Modulation of tumor necrosis factor receptors 1 and 2 in chronic hepatitis B and C: The differences and implications in pathogenesis

Tumor necrosis factor (TNF) plays a role in the pathogenesis of chronic hepatitis B (CHB) and chronic hepatitis C (CHC). The difference in the cytokine responses between hepatitis B virus (HBV) and hepatitis C virus (HCV) infections may have implications in the pathogenesis of these diseases. We performed a comparative study to examine the possible differences in the TNF-TNF receptor (TNFR) response between CHB and CHC. We studied the cytokine levels of 38 patients with CHB, 40 patients with CHC and 9 patients with dual hepatitis B and C, and compared them with the baseline levels of 12 healthy controls. The plasma levels of TNF-, interferon-, interleukin (IL)-2, IL-4, IL-10 and soluble TNFR-1 and 2 (sTNFR-1 and 2) were quantified by enzyme-linked immunosorbent assays. The expression of TNFR-1 and 2 in liver tissues was examined in 30 cases of CHB and 15 cases of CHC by semiquantitative reverse transcription polymerase chain reaction. The results showed that sTNFR-1 levels correlated with liver inflammation in all patients, whereas this correlation was not found with sTNFR-2 or other cytokines. Liver inflammation indicators were higher in HCV RNA+ than in HCV RNA– CHC. Most significantly, sTNFR-1 levels correlated with liver inflammation in CHB, but not in CHC. However, the expression of TNFR-1 and 2 in liver was similar between CHB and CHC. These findings suggest that the TNFR signal transduction pathway is modulated differently in HBV and HCV infection.

The current pattern of hepatitis B virus infectiion in Australia

Summary. There is little recent data of the seroprevalence of hepatitis B in Australia. We have surveyed a large cohort of endoscopy patients attending a teaching hospital in central Sydney, and related the presence of hepatitis B virus (HBV) markers with putative risk factors for exposure using the SAS statistical package. Of the 2115 patients tested: 2.1% (45/2115) were HBV surface antigen positive, 0.75% (14/2115) viraemic, 9.5% (200/2115) anti-HBs and anti-HBc positive, 20.1% (430/2115) vaccinated (anti-HBs only) and the remaining 70% were susceptible. The adjusted OR of HBV infection was significantly increased in patients who had been diagnosed with human immunodeficiency virus (36.3-fold), born in Asia or Pacific islands (12.4-fold), born in North Africa, Middle East & Mediterranean countries (6-fold) or born abroad elsewhere in the world (2.7-fold), had household contact with someone diagnosed with hepatitis between 1980 and 1990 (3.9-fold), injected drugs between 1980 and 1990 (4.4-fold), resided in a military establishment for 3 months (2.3-fold) or in a hospital for 3 months (2.2-fold), never been vaccinated for hepatitis B (2.8-fold), received blood transfusion due to an accident and/or a haemorrhage (1.92-fold) and finally been a male gender (1.59-fold). The prevalence of HBV in this hospital population was higher than predicted on the basis of notifications to the passive surveillance scheme. Most HBV patients had multiple risk factors for infection, but the hierarchy of odds ratios provides a rational basis for targeted programmes to identify asymptomatic HBV carriers who might benefit from treatment.

Replication of hepatitis B in HBsAg-positive siblings

Persistent hepatitis B virus (HBV) replication is important for progression of chronic liver diseases. To understand whether there is a trend of HBV replication in siblings or not, 1850 relatives of patients with hepatocellular carcinoma (HCC) were examined prospectively for liver function test, viral markers and HBV DNA. The prevalence of HBsAg in the parents', siblings', children's and grandchildren's generations were 43.4%, 57.2%, 35.5% and 32.1%, respectively. The prevalence of hepatitis B e antigen (HBeAg) in sibling's generation (mean age 44.4 years) was 19%, which is higher than that of asymptomatic HBsAg carriers. For siblings in the children's generation, the prevalence of HBeAg in hepatitis B surface antigen (HBsAg) carriers declined from 40% in the eldest siblings to 19% in the youngest siblings. In 75 families clustered with three or more HBsAg carrier siblings, the mean age for seven families of which all siblings remained HBeAg + was younger, whereas the mean age for 35 families of which all siblings had cleared HBeAg was older. For the remaining 33 families, in only 10 families had the older siblings cleared the HBeAg earlier than the younger siblings. Twenty families showed that younger siblings cleared the HBeAg earlier than the older or middle siblings. We concluded that HBV replication in HCC relatives cannot be explained by familial tendency alone. A significant number of younger siblings appeared to have a shorter HBV replication phase than their older siblings. The possible role of this in maternal–fetal transmission is discussed.

The significance of transfusion in the past as a risk for current hepatitis B and Hepatitis C infection: a study in endoscopy patients

BACKGROUND: The objective was to determine the contribution of transfusion in the past to the risk of current infection with hepatitis B or C among patients attending a large hospital for endoscopic procedures.
STUDY DESIGN AND METHODS: Blood samples had been tested for hepatitis markers by routine methods. Patients completed a comprehensive risk factor questionnaire and results were analyzed using computer software.
RESULTS: Twenty-seven percent of the 2120 participants in the study received transfusions in the past. There was no increase in prevalence of hepatitis B among those transfused. Compared with nontransfused participants, recipients of blood before the implementation of hepatitis C virus (HCV) screening in 1990 had a 4.6-fold increased risk of HCV infection, whereas those transfused with screened blood had a 3-fold increased risk. The difference between the odds ratios for patients before and after screening was not significant.
CONCLUSIONS: Because screening has almost completely eliminated HCV from the blood supply, our finding of a continuing association of HCV infection with transfusion was unexpected. It implies that there are significant other nosocomial risks for hepatitis C transmission associated with the clinical situations where patients received blood. These should be actively investigated.

Profile of dyslipodemia in psammomys obesus, an animal model of the metabolic syndrome

Objective. To investigate lipid profiles in Psammomys obesus and relationships between lipid profile and other components of the Metabolic Syndrome.

Methods. A total number of 49 adults with a wide range of body weight and glucose tolerance were studied in a cross-sectional analysis. Plasma cholesterol distribution profiles were measured by size exclusion lipid chromatography. Blood glucose was measured using an enzymatic glucose analyser, and plasma insulin was determined by radioimmunossay.

Results. Obese diabetic Psammomys obesus had elevated plasma cholesterol (P=0.003) and triglyceride levels (p>0.001) compared to their lean littermates. The hypercholesterolemia was mainly due to increased circulating levels of VLDL-cholesterol (P=0.003) and LDL-cholesterol (P=0.003) in these animals. Multiple linear regression analyses revealed that body weight was independently associated with plasma cholesterol (P=0.011) and LDL concentration (P=0.009), while plasma insulin was associated with VLDL-cholesterol concentration (P=0.005). All of the variables measured exhibited continuous distributions across a wide range of phenotypes, from a normal rodent lipid profile to profound dyslipidemia.

Conclusions. These data suggest that the dyslipidemia in obese, diabetic Psammomys obesus is closely associated with other components of the Metabolic Syndrome, including obesity and insulin resistance.