What is the recommended screening and management strategy for non‑alcoholic fatty liver disease in adult patients with human immunodeficiency virus infection?

Screening and Management of NAFLD in HIV-Infected Adults

All HIV-infected adults should be screened for NAFLD using abdominal ultrasound as the first-line diagnostic test, with particular attention to metabolic risk factors including obesity, insulin resistance, and dyslipidemia, followed by aggressive lifestyle modification as the cornerstone of treatment. 1, 2

Screening Strategy

Who to Screen

• Screen all HIV-infected patients for NAFLD, as prevalence ranges from 30-65% in this population—substantially higher than the general population 3
• HIV-infected patients face increased risk due to metabolic syndrome, antiretroviral therapy effects, chronic HIV inflammation, and gut-liver axis dysregulation 1, 2

Screening Methods

• Abdominal ultrasound is the primary screening test for detecting hepatic steatosis 2
• In overweight or obese patients where ultrasound accuracy is limited, use CT or MRI instead 4
• Obtain fasting lipid profile before starting antiretroviral therapy and within 3-6 months after starting a new regimen 5
• Assess for metabolic risk factors: obesity (BMI ≥25 kg/m²), diabetes, insulin resistance, dyslipidemia, and hypertension 4, 2

Fibrosis Assessment

• Non-invasive methods including serological markers and transient elastography are useful for assessing fibrosis severity in HIV patients 2
• Liver biopsy remains the gold standard for diagnosing non-alcoholic steatohepatitis (NASH) when non-invasive methods are inconclusive 2
• Stage 2 or greater fibrosis (≥F2) is an independent predictor of liver-related complications and mortality, making fibrosis severity the most important prognostic marker 4

Management Strategy

First-Line: Lifestyle Modifications (All Patients)

Lifestyle modifications are the cornerstone of treatment and should be applied to all HIV-infected patients with NAFLD, regardless of inflammation or fibrosis severity. 4, 2

Dietary Intervention

• Avoid refined carbohydrates, saturated fatty acids, fructose-added beverages, and processed red meat 6
• Achieve protein intake of 1.2 g/kg body weight/day during stable disease 7
• Consultation with a dietician is recommended 5

Exercise Program

• Combined dietary intervention with supervised exercise (cycling and resistance training 3 times weekly) reduces total cholesterol by 18% and triglycerides by 25% 7
• Regular aerobic exercise should be implemented 5

Weight Management

• Target weight reduction if BMI ≥25 kg/m², as obesity accelerates fibrosis progression 4, 2
• Weight loss improves both steatosis and fibrosis 4

Risk Factor Control

• Smoking cessation is mandatory—smoking increases HCC risk by 1.5-1.8 times and is associated with liver fibrosis 4
• Alcohol abstinence is required, particularly in patients with cirrhosis, as alcohol increases HCC incidence by 1.2-2.1 times 4
• Control hyperglycemia if diabetes is present 5

HIV-Specific Management

Antiretroviral Therapy Optimization

• Maintain HIV viral suppression as a priority, since effective antiretroviral therapy has decreased the incidence of metabolic complications 7, 1
• Consider switching from older NRTIs (stavudine, didanosine, zidovudine) to newer agents (abacavir, tenofovir) if metabolic toxicity is suspected 8
• If lipid levels remain elevated despite lifestyle modifications and virologic control is maintained, consider altering antiretroviral therapy 5

Metabolic Comorbidity Management

• Treat dyslipidemia according to NCEP ATP III guidelines with attention to drug interactions 5
• For elevated LDL cholesterol, use pravastatin (20-40 mg daily) or atorvastatin (10 mg daily) as first-line statins due to fewer interactions with protease inhibitors 5
• Avoid combining statins with fibrates due to increased rhabdomyolysis risk 5
• In men with fatigue, weight loss, loss of libido, or depressive symptoms, obtain morning serum total testosterone to evaluate for hypogonadism 7

Pharmacologic Treatment (Selective Use)

Who Should Receive Pharmacotherapy

Pharmacologic treatment should be reserved for patients with NASH or hepatic fibrosis (≥F2), as these patients have increased risk of liver-related complications. 4

Treatment Options

• Bariatric surgery, pioglitazone, and vitamin E can be considered in patients with significant fibrosis or high risk for progression (type 2 diabetes, metabolic syndrome, elevated transaminases, pronounced necroinflammation) 2
• However, there is no evidence supporting vitamin E or pioglitazone specifically in HIV patients with NAFLD—these agents have not been studied in this population 4, 2
• Multiple novel medications targeting hepatic fat accumulation, oxidative stress, inflammation, and fibrosis are in clinical trials 1

Surveillance for Complications

Hepatocellular Carcinoma Screening

• Patients with NASH cirrhosis require HCC surveillance according to AASLD/ACG guidelines 4
• Abdominal ultrasound is the primary surveillance test; use CT or MRI if ultrasound is inadequate in obese patients 4
• Screen for gastroesophageal varices in patients with NASH cirrhosis 4

Cardiovascular Risk Management

• HIV-infected individuals with NAFLD face increased cardiovascular morbidity, making aggressive dyslipidemia management particularly important 5, 9
• Count coronary heart disease risk factors (smoking, hypertension, low HDL, family history, age >45 for men/>55 for women) and perform 10-year risk calculation if ≥2 risk factors present 5

Common Pitfalls to Avoid

• Do not routinely repeat liver biopsy in patients with NAFLD or NASH unless clinically indicated 4
• Do not use simvastatin or lovastatin with protease inhibitors due to severe drug interactions; use pravastatin or fluvastatin instead 5
• Do not overlook opportunistic infections or malignancies as alternative causes of elevated liver enzymes in HIV patients 4
• Do not assume NAFLD treatment in HIV mirrors the general population—research is urgently needed to identify safe and effective pharmacological treatments specifically for this population 2