Editorial Note: The 2026 International AIDS Conference (AIDS 2026) was held in Rio de Janeiro, Brazil. Bringing together global specialists in infectious diseases, the conference covered a wide array of cutting-edge topics including viral prevention and control, antiretroviral therapy, and long-term health management for people living with HIV, and shared numerous innovative clinical research findings. At the conference, Dr. Florence Bascombe from University College London presented a special study on lean steatotic liver disease (SLD) among people living with HIV. Her discoveries have reshaped established clinical understanding of disease characteristics in patients with lean fatty liver disease, offering new insights into liver disease screening and management for this special population.
To discuss this clinically enlightening research in depth, Infectious Disease Frontier conducted an exclusive interview with Dr. Bascombe, focusing on critical questions including the pathogenesis of lean SLD, its distinctions from obese-type fatty liver disease, and clinical screening and intervention strategies.
Infectious Disease Frontier: Your study yielded an intriguing differentiated conclusion: people living with HIV complicated by lean SLD exhibit relatively preserved cardiometabolic phenotypes, yet their hepatic lesion severity does not differ significantly from that of non-lean patients. What potential mechanisms underpin this contradictory clinical profile of “metabolic protection unaccompanied by mitigated liver damage”?
Dr. Bascombe: As anticipated, lean patients with concurrent steatotic liver disease display overall superior metabolic markers, characterized by lower blood pressure, higher high-density lipoprotein (HDL) cholesterol, alongside lower BMI and waist circumference values. While our study was not designed to dissect underlying pathogenetic mechanisms, we can put forward several plausible hypotheses. Relevant mechanisms may be linked to HIV-induced chronic immune activation, or prior lipodystrophy and aberrant adipose tissue distribution. Beyond these, antiretroviral therapy (ART) exposure, genetic predisposition, and divergent patterns of ectopic fat distribution all represent potential contributing factors. It is important to clarify that this is a cross-sectional study, and the above remain hypothetical.
Infectious Disease Frontier: Conventional wisdom identifies obesity and metabolic dysfunction as major drivers of SLD progression. Your research centers on lean people living with HIV who lack classic metabolic risk factors. How do the triggers and progression trajectories of SLD in this population differ from those of ordinary patients with obesity-related SLD?
Dr. Bascombe: I believe these two populations arrive at identical hepatic pathological endpoints via entirely distinct biological pathways. The pathogenesis of classic obesity-associated SLD is well-defined: it is closely tied to obesity, metabolic syndrome, insulin resistance and chronic inflammation, which sequentially trigger hepatic steatosis before advancing to liver fibrosis and other hepatic injuries. In contrast, lean SLD arises through a disparate pathogenic cascade. Such patients predominantly suffer from abnormal fat partitioning or lipodystrophy, which ultimately culminate in clinically significant liver disease—though the biological pathways driving disease onset and progression diverge completely from those seen in obese SLD patients.
Our cross-sectional study confirmed an independent correlation between TAF use and SLD incidence; nevertheless, the study cannot establish a causal relationship between the two. This association may merely reflect inherent individualized characteristics of patients receiving TAF regimens.
Infectious Disease Frontier: Per your research findings, lean SLD among people living with HIV is easily overlooked clinically due to normal metabolic parameters, yet their risk of liver injury remains undiminished. Do you believe separate screening criteria, follow-up intervals and intervention regimens should be formulated specifically for this population? What are your core clinical diagnosis and treatment recommendations?
Dr. Bascombe: In my view, the results of this single study alone do not justify revisions to current clinical guidelines. That said, the research clearly signals that clinicians must not rely solely on BMI when evaluating patients with liver disease or abnormal liver function. Presently, most clinical screening protocols for SLD prioritize obesity as the primary screening indicator. Our findings highlight the need for clinicians to recognize distinct pathogenic pathways affecting lean individuals. Vigilance should be heightened particularly for patients with a history of lipodystrophy or unexplained elevated liver enzymes.
For the time being, these patients should still adhere to standardized universal diagnostic and therapeutic workflows for SLD. Once screening identifies advanced liver fibrosis, timely referral to a hepatology specialist is mandatory for further evaluation and management. Meanwhile, lifestyle intervention remains the cornerstone of fatty liver disease care. Even for non-obese patients with no weight management requirements, standardized lifestyle guidance should be routinely provided in clinical practice.
Overall, additional prospective studies are required to corroborate these conclusions. My research team is currently conducting follow-up investigations to explore body composition assessment metrics beyond BMI, aiming to refine SLD screening algorithms and enable more accurate identification of high-risk patients.
