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T Goeser

Publications and source records attributed to T Goeser.

At least 37 records · Page 2Linked to original sources
PubMed1997

[In vitro infection of the human T-cell line with the hepatitis C virus].

A human T-cell line (Molt-4) was infected with an hepatitis C virus RNA (HCV- RNA) positive serum for 12 hours and incubated continously for 1-28 days. A productive infection was demonstrated by polymerase chain reaction amplification. Viral plus-stranded RNA was detectable in Molt-4 on the 1st, 2nd, 3rd day and the 8th day post infection. Viral minus-stranded RNA was detectable on the 2nd day and 8th day post infection.

Cell Line↗
PubMed1997

Recurrent hepatitis C virus infection after liver transplantation--long-term follow-up with respect to the HCV genotypes/subtypes.

BACKGROUND/AIMS: Various factors may affect the postoperative course in recurrent hepatitis C virus (HCV) infection after liver transplantation (OLT). The aim of our study was to evaluate the potential role of HCV genotypes and immunosuppressive treatment. METHODS: 17 liver allograft recipients, HCV-RNA positive prior to OLT, were followed 26-102 months postoperatively. The diagnosis of HCV infection was based on clinical, serological and histological findings and detectable HCV-RNA in serum. The genotypes/subtypes were evaluated by a "reverse line probe" assay. RESULTS: After OLT hepatitis C viremia was evident in 16 of 17 allograft recipients (94%). Two patients acquired HCV infection after transplantation (incidence 0.84%). Clinically eight of 18 viremic patients remained asymptomatic. Ten of 18 had an acute hepatitis (eleven to 27 weeks after OLT), of those nine patients developed chronic hepatitis (hepatic activity indices: grade 1-3) with progression to fibrosis in two patients. One patient subsequently developed cirrhosis. Subtype 1 b was predominant (eleven of 18 patients). After transplantation subtype 1 b was not associated with a higher rate of recurrent hepatitis compared to other genotypes/subtypes (45% in type 1 b vs. 71% in type "non-1 b"; n.s.). CONCLUSION: Identical HCV genotypes/subtypes before and after OLT indicate a recurrent rather than a postoperatively acquired HCV infection of the allograft. Despite viremia most patients had no or mild to moderate hepatitis in the long-term follow-up. Different HCV genotypes were not associated with specific clinical courses of recurrent HCV infection after OLT.

Adolescent↗
PubMed1996

Sequence analysis of hepatitis GB virus C (GBV-C) isolates from 14 patients.

In 1995, a new human hepatitis virus belonging to the family Flaviviridae was described and designated hepatitis GBV-C. To investigate variations within the genome of GBV-C and to study the relationship of GBV-C to GBV-A/B or hepatitis C virus (HCV), we established a detection system using reverse transcriptase polymerase chain reaction (RT-PCR) of the putative helicase region (NS3). So far, isolates derived from 14 different GBV-C-positive sera were analyzed (GBV-C/S3-36), showing 80.1-89.4% (mean: 85%) identical nucleotides. The deduced amino acid sequences revealed 97.3% homology. Nucleotide sequences of GBV-C/S3-36 revealed about 60% identity to GBV-A as well as to HCV, but only 56% identity to GBV-B. Amino acid sequences revealed 73.4 and 68.6% similarity to GBV-A and GBV-B, respectively, but a slightly higher percentage of 78.5% to HCV sequences. Thus, according to the putative GBV-C helicase sequence, a subtyping of GBV-C into different genotypes may be necessary.

Adult↗
PubMed1996

A rapid and highly specific technique to detect hepatitis C RNA in frozen sections of liver.

AIMS: To develop a polymerase chain reaction (PCR) based technique that would permit the rapid and highly specific detection of hepatitis C virus (HCV) RNA extracted from frozen liver tissue. METHODS: Samples of liver tissue from 18 patients undergoing orthotopic liver transplantation were studied. Nine patients were HCV positive. Total RNA was extracted from between one and 10 sections, 10 microns thick, from each tissue sample. HCV RNA was amplified by (1) conventional, multistep reverse transcription PCR (RT-PCR) and by (2) combined, single step RT-PCR using coupled oligonucleotide primers based on the sequence of the 5' untranslated region of the viral genome. Positive results were confirmed by dot blot analysis using a digoxigenin labelled oligoprobe (Alx 89). RESULTS: HCV RNA was detected in the nine HCV positive patients by both conventional and combined RT-PCR. HCV RNA was not detected in the HCV negative patients. As little as 500 ng total RNA was needed as the template to yield detectable amounts of amplified cDNA. The digoxigenin labelled oligoprobe hybridised with HCV RNA positive specimens only. CONCLUSIONS: The combined, single step RT-PCR is a rapid and sensitive technique for detecting HCV RNA in frozen liver tissue.

Base Sequence↗
PubMed1995

[Significance of genotypes in chronic hepatitis C virus infection and hepatitis C virus induced liver cirrhosis in Germany].

