Prevalence and risk factors of hepatitis C infection after cardiac surgery in childhood before and after blood donor screening.

BACKGROUND: Since 1974, the risk of acquiring non-A non-B hepatitis by blood transfusion is well known. In 1999, children having had polytransfusions (group 1) after cardiac surgery prior to the establishment of routine blood donor screening could be identified as a risk group for hepatitis C (HCV) infection. PATIENTS AND METHODS: In 1991, Germany began screening blood donors for hepatitis C. To describe the risk after the implementation of blood donor screening, we studied 211 children (group 2) having had open heart surgery after 1991 and compared prevalence for anti-HCV antibodies and known risk factors to group 1. RESULTS: None of the 211 patients with cardiac surgery after 1991 had detectable anti-HCV antibodies, compared to 67 of the 458 patients (14.6%) of group 1 (p < 0.001). The mean number of operations in both groups was virtually the same (mean 1.7 +/- 0.9 in group 1, mean 1.6 +/- 0.9 in group 2, p = 0.075), whereas the total number of blood products per patient differed significantly (group 1 mean 8 +/- 17.6, group 2 mean 3.5 +/- 2.8; p < 0.001). Multivariate analysis of risk factors demonstrates affiliation to group 1, transfusion of fresh blood, warm whole blood, heparinized blood (p < 0.001) and plasma (p = 0.004) as significant. CONCLUSION: After the implementation of blood donor screening, the risk for HCV infection after cardiac surgery in childhood dropped significantly from 14.6% to < 0.5%. These data show the necessity of HCV screening for patients at risk (operations before 1991) and do not favor a general screening for all patients.

[Hepatitis B and C infection in late repatriates]. / Hepatitis B und C bei Spätaussiedlern.

105 late repatriates returning to Germany mostly from Russia, Ukraine and Kazakhstan were tested for present or past viral hepatitis B and 97 of them also for hepatitis C. Anti-HBc was found in 20% (95%-CI: 12,3-31,6%) and Anti-HCV in 3% (95%-CI: 1,3-8,0%) of tested individuals. 5% of tested persons were positive by PCR for HBV-DNA or HCV-DNA and therefore probably source of infection forthese viruses. All PCR positive individuals were not aware of their infection. Prevalence of hepatitis B and C infection was significantly higher than in the general population of Germany. Testing for viral hepatitis Band C should be offered to all late repatriates returning from areas with elevated prevalence of parenterally transmitted viral hepatitis. Further monitoring of the prevalence of viral hepatitis should be done in this group.

Prevalence of GB virus C/hepatitis G virus RNA and anti-E2 glycoprotein antibodies in homosexual men with HIV coinfection.

BACKGROUND: The objective of this cross-sectional, nonrandomized, prospective study was to generate data on the prevalence of GB virus C (GBV-C)/hepatitis G virus (HGV) in a cohort of HIV-infected homosexuals from Munich. PATIENTS: A total of 71 HIV-infected homosexual men were analyzed for prevalence of GBV-C RNA and antibodies to the E2 envelope glycoprotein (E2Ab). 475 healthy volunteer blood donors in southern Bavaria served as a control group. RESULTS: The prevalence of GBV-C RNA was 27% (control group: 2.3%) and the prevalence of E2Ab was 35% (control group: 6%). The total prevalence for present and past infection was 62%. The differences between the HIV-infected patients and the control group were significant (p < 0.0001). GBV-C RNA and E2Ab were not detected simultaneously in any serum sample. The E2Ab positive patients were older than the GBV-C RNA positives (mean 46 years versus 39 years, p = 0.0350). The GBV-C RNA and E2Ab negative patients were older than the GBV-C RNA positives (mean 47 years versus 39 years, p = 0.0236). The E2Ab positive patients had suffered sexually transmitted diseases more frequently than the patients negative for markers of GBV-C infection (p = 0.0308). E2Ab positive patients also had higher mean levels of alanine aminotransferase compared to patients without evidence of GBV-C infection (p = 0.0164). 59.4% of all individuals were anti-HBc IgG positive. CONCLUSION: The data can be interpreted as indirect evidence for sexual transmission of GBV-C.

Prevalence and clinical outcome of hepatitis C infection in children who underwent cardiac surgery before the implementation of blood-donor screening.

