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Biomedical subjects

G Gerken

Publications and source records attributed to G Gerken.

At least 109 records · Page 6Linked to original sources
PubMed1998

Modern oral contraceptive use and benign liver tumors: the German Benign Liver Tumor Case-Control Study.

OBJECTIVE: To analyze the association between oral contraceptive use and the risk of benign liver tumors. METHODS: Two parallel case-control studies on hepatocellular adenoma and focal nodular hyperplasia. Collaborative study of 15 German liver centers. Cases defined by histology and compared with population controls. RESULTS: Fifty-one hepatocellular adenoma and 143 focal nodular hyperplasia cases (women) were recruited between 1990 and 1997, and compared to 240 population controls with a recent abdominal imaging test. The frequency age-matched odds ratio was 1.25 (95% confidence interval (CI), 0.37-4.22) and 1.96 (95% CI, 0.85-4.57) for hepatocellular adenoma and focal nodular hyperplasia, respectively. For hepatocellular adenoma, there was neither a significantly increased risk with longer duration of oral contraceptive use, nor an association with time since first or last use. For focal nodular hyperplasia, however, a slightly increased odds ratio was found with longer duration of use and more recent last use. CONCLUSION: There is little evidence for an increased risk for hepatocellular adenoma in women using modern oral contraceptives. If there is a risk not detected by the limited study size, hepatocellular adenoma is an extremely rare, and focal nodular hyperplasia a rare, adverse effect potentially associated with long-term oral contraceptive use and likely to be without public health importance.

Adenoma, Liver Cell↗
PubMed1998

[Persistent pulmonary opacification as a sequela of portopulmonary shunt in portal vein thrombosis].

Portopulmonary venous anastomosis are a very rare complication of chronic liver diseases. We report on a patient with a cryptogenic liver cirrhosis and thrombosis of the portal vein who underwent antibiotic treatment because of recurrent pneumonias several times. Although treated successfully a pulmonal infiltrate persisted in further radiologic controls. By means of a velocity-encoded MRI a portopulmonary shunt of 30% of the cardiac output was assured. An operative correction with a distal splenorenal shunt was performed successfully. Former reports of portopulmonary anastomoses complicating chronic liver disease never were hemodynamically relevant. In the presented case, a portopulmonary anastomosis lead to recurrent pneumonias and a restrictive ventilatory disorder.

Female↗
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

Bile duct epithelia as target cells in primary biliary cirrhosis and primary sclerosing cholangitis.

Primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) are chronic autoimmune-mediated diseases of the biliary tree, resulting in a loss of bile ducts. There are morphological features that clearly distinguish them from each other: in PBC, there is overt destruction of the bile ducts with disruption of the basement membrane; in PSC there is abundant periductular fibrosis with shrinkage and subsequent loss of the bile ducts. In order to see if the disparate histopathology is paralleled by different immunohistology we looked at a panel of epitopes on bile duct epithelia especially to see if biliary epithelial cells may present as targets for cell mediated immune response. In PBC bile duct epithelial cells mostly expressed CD58 (lymphocyte function-associated antigen 3), CD80 (B7 BB1), and CD95 (Fas). In PSC, however, these epitopes were only expressed in a few examples to a lower degree. The respective effector T lymphocytes were positive for CD2 and CD28. Subtyping of the lymphocytes in the liver tissue further showed a predominance of CD4 positive T cells over CD8 cells up to 2-to-1 in both diseases. Determination of lymphocytes by cytokines to Th1 or Th2 subtype showed a majority of Th1 lymphocytes in PBC and PSC. We conclude that in PBC bile duct epithelial cells may display features of target cells of a T cell-mediated immune reaction with the Th1 cells predominating. In PSC other mechanisms of bile duct loss may play a role, since in this disease the majority of cells lack essential epitopes that constitute targets of cell mediated immunity.

Antigens, CD↗
PubMed1997

Quantification and genotyping of serum HCV-RNA in patients with chronic hepatitis C undergoing interferon treatment.

Quantification of serum HCV-RNA and HCV genotyping was studied in 27 patients with chronic hepatitis C undergoing interferon treatment. Pretreatment serum HCV-RNA levels were quantified using competitive RT-PCR and compared to a quantitative RT-PCR assay based on co-amplification of HCV-RNA with a synthetic RNA standard. HCV genotyping was performed using a line probe reversed hybridisation assay or direct solid-phase sequencing. This study shows the feasibility of performing HCV-RNA quantification. RT-PCR based on co-amplification HCV-RNA titer less than 6 x 10(4) genome equivalents/ml serum did correlate with a complete sustained response to alpha interferon in chronic hepatitis C. HCV genotype 1b was alpha predominantly associated with a high non-responder rate. Future prospective trials will be required to evaluate quantitative HCV-RNA levels and HCV genotyping as response predicting parameters for interferon-treatment.

