Joanne Micallef

Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies

Summary.  A large number of studies have reported on spontaneous viral clearance rates in acute hepatitis C infection, however most have been small, and reported rates have varied quite widely. To improve the precision of the estimated rate of spontaneous viral clearance, a systematic review was conducted of longitudinal studies. Factors associated with viral clearance were also examined. Inclusion criteria for studies were: longitudinal assessment from time of acute hepatitis C; hepatitis C virus RNA analysis as determinant of viral clearance; untreated for acute hepatitis C. Information on study population, and factors that may influence viral clearance were extracted from each study. Viral clearance was defined among individuals with at least 6 months follow‐up following acute hepatitis C. The number of subjects with viral clearance was expressed as a proportion for each study and a weighted mean for proportion was calculated. A total of 31 studies were examined. Study populations included nine studies of post‐transfusion hepatitis, 19 of acute clinical hepatitis, and three of sero‐incident cases. In total, data was available for 675 subjects and the mean study population was 22 (range 4–67). The proportion with viral clearance ranged from 0.0 to 0.8, with a weighted mean of 0.26 (95% CI 0.22–0.29). Factors associated with viral clearance were female gender and acute clinical hepatitis C study population. Further studies are required to more clearly define predictors of clearance and guide therapeutic intervention strategies.

High incidence of hepatitis C virus reinfection within a cohort of injecting drug users.

Summary.  A retrospective cohort study was established of injecting drug users (IDUs) to assess evidence for hepatitis C virus (HCV) protective immunity through a comparison of incidence of initial HCV infection and HCV reinfection. Incidence of initial HCV infection was determined among HCV seronegative IDUs, and HCV reinfection determined among IDUs with newly acquired HCV infection, HCV viraemia and subsequent HCV RNA clearance. Serum was available for HCV RNA analysis from stored samples taken at the time of prior blood‐borne virus screening. Potential HCV reinfection was defined as a positive HCV RNA following at least one negative HCV RNA. Incidence of initial HCV infection was 17/100 person‐years (95% CI, 14–20/100 person‐years). The incidence of potential HCV reinfection was 42/100 person‐years (95% CI, 25–61/100 person‐years), and after excluding cases without a change in HCV genotype and less than three consecutive HCV RNA negative assessment, incidence of reinfection was 31/100 person‐years (95% CI, 17–62/100 person‐years). Following adjustment for HCV risk behaviour variables the incidence rate ratio of HCV reinfection to initial infection was 1.11 (P = 0.8). Several cases of HCV reinfection appear to have developed persistent infection.

Clearance of hepatitis C virus after newly acquired infection in injection drug users.

A retrospective cohort of injection drug users with newly acquired hepatitis C virus (HCV) infection was established to examine viral clearance. Newly acquired HCV infection was defined by anti-HCV antibody seroconversion within a 2-year interval. Stored serum samples were tested for HCV RNA, with viral clearance defined as >/=2 consecutive negative HCV RNA test results after infection. Ninety-nine cases of HCV infection were identified; 57 had >/=2 HCV RNA test results after infection. Viral clearance occurred in 24 (42%) cases, with Kaplan-Meier estimated probabilities of 23%, 38%, and 40% at 6, 12, and 24 months, respectively.

Prevalence of thrombocytopenia among patients with chronic hepatitis C: a systematic review.

Summary.  Thrombocytopenia (TCP) is a haematological condition known to occur in chronically infected hepatitis C (HCV) patients and may interfere with diagnostic procedures, such as liver biopsy, because of risk of bleeding. It may also exclude patients from effective antiviral treatment. We conducted a systematic literature review of articles and conference abstracts, to assess the prevalence of TCP among those with HCV and to describe demographics, liver disease stage and treatment characteristics of these patients. Studies of individuals with confirmed chronic HCV infection were included in the review if the study had a clear definition of thrombocytopenia and a sample size of at least 50 subjects. The final selection included 27 studies (21 articles and six abstracts). The definitions of thrombocytopenia varied between studies and were based either on platelet counts, with threshold levels ranging between ≤100 × 109 and ≤180 × 109/L, or on criteria set in haematological guidelines. The prevalence of TCP ranged from 0.16% to 45.4% and more than half of the studies reported a TCP prevalence of 24% or more. Because of the different TCP definitions, heterogeneity in study design and insufficient data on study characteristics such as age, gender, HCV treatment rates and disease severity an overall summary estimate of TCP prevalence among patients with HCV was not feasible. However, the relatively large prevalence in the majority of the studies suggests that there may be a substantial number of HCV patients at risk of bleeding complications and reduced likelihood of successful HCV antiviral treatment.

Potential biases in estimates of hepatitis C RNA clearance in newly acquired hepatitis C infection among a cohort of injecting drug users

Estimates of hepatitis C virus (HCV) clearance following acute infection range from 14 to 46%. This wide range is likely to be due to the characteristics of the populations studied and analysis methods. This paper examines how differing definitions of clearance parameters affect estimates of viral clearance in a cohort of 85 injecting drug users with newly acquired HCV infection. Kaplan-Meier estimates of time to HCV clearance were determined using varying definitions of eligible cohort, viral clearance, date of infection and date of clearance. Based on which combinations of definitions were used, the number of subjects eligible for analysis ranged from 27 to 75, clearance rate ranged from 14 to 68% and time to achieving 25% clearance ranged from approximately 5 months to 14 months. Standardized definitions and methodologies are required to enable valid comparisons of rates of clearance across newly acquired HCV infection natural history studies.

Low incidence of HCV reinfection: exposure, testing frequency, or protective immunity?