INTRODUCTION AND OBJECTIVE: Hepatitis C virus (HCV) infection is characterized by a high chronicity rate. Several HCV genotypes have been described. As their distribution pattern in Germany had been unknown it was the aim of this study to determine it in a sizeable group of patients and to find out whether the genotypes differ in the severity of the disease caused by them. PATIENTS AND METHODS: 115 consecutive patients were studied prospectively, 62 (40 men, 22 women) with chronic HCV infection (group 1) and 53 (36 men, 17 women) with liver cirrhosis caused by HCV (group 2). The genotypes were determined by line probe assay. RESULTS: The mean age of the patients in group 1 was significantly lower than that in group 2 (40.4 +/- 13.7 vs 57.1 +/- 12.1 years; P < 0.0001). In group 1, genotype 1b was most frequent (53%; 1a: 21%, 3a: 21%, 2b: 3%, 2a: 2%). Genotype 1b also predominated in group 2 (78%; 1a: 17%, 2a: 4%, 3a: 2%). The differences in frequency between the two groups were significant regarding genotypes 1b (P = 0.01) and 3a (P = 0.005). Genotype 3a was found only in the younger patients. Mean age of patients with genotype 3a and chronic hepatitis C was significantly lower than that of the other patients in this group (34.2 +/- 4.6 vs 42.0 +/- 14.8 years; P < 0.002). CONCLUSIONS: The results show that in Germany genotype 1b predominates and seems to be associated more often with the advanced stages of liver disease. The fact that genotype 3a occurs exclusively in younger patients points to a change in genotype spectrum: infection with this genotype may take a less aggressive course since fewer cases of liver cirrhosis have been observed.

Adult↗
PubMed1994

Characterization of antigenic determinants in the core antigen of the hepatitis C virus.

Antibodies to the hepatitis C virus (HCV) core protein are present in the majority of patients with chronic HCV infection. To characterize the corresponding determinants, synthetic peptides and various deletion clones of the core gene expressed in Escherichia coli were used to test human anti-core positive sera or rabbit anti-peptide antibodies in enzyme-linked immunosorbent assays, immunoblots, and competition assays. Two distinct linear antigenic determinants which are located within aa 1 to 20 and between aa 30 and 47 were found. Further studies using reactive serum after preabsorption of antibodies with N- and C-terminal-deleted HCV core proteins or with peptides directed to the linear epitopes revealed an additional determinant that requires for presentation the participation of the N-terminal 69 amino acids. It is postulated that the HCV core protein forms a three-dimensional structure exposing two linear epitopes and, in addition, presents a conformational determinant within the N-terminal 69 amino acids. The remaining core amino acid sequence spanning from position 69 to 191 does not seem to expose further determinants to induce additional anti-core antibodies.

Animals↗
PubMed1994

B-lymphocytes are predominantly involved in viral propagation of hepatitis C virus (HCV).

Recent reports have shown that HCV infection is not only restricted to hepatocytes. Like hepatitis B virus (HBV), which also was thought to be strictly hepatotropic in early molecular and cellular investigations, infection of lymphoid cells by HCV in vivo has been demonstrated. We showed that total peripheral blood leukocytes of chronically HCV-infected patients are infected by detection of plus- and minus-stranded HCV RNA using strand-specific oligonucleotide primers in the RT-PCR. These cells also represent extrahepatic sites for the viral replication, as demonstrated by incorporation of [3H]-uridine into nascent RNA after stimulation of the cells with a mitogen. Furthermore, total PBML from an uninfected person could be infected in vitro using an HCV-positive serum. It could be shown that replication of HCV RNA takes place in these cells. Examination of different subsets of PBML showed predominant infection of B-lymphocytes during HCV disease. Additionally, infection of T-lymphocytes was detected in about 50% of all chronically HCV-infected patients.

B-Lymphocytes↗
PubMed1994

Therapy of chronic viral hepatitis.

Interferon is currently the only established therapeutical option for chronic viral hepatitis. Sustained response can be achieved in approximately 25% of patients with chronic HBV or HCV infection. Results in chronic HDV infection are disappointing. Whether combination of interferon with other lymphokines or antiviral drugs will lead to higher response rates, remains to be established. The argument that interferon will only place spontaneous seroconversion on an earlier date has not been disproved yet. Long-term follow-ups are necessary to show that therapy with interferon will improve survival and reduce the incidence of hepatocellular carcinoma in patients with chronic viral hepatitis.

Chronic Disease↗
PubMed1994

Hepatitis C virus, alcoholic cirrhosis, and hepatocellular carcinoma.

We undertook a retrospective study to determine the prevalence of hepatitis C virus (HCV) and hepatitis B virus (HBV) infection in 81 Caucasian patients with confirmed hepatocellular carcinoma (HCC). Besides HBV and HCV serological markers, HCV RNA and HBV DNA were detected in serum and liver tissue by polymerase chain reaction. Overall, HCV RNA was found in 20 cases (25%), HBV DNA in 21 patients (26%), and coinfection in 3 patients (3%). HCV RNA in liver tissue was not found without virus in serum, whereas HBV DNA was found in the liver tissue of one patient without viremia. In an additional analysis, 32 patients with HCC and alcoholic cirrhosis (HCC-AC) were compared to 35 cases with AC without HCC and 35 cases with alcoholic hepatitis. The prevalence of HCV RNA in HCC-AC (19%) was significantly higher than in the other groups (AC, 3%; alcoholic hepatitis, 0%). HBV DNA was present in 19% of HCC-AC as compared to 3% of AC and 0% of alcoholic hepatitis. We conclude that the form of HCC in 50% of the patients in a Western European country is related to chronic viral hepatitis. Our data obtained from a group of patients having alcoholic liver disease with or without HCC suggest that the prevalence of HCV RNA or HBV DNA in these populations increases with the severity of hepatic injury.

