Markers and risk factors for HCV, HBV and HIV in a network of injecting drug users in Melbourne

Background and aims: Current injecting drug users (IDU) in major street drug markets within greater Melbourne were recruited to a longitudinal study on blood borne viruses. Here we investigated risk factors for hepatitis C virus (HCV), hepatitis B virus (HBV) and HIV infection in these IDU at the time of their recruitment.

Methods : Three hundred and eighty-two IDU completed detailed questionnaires on their drug use and risk behaviours, and provided blood samples for serology testing. These data were analysed using univariate and multivariate techniques.

Results : The overall prevalence of exposure to HCV, HBV and HIV was estimated at 70%, 34% and <1%, respectively. Independent predictors of HCV exposure were history of imprisonment (RR 1.34, 95% CI 1.19–1.52), use of someone else's needle or syringe (RR 1.23, 95% CI 1.07–1.42), >7.6 years length of time injecting (RR 1.21, 95% CI 1.07–1.37), and originating from Vietnam (RR 1.12, 95% CI 1.07–1.18). Independent predictors of HBV exposure were HCV exposure (RR 2.15, 95% CI 1.35–3.43), >7.6 years length of time injecting (RR 1.57, 95% CI 1.17–2.13) and originating from outside Australia (RR 1.60, 95% CI 1.22–2.10). Neither prison- nor community-applied tattoos predicted HCV or HBV exposure. Up to 31% of IDU who injected for 1 year or less were HCV antibody positive, as were 53% of those who injected for 2 years or less.

Conclusions : Ongoing engagement with young IDU, through the provision of harm reduction education and resources, is critical if we are to address blood borne viral infections and other health and social harms associated with injecting drug use.

Australian women`s experiences of living with hepatitis C virus: results from a cross-sectional survey

Background: Of the estimated 160 000 Australians currently infected with the hepatitis C virus (HCV), over one-third are women and very few have received clinical treatment, with most managing their illness in non-specialist settings. Little is known about the experiences of women living with HCV in the general community. The present study provides the results from the first comprehensive social survey of Australian women's experiences of living with HCV.

Methods: In 2000, a questionnaire was administered to a largely non-clinical sample of women with HCV (n = 462) living in the state of Victoria and the Australian Capital Territory, Australia. The questionnaire was self-administered with a return rate of 75%. The mean age was 35 years and 83% were 'current' or 'past' injecting drug users. The mean time since diagnosis was 4.6 years (SD = 4.0) and the mean time since infection was 10.5 years (SD = 8.2).

Results: Fifty-eight percent of women reported experiencing symptoms related to their HCV, the most common being tiredness (78%) and nausea (44%). Of the sample, 56% currently saw a doctor for their HCV, and while 52% had ever been referred to a specialist, only 17% of the total sample had ever begun interferon-based combination or monotherapy. Forty-eight percent of women reported experiencing less favorable treatment by a health professional because of their HCV. Age-related self-assessed health status was significantly lower than Australian norms, as were SF-12 physical and mental health scores. The SF-12 physical and mental health scores were highly correlated, indicating a significant physical and mental health burden associated with HCV.

Conclusion: The social, physical and mental health needs of women living with HCV are considerable. Most women had not accessed specialist treatment and the response of the primary health care system to HCV-related women's health issues requires improvement.

Emerging host cell targets for hepatitis C therapy

Chronic hepatitis C virus (HCV) infection is a major burden on humanity. The current HCV therapy has limited efficacy, and there is pressing need for new and more effective therapies. Host cell factors that are required for HCV infection, replication and/or pathogenesis represent potential therapeutic targets. Of particular interest are cellular receptors that mediate HCV entry, factors that facilitate HCV replication and assembly, and intracellular pathways involving lipid biosynthesis, oxidative stress and innate immune response. A crucial challenge now is to manipulate such cellular targets pharmacologically for chronic HCV treatment, without being limited by side effects.

