Sexual transmission of hepatitis C virus and its relation with hepatitis B virus and HIV.

OBJECTIVE--To determine the extent of transmission of hepatitis C virus in sexual partners of intravenous drug misusers and to examine the relation between the prevalences of HIV, hepatitis B virus, and hepatitis C virus infections in homosexual men and intravenous drug misusers and their sexual partners. DESIGN--Serum samples collected between 1984 and 1988 were tested for hepatitis B virus markers and antibodies against hepatitis C virus by enzyme linked immunosorbent assay (ELISA) and for HIV antibody by enzyme immune analysis and western blotting. SETTING--Large referral university hospital with an external AIDS clinic in the metropolitan area of Barcelona, Spain. SUBJECTS--243 Intravenous drug misusers, 143 of their regular heterosexual partners, and 105 homosexual men. MAIN OUTCOME MEASURES--Prevalences of hepatitis C virus, hepatitis B virus, and HIV infections. RESULTS--In all, 178 of the 243 (73%) intravenous drug misusers, 16 out of 143 (11%) of their partners, and 17 of the 105 (16%) homosexual men had antibodies against hepatitis C virus. The presence of hepatitis C virus infection was unrelated to sex, age, the presence of HIV or hepatitis B virus infections, or the Centers for Disease Control stage of HIV. In sexual partners of intravenous drug misusers there were strong correlations between the presence of hepatitis C virus infection and that of HIV (p = 0.001) and hepatitis B virus (p = 0.013) infections. CONCLUSIONS--Intravenous drug misusers have a high risk of acquiring hepatitis C virus, hepatitis B virus, and HIV infections, but the presence of hepatitis C virus infection seems to be unrelated to the presence of the other two viruses. Homosexual men have a high prevalence of HIV and hepatitis B virus infections with a low prevalence of hepatitis C virus infection, the presence of which is not related to that of the other two infections. Conversely, heterosexual partners of intravenous drug misusers have low prevalences of the three virus infections, but the presence of hepatitis C virus infection correlates significantly with the presence of HIV and hepatitis B infections. The rate of sexual transmission of hepatitis C virus seems to be low, even in partners of people known to be seropositive for this virus.     

Unemployment and mortality among Finnish men, 1981-5.

OBJECTIVE--To ascertain whether, after controlling for several relevant background variables simultaneously, unemployment is related to mortality and to assess whether this relation is causal or whether unhealthy people are more likely to become unemployed. DESIGN--Prospective study of mortality in Finland during 1981-5 based on 1980 census data on 30-54 year old wage earner men and with particular attention to unemployment in the year before the census. SETTING--Research project at the University of Helsinki. SUBJECTS--All wage earner men in Finland aged 30-54 at the 1980 census. MAIN OUTCOME MEASURES--Causes of death during 1981-5 and duration of unemployment in the year before the census. Background variables controlled for were age, socioeconomic state, marital state, and health. The data were analysed by log linear regression models. RESULTS--During the study period 1981-5, which covered almost 2.7 million person years, there were 9810 deaths. After controlling for all background variables relative total mortality among unemployed versus employed men was 1.93 (95% confidence interval 1.82 to 2.05). The excess mortality was highest in accidental and violent causes of death (relative mortality 2.51; 95% confidence interval 2.28 to 2.76). For circulatory diseases the relative death rate was 1.54 (95% confidence interval 1.40 to 1.70), but among neoplasms only lung cancer was associated with excess mortality. Selection for unemployment based on age, socioeconomic state, and marital state was evident but no such selection was detected based on health. Effects of unemployment on mortality were more pronounced with increasing duration of unemployment. CONCLUSIONS--The relative excess mortality of unemployed men in Finland cannot fully be explained by demographic, social, and health variables preceding unemployment. Unemployment therefore seems to have an independent causal effect on male mortality. Further studies are needed to elucidate the mechanisms between unemployment and mortality.     

