Per-event probability of hepatitis C infection during sharing of injecting equipment.

BACKGROUND: Shared injecting apparatus during drug use is the premier risk factor for hepatitis C virus (HCV) transmission. AIMS: To estimate the per-event probability of HCV infection during a sharing event, and the transmission probability of HCV from contaminated injecting apparatus. METHODS: Estimates were obtained using a maximum likelihood method with estimated IDU and sharing events obtained from behavioural data. SETTINGS: Cohort study in multiple correction centres in New South Wales, Australia. PARTICIPANTS: Subjects (N = 500) with a lifetime history of injecting drug use (IDU) who were followed up between 2005 and 2012. During follow-up, interviews for risk behaviours were taken and blood sampling (HCV-antibody and RNA testing) was performed. MEASUREMENTS: Self-reported frequencies of injecting drugs and sharing events, as well as other risk behaviours and details on the nature of injecting events. FINDINGS: The best estimate of the per-event probability of infection was 0.57% (CI: 0.32-1.05%). A sensitivity analysis on the likely effect of under-reporting of sharing of the injecting apparatus indicated that the per event infection probability may be as low as 0.17% (95% CI: 0.11%-0.25%). The transmission probability was similarly shown to range up to 6%, dependent on the presumed prevalence of the virus in injecting equipment. CONCLUSIONS: The transmission probability of HCV during a sharing event is small. Hence, strategies to reduce the frequency and sharing of injecting equipment are required, as well as interventions focused on decreasing the per event risk.

Assessment of HBV flare in a randomized clinical trial in HIV/HBV coinfected subjects initiating HBV-active antiretroviral therapy in Thailand.

BACKGROUND: Hepatic Flare (HF) after initiation of highly active antiretroviral therapy (HAART) in HIV-HBV coinfected individuals is well recognized but prospective data on predictors and subsequent outcome are limited. METHODS: The Tenofovir in HIV-HBV coinfection study was a randomized clinical trial of HBV-active HAART including lamivudine and/or tenofovir in antiretroviral naïve HIV-HBV individuals in Thailand. RESULTS: Early HF (EHF) was defined as ALT > 5 × ULN during the first 12 weeks. EHF was observed in 8 (22%) of individuals at a median of 56 days. 6/8 EHF cases were asymptomatic and resolved with HAART continuation, however one subject with underlying cirrhosis died following rapid hepatic decompensation. EHF was significantly associated with higher baseline ALT (79 IU/L vs 36 IU/L non-EHF, p = 0.008) and HBV DNA (9.9 log10 c/ml vs 8.4 log10 c/ml non EHF, p = 0.009), and subsequent serological change. HBeAg loss occurred in 75% of EHF cases versus 22% in non-EHF (p = 0.04), and HBsAg loss in 25% of EHF cases versus 4% of non-EHF (p = 0.053). CONCLUSION: EHF after HBV active HAART initiation was frequently observed in this population. Timing of EHF, association with elevated ALT and HBV DNA and high rate of seroconversion are all consistent with immune restoration as the likely underlying process. CLINICAL TRIAL NUMBER: NCT00192595.

Evidence of a large, international network of HCV transmission in HIV-positive men who have sex with men.

BACKGROUND & AIMS: Since 2000, there has been a marked rise in acute hepatitis C virus (HCV) in human immunodeficiency virus (HIV)-positive men who have sex with men (MSM). We conducted an international phylogenetic study to investigate the existence of an HCV transmission network among MSM. METHODS: HIV-positive MSM diagnosed with recent HCV (n = 226) in England (107), The Netherlands (58), France (12), Germany (25), and Australia (24) between 2000 and 2006 were enrolled into a molecular phylogenetic study. Using real-time polymerase chain reaction (PCR), the NS5B region of the HCV genome (436 base pair) was amplified, sequenced, and compared with unrelated NS5B sequences. RESULTS: NS5B sequences were obtained from 200 (89%) cases. Circulating HCV genotypes were 1a (59%), 4d (23%), 3a (11%), 1b (5%), and 2b/c (3%). Phylogenetic analysis revealed 156 (78%) sequences that formed 11 clusters (bootstrap value > 70%) containing between 4 and 37 individual sequences. Country mixing was associated with larger cluster size (17 vs 4.5 sequences; P = .03). "Molecular clock" analysis indicated that the majority (85%) of transmissions occurred since 1996. CONCLUSIONS: Phylogenetic analysis revealed a large international network of HCV transmission among HIV-positive MSM. The rapid spread of HCV among neighboring countries is supported by the large proportion (74%) of European MSM infected with an HCV strain co-circulating in multiple European countries, the low evolutionary distances among HCV isolates from different countries, and the trend toward increased country mixing with increasing cluster size. Temporally, this epidemic coincides with the introduction of highly active antiretroviral therapy and associated increases in sexual risk behaviors. International collaborative public health efforts are needed to mitigate HCV transmission among this population.

Prevalence and risk factors of hepatitis C in HIV-negative homosexual men in Sydney, Australia.

OBJECTIVE: To determine the prevalence and risk factors for hepatitis C (HCV) in HIV-negative homosexual men in Sydney. METHODS: A cohort study was conducted in a sample of community-based, HIV-negative, homosexual men in Sydney. Participants underwent a face-to-face interview regarding sexual behaviour, sexually transmissible infections, and injecting drug use (IDU). RESULTS: Eight hundred and twenty-four men consented to HCV testing, and the prevalence was 0.85% (95% CI 0.34-1.74). HCV seropositivity was strongly associated with a history of IDU (OR = 60.43, 95% CI 6.70-544.79). All HCV seropositive individuals reported a history of either IDU or other means by which they may have had parenteral exposure to HCV. There was no evidence of an independent association between sexual behaviour and HCV infection. CONCLUSION: The prevalence of HCV in this cohort was about the same as in the general population in Australia, and there was no evidence for sexual transmission in this population.

Severe diverticulitis after heart, lung, and heart-lung transplantation.

BACKGROUND: In this study, we reviewed our experience with severe diverticulitis in patients who have undergone heart and/or lung transplantation to assess whether transplant recipients are at increased risk of having severe diverticulitis compared with the general population. METHODS: We reviewed the records of patients who underwent heart and/or lung transplantation from 1984 to 2000, inclusive, and identified patients with severe diverticulitis that required surgery or that resulted in death. We compared this incidence with the incidence of such complications in the general population, served by the same institution during a 2-year period, 1999 to 2000. RESULTS: A total of 953 patients underwent transplantation in the study period. The mean follow-up was 57 months, a total follow-up of 4528 patient-years. Nine patients (mean age, 54 years) had severe diverticulitis that required surgical intervention (8 patients) or that resulted in death (1 patient died without surgical intervention). During 1999 to 2000, 16 patients (mean age, 66 years) from the general population were treated for severe diverticulitis that required surgical intervention, 3 of whom died. From census and area health data, we found that the study institution serves approximately 90000 people older than 40 years, with a total follow-up of 180000 patient-years. The incidence rate ratio for severe diverticulitis when comparing the transplant with the non-transplant groups was 22.2 (95% confidence interval; 9.9-50.0; p < 0.001). CONCLUSIONS: Patients with severe diverticulitis who have undergone heart and/or lung transplantation can be treated surgically with a small mortality rate. Transplant recipients probably are at substantially increased risk of experiencing severe diverticulitis.