Adult↗
PubMed1993

Genetic variability of German hepatitis C virus isolates.

Heterogeneity of hepatitis C viral (HCV) genomes of several isolates from different countries has been reported, but there is little information on HCV isolates for the Federal Republic of Germany. Therefore, the nucleotide (nt) and deduced amino acid (aa) sequences of interesting parts of the viral genome derived from different human isolates in Germany were compared with each other and with the nt and predicted aa sequences of recently published isolates. HCV sequences were obtained by reverse transcription of viral RNA extracted from serum followed by polymerase chain reaction (PCR) amplification. Within the 5' nontranslated region we found only 3 single nucleotide exchanges among 2 of our isolates, and in comparison to sequences of Japanese isolates 2 to 3 exchanges, and to U.S. isolates 1 to 5 exchanges (homologies 98% to > 99%). Determination of a 249-bp core sequence from two German isolates exhibited 3% sequence divergence. The sequence of the core region (nt 342-911) showed a homology of about 88-91% on nt level and 96-97% on aa level as compared to U.S. isolates and other German isolates, and a homology of 95-96% (nt) and 96-98% (aa), respectively, to Japanese isolates. Less homologies were noticed for the E1 and E2/NS1 genes, especially in the N-terminal E2/NS1 hypervariable domain. Our isolates HD1 and HD2 showed nt sequence homologies of about 72-81% and aa homologies of 76-88% to U.S., German, and French isolates, and 89-91% (nt) and 88-96% (aa), respectively, to Japanese isolates. These results indicate that various German isolates are more closely related to Japanese isolates and differ from other European isolates as reported so far. Because of a nucleotide sequence heterogeneity of up to 10% among the tested isolates, we conclude that more than one closely related but distinct viral genotype of HCV exists in Germany. Furthermore, heterogeneous sequences of HCV can be detected in a single patient suggesting multiple infection with different genomic variants or, alternatively, a genetic drift forced by mutational events as a consequence of host immune selection.

Amino Acid Sequence↗
PubMed1993

Peripheral blood leukocytes serve as a possible extrahepatic site for hepatitis C virus replication.

To study possible extrahepatic sites for the replication of hepatitis C virus (HCV), we examined fresh and cultured peripheral blood mononuclear leukocytes (PBML), as well as different subpopulations of PBML of HCV-infected patients, for the presence of viral genomic and antigenomic RNA. Sense and antisense oligonucleotide primers derived from HCV sequences were used for reverse transcription (RT) followed by an amplification with the polymerase chain reaction assay (PCR). Using antisense primers for RT, genomic viral RNA could be detected in serum, liver, total PBML and B lymphocytes of chronically infected patients. However, only liver tissue and PBML specimens were positive when a sense primer was used. To demonstrate further the specificity of these findings, total PBML were stimulated using pokeweed mitogen and synthesis of HCV RNA was determined by incorporation of [3H]uridine into nascent viral RNA molecules using a hybrid release assay. Additionally, total PBML from an uninfected person could be infected in vitro using an HCV RNA-positive serum. The PCR products obtained from serum, liver and PBML specimens of an HCV-positive individual were found to have nearly identical sequences. Our findings suggest that PBML could be a site for viral replication of HCV during the natural course of infection and may represent a reservoir for hepatitis C virions.

B-Lymphocytes↗
PubMed1992

Follow-up of patients with hepatitis non-A, non-B: incidence and persistence of anti-HCV depend on route of transmission.

Of 32 patients with non-A, non-B hepatitis, 10 (31%) were still anti-HCV-positive 12.8 years after the acute phase of the disease. Seven of the patients (21.9%) still had elevated ALT levels, and among these, 5 out of 5 patients who had been subject to parenteral risk were anti-HCV-positive. In contrast, none of the patients who had not been subject to parenteral risks were positive.

Follow-Up Studies↗
PubMed1992

Role of hepatitis C virus infection in German patients with fulminant and subacute hepatic failure.

To investigate the possible role of hepatitis C virus (HCV) in fulminant and subacute liver failure, we tested serum and liver of 13 patients undergoing orthotopic liver transplantation for the presence of HCV RNA. HCV RNA was detected in specimens from two out of eight patients negative for all viral markers with suspected hepatitis non-A, non-B infection and in one out of four patients with hepatitis B virus infection. Only in this patient replication of HCV could be demonstrated. We conclude, that fulminant and subacute hepatic failure is induced by hepatitis C virus only in few patients with hepatitis non-A, non-B.

Adult↗