Infection with HIV and hepatitis C virus among injecting drug users in a prevention setting: retrospective cohort study

Objectives: To estimate the incidence of HIV and hepatitis C virus and risk factors for seroconversion among a cohort of injecting drug users. Design: Retrospective cohort study. Setting: Primary healthcare facility in central Sydney. Subjects: Injecting drug users tested for HIV-1 antibody (n=1179) and antibodies to hepatitis C virus (n=1078) from February 1992 to October 1995. Main outcome measures: Incidence of HIV-1 and hepatitis C virus among seronegative subjects who injected drugs and underwent repeat testing. Demographic and behavioural risk factors for hepatitis seroconversion. Results: Incidence of HIV-1 among 426 initially seronegative injecting drug users was 0.17/100 person years (two seroconversions) compared with an incidence of hepatitis C virus of 20.9/100 person years (31 seroconversions) among 152 injecting drug users initially negative for hepatitis C virus. Incidence of hepatitis C virus among injecting drug users aged less than 20 years was 75.6/100 person years. Independent risk factors for hepatitis C virus seroconversion were age less than 20 years and a history of imprisonment. Conclusions: In a setting where prevention measures have contributed to the maintenance of low prevalence and incidence of HIV-1, transmission of hepatitis C virus continues at extremely high levels, particularly among young injecting drug users.

Key messages

• The prevalence and incidence of hepatitis C virus is high, while the prevalence and incidence of HIV remains low among injecting drug users
• Young age and history of imprisonment are risk factors for acquisition of hepatitis C virus infection
• HIV prevention strategies have been relatively ineffective in preventing hepatitis C virus infection in this population
• The role of imprisonment in the acquisition of hepatitis C infection should be further investigated

     

Mortality among patients with cleared hepatitis C virus infection compared to the general population: a Danish nationwide cohort study

Background

The increased mortality in HCV-infected individuals partly stems from viral damage to the liver and partly from risk-taking behaviours. We examined mortality in patients who cleared their HCV-infection, comparing it to that of the general population. We also addressed the question whether prognosis differed according to age, substance abuse (alcohol abuse and injection drug use) and comorbidity.

Methodology/Principal Findings

Patients with cleared HCV-infection were categorized into one of 8 groups according to age (20–39 years or 40–69 years) and patient characteristics (no substance abuse/no comorbidity; substance abuse/no comorbidity; no substance abuse/comorbidity; and substance abuse/comorbidity). For each patient, 4 age- and gender-matched individuals without substance abuse or comorbidity were selected from the general population, comprising a total of 8 comparison cohorts. We analyzed 10-year survival and used stratified Cox Regression analysis to compute mortality rate ratios (MRRs), comparing mortality between the 8 patient groups and the comparison cohorts, adjusting for personal income. Among patients without substance abuse or comorbidity, those aged 40–69 years had the same mortality as the comparison cohort (10-year survival: 95% (95% confidence interval [CI]: 93%–97%), MRR: 1.3 (95% CI: 0.8–2.3)), whereas those aged 20–39 years had higher mortality than the comparison cohort (10-year survival: 93% versus 99%, MRR: 5.7 (95% CI: 2.3–14.0). For both age categories, substance abuse and comorbidity decreased survival and increased MRRs. Patients aged 40–69 years with substance abuse and comorbidity suffered from substantial mortality (MRR: 12.5 (95% CI: 5.1–30.6)).

Conclusions

Mortality in patients aged 40–69 years with cleared HCV-infection is comparable to individuals without HCV, provided they have no substance abuse or comorbidity. Any substance abuse and/or comorbidity not captured in the registries used for our study could explain the increased mortality in patients aged 20–39 years without documented substance abuse or comorbidity.     

Clinical course of hepatitis C virus during the first decade of infection: cohort study

ObjectiveTo determine the clinical course of hepatitis C virus in the first decade of infection in a group of patients who acquired their infections on a known date.DesignCohort study.SettingClinical centres throughout the United Kingdom.Participants924 transfusion recipients infected with the hepatitis C virus (HCV) traced during the HCV lookback programme and 475 transfusion recipients who tested negative for antibodies to HCV (controls).ResultsAll cause mortality was not significantly different between patients and controls (Cox''s hazards ratio 1.41, 95% confidence interval 0.95 to 2.08). Patients were more likely to be certified with a death related to liver disease than were controls (12.84, 1.73 to 95.44), but although the risk of death directly from liver disease was higher in patients than controls this difference was not significant (5.78, 0.72 to 46.70). Forty per cent of the patients who died directly from liver disease were known to have consumed excess alcohol. Clinical follow up of 826 patients showed that liver function was abnormal in 307 (37.2%), and 115 (13.9%) reported physical signs or symptoms of liver disease. Factors associated with developing liver disease were testing positive for HCV ribonucleic acid (odds ratio 6.44, 2.67 to 15.48), having acquired infection when older (at age ⩾ 40 years; 1.80, 1.14 to 2.85), and years since transfusion (odds ratio 1.096 per year, 1.00 to 1.20). For patients with severe disease, sex was also significant (odds ratio for women 0.38, 0.17 to 0.88). Of the 362 patients who had undergone liver biopsy, 328 (91%) had abnormal histological results and 35 (10%) of these were cirrhotic.ConclusionsHepatitis C virus infection did not have a great impact on all cause mortality in the first decade of infection. Infected patients were at increased risk of dying directly from liver disease, particularly if they consumed excess alcohol, but this difference was not statistically significant.