Survival of relatives of patients with hepatocellular carcinoma

Background:Families of patients with hepatocellular carcinoma (HCC) carry a high risk of developing HCC. We determine the number of fatalities in relatives of HCC patients during an 8-year period to understand the risk and cause of HCC in relatives of patients with HCC.
Methods:From 1992 to 1997, 15 410 relatives of HCC patients in three generations were screened prospectively for HCC by ultrasonography, α-fetoprotein, liver biochemistry and viral markers. By using national citizen identification numbers, we searched the total fatalities in relatives of HCC patients between 1992 and 1999 from the national mortality data bank. The results were compared among different viral infection groups.
Results:Of the relatives studied, 37.8% were hepatitis B s antigen (HBsAg) positive (+), 4.3% were anti-hepatitis C virus (HCV) (+) and 1.7% were both HBsAg (+) and anti-HCV (+). A total of 399 fatalities, including 139 because of HCC (34.8%), 37 because of liver diseases (9.3%), 88 because of other cancers (22.1%) and 135 because of other diseases (33.8%), were found. Relatives who were HBsAg (+) or anti-HCV (+)showed a lower cumulative survival than did relatives who were negative for both HBsAg and anti-HCV. Relatives with dual infection of hepatitis B and C virus showed the highest mortality due to HCC or terminal liver diseases.
Conclusions:Chronic viral infection rather than a hereditary factor is the main cause of a familial tendency for HCC. Dual infection of hepatitis B and C virus increases the risk of HCC or decompensated liver diseases.
Background:Families of patients with hepatocellular carcinoma (HCC) carry a high risk of developing HCC. We determine the number of fatalities in relatives of HCC patients during an 8-year period to understand the risk and cause of HCC in relatives of patients with HCC.
Methods:From 1992 to 1997, 15 410 relatives of HCC patients in three generations were screened prospectively for HCC by ultrasonography, α-fetoprotein, liver biochemistry and viral markers. By using national citizen identification numbers, we searched the total fatalities in relatives of HCC patients between 1992 and 1999 from the national mortality data bank. The results were compared among different viral infection groups.
Results:Of the relatives studied, 37.8% were hepatitis B s antigen (HBsAg) positive (+), 4.3% were anti-hepatitis C virus (HCV) (+) and 1.7% were both HBsAg (+) and anti-HCV (+). A total of 399 fatalities, including 139 because of HCC (34.8%), 37 because of liver diseases (9.3%), 88 because of other cancers (22.1%) and 135 because of other diseases (33.8%), were found. Relatives who were HBsAg (+) or anti-HCV (+)showed a lower cumulative survival than did relatives who were negative for both HBsAg and anti-HCV. Relatives with dual infection of hepatitis B and C virus showed the highest mortality due to HCC or terminal liver diseases.
Conclusions:Chronic viral infection rather than a hereditary factor is the main cause of a familial tendency for HCC. Dual infection of hepatitis B and C virus increases the risk of HCC or decompensated liver diseases.

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 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.

Hepatitis C virus infection in South Australian prisoners : seroprevalence, seroconversion, and risk factors

Objectives : To determine entry antibody seroprevalence and seroconversion to hepatitis C virus (HCV) and associated risk factors in newly incarcerated prisoners.

Methods : Males and females entering South Australian prisons completed risk factor surveys and were offered HCV-antibody testing. Participants completed additional surveys and, if HCV-negative at last test, underwent further antibody tests at 3-monthly intervals for up to 15 months. Data were analyzed using univariate and multivariate techniques.

Results : HCV seroprevalence among 662 prison entrants was estimated at 42%. Previous injecting history was highly prevalent at entry (64%) and both community and prison injecting independently predicted entry HCV status. Tattooing was not an important risk factor. While community exposure could not be ruled out, three seroconversions were noted in 148 initially HCV-seronegative individuals occurring in a median 121 days – 4.6 per 100 person-years. Prison injecting was infrequently reported, but HCV-seropositive participants were significantly more likely to commence IDU in prison than seronegative participants (p = 0.035).

Conclusions : Entry HCV seroprevalence in South Australian prisoners is extremely high and may have contributed to a ‘ceiling effect’, minimizing the observable seroconversion rate. Greater frequency of injecting among those already infected with HCV represents a significant threat to other prisoners and prison staff.

Computer-assisted image analysis of liver collagen: relationship to Ishak scoring and hepatic venous pressure gradient

Histopathological scoring of disease stage uses descriptive categories without measuring the amount of fibrosis. Collagen, the major component of fibrous tissue, can be quantified by computer-assisted digital image analysis (DIA) using histological sections. We determined relationships between DIA, Ishak stage, and hepatic venous pressure gradient (HVPG) reflecting severity of fibrosis. One hundred fifteen patients with hepatitis C virus (HCV) who had undergone transplantation had 250 consecutive transjugular liver biopsies combined with HVPG (median length, 22 mm; median total portal tracts, 12), evaluated using the Ishak system and stained with Sirus red for DIA. Liver collagen was expressed as collagen proportionate area (CPA). Median CPA was 6% (0.2-45), correlating with Ishak stage (stage 6 range, 13%-45%), and with HVPG (r = 0.62; P < 0.001). Median CPA was 4.1% when HVPG was less than 6 mm Hg and 13.8% when HVPG was 6 mm Hg or more (P < 0.0001) and 6% when HVPG was less than 10 mm Hg and 17.3% when HVPG was 10 mm Hg or higher (P < 0.0001). Only CPA, not Ishak stage/grade, was independently associated by logistic regression, with HVPG of 6 mm Hg or more [odds ratio, 1.206; 95% confidence interval (CI), 1.094-1.331; P < 0.001], or HVPG of 10 mm Hg or more (odds ratio, 1.105; 95% CI, 1.026-1.191; P = 0.009). CPA increased by 50% (3.6%) compared with 20% in HVPG (1 mm Hg) in 38 patients with repeated biopsies. Conclusion: CPA assessed by DIA correlated with Ishak stage scores and HVPG measured contemporaneously. CPA was a better histological correlate with HVPG than Ishak stage, had a greater numerical change when HVPG was low, and resulted in further quantitation of fibrosis in cirrhosis.

