined non-A, non-B hepatitis. Manifold investigation showed an intermittent excretion which correlated to the typical increases and decreases of transaminases in this disease. Positive results could be obtained by a randomized study in 30% of patients with NANB-hepatitis. Selected cases of sporadic and posttransfusion NANB-hepatitis showed an overall frequency of 50%. The test was predominantly negative in healthy persons and disease controls. The frequency of about 3% in fece cases was thought to be due to detection by chance.

Feces↗

Characterization of a non-A, non-B hepatitis associated substance in stools.

Using the 125J-labeled isolated IgG-fraction of reconvalescent sera from patients with NANB-hepatitis a radioimmunoassay for the detection of the NANB-hepatitis associated antigen in stool was established (RS). To characterize the antigen, stool suspensions of healthy persons and NANB-patients were analyzed by sedimentation on sucrose gradient (3-35%) before and after incubation of 125J-labeled normal IgG or IgG from reconvalescent patients. Stool was spiked with normal sera and with serum completely free from immunoglobulins. The antigen could be recovered in a fraction with similar sedimentation rate as IgG. Preincubation of Ag-positive stool with 125J-labeled IgG of reconvalescent serum resulted in a significantly higher sedimentation rate of the labeled IgG. The spiking of stool suspensions with serum of healthy donors and serum free of immunoglobulins resulted in a negative RIA-Test. The antigen could be absorbed on polystyrol beads preincubated with human serum of healthy donors. A positive test was achieved, however, only with the labeled IgG-fraction of reconvalescent serum and not with that of healthy donors. The results permit the following preliminary conclusions: The NANB associated antigen in stools which was detected by isolated IgG from reconvalescent sera shows no cross reactions with IgG of healthy donors, which excludes nonspecific binding to immunoglobulins. The sedimentation coefficient is in the range of 7s. Normal human sera may contain an antigen-masking substance, which inhibits its accessibility for specific antibodies. This may explain the well-known difficulties in establishing a valid radioimmunoassay for the detection of NANB-antigen or corresponding antibodies in the patient's sera.

Antigens, Viral↗

[Nonalcoholic fatty liver hepatitis and fatty cirrhosis mimicking alcoholic liver diseases].

Non-alcoholic steatosis hepatitis and fatty cirrhosis represents an unfamiliar liver disease of yet unknown etiology, which is usually indistinguishable from alcoholic lesions by histological criteria. For the affected patients this means automatically the inappropriate assumption of hidden alcohol abuse. Out of 1467 liver biopsies during 1979 to 1982 we selected 25 patients (group I), who either denied alcohol intake or reported negligible consumption. None of them had taken steatogenous drugs or had been treated by jejuno-ileal bypass operation for morbid obesity. Nevertheless, in all cases liver biopsy demonstrated changes that were thought to be characteristic of alcoholic liver disease. This group was compared with an additional series of 25 patients (group II, selected out of 342 alcoholics), who admitted to a mean daily alcohol ingestion of 145 +/- 37 g. According to body weight, sex ratio, estimated degree of hepatocellular fat deposition and relation of steatosis hepatitis (n = 15) to fatty cirrhosis (n = 12) there were no differences between both groups. In contrast to the alcoholics (group II) significantly lower (p less than 0.001) values of serum gamma-glutamyltransferase (127 +/- 138 vs 669 +/- 588 U/l) and mean corpuscular erythrocyte volume (89 +/- 4,7 vs 102 +/- 7,8 fl) occurred among the abstinent patients (group I). However, the considerable overlap of measured values argued against a sufficiently discriminative function of both parameters. On the other hand, the serum SGOT/SGPT ratio (I: 1,0 +/- 0,4 vs II: 3,5 +/- 1,4) as well as the serum immunoglobulin-index IgG/IgA (I: 5,6 +/- 2,1 vs II: 2,7 +/- 0,7) allowed a more than 90% separation between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