High hepatitis C mortality and low clearance rates in HIV/HCV-co-infected patients in France

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Mortality rates are high among French patients co-infected with HIV and hepatitis C, investigators report in BMC Infectious Diseases. Over 40% of deaths were directly attributable to hepatitis C.

Only a fifth of patients with hepatitis C genotype 1 and 36% of those with genotype 4 treated since 2005 had a successful response to treatment, a finding broadly in line with the results of clinical trials in co-infected people. Only 21% of patients in the French cohort had HCV genotypes 2 or 3, which have proved more likely to respond to treatment.

A low overall success rate was seen in individuals who received a second course of treatment for hepatitis C.

Glossary

cirrhosis

Severe fibrosis, or scarring of organs. The structure of the organs is altered, and their function diminished. The term cirrhosis is often used in relation to the liver. 

person years

In a study “100 person years of follow-up” could mean that information was collected on 100 people for one year, or on 50 people for two years each, or on ten people over ten years. In practice, each person’s duration of follow-up is likely to be different.

depression

A mental health problem causing long-lasting low mood that interferes with everyday life.

fatigue

Tiredness, often severe (exhaustion).

 

biopsy

A procedure to remove a small sample of tissue so that it can be examined for signs of disease.

However, treatment for depression not only improved mood but also fatigue and other aspects of health.

Approximately a quarter of HIV-positive patients in France are co-infected with hepatitis C. Investigators wanted to gain a better understanding of these patients, and in 2005 established ANRS CO 13 HEPAVIH cohort.

The investigators describe the cohort as “a unique nation-wide collaboration of HIV treatment, infectious diseases, internal medicine and hepatology centres”.

Between 2006 and 2008 a total of 1175 adults were recruited to the cohort. All were HIV-positive, 1048 had chronic hepatitis C infection and 127 had had a sustained response to hepatitis C therapy.

The patients’ median age was 45 years, 70% were men, their median CD4 cell count was 442 cells/mm3 and 68% had an undetectable HIV viral load.

Most of the patients (71%) were infected with hepatitis C through injecting drug use and the median time since diagnosis of hepatitis C was ten years. The median hepatitis C viral load was 6.2 logUI/ml.

A variety of tests were used to assess the extent of liver damage caused by hepatitis C. The proportion of patients diagnosed with cirrhosis varied according to which test was used.

FibroTest  detected cirrhosis in 46% of patients, FibroScan in 30% and a liver biopsy in 27%. Nevertheless, all the tests had a high positive predictive value for cirrhosis diagnosis.

At the time of enrolment to the cohort, 72% of patients were taking antiretroviral therapy. The majority of patients (58%) were taking a combination of drugs based on a ritonavir-boosted protease inhibitor.

Overall, 51% of patients had received hepatitis C therapy. Most (35)% received this treatment before they entered the cohort.

Outcome data were available for 127 patients who had received hepatitis C treatment after entering the cohort.

A total of 32% had a sustained virologic response (SVR). The clearance rate was 34% for those taking anti-hepatitis C drugs for the first time, and fell to 27% for individuals taking a second course of therapy.

Outcomes were also analysed according to hepatitis C genotype. Only 20% of patients infected with genotype 1 had a successful response to therapy, and 36% of those with genotype 4 cleared the infection.

By January 2010, a total of 13 new cases of cirrhosis had been diagnosed. All were in patients with chronic hepatitis C. There were nine new cases of liver cancer, three of which were in patients who had had a sustained response to therapy with anti-hepatitis C drugs.

There were 49 deaths, and 41% were attributed to hepatitis C.

The investigators calculated that the rate of severe hepatitis C-related events was 2 per 100 person-years of follow-up.

Event rates were notably higher in patients with cirrhosis (7 vs 0.35 per 100 person years). The investigators note that this was expected, but nevertheless emphasised the importance of accurately diagnosing cirrhosis. All three types of tests detected over 99% of cases of cirrhosis.

A low baseline CD4 cell count (below 200 cells/mm3) also significantly increased the risk of a serious hepatitis C-related outcome (5.5 vs 1.4 per 100 person-years; p = 0.002). Patients co-infected with hepatitis C are especially recommended to start antiretroviral therapy when their CD4 cell count is around 350 cells/mm3.

Using information gathered from questionnaires completed by the patients, the investigators found that treating depression not only improved mood, but also had an impact on fatigue, as well as boosting cognitive, physical and social functioning.

The researchers conclude that cohorts such as theirs “will be critical to address future clinical and public health questions of chronic diseases of infectious origin”.

References

Loko M-A et al. The French national prospective cohort of patients co-infected with HIV and HCV (ANRS CO13 HEPAVIH): Early findings, 2006-2010. BMC Infectious Diseases, 10: 303doi:10.1186/1471-2334-10-303, 2010 (click here for access to article text).

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