People with HIV who have non-alcoholic fatty liver disease have a higher risk of serious cardiovascular outcomes including heart attack, heart failure and stroke, a large study of people with HIV in the United States has found.
Non-alcoholic fatty liver disease (NAFLD) is caused by a build-up of fats in liver cells. Fatty liver disease (steatosis) is a consequence of metabolic disturbances including raised lipid levels, type 2 diabetes, overweight and obesity. It is more common in people with HIV than the rest of the population, partly because risk factors for fatty liver disease are more common in people with HIV. However, inflammation caused by HIV, immune activation and some antiretroviral drugs may also play a role in the development of fatty liver disease in people with HIV.
Non-alcoholic fatty liver disease is a risk factor for cardiovascular disease in the general population, although the mechanisms that lead from fat accumulation in the liver to heightened risk of heart attack and other major cardiovascular events are not fully understood. Fat in the liver promotes inflammation, insulin resistance and disordered lipid metabolism. Some antiretroviral drugs, notably integrase inhibitors and tenofovir alafenamide, have been associated with a higher risk of NAFLD.
There has been little research on the relationship between NAFLD and cardiovascular disease in people with HIV and those studies that have been carried out have been small or lacking in a suitable control group.
To investigate the relationship between non-alcoholic fatty liver disease and cardiovascular disease in people with HIV, US researchers identified everyone with HIV receiving care between 2008 and 2020 in 25 healthcare organisations in the United States through the TriNetX electronic medical records database.
They used a validated algorithm to identify people with non-alcoholic fatty liver disease, excluding anyone with alcoholic liver disease, alcohol use disorder, liver cancer or any the form of cancer, cirrhosis or a history of kidney dialysis during the follow-up period. Each person with NAFLD was matched with another person with HIV without NAFLD, matching by age, ethnicity, CD4 count, comorbidities, body mass index and antiretroviral therapy.
The study identified 4,969 people with NAFLD from a population of 371,240 people with HIV. Those with NAFLD had a mean age of 42 years, 60% were male, 55% were White, 23% Black, the mean body mass index was 29, 12% had type 2 diabetes and 16% had hypertension. People with NAFLD were more likely to be Hispanic, and to have elevated lipid levels, chronic kidney disease, chronic respiratory diseases, hypothyroidism, vitamin D deficiency and obstructive sleep apnea. They were significantly more likely to be taking medications to treat cardiovascular risk factors.
People with NAFLD were followed for a mean of 4.8 years.
The researchers compared the risk of four cardiovascular outcomes in people with NAFLD and matched controls. People with NAFLD were at higher risk of myocardial infarction (heart attack) (111 events, hazard ratio 1.49), major cardiovascular event (heart attack, heart failure, unstable angina or clinical intervention) (298 events, HR 1.49), heart failure (188 events, HR 1.73) and any cerebrovascular event (stroke, transient ischemic attack or clinical intervention) (294 events, HR 1.25). A sensitivity analysis which excluded events that occurred within one year of cohort entry calculated similar hazards to the primary analysis for each of the outcomes.
Kaplan-Meier survival analysis for each of the outcomes showed that people with NAFLD had a significantly lower probability of surviving without one of the four cardiovascular outcomes during seven years of follow-up.
The researchers say that further studies are needed to assess pharmacological and non-pharmacological interventions that can reduce the prevalence of NAFLD, and cardiovascular risks associated with NAFLD in people with HIV. Greater awareness of the cardiovascular risks associated with NAFLD is also needed among healthcare providers and people with HIV, as well as the development of multidisciplinary care and prevention.
Krishnan A et al. Risks of adverse cardiovascular outcomes among people with HIV and nonalcoholic fatty liver disease. AIDS, 37: 1209-16, 2023.