Hepatitis coinfection: incidence in Europe and response to transplant
Simon Collins, HIV i-Base
Several studies presented at the conference covered issues related to hepatitis coinfection.
In Europe, 9% of HIV patients have hepatitis B and more than 30% hepatitis C: link to higher mortality
The EuroSIDA study is a large collaborative study involving mainly European national cohorts and two studies looked at the incidence and implications for coinfection with hepatitis B or C.
Dr Stephane DeWit presented the results of coinfection with hepatitis B. 
An analysis of the databases in this cohort showed an incidence of 9% HBV coinfection across the cohorts, but that this also included large national differences. Of 5,883 patients tested for HbsAg at time of recruitment in EuroSIDA, 530 patients were positive. The highest prevalence was found in Argentina (17.8%) vs Northern (9.7%), Central (9.2%), Southern (9.1%) and Eastern Europe (6%).
Median CD4 count at recruitment was lower in HbsAg-positive persons (234 cells/mm3) vs HBsAg-negative (274 cells/mm3, p<0.0001). Coinfection with HCV was found in 158 HbsAg-positive (29.8%) and 1,363 HBsAg-negative patients (25.5%) (p=0.023).
Although incidence of any new AIDS diagnosis was higher for HbsAg-positive subjects, this was not significant after adjustment for CD4, age, AIDS diagnosis, HAART, risk group, gender, ethnic origin, region of Europe, date of recruitment, and HCV status (Poisson regression model).
The incidence of global and liver-related mortality was significantly higher in HbsAg-positive patients (12 vs 2.6 and 0.5 vs 0.2 /100 person-years respectively), and remained significantly higher in multivariate analysis (including HCV status) with incidence rate ratios of 1.55 (global;95%CI:1.24-1.93) and 3.77 (liver-related mortality;2.07-6.87).
HbsAg status did not influence virological or immunological response among the 1,752 subjects starting HAART.
Jurgen Rockstroh presented the results of hepatitis C (HCV) coinfection. HCV serology was available from almost 5,000 patients in EuroSIDA and was positive in 34% of cases (75% IVDU). There was a higher incidence and wider variation between cohorts than with hepatitis B.
The highest HCV-prevalence was found in Southern and Eastern Europe with 44.9% (623/1,387) and 47.7% (412/864) vs 22.9% (280/1,221) in Central and 24.5% (346/1,410) in Northern Europe. The higher incidence of AIDS or death in HCV-positive versus HCV-negative patients (5.6 vs 4.2 per 100 PYFU p<0.0001) was not significant after adjustment for CD4, age, prior AIDS, HAART, recruitment date, hepatitis B status, gender and ethnic origin (incidence rate ratio 0.92; 95% CI 0.79 – 1.07, p = 0.27).
In further multivariate analyses, there was an increased risk of liver-related deaths in HCV-positive vs HCV-negative patients (IRR 3.18, 95% CI 1.23 – 6.18, p = 0.014) but not of AIDS (p = 0.061) or global-mortality (p = 0.4).
As with HBV, no significant difference was found in the response to treatment. Median time to viral load <400 copies/mL or time to 50% increase in CD4 count was found between HCV-positive and negative individuals.
The authors concluded that one in three HIV-infected patients in the EuroSIDA Cohort are coinfected with HCV. While HCV-coinfection did not influence virological and immunologic response to HAART, HCV-positive patients experienced a higher mortality rate due to liver disease related causes.
Response to liver transplant higher when not coinfected with HCV
Norris and colleagues from Kings College Hospital in London reported responses to liver transplant in 12 HIV-positive patients (10 men, two women, age range 26-59 years) carried out between January 1995 and March 2002. 
Indications for transplant were HCV (n=5), HBV (n=4), ALD (n=2), and NonANonB (n=1); three patients presented with acute liver failure. Mean CD4 count at transplant was 267 cells/mm3 (range 124 – 500), and HIV viral load ranged from <50 to 197,000 copies/mL. Only seven patients used HAART prior to transplant.
All patients in the non-HCV group (n=7) are alive, with five patients surviving more than 365 days (range 4 – 67 months). No patient experienced HBV recurrence, and graft function is normal in all seven recipients.
However, despite some initial responses, all HCV patients have died, with median survival post-transplant of 161 days (range 95-784 days). Four of these patients died of complications due to recurrent HCV infection and sepsis, despite antiviral therapy in three. Three patients experienced complications relating to HAART therapy.
This is a comprehensive look at the prevalence of HBV and HCV co-infection in the EuroSIDA cohort. As with other cohort studies in ‘low’ prevalence areas for HBV, co-infection as assessed by HbsAg positivity is at around 10%, implying higher rates of infection and chronicity in patients infected with HIV.
The reasons for higher prevalence rates in Argentina are not obvious but may be due to low HBV vaccine coverage or possibly a selection bias in terms of the HIV population reported to EuroSIDA. More importantly, this cohort study shows higher rates of liver-related mortality in both the HBV and HCV co-infected patients and has implications for the management of co-infections in these patients.
There is still some debate about the impact of HCV on virological and immunological response to HAART. The Swiss Cohort study demonstrated a clear reduction in CD4 response to HAART in patients co-infected with HCV, although this was certainly not the case in the EuroSIDA cohort. More data is needed.
The poor outcomes associated with liver transplantation in HCV/HIV co-infected patients in the Kings College Hospital cohort have not been duplicated in the recently reported Miami and Pittsburgh cohorts from the USA ( Neff et al. Liver Transplantation 2003). As HAART improves survival in HIV-infected patients, there may be an increase in morbidity and mortality from hepatic disease in these patients and the demand for liver transplantation may increase. In the post-HAART, there is an urgent need to re-visit the concept of solid organ transplantation in HIV-infected patients.
HIV infection should no longer be a relative contra-indication to solid-organ transplantation. National and International databases need to be established to share the transplant experience and delineate factors associated with poor outcomes.
- Konopnicki D, De Wit S, Antunes F et al for the EuroSIDA Group. Hepatitis B (HBV) in the EuroSIDA cohort: prevalence and impact on mortality, AIDS progression and response to HAART. 9th EACS, Warsaw. 25-29 October 2003. Abstract F9/3.
- Rockstroh J, Mocroft A, Soriano V et al. Influence of Hepatitis C coinfection on HIV disease progression within the EuroSIDA cohort. 9th EACS, Warsaw. 25-29 October 2003. Abstract F12/4.
- Norris S, Taylor C, McDonald C et al. Survival in HIV-infected individuals following liver transplantation is influenced by viral co-infections: the negative impact of HCV infection. 9th EACS, Warsaw. 25-29 October 2003. Abstract F12/5.