Search PubMed⌕ Search

Biomedical subjects

T Goeser

Publications and source records attributed to T Goeser.

At least 19 recordsLinked to original sources
PubMed1999

Hepatitis virus-related and ethanol-induced chronic liver disease with or without cryoglobulins--is there a difference concerning clinical or laboratory manifestation?

Mixed cryoglobulinemia is frequent in southern Europe and attributed to hepatitis C infection. We analyzed prevalence and clinical symptoms of mixed cryoglobulinemia in our region among patients with chronic hepatitis C (n = 29) and B (n = 7) in comparison to alcoholic liver cirrhosis without evidence of hepatitis virus infection (n = 10). Cryoglobulinemia was found in 13/29 patients with hepatitis C (11 type III, one type I1-III and one type II), 2/7 with hepatitis B (one type II, one type III) and 4/10 with alcoholic liver cirrhosis (one type II, three type III). Patients with moderate active hepatitis had more type II than type III cryoglobulins. Concerning clinical symptoms, only sicca syndrome was more frequent in patients with hepatitis C. Rheumatoid factor (RF) and immune globulin M (IgM) levels were higher in hepatitis C than in the other groups. Renal disease was rare in all but not different between the groups. Mixed cryoglobulinemia in hepatitis C (and B) is most frequently of type III. Patients with hepatitis C had the same prevalence of cryoglobulins as patients with alcoholic liver cirrhosis. Cryoglobulins had no influence on clinical syndromes or organ damage.

Adolescent↗
PubMed1999

Hepatotropism of GB virus C (GBV-C): GBV-C replication in human hepatocytes and cells of human hepatoma cell lines.

BACKGROUND/AIMS: Recently, GB virus C (GBV-C) has been identified as another virus potentially causing viral hepatitis. However, its hepatotropism and pattern of infection in humans is still unknown. To elucidate the presence and replication of GBV-C in the human liver, we investigated tissue samples of six explanted livers from five GBV-C mono- or GBV-C/HCV co-infected patients for GBV-C RNA plus- and minus-strand RNA. METHODS: These tissues were examined using nested RT-PCR followed by Southern blot hybridization as well as fluorescence in situ hybridization on liver cryosections. To further substantiate susceptibility of liver cells for GBV-C, in vitro infection of human hepatoma cells (HuH7, HepG2) with GBV-C mono-infected serum was performed. RESULTS: By reverse transcription followed by nested PCR (RT-PCR), 5 of 6 liver specimens (4/5 patients) were positive for GBV-C plus-strand RNA, and viral minus-strand RNA could be detected in 4 of 6 liver specimens (4/5 patients). One liver sample was negative for GBV-C RNA. In two specimens we could identify GBV-C infection by in situ hybridization. Virus infection appeared to be restricted to hepatocytes and detection of minus-strand RNA showed viral replication in a few highly infected liver cells. In vitro infection of HepG2 or HuH7 cells confirmed these findings by a release of virions into supernatant. CONCLUSION: In conclusion, our results establish GBV-C as a hepatotropic virus infecting human cells of hepatic origin in vivo and in vitro.

Carcinoma, Hepatocellular↗
PubMed1998

Incidence, prevalence, and clinical outcome of hepatitis GB-C virus infection in liver transplant patients.

