Application of Guidelines for the Management of Nonalcoholic Fatty Liver Disease in Three Prospective Cohorts of HIV-Monoinfected Patients

G Sebastiani; S Cocciolillo; G Mazzola; A Malagoli; J Falutz; A Cervo; S Petta; T Pembroke; P Ghali; G Besutti; I Franconi; J Milic; A Cascio; G Guaraldi


HIV Medicine. 2020;21(2):96-108. 

In This Article

Abstract and Introduction


Objectives: Current guidelines recommend use of a diagnostic algorithm to assess disease severity in cases of suspected nonalcoholic fatty liver disease (NAFLD). We applied this algorithm to HIV-monoinfected patients.

Methods: We analysed three prospective screening programmes for NAFLD carried out in the following cohorts: the Liver Disease in HIV (LIVEHIV) cohort in Montreal, the Modena HIV Metabolic Clinic (MHMC) cohort and the Liver Pathologies in HIV in Palermo (LHivPa) cohort. In the LIVEHIV and LHivPa cohorts, NAFLD was diagnosed if the controlled attenuation parameter (CAP) was ≥ 248 dB/m; in the MHMC cohort, it was diagnosed if the liver/spleen Hounsfield unit (HU) ratio on abdominal computerized tomography scan was < 1.1. Medium/high-risk fibrosis category was defined as fibrosis-4 (FIB-4) ≥ 1.30. Patients requiring specialist referral to hepatology were defined as either having NAFLD and being in the medium/high-risk fibrosis category or having elevated alanine aminotransferase (ALT).

Results: A total of 1534 HIV-infected adults without significant alcohol intake or viral hepatitis coinfection were included in the study. Of these, 313 (20.4%) patients had the metabolic comorbidities (obesity and/or diabetes) required for entry in the diagnostic algorithm. Among these patients, 123 (39.3%) required specialist referral to hepatology, according to guidelines. A total of 1062 patients with extended metabolic comorbidities (any among obesity, diabetes, hypertension and dyslipidaemia) represented most of the cases of NAFLD (79%), elevated ALT (75.9%) and medium/high-risk fibrosis category (75.4%). When the algorithm was extended to these patients, it was found that 341 (32.1%) would require specialist referral to hepatology.

Conclusions: According to current guidelines, one in five HIV-monoinfected patients should undergo detailed assessment for NAFLD and disease severity. Moreover, one in ten should be referred to hepatology. Expansion of the algorithm to patients with any metabolic comorbidities may be considered.


In Western countries, people infected with HIV now live longer thanks to the widespread use of antiretroviral treatment (ART).[1] In this newly aging HIV-infected population, liver cirrhosis has become a leading cause of death.[2] In addition to coinfections with the hepatitis B (HBV) and C (HCV) viruses, nonalcoholic fatty liver disease (NAFLD) is an emerging concern for people aging with HIV infection.[3] NAFLD is characterized by excessive hepatic fat accumulation, defined as the presence of steatosis in > 5% of hepatocytes in the absence of other causes of liver disease. NAFLD is the most frequent hepatic disease in Western countries. Nonalcoholic steatohepatitis (NASH) is the progressive form of the disease characterized by liver fibrosis leading to cirrhosis and related complications.[4] NASH has become the second most common indication for liver transplantation in North America and is projected to become the leading indication in the next 10–20 years.[5] Furthermore, NASH is the fastest rising cause of hepatocellular carcinoma (HCC), the second leading cause of cancer-related death in the world.[6] HIV-infected patients are at higher risk of NAFLD than the general population as a result of multiple cofactors, including lifelong use of ART, HIV itself, host factors and highly prevalent metabolic comorbidities.[7,8] The reported prevalence of NAFLD ranges from to 13% to 65% in HIV-monoinfected patients.[3,9–13] Moreover, NASH and significant liver fibrosis may be at least twice as frequent in HIV-monoinfected patients as in the general population.[14–18]

Recent guidelines from the European Association for the Study of the Liver (EASL) recommend use of a diagnostic algorithm to assess and monitor disease severity in the presence of suspected NAFLD and metabolic risk factors.[19] This stepwise algorithm is used to screen for NAFLD in order to define subsequent follow-up strategies and identify patients in need of specialist referral to hepatology, defined as those with elevated liver enzymes or the presence of NAFLD with medium/high risk of liver fibrosis as determined using serum biomarkers, such as fibrosis-4 (FIB-4) score. A similar pathway has been recommended by the European AIDS Clinical Society (EACS).[20] Thus far, these guidelines have not been applied to HIV-monoinfected patients, a population potentially at higher risk for NAFLD.

The aim of this study was to apply the diagnostic algorithm recommended by EASL and EACS guidelines to assess and monitor disease severity in the presence of suspected NAFLD and metabolic comorbidities in three large cohorts of HIV-monoinfected patients.