BACKGROUND AND METHODS: There are few data on the prevalence and clinical outcome of hepatitis C infection in children. We studied 458 children who underwent cardiac surgery in Munich, Germany, before 1991, when blood-donor screening for hepatitis C was introduced in Germany. Their mean age at first operation was 2.8 years; none of the children had received blood transfusions before or 'after cardiac surgery, and none of their mothers had antibodies to the hepatitis C virus (anti-HCV). We compared these patients with 458 control subjects matched for age and sex. RESULTS: Sixty-seven (14.6 percent) of the 458 patients who had undergone cardiac surgery had anti-HCV, as compared with 3 (0.7 percent) of the control subjects (P<0.001). At a mean interval of 19.8 years after the first operation, 37 (55 percent) of the 67 patients who were positive for anti-HCV had detectable HCV RNA in their blood. The infection had cleared in the other 30 patients, as evidenced by negative results on three polymerase-chain-reaction analyses performed at six-month intervals. Only 1 of the 37 patients who were positive for HCV RNA had elevated levels of liver enzymes; that patient had severe right-sided congestive heart failure. Of the 17 patients who underwent liver biopsies, only 3 had histologic signs of progressive liver damage. These three patients had additional risk factors: two had congestive heart failure, and the third had also been infected with hepatitis B virus. CONCLUSIONS: Children who had undergone cardiac surgery in Germany before the implementation of blood-donor screening for hepatitis C had a substantial risk of acquiring the infection. However, after about 20 years, the virus had spontaneously cleared in many patients. The clinical course in those still infected seems more benign than would be expected in people infected as adults.

[General insecurity, "false" and "real" security: arguments for the routine study of hospital patients for anti-HIV]. / Allgemeine Unsicherheit, "falsche" und "echte" Sicherheit: Argumente für die routinemässige Untersuchung von Krankenhauspatienten auf anti-HIV.

HIV infection has become an important risk for medical personal. Use of sufficient preventive measures with all patients and patient materials is time consuming, expensive and impracticable. In the present epidemiological situation anti-HIV testing of all hospital patients will give correct information on the presence or absence of HIV infection for 999 of 1000 patients. In addition to the increased safety of medical personal, testing will have several other advantages, some for the HIV infected persons: (1) In patients with HIV-related diseases time consuming delays in diagnosing the disease can be avoided. An earlier start of therapy will improve prognosis. (2) In HIV-infected persons a therapy can be chosen which exerts the least stress to the immune system. This may delay manifestation or progression of HIV-related diseases. (3) By medical surveillance of HIV-infected persons prophylaxis and immediate therapy of opportunistic infections is possible, which may prolong survival time. (4) Counselling of persons previously unaware of their HIV infection will slow down spread of HIV in the population. (5) Missing data on prevalence and incidence of HIV infection in different geographical areas will be available. Apart from the considerable cost reduction by reducing the use of extensive preventive measures to less than 10% of patients, routine screening of all patients is already economic if testing of 10,000 patients will prevent one single new infection by counselling of people with previously unknown HIV infection.

Expression of hepatitis B virus core antigen gene is induced in human hepatoma cells by their growth in nude mice.

The human hepatoma cell line PLC/PRF/5 is persistently infected with hepatitis B virus. Cells cultured in vitro are known to produce the virus surface antigen but not be other structural virus proteins, the core and the e antigen. It is shown here that expression of the core antigen gene was inducible by growing the cells as a nude mouse tumour. The buoyant density in CsCl (1.31 to 1.32 g/ml) of core or e antigen produced in the tumours was very similar to that of virus core particles. Expression of the core antigen gene was shunt off by culture in vitro of core or e antigen-producing nude mouse tumour cells and induced again by subsequent passage of cells in the nude mouse. The experimental system thus allows studies on the regulation of expression of the core antigen gene.

Immunosuppressive serum factors in viral hepatitis. III. Prognostic relevance of rosette inhibitory factor and serum inhibition factor in acute and chronic hepatitis.

Two immunosuppressive serum factors, serum inhibition factor (SIF) and rosette inhibitory factor (RIF), were studied in sera from patients with acute and chronic viral hepatitis. In a study of 30 patients with acute viral hepatitis, an association was found between RIF, SIF, and biochemical and virological parameters in 27 patients (90%), 25 of whom recovered completely; two had a protracted course. In three patients, the clinical course was not reflected by the immunosuppressive factors. In 26 patients with chronic persistent hepatitis, 3 had RIF and 7 had SIF of low activity. In patients with HBsAg-positive and -negative chronic active hepatitis, 32 of 47 had RIF and 24 had SIF. SIF activity was significantly increased in HBsAg positive as compared to -negative cases. There was no correlation between RIF and SIF activity at any stage of viral hepatitis. Although SIF was demonstrated in patients with various infectious and other inflammatory diseases, RIF was infrequently detected in nonviral liver disorders, and was not present in any of the nonhepatic diseases tested. It was confirmed that RIF is associated with the beta-lipoprotein fraction. RIF was easily separated from SIF by density gradient ultracentrifugation. The evaluation of SIF and RIF may be helpful in determining the outcome of acute viral hepatitis. In chronic hepatitis, RIF was a better indicator of disease activity than was SIF. These clinical data support previous findings that SIF may be related to the immune response whereas RIF is associated with liver cell damage.