A novel RNA virus of the Flaviviridae family has been discovered recently and designated hepatitis GB-C virus (GBV-C). Previous studies have reported that GBV-C is associated with posttransfusion hepatitis, chronic viral hepatitis, and cryptogenic hepatitis. However, the clinical significance of GBV-C infection has been questioned increasingly in patients not undergoing transplantation. To investigate whether GBV-C infection under immunosuppression affects the clinical or the histological outcome in liver transplant recipients, we determined the prevalence and incidence of GBV-C infections and the clinical and histological signs in patients after orthotopic liver transplantation (OLT). The presence of GBV-C was tested in sera from patients before and in regular intervals up to 6 years after OLT by nested reverse transcription-polymerase chain reaction using primers derived from the NS3 region. A total of 72 patients were studied. Before OLT, 8 of 72 (11.1%) patients were positive for GBV-C. After OLT, 7 of 8 (87.5%) remained positive. Of 64 patients who were negative for GBV-C before OLT, 23 became positive after OLT, resulting in a de novo rate of GBV-C infection of 35.9%. We could not detect a higher rate of histologically proven hepatitis in GBV-C-positive patients (29.1%) than in GBV-C-negative patients (14.6%, P > 0.057). Comparing GBV-C-positive with GBV-C-negative liver transplant patients, we could not find any differences in age, gender, liver function tests, number of blood transfusions, histological degree of hepatitis, or number of rejection episodes. Survival was not negatively influenced by GBV-C positivity. In conclusion, the presence of GBV-C did not influence the clinical or histological outcome in liver transplant patients.

Adult↗
PubMed1998

Establishment of a highly specific detection system for GB virus C (GBV-C) minus-strand RNA.

Although the clinical relevance of GB virus C (GBV-C) is still elusive, this virus has been found with high prevalence in several groups of patients with liver disease. As was shown for hepatitis C virus (HCV), minus-strand RNA is supposed to function as a replicative intermediate. We have established a reliable and sensitive detection system for GBV-C minus-strand RNA based on nested RT-PCR (reverse transcription-polymerase chain reaction) with a tagged primer system. Sensitivity and specificity was extensively tested using in-vitro transcribed GBV-C sequences and genomic viral RNA. Specificity of the amplified fragments was proven by Southern blot hybridization. Using this detection system, we found the presence of GBV-C minus-strand RNA in 6/41 (14.6%) sera of GBV-C infected or GBV-C/HCV coinfected patients. No correlation with virological parameters such as amount of GBV-C plus-strand RNA, genotype or titer of HCV could be detected.

Adult↗
PubMed1998

The distribution of HBV, HCV and HGV among livers with fulminant hepatic failure of different aetiology.

BACKGROUND/AIMS: The aim of the study was to assess the impact factor of HCV and HGV in fulminant hepatic failure. METHODS: The 5'-untranslated regions of HCV RNA and HGV RNA and a segment of the core antigen sequence of HBV were amplified after extracting the nucleic acids from snap-frozen tissue aliquots from explanted livers of 26 consecutive patients undergoing orthotopic liver transplantation for fulminant hepatic failure preoperatively diagnosed as either autoimmune (n=2), HAV/HBV (n=8), toxic (n=4) or aetiologically unknown (n=12). RESULTS: HCV RNA was detected in five of 26 (19.2%) livers with fulminant hepatic failure. All five HCV RNA-positive livers belonged to the group of non-toxic, non-autoimmune liver failure (n=20), three of them were found in the group of liver failure with unknown aetiology (n=12) and two in the group of HBV-associated liver failure (n=7), making an HCV incidence of 25%, 25% and 28.6%, in the different groups, respectively. HGV RNA was detected in 10 of 17 (58.8%) explants and in all four groups of fulminant hepatic failure as defined preoperatively. HBV DNA was identified in six livers of 26 patients (23.1%) with fulminant hepatic failure. Neither HCV RNA nor HBV DNA was detected in the livers of patients with toxic or autoimmune fulminant hepatic failure. CONCLUSIONS: These results indicate that HBV and HCV, but not HGV, play an aetiologic role in fulminant hepatic failure. HCV-positive cases were concentrated either in the group of otherwise unexplained fulminant hepatic failure or in the group of HBV fulminant hepatic failure. HGV-positive cases, on the other hand, were found within all four preoperatively defined groups, indicating a role as cofactor rather than as single aetiologic agent.

Adolescent↗
PubMed1997

Clinical presentation of GB-C virus infection in drug abusers with chronic hepatitis C.

