A signal of early liver disease was 4 times more frequent in HIV-positive youth 15 to 20 years old than in HIV-negative people that age.1 In the group with HIV infection, liver disease signals got worse every year, especially in those with a low CD4 count, a detectable viral load, or not taking antiretroviral therapy. None of the young people in this study had hepatitis B or C infection (HBV or HCV).
HBV or HCV infection is common in people with HIV and can cause serious liver damage if left untreated. But HIV itself can cause liver damage even in people without HBV or HCV. HIV probably affects the liver because it causes inflammation. This inflammation can continue at a low level even in people whose antiretroviral therapy makes their viral load undetectable.
Simple blood tests can tell which people may have liver damage called fibrosis or cirrhosis (liver scar tissue) (Figure 1). Using these tests could help HIV providers find out who may have fibrosis or cirrhosis and needs further studies. But these tests have not been closely analyzed in children, adolescents, or young adults with HIV. U.S. researchers conducted this study to see if these tests indicate liver damage more in young people with HIV than without HIV, and to learn whether the tests show that liver damage gets worse over time.
How the Study Worked
The study focused on young people in the United States with blood samples available for liver function tests between the ages of 15 and 20 years. Study participants came from two previous study groups that included children with or without HIV infection. The children with HIV could have been infected around the time of their birth or later through sex or drug use. The study group included no one known to have HBV or HCV infection.
The researchers determined two established liver function markers in these young people, FIB-4 and APRI.2 In adults a FIB-4 greater than 1.45 or an APRI greater than 0.5 suggests mild to moderate liver fibrosis. A FIB-4 greater than 3.25 or an APRI greater than 1.5 suggests advanced liver fibrosis.
First the researchers determined FIB-4 and APRI a single time in all study participants with and without HIV infection. Then the investigators focused only on HIV-infected young people who had two or more study visits and determined FIB-4 and APRI at each study visit to create FIB-4 and APRI records over time. Within this group of HIV-infected youth with two or more study visits, the researchers looked at young people with low initial APRI (at or below 0.5) and low initial FIB-4 (at or below 1.5) and determined how many people had higher (worse) scores over time.
What the Study Found
The 1785 young people in the study included 1612 with HIV and 173 without HIV. The 1612 people with HIV included 1042 infected around the time of birth and 570 infected later in life through sex or drug use. The overall group of young people with and without HIV had a median (midpoint) age of 17.3 years when FIB-4 and APRI liver tests were done, and 1055 people (59%) were women. While 57% of the study group were black, 27% were Hispanic, 13% white, and 3% in another racial or ethnic group.
The researchers measured an APRI score indicating mild to moderate liver fibrosis in 13% of young people with HIV versus 3% without HIV. This difference is statistically significant, meaning the difference probably cannot be explained by chance. FIB-4 indicating mild to moderate fibrosis was less frequent in young people with HIV (2%) and without HIV (1%).
In the whole study group, statistical analysis identified three factors that made mild to moderate fibrosis more likely regardless of whatever other fibrosis risk factors a person had: having HIV infection, being a man, and having low weight measured as body mass index. In an analysis focused just on people with HIV, three factors made mild to moderate fibrosis more likely regardless of whatever other fibrosis risk factors a person had: being a man, having a CD4 count below 350, and having a viral load above 400 copies/mL.
In the analysis of HIV-infected young people who had two or more liver function assessments, APRI indicated that 7.5% of the group went from no fibrosis to mild-to-moderate fibrosis every year. FIB-4 indicated that 1.6% went from no fibrosis to mild-to-moderate fibrosis every year. Rates of progression to advanced fibrosis were lower -- 1.4% per year with APRI and 0.3% per year with FIB-4.
Among all young people with HIV, FIB-4 rose by an average 6% every year. Among young people infected with HIV around the time of birth, APRI rose by an average 2% per year.
Finally, the researchers figured the impact of four factors on increases in FIB-4 and APRI over time in people with HIV (Figure 2). For FIB-4 the increase over time was 13% higher in men than women, 19% higher in people with a CD4 count below 350, 17% higher in people with a detectable viral load, and 12% higher in people not taking antiretroviral therapy. For APRI the increase over time was 24% higher in men than women, 21% higher in people with a CD4 count below 350, 23% higher in people with a detectable viral load, and 17% higher in people not taking antiretroviral therapy.
What the Results Mean for You
This large study of young people without hepatitis virus infection (HBV or HCV) found that a significantly higher proportion of youth with HIV than without HIV had mild to moderate liver damage (fibrosis) indicated by a liver test called APRI. This score rose 2% yearly in young people with HIV, and the score of another liver test called FIB-4 rose 6% yearly. Although those yearly increases sound small, they are concerning in a 15- to 20-year-old group that will probably live to old age thanks to antiretroviral therapy.
The study also found that yearly increases in APRI and FIB-4, indicating worsening liver health, were higher in young men than young women with HIV and in people with a low CD4 count, a detectable viral load, or not taking antiretroviral therapy. Those findings strongly suggest another advantage of starting and continuing antiretroviral therapy and taking antiretroviral pills regularly -- better liver health throughout life.
About the size of a football in adults, the liver is crucial to the health of all people. It cleans the blood, makes an important digestive liquid called bile, stores energy in the form of a sugar called glycogen, and helps process many drugs in the body,3 including many antiretrovirals. This study underlines the importance of measuring liver function regularly in people with HIV, including young people. Your HIV provider may plug the results of liver function tests into the formula that calculates FIB-4 or APRI2 to get a closer look at your liver health. Although young people in this study did not have HBV or HCV infection, tracking liver health is especially important in people with those hepatitis viruses and in people whose liver might be threatened by other illnesses or by drugs that affect the liver.
Because this study shows that HIV poses a threat to the liver even in young people, everyone with HIV should avoid or control known risk factors for liver disease -- drinking too much alcohol, high cholesterol and triglycerides, and obesity. People without HBV infection should get the HBV vaccine.
- Kapogiannis BG, Leister E, Siberry GK, et al. Prevalence of and progression to abnormal noninvasive markers of liver disease (aspartate aminotransferase-to-platelet ratio index and Fibrosis-4) among U.S. HIV-infected youth. AIDS. 2016;30:889-898.
- Fibrosis-4 (FIB-4) = age x AST/(Platelet count x Square root of ALT) (www.hepatitisc.uw.edu/page/clinical-calculators/fib-4). Aspartate aminotransferase-to-platelet ratio index (APRI) = (AST/AST upper limit of normal)/platelet count x 100 (www.hepatitisc.uw.edu/page/clinical-calculators/apri).
- Kidshealth.org. Your liver.