Screening and Follow-up in Patients With HIV Infection Combined With Metabolic Associated Fatty Liver Disease

Fibrosis, HIV/AIDS, Nonalcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis

integrase inhibitors, non-nucleoside reverse transcriptase inhibitors, transient elastography, iLivTouch

Acquired immunodeficiency syndrome (AIDS) remains a severe global infectious disease, with over 38 million people living with HIV and around 35 million cumulative deaths worldwide by 2023; approximately 1.24 million HIV-positive individuals and 100,000 new infections are reported annually in China. Widespread use of HAART has prolonged HIV patients' survival and reduced AIDS-related mortality, yet non-AIDS comorbidities dominated by chronic liver disorders, particularly metabolic dysfunction-associated fatty liver disease (MAFLD), have become a major challenge in long-term HIV management. Triggered by elevated blood lipids from lifestyle, antiretroviral agents and inherited metabolic factors, MAFLD initiates with hepatic steatosis and may progress to NASH, liver fibrosis, cirrhosis and even hepatocellular carcinoma (HCC) without timely intervention. HIV-positive patients develop more severe MAFLD progression than HIV-negative counterparts; existing biopsy data shows 91% of ART-treated HIV patients have NAFLD, among whom 65% suffer from NASH complicated with liver fibrosis. Fatty liver prevalence keeps rising with younger onset age in China, which highlights the necessity of early screening. Liver biopsy, the historical diagnostic gold standard for liver injury grading, is restricted by invasiveness, bleeding risks and poor reproducibility. Transient elastography (TE), a novel non-invasive ultrasonic technique, quantifies hepatic steatosis via the ultrasound attenuation parameter (UAP) and liver fibrosis via liver stiffness measurement (LSM), and has been validated and guideline-endorsed for multiple chronic liver diseases globally. Published foreign data report 35%, 42% and 22% prevalence of NAFLD, NASH and fibrosis in PLWH, while domestic evidence on HIV-associated MAFLD is limited, especially liver-related discrepancies among varied ART regimens. With the implementation of China's new medical insurance policy, numerous patients are shifting from non-INI regimens to once-daily single-tablet INSTI STR regimens, whose hepatic and lipid impacts remain unclear. This study targets early detection of HIV patients with concomitant fatty liver to optimize management strategies and improve clinical outcomes. Our preliminary cohort at Peking Union Medical College Hospital included 188 virologically suppressed HIV patients on ART, 56.9% (107/188) of whom developed fatty liver (mild:27.1%, moderate:19.7%, severe:10.1%). Liver fibrosis (LSM≥7.3 kPa) was found in 12.8% (24/188) subjects, with 1.1% having advanced cirrhosis, and no significant inter-group difference in fatty liver incidence was noted between INSTI and NNRTI recipients. These findings lay a foundation for early diagnosis and follow-up intervention of metabolic liver disease among HIV-infected populations.

Acquired immunodeficiency syndrome (AIDS) is a severe infectious disease. As of 2023, over 38 million people globally are living with HIV/AIDS, and approximately 35 million deaths have been attributed to the disease. China faces a notable AIDS epidemic, with roughly 1.24 million registered people living with HIV/AIDS and around 100,000 new infections annually. Widespread application of Highly Active Antiretroviral Therapy (HAART) has markedly improved clinical outcomes for HIV-infected individuals and reduced AIDS-related mortality. Nevertheless, non-AIDS comorbidities including chronic liver disease have become core concerns in long-term clinical management of people living with HIV. Among these conditions, Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD) has emerged as a critical clinical challenge for HIV patient care. MAFLD arises from excessive hepatic fat accumulation; HIV infection, combined with lifestyle changes, antiretroviral medications, and inherited metabolic predispositions, elevates serum low-density lipoprotein, total cholesterol and triglyceride levels, ultimately triggering intrahepatic lipid deposition and MAFLD development. MAFLD typically initiates with simple hepatic steatosis. Without timely clinical intervention, it can progress to nonalcoholic steatohepatitis (NASH) and subsequent liver fibrosis. In fibrotic cases, NASH may further advance to liver cirrhosis, or even hepatocellular carcinoma (HCC) in the absence of established cirrhosis. In HIV-negative populations, 25%-30% of patients with NAFLD progress to NASH. By contrast, HIV-positive individuals tend to develop NAFLD and experience disease progression at higher clinical severity. Relevant histopathological data remain limited, yet liver biopsy findings from ART-treated HIV patients confirm NAFLD in 91% of participants, 65% of whom have NASH with prevalent hepatic fibrosis. Nationwide epidemiological data show a rising incidence of fatty liver disease alongside younger age at onset in China, highlighting the urgent need for early screening. Percutaneous liver biopsy has long remained the clinical gold standard to grade hepatic inflammation, fibrosis and steatosis via histopathology. However, this invasive procedure carries bleeding risk, procedural complications and poor repeatability, limiting patient acceptance and clinical application. Advances in non-invasive diagnostic modalities and hepatic imaging have overcome such drawbacks. Transient Elastography (TE), an emerging ultrasound-based technique, enables quantitative assessment of hepatic fibrosis and fatty liver. ##（接第二段） For fatty liver assessment, ultrasound signals decay substantially when propagating through lipid-laden hepatocytes; this property enables quantitative grading of hepatic steatosis via the Ultrasound Attenuation Parameter (UAP). Meanwhile, Liver Stiffness Measurement (LSM) quantifies liver fibrosis based on the positive correlation between propagation velocity of low-frequency shear waves and hepatic tissue rigidity. TE is now widely adopted in global clinical practice and well validated across chronic hepatitis B, chronic hepatitis C and fatty liver cohorts, with robust correlation between TE-derived LSM/UAP values and histopathological findings, and formal endorsement in multiple international clinical guidelines. Overseas clinical data report NAFLD, NASH and hepatic fibrosis prevalence of 35%, 42% and 22% respectively among people living with HIV. In China, however, real-world research on HIV-associated MAFLD remains scarce, especially regarding differential hepatic steatosis and liver function impacts across distinct antiretroviral regimens. Following China's updated national medical insurance policies, patients previously on non-INI-based regimens are being switched to once-daily single-tablet INSTI STR formulations, whose long-term effects on lipid metabolism and liver status are yet to be defined. This study aims to facilitate early identification of HIV patients complicated with fatty liver, optimize clinical management and therapeutic strategies to improve patient quality of life and reduce disease-related mortality. A preliminary single-center study previously completed at Peking Union Medical College Hospital enrolled 188 virologically suppressed HIV patients under antiretroviral treatment, among whom 107 (56.9%) developed fatty liver: mild, moderate and severe steatosis accounted for 51 (27.1%), 37 (19.7%) and 19 (10.1%) cases respectively. Twenty-four participants (12.8%) presented with hepatic fibrosis (LSM≥7.3 kPa), including 2 (1.1%) with advanced cirrhosis. No statistically significant difference in fatty liver incidence was observed between patients receiving INSTI versus NNRTI-based regimens. These preliminary findings provide critical evidence supporting early identification, diagnosis and long-term follow-up intervention for metabolic liver disease in HIV-infected populations.

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