BACKGROUND/AIMS: Recently, the hepatitis GB-C virus (GBV-C) has been identified as another virus potentially causing chronic hepatitis. Although high rates of coinfection are emerging in drug addicts with chronic hepatitis C virus infection, no detailed data on clinical presentation are available. Therefore, co-infection was sought in hepatitis C virus patients to determine the impact of GB-C virus on clinical presentation. METHODS: GBV-C was determined by nested reverse transcriptase-polymerase chain reaction in serum of 70 HIV negative intravenous drug abusers with chronic hepatitis C. Biochemical, histological and virological parameters were compared between patients with or without GBV-C coinfection. RESULTS: Hepatitis C virus and GBV-C coinfection was found in 18 of 70 (25.7%) patients. Cases with coinfection were younger and had shorter duration of disease (31.4+/-6.2 vs. 35.3+/-7.3 (p=0.09) and 9.9+/-6.8 vs. 12.9+/-7.7 (p=0.17) years) than those without coinfection. Neither hepatitis C virus genotype distribution and HCV RNA levels nor serum liver function tests, titers of immunoglobulins or autoantibodies differed between the two groups. Histologically, chronic active hepatitis (16.7 vs. 46.4%, p=0.07), fibrosis (8.3% vs. 21.4%, p=0.3), and cirrhosis (0% vs. 8.2%, p=0.31) were less prevalent in coinfected patients. After interferon treatment, 5/6 coinfected and 11/19 patients with hepatitis C virus infection alone had cleared HCV RNA and 4/6 lost GBV-C RNA from serum. The two patients with GBV-C/HCV infection who persistently cleared hepatitis C virus but not GBV-C from serum had normal transaminases during follow-up despite persistence of GBV-C. CONCLUSIONS: Coinfection of chronic hepatitis C patients with GBV-C does not lead to a significant change in clinical presentation, severity of liver disease, hepatitis C viremia, or response to interferon treatment.

Adult↗
PubMed1997

Primary hepatic high-grade non-Hodgkin's lymphoma and chronic hepatitis C infection.

Little is known about the coincidence of hepatitis C virus infection (HCV) and non-Hodgkin's lymphoma, although there is an increased incidence of chronic HCV infection with cryoglobulinemia type II and, interestingly, low-grade non-Hodgkin's lymphoma (NHL) in a few patients. We therefore report on a 74-year-old white male with known chronic hepatitis C virus infection who was admitted to the clinic due to weight loss and pain in the right upper quadrant. Ultrasound examination was performed for suspected hepatocellular carcinoma since a lesion in the left lobe of the liver was seen. X-ray of the lungs showed a few scattered lesions, suggestive of metastases. The ultrasound-guided fine-needle puncture revealed a high-grade malignant B-cell NHL While alpha-fetoprotein was normal, both cryoglobulin type II and the polymerase chain reaction (PCR) for HCV were positive. After six cycles of chemotherapy consisting of CHOP, the patient showed complete remission over three years. Ultimately, he died due to a sudden myeloic blast crisis. In summary, we discuss the possible etiopathologic role of the hepatitis viruses in the occurrence of non-Hodgkin's lymphoma. As we and others showed that HCV infects peripheral mononuclear blood cells (PBML), the infected PBML not only may be a source for reinfection after orthotopic liver transplantation, but also could be the cause for transformation and monoclonal propagation of lymphomatous tissue.

Aged↗
PubMed1997

Virus inactivation and prevalence of GBV-C in haemophiliacs.

A new putative hepatitis virus has recently been discovered and termed GB virus C (GBV-C). We investigated the prevalence of this virus among 50 haemophiliacs treated with non-virus-inactivated clotting factor concentrates prior to 1985 and 21 haemophiliacs treated exclusively with virus-inactivated clotting factor concentrates. In the first group the prevalence of GBV-C based on PCR and ELISA was 46%. In the second group the prevalence of GBV-C was similar to that of healthy blood donors (5%). We therefore conclude that GBV-C is reliably inactivated by modern virucidal methods such as vapour heating, pasteurization and treatment with solvent/detergent mixtures.