Adult↗
PubMed1997

Receptor-mediated entry of hepatitis B virus particles into liver cells.

In previous reports several receptors for either natural hepatitis B virus (HBV) particles or genetically engineered virus have been described, whereby endocytosis represents a putative uptake mechanism for HBV particles. We have found that HBV-particles from viremic carriers could bind to the human asialoglycoprotein receptor (ASGPR), which mediates glycoprotein uptake into liver cells. The HBV-ASGPR interaction was studied in a cell culture system using hepatoma HepG2 and HuH7 cells compared to COS cells as controls. About 50% of HBsAg-secretion into the cell culture supernatant after HBV-inoculation as a function of HBV-uptake could be inhibited by the specific ASGPR-ligand asialofetuin. COS-cells did not show HBsAg-secretion. If the cells were grown as clones, 15% of HepG2-cells demonstrated HBsAg-secretion but only 5% in the presence of asialofetuin. HBV-particle uptake was further confirmed by HBV-DNA analysis using PCR. HBV-ASGPR interaction was studied with purified, biotin-conjugated human ASGPR. Quantitative inhibition with asialofetuin indicated a high-affinity binding of HBV-particles to purified ASGPR. After denaturing polyacrylamid gel electrophoresis and transblotting of isolated HBV-particles a receptor-blotting system was established which identified distinct binding sites for biotinylated receptors. These results suggest that the ASGPR is capable of specifically binding HBV-particles and, moreover, to mediate their hepatic endocytosis which ultimately could be responsible for the HBV-infection of liver cells.

Animals↗
PubMed1997

Actin is a target antigen of anti-neutrophil cytoplasmic antibodies (ANCA) in autoimmune hepatitis type-1.

BACKGROUND/AIM: Anti-neutrophil cytoplasmic antibodies (ANCA) are a group of autoantibodies first associated with Wegener's granulomatosis and microscopic polyangiitis. The significance of ANCA in autoimmune hepatitis remains uncertain; the nature of the antigen or antigens has not been defined yet. The purpose of this study was to identify the target antigen of ANCA in patients with autoimmune hepatitis. METHODS/RESULTS: Sera from 32 type-1 autoimmune hepatitis patients were used in the present study. ANCA were detected in 24 of 32 sera (75%). A diffuse cytoplasmic staining pattern (C-ANCA) was detected in 14 patients; the P-ANCA pattern was observed in 10 patients. An extract of human neutrophils was prepared and subjected to SDS-PAGE and Western Blot analysis. A 43-kD dominant immunoreactive protein was found in 20 (63%) autoimmune hepatitis patients. Aminoacid sequence analysis of the 43 kD protein identified actin. Cytoplasmic or perinuclear staining pattern could be reduced after absorption of sera with actin and after removing anti-actin antibodies by affinity chromatography. This was observed for all C-ANCA and for 8 out of 10 P-ANCA. Moreover in double-staining indirect immunofluorescence, the same type of diffuse cytoplasmic staining was observed with autoimmune hepatitis-sera and anti-actin antibodies. In Western Blot analysis with actin, 17 (53%) patients gave a positive result, while 15 (47%) patients had a positive actin-ELISA. CONCLUSION: This is the first report to identify the cytoskeletal protein actin as an ANCA antigen.

Actins↗
PubMed1997

MHC class II genes influence the susceptibility to chronic active hepatitis C.

BACKGROUND/AIMS: Chronic hepatitis C develops in more than 70% of hepatitis C virus infected subjects. Viral factors influence the disease course, but little is known about the importance of host factors. METHODS: Frequencies of major histocompatibility complex (MHC) class I and class II antigens were analyzed in two groups of patients with chronic hepatitis C virus infection and in control subjects. MHC class I typing was done by standard microlymphocytotoxicity assays. DRB1 and DQA1 genotyping was done by PCR based typing methods. RESULTS: DRB1*0301 was found in 26 of 75 patients with chronic hepatitis C virus infection (34.7%) and in 12 of 101 control subjects (11.9%) (relative risk 3.9; p < 0.001). Homozygosity for this allele appeared to confer a stronger risk. In contrast, DRB1*1301 was detected in three subjects with persistent infection (4.0%) compared to 21 control subjects (20.8%) (relative risk 0.2; p < 0.008). This allele was linked with DQA1*0103, which was found in 10 patients (13.3%) compared to 34 control subjects (33.7%) (relative risk 0.31; p < 0.003). An even stronger protective effect was provided by the presence of DRB1*1301 and DQA1*0103 (relative risk 0.08; p < 0.005). These findings were confirmed in a second group of chronic hepatitis C virus infected patients. CONCLUSIONS: The MHC class II allele DRB1*0301 appears to predispose to progression to chronic active hepatitis C, whereas the class II alleles DRB1*1301 and DQA1*0103 appear to provide protection against chronic active infection with hepatitis C virus.