Nurse-led clinic: Effective and efficient delivery of assessment and review of patients with Hepatitis B and C

Hepatology and gastroenterology services are increasingly utilising the skills and experience of nurse practitioners and nurse specialists to help meet the increasing demand for health care. A new nurse-led assessment clinic has been established in the liver clinic at Geelong Hospital to utilise the expertise of nurses to assess and triage new patients and streamline their pathway through the health care system. The aim of this study is to quantitatively assess the first two years of operation of the nurse assessment clinic at Geelong Hospital, and to assess advantages and disadvantages of the nurse-led clinic. Data was extracted retrospectively from clinical records of new patients at the liver clinic. Quarterly one-month periods were recorded over two-years. Patients were categorised according to the path via which they saw a physician, including missed and rescheduled appointments. The number of appointments, the waiting time from referral to appointments and the number of ‘did-not-attend’ occasions were analysed before and after the institution of the nurse-led assessment clinic. The Mann-Whitney rank sum test of ordinal data was used to generate median wait times. There was shown to be a statistically significant longer waiting time for physician appointment if seen by the nurse first. The difference in waiting time was 10 days. However, there was also a reduction in the number of missed appointments at the subsequent physician clinic. Other advantages have also been identified including effective triage of patients, and organisation of appropriate investigations from the initial nurse assessment.

Hepatitis C virus treatment in the 'real-world': how well do 'real' patients respond?

Background: Published clinical trials of the treatment of HCV are largely multicentre prospective pharmaceutical trials. Patients in clinical trials tend to have more favorable outcomes than patients in the 'real-world', due to strict patient selection and differences in treatment conditions and available resources. Objectives: To assess the outcomes of Hepatitis C infected patients treated at the Barwon Health Liver Clinic with combination Pegylated interferon (PEG-IFN) and Ribavirin (RBV) therapy and to determine factors associated with a treatment response. Methods: Retrospective review of patients who received treatment for Hepatitis C at our institution's Liver Clinic from January 2001-September 2011. Patient demographics, comorbidities, treatment-related parameters and side effects were extracted from medical records and analyzed. Results: A total of 190 patients (120 male, 70 female) with a mean age of 42.8 years (range 20-68 years) commenced treatment. The most common genotype was genotype 3 (48.9%), followed by genotype 1 (42.6%). 150 of 190 patients (78.9%) completed treatment and had end of treatment data available. 107 of 182 patients, (58.8%) for whom sustained virologic response (SVR) rate data was available achieved an SVR. Overall response rates were; 46.9%, 68.8% and 62.4% in genotypes 1, 2 and 3 respectively. The response rate was significantly lower in 29 patients with documented cirrhosis (20.7%). Age, diabetes and alcohol abuse did not predict treatment response in our cohort. Side effects reported in 81.6% of patients included general malaise, hematological disturbance and psychiatric issues, and necessitated cessation of therapy in 16 patients (8.4%) and dose reduction in 26 patients (13.7%). Conclusions: Response rates to combination PEG-IFN and RBV therapy at our institution are comparable to other 'real-world' and pharmaceutical registration trials. Side effects of combination therapy were prominent but resulted in fewer discontinuations of therapy compared to pharmaceutical trials.

Australians living with and managing hepatitis C

This paper discusses the psychosocial impact of being diagnosed with hepatitis C virus (HCV). The paper clarifies some of the key misconceptions about the virus, especially the impact HCV has on people who have been recently diagnosed. An individual's reaction to the HCV diagnosis and the subsequent lifestyle challenges to maintain health, well-being, family, and social networks are discussed, particularly the issues surrounding mental health in respect to a recent chronic illness diagnosis and how to manage the trajectory of the illness in the community and individually. HCV disclosure and its effect on intimacy are also detailed.

For people living with both a diagnosed mental illness and HCV, managing the illness can be complicated. Not only are these individuals concerned about their mental illness, its treatment, and the social stigma and discrimination associated with it, they also may be alarmed over their future physical health. The paper is preliminary to research using the psychotherapeutic approach of Cognitive Behavioural Therapy (CBT) in groups of persons with a dual diagnosis of mental illness and HCV.