A Review of Non-Alcoholic Fatty Liver Disease in HIV-Infected Patients: The Next Big Thing?

Abstract

The burden of liver-related morbidity remains high among HIV-infected patients, despite advances in the treatment of HIV and viral hepatitis. Especially, the impact of non-alcoholic fatty liver disease (NAFLD) is significant with a prevalence of up to 50%. The pathogenesis of NAFLD and the reasons for progression to non-alcoholic steatohepatitis (NASH) are still not fully elucidated, but insulin resistance, mitochondrial dysfunction and dyslipidemia seem to be the main drivers. Both HIV-infection itself and combination antiretroviral therapy (cART) can contribute to the development of NAFLD/NASH in various ways. As ongoing HIV-related immune activation is associated with insulin resistance, early initiation of cART is needed to limit its duration. In addition, the use of early-generation nucleoside reverse transcriptase inhibitors and protease inhibitors is also associated with the development of NAFLD/NASH. Patients at risk should therefore receive antiretroviral drugs with a more favorable metabolic profile. Only weight reduction is considered to be an effective therapy for all patients with NAFLD/NASH, although certain drugs are available for specific subgroups. Since patients with NASH are at risk of developing liver cirrhosis and hepatocellular carcinoma, several non-antifibrotic and antifibrotic drugs are under investigation in clinical trials to broaden the therapeutic options. The epidemiology and etiology of NAFLD/NASH in HIV-positive patients is likely to change in the near future. Current guidelines recommend early initiation of cART that is less likely to induce insulin resistance, mitochondrial dysfunction and dyslipidemia. In contrast, as a result of increasing life expectancy in good health, this population will adopt the more traditional risk factors for NAFLD/NASH. HIV-treating physicians should be aware of the etiology, pathogenesis and treatment of NAFLD/NASH in order to identify and treat the patients at risk.

Keywords: Antiretroviral therapy; Fibrosis; HIV; NASH; Non-alcohol fatty liver disease.

Fig. 1

Schematic representation of the natural history of non-alcoholic fatty liver disease (NAFLD). NASH non-alcoholic steatohepatitis. *In 3–6 years of follow-up **In 5–7 years of follow-up

Fig. 2

Schematic representation of the pathogenesis of NAFLD. As shown, there are four major hallmarks in the pathogenesis of NALFD—insulin resistance, dyslipidemia, hepatic accumulation and the microbiome—with a certain overlap between these factors. As mentioned, genetics play an important role in the overall pathogenesis influencing most of these factors. The arrows represent a direct impact of a certain hallmark on the development of NAFLD. The contributing factors are mentioned below the hallmarks. Risk factors more common in HIV-infected population are marked with an asterisk