Post-transfusion hepatitis and its association with pooled clotting factors.

A prospective study of post-transfusion hepatitis was conducted in 97 adult patients undergoing open heart surgery. Twelve patients developed presumed non-A, non-B hepatitis (five of these were hospitalized and three were jaundiced), and all 12 had received clotting factors from pooled plasma (fibrinogen, factor VIII, factor IX complex) from different manufacturers. Of the remaining 85 patients none received these high risk plasma derivatives and none developed hepatitis. Multiple peak ALT elevation seems to be an indication of development of chronic non-A, non-B hepatitis. In addition to the 12 cases of presumed non-A, non-B hepatitis, nine cases of serological changes related to hepatitis B virus were observed as follows: six early booster reactions of anti-HBs, but not anti-HBc, in anti-HBs and anti-HBc positive persons; one late immunization-like response for anti-HBs and two serological hepatitis B infections without transaminase elevation. Five of the nine cases were also associated with the administration of pooled clotting factors.

Topology and immunoreactivity of capsid proteins in hepatitis A virus.

Hepatitis A virus (HAV) was propagated in a hepatoma cell line and complete viral particles with a density of 1.34 g/ml were purified from cell extracts. The topography of the viral proteins (VPs) was studied by surface labelling with 125I and a solid-phase oxidant. The order of labelling intensity in complete particles was VP1 much greater than VP3 greater than VP2; labelling of VP4 was undetectable. When the particles were denatured with sodium dodecyl sulfate at 100 degrees C before iodination, the labelling efficiency was 6 times higher and the order of labelling intensity was VP3 greater than VP2 greater than VP1. After denaturation, the viral proteins no longer reacted with human anti-HAV antibody. The results suggest that (i) as with other picornaviruses, HAV exposes an essential part of VP1 at its surface whereas VP3 and especially VP2 are more hidden; (ii) naturally immunized individuals do not form detectable amounts of antibodies against the denatured capsid proteins. The apparent molecular weights of the VPs were 33000, 29000 and 28000 daltons.

Renal changes in cytomegalovirus infection.

Renal biopsy was performed in 20 graft recipients to characterise the histological features associated with poor renal function concomitant with cytomegalovirus infection (CMV). Eight patients presented with proteinuria, three had microscopic haematuria at onset, and five were hypertensive. Infection was accompanied by clinical symptoms (fever, leucopenia, mild hepatic damage, or pneumonitis) in 15 patients. In all cases, serum creatinine was greater than 2 mg/dl. All patients showed some glomerular alteration on biopsy, and vascular changes were the predominant feature in seven cases. IgM and complement (C3) were found in the glomeruli of five of six patients studied by immunofluorescence. Serum creatinine was below 2 mg/dl at ten to 26 months following the infectious episode in four patients and between 2-3 mg/dl in three patients. The remaining 13 developed irreversible rejection and end-stage renal failure. We conclude that CMV, the most commonly recognised viral infection following transplantation, can cause renal changes, both glomerular (CMV glomerulopathy) and vascular (transplant vasculopathy), which may induce poor graft function.

Clearance of hepatitis B e-antigen in chronic hepatitis B infection.

HBeAg and anti-HBe were determined by radioimmunoassay (Abbott HBe) in serial serum samples from 22 patients who had been HBsAg-positive for more than 1 year. Seventeen patients (77%) were HBeAg-positive at onset of illness. Eight of these patients were persistently HBeAg-positive during 2.5-8.5 years' follow-up study (mean, 5.4 years). Chronic persistent hepatitis (CPH) developed in one of these patients and chronic active hepatitis (CAH) in seven patients. Nine persistently HBsAg-positive patients were transiently HBeAg-positive. Seven of these patients developed CPH, and they all lost HBeAg within 2 years of onset of illness. One patient, who was HBeAg-positive for 4 years, developed CAH with cirrhosis after loss of HBeAg. In five patients, HBeAg could not be detected. They were anti-HBe-positive at onset of illness; four developed CAH and/or cirrhosis, and one developed CPH. Progression from CPH or nonspecific reactive hepatitis to CAH was observed in two persistently HBeAg-positive patients. Prolonged detection of HBeAg in CPH is a reason for repeated liver biopsy to reevaluate the diagnosis. The behaviour of the e-antigen system in CAH seems to be more complex than in CPH, perhaps indicating a different pathogenetic mechanism of chronicity in CAH.