We read with interest the report wherein Grebely and colleagues found lower incidence of HCV reinfection following natural HCV clearance than incidence of initial HCV infection within a Vancouver, Canada, community-based cohort.1 These findings are given as evidence of protective immunity provided by prior HCV infection. However, the comparison of initial HCV infection and HCV reinfection incidence has several inherent methodological difficulties, particularly when conducted retrospectively. First, demographic and behavioral characteristics generally differ among the denominator populations: uninfected individuals for initial HCV infection and previously infected individuals with viral clearance for HCV reinfection. The latter group is often older and may have reduced risk behavior after HCV diagnosis. Adjustment for baseline characteristics as performed by Grebely et al. reduces but does not remove this concern. Second, longitudinal reporting of injection risk behavior may not be available to cover the at-risk study period. Third, the HCV testing interval is generally heterogeneous and may be relatively broad. Variability in testing interval is a minor issue for determination of incidence of initial HCV infection, because long-lasting seroconversion to anti-HCV antibody following infection supports detection of all new cases. However, an incident case of HCV reinfection requires detection of new HCV viremia, which is dependent on the proportion of cases with persistent viremia, duration of viremia in clearance cases and interval of HCV RNA testing. A previous study of HCV reinfection demonstrated that HCV viremia in the setting of HCV reinfection was at a lower level, generally transient, and shorter in duration compared to initial HCV viremia.2 The duration of HCV viremia among individuals with natural HCV clearance following initial HCV infection is generally less than 12 weeks.3 Thus, a testing interval for HCV RNA longer than 12 weeks in an HCV reinfection cohort where a majority of new viremic cases could be expected to clear viremia may miss many HCV reinfection cases. Studies of HCV reinfection from community-based and primary care–based cohorts in Baltimore,2 Vancouver,1 and Sydney4 are outlined in Table 1. In contrast to the findings in Vancouver and Baltimore, we found no evidence for lower incidence of HCV reinfection compared to initial infection. Key features of our study were a young aged cohort, with the same median age in both uninfected and previously infected subgroups, high rate of frequent (daily) injection drug use, and a relatively short interval for HCV RNA testing. An evaluation of the HCV RNA testing interval within the Vancouver study, including a comparison among HCV reinfection cases and noncases in the previously infected group, may provide some explanation for the apparent lower incidence of HCV reinfection. A relatively long testing interval (greater than 6 months) would suggest than many HCV reinfection cases may have been undetected. The absence of persistent HCV viremia following HCV reinfection may reflect partial protective immunity, but alternatively could relate to the same host factors that influenced viral clearance following initial HCV infection.5,6 As suggested by Grebely et al., prospective studies of HCV clearance, reinfection, and potential protective immunity are crucial to advance the understanding of early HCV immunopathogenesis.

Evaluation of Chlamydia Partner Notification Practices and Use of the “Let Them Know” Website by Family Planning Clinicians in Australia: Cross-Sectional Study

Background Chlamydia, caused by Chlamydia trachomatis, is the most common reportable infection in many developed countries. Testing, treatment, and partner notification (PN) are key strategies for chlamydia control. In 2008 the Let Them Know (LTK) PN website was established, which provided means for people to send anonymous PN messages by text messaging (short message service, SMS), email, or letter. Objective We evaluated PN practices among Australian family planning clinicians following chlamydia diagnosis and assessed how often clinicians refer their patients to the LTK website. Methods A mixed methods approach included a Web-based cross-sectional survey of Australian family planning clinicians to examine PN attitudes and practices and focus groups to explore the context of LTK website use. Results Between May 2012 and June 2012, all clinicians from 29 different family planning services (n=212) were invited to complete the survey, and 164 participated (response rate=77.4%); of the clinicians, 96.3% (158/164) were females, 56.1% (92/164) nurses, and 43.9% (72/164) doctors. More than half (62.2%, 92/148) agreed that PN was primarily the clients responsibility; however, 93.2% (138/148) agreed it was the clinicians responsibility to support the client in informing their partners by providing information or access to resources. Almost half (49.4%, 76/154) of the clinicians said that they always or usually referred clients to the LTK website, with variation across clinics in Australian states and territories (0%-77%). Eleven focus groups among 70 clinicians at 11 family planning services found that the LTK website had been integrated into routine practice; that it was particularly useful for clients who found it difficult to contact partners; and that the LTK letters and fact sheets were useful. However, many clinicians were not aware of the website and noted a lack of internal clinic training about LTK. Conclusions The LTK website has become an important PN tool for family planning clinicians. The variation in referral of patients to the LTK website and lack of awareness among some clinicians suggest further promotion of the website, PN training, and clinic protocols are warranted.

Sexual risk and healthcare seeking behaviour in young Aboriginal and Torres Strait Islander people in North Queensland

UNLABELLED Background Compared with non-Indigenous Australians, Aboriginal and Torres Strait Islander people have higher rates of sexually transmissible infections (STI). The identification of the sexual risk and healthcare seeking behaviours of young Aboriginal and Torres Strait Islander people in a regional Australian setting was sought. METHODS A cross-sectional survey of 155 young Aboriginal and Torres Strait Islander people (16-24 years) in Townsville was conducted. RESULTS Most participants (83%) reported ever having had sex, with a median age of 15 years at first sex and a range from 9 to 22 years. While young men reported more sexual partners in the last 12 months than young women, they were also more likely to report condom use at the last casual sex encounter (92% vs 68%, P=0.006). Young women were significantly more likely than young men to report never carrying condoms (35% vs 16%); however, they were more likely to have had STI testing (53% vs 28%, P=0.004). Of those reporting previous STI testing, 29% reported ever being diagnosed with an STI. CONCLUSIONS The sample of young Aboriginal and Torres Strait Islander people reported an early age at first sex, variable condom use and low uptake of STI testing. The high prevalence of self-reported STI diagnoses indicate a need for opportunistic sexual health education and efforts designed to promote the uptake of STI screening in this group.