Spontaneous hepatitis C virus clearance occurs in up to 42% recently infected, HIV-negative IDUs

Between 24% and 42% of HIV-negative injecting drug users (IDUs) recently infected with the hepatitis C virus (HCV) became spontaneously HCV-negative within two years of being diagnosed with acute HCV infection, according to a retrospective cohort study from Australia appearing in the latest issue of the Journal of Infectious Diseases, now available online. The proportion of patients clearing HCV depends on the HCV diagnosis: HCV antibody-positive (42%) or with a detectable HCV viral load (24%).

Previous studies of spontaneous HCV clearance have estimated that between 10% and 50% of people newly infected with HCV spontaneously clear their infection in the absence of anti-HCV therapy before it becomes chronic - usually defined as the persistence of HCV viral load for more than six months. However, the majority of these studies have been based on the presence of clinical symptoms of acute HCV infection, which do not always appear, and not always in IDUs, despite the fact the majority of new HCV infections occur through injecting drug use.

The authors of this study used data collected from a central Sydney free health clinic, aimed at the prevention of HIV and other sexually transmitted infections in those at-risk, including IDUs. A total of 99 IDUs who attended the clinic between January 1992 and May 2002 had evidence of newly acquired HCV infection, of whom only two were also HIV-positive. Just over half (53%) were female, and 12% self-identified as Aboriginal.

The cohort began injecting drugs at a median age of 15, and became HCV infected at an estimated median age of 22. The drug most commonly injected in the year prior to HCV infection was heroin, with 64% injecting at least daily and 63% reporting sharing drug injecting equipment. The appearance of clinical symptoms was rare, with only eight percent diagnosed with documented jaundice - the majority were diagnosed through a positive HCV-antibody test.

This study did not document cases acquired through sexual transmission.

Fifty-seven (58%) of the 99 IDUs in this clinic cohort had two or more documented HCV viral load (RNA) test results after the estimated date of infection, and viral clearance (defined as two consecutive undetectable HCV RNA test results) occurred in 24 of the 57 (42%), with a median time to viral clearance of 5.9 months. However, there was a wide variation in the time taken for viral clearance to occur, from 1.4 to 11.2 months. Analysis of the data using Kaplan-Meier estimates suggested that 23%, 38% and 40% would spontaneously clear their HCV infection after six, twelve and 24 months, respectively.

Aware that some individuals receive a false positive diagnosis of HCV, the authors then restricted their analysis to the 33 (58%) of the 57 IDUs who also had a detectable HCV viral load within a year of the estimated time of infection. Here, eight of the 33 (24%) experienced spontaneous viral clearance. Analysis of the data using Kaplan-Meier estimates suggested that 6%, 23% and 26% would spontaneously clear their HCV infection after six, twelve and 24 months, respectively.

Further analysis revealed no significant differences in demographic, clinical or behavioural factors between those who cleared HCV and those who became chronically infected. There were also no significant differences seen between the 57 with HCV viral load data and the rest of the cohort. Although those IDUs whose alanine aminotransferase (ALT) liver function test normalised to less than 40 IU/L were almost twice as likely to clear HCV than those who did not, this did not reach statistical significance (hazard ratio, 1.90; 95% confidence interval, 0.77 - 4.65: p = 0.16). Previous studies have found several factors that predict viral clearance, including female gender, ethnicity, symptomatic HCV, and lack of HIV co-infection. The authors suggest that this cohort may be too homogenous (the majority being female, white, asymptomatic and HIV-negative) to tease out these differences. Of note, the one individual with documented HIV co-infection out of the 57 included in the analysis did not clear their HCV.

The authors conclude that in this cohort of young, mostly white, injecting drug users, of whom 98% were HIV-negative, between 24% and 42% cleared their HCV spontaneously in the two years following a positive HCV antibody test. “Although estimated viral clearance rates varied according to the strictness of the case definition, there were no baseline demographic, clinical or behavioural factors associated with clearance,” they write, adding that “the vast majority of clearances occurred within the initial 12 months after the estimated time of infection."

"The inclusion of IDUs who had experienced HCV antibody seroconversion, rather than acute clinical hepatitis alone, makes our study more broadly representative of newly acquired HCV infection than most previous studies have been.”