What is already known on this topic

The clinical course of HCV infection is unclear because most information has come from studies of patients with established chronic liver diseaseStudies that follow patients from disease onset are rare because most HCV infections are asymptomatic

What this study adds

HCV infection does not have a great impact on all cause mortality in the first decade of infectionInfected patients have an increased risk of dying from a liver related cause, particularly if they consumed excess alcohol     

Prevalence of hepatitis C virus (HCV) genotypes among positive UAE patients

A molecular study was conducted to investigate the prevalence of Hepatitis C virus genotypes in HCV infected population of UAE. 67 HCV seropositive samples were collected from different health care centres. Quantitative analysis of these samples using PCR resulted in 67 positive samples. The PCR positive samples were subjected to genotyping using the method described by Simmonds et al. (J Gen Virol 74: 2391–2399, 1993). HCV genotype 4 was the predominant genotype (46.2%) followed by genotype 3a (23.8%) and 1a (15%). The predominant genotype among the female patients was genotype 4 (65.6%), while genotype 3a was the predominant among the male patients (42.8%). The predominance of HCV genotype 4 in our population confirms the predominance of HCV genotype 4 in UAE and most of the Arab countries in the Middle East. Implications of genotyping for clinical outcome of HCV infection, response to treatment as well as for vaccine development are discussed.     

Course of HIV-I infection in a cohort of homosexual and bisexual men: an 11 year follow up study.

OBJECTIVE--To characterise the natural history of sexually transmitted HIV-I infection in homosexual and bisexual men. DESIGN--Cohort study. SETTING--San Francisco municipal sexually transmitted disease clinic. PATIENTS--Cohort included 6705 homosexual and bisexual men originally recruited from 1978 to 1980 for studies of sexually transmitted hepatitis B. This analysis is of 489 cohort members who were either HIV-I seropositive on entry into the cohort (n = 312) or seroconverted during the study period and had less than or equal to 24 months between the dates of their last seronegative and first seropositive specimens (n = 177). A subset of 442 of these men was examined in 1988 or 1989 or had been reported to have developed AIDS. MAIN OUTCOME MEASURES--Development of clinical signs and symptoms of HIV-I infection, including AIDS, AIDS related complex, asymptomatic generalised lymphadenopathy, and no signs or symptoms of infection. MEASUREMENTS AND MAIN RESULTS--Of the 422 men examined in 1988 or 1989 or reported as having AIDS, 341 had been infected from 1977 to 1980; 49% (167) of these men had died of AIDS, 10% (34) were alive with AIDS, 19% (65) had AIDS related complex, 3% (10) had asymptomatic generalised lymphadenopathy, and 19% (34) had no clinical signs or symptoms of HIV-I infection. Cumulative risk of AIDS by duration of HIV-I infection was analysed for all 489 men by the Kaplan-Meier method. Of these 489 men, 226 (46%) had been diagnosed as having AIDS. We estimated that 13% of cohort members will have developed AIDS within five years of seroconversion, 51% within 10 years, and 54% within 11.1 years. CONCLUSION--Our analysis confirming the importance of duration of infection to clinical state and the high risk of AIDS after infection underscores the importance of continuing efforts both to prevent transmission of HIV-I and to develop further treatments to slow or stall the progression of HIV-I infection to AIDS.     