Enzyme-linked immunosorbent assay for acute adenovirus infection.

An enzyme-linked immunosorbent assay (ELISA) is described for demonstrating antibodies to the hexone antigen of adenoviruses. The antigen-coated, flat-bottomed microtiter plates are incubated sequentially with dilutions of patients' sera (2 h at 37 degrees C) and peroxidase-coupled anti-human IgG (2 h at 37 degrees C). After a final washing, orthophenylenediamine is added to the plates, and the absorbance (A) measured 30 min later. The ELISA was found to be a hundred-fold more sensitive than complement fixation. An evaluation methods for determining antibody concentration is described which correlates the absorbance of sera diluted 10(-3) to the absorbance of a reference serum containing an arbitrary value (100) of antibody. This methods avoids titration of sera and day-to-day assay variations by different background reactions. A significant increase in antibody concentration of acute-phase serum over that of convalescent phase serum is observed. The ability to test sera in a single dilution and the automatic reading of results and their evaluation by computer make this assay suitable for diagnostic laboratories.

The physicochemical properties of infectious hepatitis A virions.

The propagation of hepatitis A virus (HAV) in the cell line PLC/PRF/5 made possible the radiolabelling in vivo of mature, infectious hepatitis A virions and the determination of their physicochemical properties. In contrast to poliovirus type 2 (160S, 1.340 g/ml), HAV had a sedimentation coefficient of 156 +/- 2S and a buoyant density of 1.332 g/ml in CsCl. The genome of HAV consisted of linear single-stranded RNA which sedimented at 32.5S under non-denaturing conditions. Compared to the size and sedimentation behaviour of poliovirus RNA (2.6 X 10(6) mol. wt., 35S) this corresponds to a mol. wt. of 2.3 X 10(6). Electrophoresis under fully denaturing conditions, however, revealed a mol. wt. of 2.8 X 10(6) and indicates the existence of relatively extended regions with secondary structure. The purified virus genome, containing a poly(A) sequence, served as a messenger for the synthesis of virus antigen in PLC/PRF/5 cells. Finally, in accordance with previous observations, the capsid of the virion was found to be constructed of three major polypeptides (VP1, 31 X 10(3); VP2, 26 X 10(3); VP3, 21 X 10(3) mol. wt.) and of two less readily demonstrable components probably corresponding to VP4 (8 X 10(3) to 10 X 10(3) mol. wt.) and the precursor polypeptide VP0 (40 X 10(3) mol. wt.).

Cloning of hepatitis A virus genome.

Hepatitis A virus (HAV) was highly purified from faeces. The genomic RNA was transcribed to cDNA and this DNA was then cloned into plasmid pBR 322 at the Pst I site, and clones were selected in presence of tetracycline. Most clones contained inserts which hybridized to HAV-specific RNA isolated from HAV-infected cell cultures derived from a human hepatocellular carcinoma. Two clones expressed low amounts of viral antigens.

[Non-A, non-B viral hepatitis: occurrence, epidemiology and prognosis]. / Non-A-non-B-virushepatitis: Häufigkeit, epidemiologie und prognose.

Out of 117 cases with acute viral hepatitis, 37 (32%) were classified as hepatitis A, 50 (43%) as hepatitis B and 30 (25%) as hepatitis non-A-non-B (NANB). In 21 of the 30 patients with hepatitis NANB, a possible mode of parenteral transmission could be found. The mean incubation period was 53 days. Only 3 patients had had blood transfusions. 14 (52%) of the 27 patients with sporadic hepatitis (without transfusions) had a mild course of the acute illness without, or with only mild, jaundice and transaminase values below 500 IU. The remaining 13 patients had a more severe form of acute hepatitis (bilirubin above 5 mg/dl, GPT above 500 IU), and in 11 of these 13 cases confluent necrosis was demonstrable on liver biopsy. 10 (37%) of the sporadic cases, of whom 8 had a mild form of acute hepatitis, and the 3 cases of posttransfusion hepatitis, were followed by a chronic course.