Blood Coagulation Factors↗
PubMed1997

Effect of fasting on the uptake of bilirubin and sulfobromophthalein by the isolated perfused rat liver.

BACKGROUND & AIMS: Occurrence of hyperbilirubinemia after fasting has been recognized for many years. The pathogenesis of this syndrome is unclear. Although recent studies suggest that increased intestinal deconjugation and reabsorption of bilirubin may play a major role in establishment of hyperbilirubinemia during fasting, other studies have suggested that fasting down-regulates intrinsic hepatocyte transport of bilirubin. The present study was designed to examine this possibility in the isolated perfused rat liver. METHODS: Transport of 3H-bilirubin and 35S-sulfobromophthalein (BSP) was examined in isolated perfused livers from 48-hour fasted or control rats using a multiple indicator dilution technique. Data were analyzed to quantify single-pass extraction (model-independent analysis) and were also fit by computer to the model of Goresky to quantify unidirectional fluxes. RESULTS: Fasting for 48 hours resulted in an approximately 40% reduction in liver weight but had no effect on model-dependent or model-independent parameters of transport. Despite the fact that the liver was smaller, single-pass extraction of bilirubin and BSP by livers from fasted animals did not differ from control, indicating a greater efficiency at uptake of bilirubin and BSP. CONCLUSIONS: Enhanced enterohepatic circulation of bilirubin, not altered hepatic transport, is a major factor in the pathogenesis of fasting-induced hyperbilirubinemia.

Animals↗
PubMed1997

[The hydro-MRT of chronic inflammatory bowel diseases].

PURPOSE: Evaluation of hydro-MRI in the diagnosis of chronic inflammatory bowel disease (IBD). MATERIAL AND METHODS: 33 patients with suspected Crohn's disease or ulcerative colitis were studied prospectively. After distension of the colon by a rectal enema, breathhold MR imaging was performed during bowel relaxation. Results were compared to the clinical diagnosis, endoscopy, barium studies and histopathology. RESULTS: 24/24 patients with active Crohn's disease were correctly diagnosed by MRI. Conversely, MRI was positive in only 2/5 patients with ulcerative colitis. In 5 patients the presence of IBD was excluded. There were no false positives. CONCLUSION: Hydro-MRI is a very reliable modality in the diagnosis of Crohn's disease. In the differentiation of Crohn's disease from ulcerative colitis, hydro-MRI seems to be a promising imaging procedure.

Adolescent↗
PubMed1997

Establishment of persistent hepatitis C virus infection and replication in vitro.

Hepatitis C virus (HCV) is a major cause of chronic viral hepatitis. Development of anti-viral strategies has been hampered by the lack of efficient cell systems to propagate HCV in vitro. To establish a long-term culture system, we tested human hepatoma (HuH7, HepG2) and porcine non-hepatoma (PK15, STE) cell lines, as well as several culture and infection conditions. As a marker for virus replication, minus-strand HCV RNA in infected cells was detected by an enhanced detection system using nested RT-PCR followed by hybridization analysis. Short-term efficiency of HCV infection (10 days) was slightly increased by addition of polyethylene glycol (PEG) and/or dimethyl sulfoxide (DMSO) to culture media during inoculation of HuH7, PK15 and STE cells, but no augmentation in long-term culture was achieved, suggesting enhanced attachment of HCV to cells rather than more efficient infection. A stabilizing effect on HCV propagation was observed for 50 days in a serum-free medium with stimulation of the low-density lipoprotein (LDL) receptor expression by lovastatin. Using partially serum-free culture conditions, long-term persistence of HCV in cells and release of virions into supernatant was achieved for up to 130 days. Infectivity of released virions in supernatants after long-term culturing (day 30-80) was shown by successful infection of fresh cells. In conclusion, supplementation with PEG, DMSO and lovastatin during inoculation did not enhance virus replication substantially, but continued stimulation of LDL-receptor expression resulted in infections which persisted for over 4 months. These data support the hypothesis of an LDL-receptor mediated uptake of HCV into cells in vitro.

Aged↗
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↗