Investigating the endemic transmission of the hepatitis C virus

The hepatitis C virus (HCV) infects at least 3% of people worldwide and is a leading global cause of liver disease. Although HCV spread epidemically during the 20th century, particularly by blood transfusion, it has clearly been present in human populations for several centuries. Here we attempt to redress the paucity of investigation into how long-term endemic transmission of HCV has been maintained. Such transmission not only represents the 'natural' route of infection but also contributes to new infections today. As a first step, we investigate the hypothesis that HCV can be mechanically transmitted by biting arthropods. Firstly, we use a combined bioinformatic and geographic approach to build a spatial database of endemic HCV infection and demonstrate that this can be used to geographically compare endemic HCV with the range distributions of potential vector species. Second, we use models from mathematical epidemiology to investigate if the parameters that describe the biting behaviour of vectors are consistent with a proposed basic reproduction number (R0) for HCV, and with the sustained transmission of the virus by mechanical transmission. Our analyses indicate that the mechanical transmission of HCV is plausible and that much further research into endemic HCV is needed.     

Intestinal parasitic infections in homosexual men: prevalence,symptoms and factors in transmission.

In a controlled study 67.5% of 200 homosexual men but only 16% of 100 heterosexual men were found to be infected with intestinal parasites. Entamoeba histolytica was isolated from 27% of the homosexual and 1% of the heterosexual men, and Giardia lamblia was isolated from 13% of the homosexual and 3% of the heterosexual men. The presence of symptoms could not be correlated with infection except when the infection was caused by more than one organism, including G. lamblia. Symptoms were much more common in both infected and uninfected homosexuals than in heterosexuals. Among the homosexual men recent foreign travel, living in a homosexual household and promiscuity were not correlated with intestinal parasitic infection, but cleansing of the anus before and sex was associated with a significantly lower prevalence of infection. These findings suggest that the male homosexual community may be an important reservoir of potentially pathogenic protozoa.     

In vitro study of the NS2-3 protease of hepatitis C virus.

Processing at the C terminus of the NS2 protein of hepatitis C virus (HCV) is mediated by a virus-encoded protease which spans most of the NS2 protein and part of the NS3 polypeptide. In vitro cotranslational cleavage at the 2-3 junction is stimulated by the presence of microsomal membranes and ultimately results in the membrane insertion of the NS2 polypeptide. To characterize the biochemical properties of this viral protease, we have established an in vitro assay whereby the NS2-3 protease of HCV BK can be activated posttranslationally by the addition of detergents. The cleavage proficiency of several deletion and single point mutants was the same as that observed with microsomal membranes, indicating that the overall sequence requirements for proper cleavage at this site are maintained even under these artificial conditions. The processing efficiency of the NS2-3 protease varied according to the type of detergent used and its concentration. Also, the incubation temperature affected the cleavage at the 2-3 junction. The autoproteolytic activity of the NS2-3 protease could be inhibited by alkylating agents such as iodoacetamide and N-ethylmaleimide. Metal chelators such as EDTA and phenanthroline also inhibited the viral enzyme. The EDTA inhibition of NS2-3 cleavage could be reversed, at least in part, by the addition of ZnCl2 and CdCl2. Among the common protease inhibitors tested, tosyl phenylalanyl chloromethyl ketone and soybean trypsin inhibitor inactivated the NS2-3 protease. By means of gel filtration analysis, it was observed that the redox state of the reaction mixture greatly influenced the processing efficiency at the 2-3 site and that factors present in the rabbit reticulocyte lysate, wheat germ extract, and HeLa cell extract were required for efficient processing at this site. Thus, the in vitro assay should allow further characterization of the biochemical properties of the NS2-3 protease of HCV and the identification of host components that contribute to the efficient processing at the 2-3 junction.     

Perinatal transmission of hepatitis B virus.

Transmission of hepatitis B virus from carrier mothers to their infants seems most likely to occur during birth. Both cord blood and breast milk have been found to be positive (in 35% and 72% of cases respectively) for hepatitis B surface antigen (HBsAg), but they do not appear to play an important role in transmission. To control this problem high-risk women should be tested during pregnancy for HBsAg. The infants of infected women should be given several doses of hepatitis B immunoglobulin starting at birth. In less developed regions, where hepatitis B is endemic, administration of the immunoglobulin in combination with vaccine, or even the vaccine alone, may be preferable in order to provide infants with lasting protection.