Back HIV-Related Conditions Liver & Kidney Liver Fibrosis Common in HIV+ People without Viral Hepatitis

Liver Fibrosis Common in HIV+ People without Viral Hepatitis

Non-invasive blood tests indicate that people with HIV have a significant risk of liver fibrosis progression even if they do not have hepatitis B or C coinfection.

As effective antiretroviral therapy has dramatically reduced the risk of death due to AIDS-defining opportunistic illnesses, liver disease has become an increasingly common cause of morbidity and mortality among people with HIV.

In many cases liver fibrosis -- which can progress to liver cirrhosis or cancer -- is caused by coinfection with hepatitis B or C. Less is known about the incidence of liver fibrosis and its progression and risk factors in people with HIV alone.

As reported in the May 1, 2011, issue of Clinical Infectious Diseases, Monia Mendeni and colleagues looked at the evolution and predictors of liver fibrosis in HIV positive people without hepatitis B or C, as determined by 2 non-invasive biomarker indices, FIB-4 and APRI.

FIB-4 is calculated based on alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, platelet count, and patient age. APRI uses the AST-to-platelet ratio. These non-invasive tests are not as reliable as liver biopsy for detecting and staging fibrosis, but they are safer, less expensive, and easier to repeat to assess changes over time.

This prospective observational study included 1112 HIV patients who started highly active antiretroviral therapy (HAART) at 2 large Italian referral centers between 1996 and 2006. The study -- Hepatotoxicity of Different Kinds of Antiretrovirals -- was initially designed to look at liver toxicity associated with HIV drugs.

About 60% of participants were men and the mean age was 38 years. The median CD4 cell count was 201 cells/mm3, indicating that half had serious immune suppression. Nearly 60% were on boosted protease inhibitor-based HAART, with most of the remainder taking NNRTIs. About 25% used "d-drugs" -- didanosine (ddI; Videx), stavudine (d4T; Zerit), or zalcitabine (ddC; Hivid) -- which have been linked to liver toxicity.

Participants were tested for liver function, HIV RNA levels, and CD4 T-cell counts every 3 months. The average follow-up duration was 2249 days (about 6 years). FIB-4 and APRI scores fell into 3 classes, based on standard cut-off values, corresponding to absent or minimal fibrosis, moderate fibrosis, and advanced or severe fibrosis.

The researchers looked at concordance or agreement between FIB-4 and APRI scores, and used Cox regression analysis to analyze predictors of transition between fibrosis classes. Patients who started out with class 3 scores at baseline were excluded from the progression analysis.

Results

  • The concordance between FIB-4 and APRI was found to be "moderate" (kappa 0.57).
  • Among 1074 patients with FIB-4 class 1 or 2 at baseline, the incidence of transition to a higher class was 24%, or 0.064 per person-year of follow-up.
  • Among 1079 people with APRI class 1 or 2 at baseline, the incidence of transition to a higher class was greater at 31%, or 0.099 per person-year.
  • The incidence of transition to a FIB-4 score > 3.25 or APRI > 1.5 -- indicating advanced fibrosis -- was 6% (0.013 per person-year) and 8% (0.018 per person-year), respectively.
  • 45% of patients according to FIB-4 and 52% according to APRI reverted back to lower fibrosis classes, with no further worsening.
  • In a multivariate analysis, having HIV viral load < 500 copies/mL predicted lower risk of transition to a higher fibrosis class according to both FIB-4 and APRI, while higher CD4 count was protective only according to FIB-4.
  • There was a trend toward protection in patients who continued ART with no interruptions.
  • Additional risk factors for fibrosis progression were age >40 years, male sex, history of injection drug use, higher degree of fibrosis at baseline, higher baseline gamma-glutamyl transpeptidase level, and use of "d-drugs."
  • Risk factors were similar for transition to FIB-4 > 3.25 and APRI > 1.5.

Based on these findings, the researchers concluded, "our results suggest a possible benefit associated with earlier HAART initiation, provided that the effectiveness of HAART is sustained and treatment with [d-drugs] is avoided."

The concordance study showed "moderate agreement" between FIB-4 and APRI, they elaborated in their discussion. "FIB-4 considers patient age and ALT level, whereas APRI does not, which produced different results with the predefined cut-off values. In particular, several patients who were in class 1 according to FIB-4 were in class 2 according to APRI. Therefore, APRI seemed to be stricter than FIB-4, but the clinical meaningfulness of this finding is questionable. In fact, both FIB-4 and APRI were shown to have the highest positive predictive value only for the most severe stages of liver fibrosis."

"The effect of HAART as first-line treatment (including either an NNRTI or a [boosted] PI) and the trend toward significant protection in patients who continued [combination] ART without any interruption provided consistent results," they added. "Overall, the positive impact of the control of HIV infection suggests that early initiation of HAART may provide an opportunity to prevent liver fibrosis progression."

Investigator affiliations: Institute of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy; Spedali Civili di Brescia, Brescia, Italy; Institute of Infectious Diseases, Policlinico di Bari, Bari, Italy.

5/3/11

Reference
M Mendeni, E Foca, D Gotti, et al. Evaluation of Liver Fibrosis: Concordance Analysis between Noninvasive Scores (APRI and FIB-4) Evolution and Predictors in a Cohort of HIV-Infected Patients without Hepatitis C and B Infection. Clinical Infectious Diseases 52(9):1164-1173 (free full text). May 1, 2011.