Alleles↗
PubMed1997

Chronic hepatitis C: the viral load per liver cell before treatment as a new marker to predict long-term response to IFN-alpha therapy.

BACKGROUND/AIMS: So far, there are no reliable parameters that can predict the long-term sustained response to treatment with interferon-alpha in patients with chronic hepatitis C. In this study, we have developed a semi-quantitative method to determine the viral load per liver cell and have correlated this factor with the outcome of hepatitis C patients treated with interferon-alpha. METHODS: Hepatitis C virus RNA levels were measured in serum, peripheral blood mononuclear cells and liver cells of randomly chosen hepatitis C patients before treatment with interferon-alpha (n=37). The number of cells present in the liver biopsies was determined by a polymerase chain reaction-based quantitation of the housekeeping gene beta-globin. The patients were divided into a responder ("R", n=15, 41%) and a non-responder ("NR", n=22, 59%) group, as defined by normal liver enzymes and negative hepatitis C virus-polymerase chain reaction 6 months after treatment. RESULTS: Long-term sustained responders had a significantly lower viral load per liver cell (median: 5 vs. 650 copies/1000 liver cells, p-value: 0.0001), lower age (median: 32 vs. 54 years, p-value: 0.006) and lower percentage of geno- or serotype 1 (46% vs. 91%). Regarding viral load in serum and peripheral blood mononuclear cells, alanine aminotransferase levels, gamma-globulin levels and histological changes, no statistically significant differences were observed. CONCLUSIONS: In chronic hepatitis C infection, a high viral load per liver cell represents a new marker to predict long-term response to therapy with IFN-alpha.

Adult↗
PubMed1997

HLA-DRB1*1301 and *1302 protect against chronic hepatitis B.

BACKGROUND/AIMS: The outcome of acute hepatitis B infection may be influenced by host factors like the major histocompatibility complex (MHC). We have investigated MHC class I and class II antigens in patients with chronic hepatitis B compared to a healthy control population. To confirm the findings of this first study we performed a second study in a group of subjects who had spontaneously recovered from acute hepatitis B infection. METHODS: Frequencies of MHC class I and class II antigens were analyzed in patients with chronic hepatitis B virus infection and in control subjects. MHC class I typing was done by standard microlymphocytotoxicity assays. DRB1 and DQA1 genotypes were determined by polymerase chain reaction based typing methods. RESULTS: In the first study the class II allele HLA-DRB1*1301-02 was found in 4 of 70 subjects with chronic hepatitis B virus infection (5.7%) compared to 27 of 101 healthy controls (26.7%, relative risk 0.17; p=0.001; p(corr)=0.025). This protective effect of the DRB1*1301-02 allele was confirmed in the second study. Eight of 24 patients (33.3%) who cleared hepatitis B virus spontaneously were positive for DRB1*1301-02 (relative risk of developing chronic infection compared to chronic hepatitis B subjects 0.12; p=0.004). Subtyping confirmed that 1301 and 1302 were both decreased in frequency in patients with chronic hepatitis B. CONCLUSIONS: The MHC class II allele DRB1* 1301-02 is associated with protection from chronic hepatitis B in Caucasian patients.

Adult↗
PubMed1997

Regulation of endotoxin-induced IL-6 production in liver sinusoidal endothelial cells and Kupffer cells by IL-10.

Sinusoidal endothelial cells and Kupffer cells are the first cell populations in the liver that come into contact with gut-derived endotoxin in portal blood. Although endotoxin concentrations as high as 1 ng/ml are physiologically present in portal blood, no local inflammation is seen. We show that the proinflammatory cytokine IL-6, which is central to the development of inflammatory reactions in the liver, is produced by sinusoidal endothelial cells and Kupffer cells in response to low concentrations of endotoxin (100 pg/ml to 1 ng/ml). The anti-inflammatory cytokine IL-10 down-regulated endotoxin-induced IL-6 release in endothelial and Kupffer cells. Importantly, Kupffer cells secreted IL-10 after endotoxin stimulation and may therefore participate in the local regulation of inflammation. We have found that IL-6 secretion in Kupffer cells is tightly regulated by endogenous IL-10, because increased IL-6 secretion resulted when neutralizing antibodies to IL- 10 were added to resting and endotoxin-challenged Kupffer cells. Furthermore, repeated exposure of endothelial cells to endotoxin induced a state of tolerance which resulted in decreased release of IL-6 in response to a second endotoxin challenge. Our results support the notion that inflammatory reactions in the liver in response to endotoxin are down-regulated by local release of the anti-inflammatory cytokine IL-10 that is produced by Kupffer cells.

Animals↗