People with HIV and hepatitis C (HCV) coinfection with high HCV viral loads and advanced HIV-related immune damaged, have rapid progression to liver fibrosis irrespective of the success of HAART at restoring immune function.
This is the core finding of a study conducted at the University Hospital of Puerta Del Mar in Cadiz, Spain and published in the 15th February 2003 edition of the journal Clinical Infectious Diseases, which is now available on-line.
Starting in 1996, investigators recruited 41 HIV/HCV coinfected patients and 147 HCV monoinfected patients. HCV infection was confirmed by liver function tests, HCV antibody and genotype tests and liver biopsy. Patients with decompensated cirrhosis, hepatitis B , or who had received anti-HCV therapy were excluded from the study.
Patients’ background data, including age, sex, mode of HCV infection, year of HCV infection, and HCV genotype were collected. For HIV coinfected patients, CD4 count and HIV viral load were recorded for both the time of HIV diagnosis and liver biopsy.
Details of alcohol consumption were also noted, with a person defined as alcoholic if they consumed more than 50g of alcohol a day for five years. Where possible, investigators established the date of both HIV and HCV infection.
All the HIV patients were treated with HAART consisting of two NRTIs and a protease inhibitor. Investigators defined immune reconstitution as an increase in CD4 count to at least 500 cells/mm3 after starting HAART. Patients whose CD4 count was above 500 cells/mm3 before starting HAART were also defined as having experienced immune reconstitution.
Liver samples taken from the study patients were graded according to the degree of inflammation and fibrosis. The speed with which a patient was developing fibrosis (FBR) was calculated as the ratio of the fibrosis stage reached to the duration of HCV infection.
The background data for the HIV/HCV coinfected patients and the HCV patients were comparable in all respects, other than mode of HCV transmission, with significantly more coinfected patients acquiring HCV infection from injecting drug use.
HIV-positive patients had received their HIV diagnosis an average of eight years before enrolment onto the study (range three years to 14 years). At diagnosis the overwhelming majority of HIV patients had already experienced immune damage due to HIV, as the average CD4 count was 334 cells/mm3 (range 244-424). A CD4 count below 500 cells/mm3 was detected in 81% at diagnosis with 31% having a CD4 count below 200 cells/mm3.
The average duration of HAART was three years, with 32 patients achieving an undetectable viral load. At the time the study liver biopsy was performed, 56% of HIV/HCV coinfected patients had a CD4 count above 500 cells/mm3.
Although both the coinfected and monoinfected patients were infected with similar HCV genotypes, the HIV patients had significantly higher HCV viral load. This was particularly observed amongst patients with lower CD4 counts and those who had been infected with HCV for longer.
Furthermore, fibrosis scores (FBR) were significantly higher amongst HIV patients. What’s more, 22% of coinfected patients had cirrhosis at the time of liver biopsy compared to 6% of monoinfected patients. Coinfected patients also progressed much more rapidly to cirrhosis. After 15 years of HCV infection, 19% of coinfected patients had cirrhosis, and this had risen to 35% after 20 years. By contrast, just 2% of monoinfected patients had cirrhosis at 15 years and 3% at 20 years.
The degree of immune damage experienced by HIV/HCV patients was found by the investigators to be a strong predictor of cirrhosis. Patients with CD4 counts below 200 cells/mm3 at the time of their HIV diagnosis or below 500 cells/mm3 when their liver biopsy was take, had a higher percentage of cirrhosis than patients with CD4 counts above these levels.
Accelerated fibrosis progression was also noted amongst immunosuppressed coinfected patients, with patients whose CD4 count was 200 cells/mm3 or below significantly more likely to experience rapid fibrosis.
There was no statistically significant difference in the rates of fibrosis experienced in good responders to HAART (an increase in CD4 count to 500 cells/mm3 or more) and poor responders.
In non-HIV patients, being an alcoholic, or infection with HCV after age 20, were found to be associated with a rapid rate of fibrosis. However, in HIV/HCV coinfected patients at infection, HCV viral load and a CD4 count of 200 cells/mm3 or less at the time of HIV diagnosis were found to be independently associated with rapid progression of fibrosis.
Commenting on their findings the investigators say, “our work could be considered the first study in which...the effects of the immune response to HAART on liver lesions was evaluated.” Adding, “it could be stated that anti-HIV regimens and improvement of immunologic parameters are not sufficient to control HCV infection."
The investigators conclude that, “a higher HCV load and a lower immunocompetence level influence the natural history of chronic hepatitis C, with rapid progression of fibrosis and cirrhosis occurring in HIV-HCV-coinfected patients. Immune reconstitution induced by HAART did not modify the progression of liver fibrosis.” They add that these findings support the aggressive treatment of HCV in coinfected patients.
Further information on this website
Hepatitis C - Overview
HIV and hepatitis - PDF of booklet in the Information for HIV positive people series
Martinez-Sierra C et al. Progression of chronic hepatitis C to liver fibrosis and cirrhosis in patients coinfected with hepatitis C virus and human immunodeficiency virus. Clinical infectious Diseases, 36 (online edition), 2003.