Only 4% of Spanish patients starting anti-HIV therapy in 2004 experienced hepatotoxicity, according to a study presented to the 45th Interscience Conference on Antimicrobial Agents and Chemotherapy in Washington DC last month. The investigators found that the only factors associated with a risk of developing hepatotoxicity were coinfection with hepatitis C virus and frequent alcohol use.
Another Spanish study presented to the conference indicated that almost a third of HIV and hepatitis C virus coinfected patients with cirrhosis who start anti-HIV therapy will experience serious liver-related side-effects in the first year of treatment. Investigators from Italy found that coinfected patients who were infected with hepatitis C virus genotype 3 were significantly more likely to experience elevations in their liver enzymes after starting a new HIV treatment regimen than individuals infected with other hepatitis C virus genotypes.
Incidence of hepatotoxicity in patients starting HIV therapy
Spanish investigators conducted a prospective, multicentre study involving 256 individuals who started antiretroviral therapy in 2004 to determine the incidence and risk factors for hepatotoxicity. The investigators defined hepatotoxicity as an increase in ALT or AST liver enzymes of five times or more the upper normal limit, or an increase of 3.5 times the normal upper limit if liver enzymes were already abnormal at baseline.
The patients had a mean age of 40 years, 79% were men, 27% were former injecting drug users and 30% were coinfected with hepatitis C virus.
Prior to initiating HIV therapy, the median CD4 cell count was 176 cells/mm3, and the median HIV viral load was 108,000 copies/ml. The most frequently prescribed drugs were Kaletra (39%), efavirenz (Sustiva)(43%), and abacavir (Ziagen) (31%).
A total of ten episodes (4%) of hepatotoxicity were seen. There was no association between the development of liver side-effects and age, sex, HIV risk group, CD4 at baseline or CD4 increase during therapy, or viral load. Nor did the investigators find any association between antiretroviral regimen and liver toxicities, or between baseline liver enzyme levels and later serious elevations in ALT and AST levels.
The only factors found to have a significant association with hepatotoxicity were coinfection with hepatitis C virus and frequent alcohol use. All in all, 88% of patients with liver-related side-effects had hepatitis C virus (risk ratio 3.3, p
Cirrhosis, anti-HIV therapy and the risk of hepatotoxicity
Spanish investigators also presented data to the conference indicating that a third of HIV-positive patients who are coinfected with hepatitis C virus and have cirrhosis will develop serious liver side-effects after starting anti-HIV treatment.
The prospective study included 226 coinfected patients treated at the Ramon y Cajal Hospital in Madrid who underwent a biopsy to grade the stage of their liver disease between 2000 and 2004. The patients had a mean age of 40 years and 88% were former injecting drug users.
In total 14% of patients (32 individuals) were diagnosed as having cirrhosis. Patients with cirrhosis were more likely to be male (97% versus 87%, p = 0.004), have had hepatitis C virus for longer (21 years versus 17 years, p
After starting anti-HIV drugs, the incidence of liver toxicity was higher amongst patients with cirrhosis (6 per 100 patient years versus 4 per 100 patient years), although this did not achieve statistical significance.
The investigators noted, however, that patients with cirrhosis who took nevirapine were more likely to experience hepatotoxicity after starting HIV treatment than patients with cirrhosis who took Kaletra (12 episodes per 100 patient years versus 5 per 100 patient years).
Hepatitis C virus genotype and liver enzyme elevations after starting HIV therapy
HIV-positive patients who are coinfected with hepatitis C virus genotype 3 are at greater risk of experiencing serious elevations in their liver enzymes when starting a new anti-HIV treatment regimen than patients coinfected with other hepatitis C virus genotypes, according to an Italian study presented to the conference.
The incidence of grade III or IV elevations in liver enzymes was 31 per 100 patient years in patients infected with hepatitis C virus genotype 3 compared to ten per 100 patient years amongst patients infected with other hepatitis C virus genotypes (p = 0.01). The investigators also found that having hepatitis B virus infection (p = 0.005), being previously naive to HIV therapy (p = 0.003), and previous severe elevations in liver enzymes (p = 0.046) were predictive of experiencing grade III or IV elevations after the commencement of anti-HIV drugs.
Higher baseline triglycerides, however, were protective of developing serious elevations in liver enzymes (p = 0.01 per 10mg/dl higher). Triglycerides were lower at baseline and remained lower in patients infected with hepatitis C virus genotype 3, compared to patients infected with other hepatitis C genotypes. The investigators call for further research into this.
Aranzabal L et al. Hepatotoxicity in HIV-infected patients starting HAART. 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington DC, abstract H-1485, 2005.
Aranzabal L et al. Risk of HAART-associated hepatotoxicity in HIV/HCV coinfected patients with cirrhosis. 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington DC, abstract H-1489, 2005.
Torti C et al. The influence of genotype 3 hepatitis C coinfection on liver enzyme elevations in HIV-infected patients after commencement of a new HAART: results from the MASTER EPOKA cohort. 45th Interscience Conference on Antimicrobial Agents and Chemotherapy, Washington DC, abstract H-1484, 2005.