How should I manage a 40‑year‑old man with well‑controlled hypertension on telmisartan 40 mg, non‑alcoholic fatty liver disease on pitavastatin 4 mg, who has a very low‑density lipoprotein of 1.05 mmol/L, triglycerides of 2.29 mmol/L, alanine aminotransferase of 107 U/L and aspartate aminotransferase of 58 U/L?

Management of Elevated Liver Enzymes and Dyslipidemia in a 40-Year-Old Male with NAFLD on Telmisartan and Pitavastatin

Immediate Action: Continue Current Medications

Continue both telmisartan 40mg and pitavastatin 4mg without interruption, as statins are not contraindicated in NAFLD and provide cardiovascular benefit that outweighs concerns about transaminase elevation. 1, 2

The ALT of 107 U/L (approximately 2.7× upper limit of normal assuming ULN ~40 U/L) and AST of 58 U/L represent moderate elevation consistent with underlying NAFLD rather than statin hepatotoxicity. 1, 2 Statins are safe in stable liver disease and may actually provide histological benefit by reducing steatohepatitis and fibrosis. 1

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Primary Management Strategy: Intensive Lifestyle Modification

Weight Loss and Exercise (First-Line Therapy)

• Target 7-10% body weight reduction through caloric restriction, as this is the only intervention proven to resolve NASH and improve fibrosis in clinical trials. 1
• Prescribe 150-300 minutes per week of moderate-intensity aerobic exercise over minimum 3 days per week, as both aerobic and resistance training reduce liver fat independent of weight loss. 1
• Add resistance exercise on at least 2 days per week, which has lower cardiorespiratory demand and may be preferable if baseline fitness is poor. 1
• Reassess alcohol consumption quantitatively at this visit and every follow-up, as even moderate intake (>14 drinks/week in women, >21 drinks/week in men) accelerates NAFLD progression and must be minimized or eliminated. 1

Dietary Modifications

• Reduce saturated fat intake and increase fruits and vegetables, as dietary modification is essential for achieving weight loss targets. 2
• Restrict alcohol to minimize additional caloric intake, which can worsen metabolic risk factors and hepatic steatosis. 1, 2

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Lipid Management: Optimize Current Therapy

Triglyceride Control

• Add omega-3 fatty acids (EPA/DHA 2-4 grams daily) as first-line therapy for triglycerides of 2.29 mmol/L (203 mg/dL), as they are safe, well-tolerated, and effective in reducing triglycerides while potentially improving liver disease in NAFLD. 3
• The VLDL of 1.05 mmol/L (approximately 48 mg/dL) and triglycerides of 2.29 mmol/L indicate atherogenic dyslipidemia, which is characteristic of NAFLD and requires aggressive treatment to reduce cardiovascular mortality—the leading cause of death in NAFLD patients. 1, 3

Statin Continuation

• Do NOT discontinue pitavastatin despite ALT elevation, as the American College of Cardiology recommends continuing therapy when ALT is <3× ULN and rechecking in 4-6 weeks. 2
• Pitavastatin 4mg is appropriate for this patient, as it has potent LDL-lowering activity, superior HDL-elevating effects compared to atorvastatin, minimal CYP-mediated drug interactions, and favorable safety profile in metabolic syndrome. 4
• Recheck liver enzymes in 4-6 weeks, then monitor every 8±4 weeks after any dose adjustments. 2

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Hypertension Management: Continue Telmisartan

• Maintain telmisartan 40mg daily, as it provides dual benefit: blood pressure control and potential improvement in NAFLD through modulation of the renin-angiotensin system and favorable effects on lipid and glucose metabolism. 5, 6
• Telmisartan has been shown to reduce total cholesterol by 12-45 mg/dL in hypertensive patients, with particularly striking effects in those with baseline cholesterol ≥220 mg/dL, and also reduces triglycerides in patients with baseline TG ≥150 mg/dL. 6
• Target blood pressure <130/80 mmHg per NICE guidelines for patients with NAFLD, as hypertension is present in ~50% of NAFLD patients and increases cardiovascular mortality. 1

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Fibrosis Risk Stratification: Calculate FIB-4 Score

Calculate FIB-4 score immediately using age, AST, ALT, and platelet count to stratify fibrosis risk and determine need for secondary assessment. 1

FIB-4 Interpretation and Action

• FIB-4 <1.3 (or <2.0 if ≥65 years): Low risk—reassess annually with FIB-4. 1
• FIB-4 1.3-2.67: Intermediate risk—perform secondary assessment with vibration-controlled transient elastography (VCTE) or enhanced liver fibrosis (ELF) score. 1
• FIB-4 >2.67: High risk—refer to hepatologist for VCTE or magnetic resonance elastography (MRE) and consideration of liver biopsy. 1

Secondary Assessment Thresholds (if FIB-4 intermediate/high)

• VCTE ≤8.0 kPa or ELF <7.7 or MRE <2.6 kPa: Low risk—annual monitoring. 1
• VCTE 8.1-12 kPa or ELF 7.7-9.8 or MRE 2.6-3.6 kPa: Intermediate risk—annual VCTE/MRE monitoring, consider hepatology referral. 1
• VCTE >12 kPa or ELF >9.8 or MRE >3.6 kPa: High risk (advanced fibrosis)—refer to hepatologist for management and clinical trial consideration. 1
• VCTE >15 kPa or ELF >11.3 or MRE >4.6 kPa: Cirrhosis—refer urgently for hepatocellular carcinoma surveillance and variceal screening. 1

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Metabolic Screening: Annual Diabetes Assessment

• Screen for type 2 diabetes annually with HbA1c, as NAFLD is a high-risk group for diabetes development. 1
• HbA1c ≥48 mmol/mol (6.5%) is diagnostic for type 2 diabetes and would mandate addition of GLP-1 receptor agonist or SGLT2 inhibitor, which provide dual benefit for cardiometabolic disease and NAFLD. 1

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Cardiovascular Risk Assessment

• Calculate QRISK3 score to assess 10-year cardiovascular risk, as cardiovascular disease is the leading cause of death in NAFLD patients. 1
• If QRISK3 ≥10% or if type 2 diabetes develops, continue statin therapy for primary prevention, as the cardiovascular benefit far outweighs any theoretical hepatotoxicity risk. 1

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Monitoring Schedule

4-6 Weeks

• Recheck ALT, AST, alkaline phosphatase to ensure transaminases are stable or improving. 2
• Assess adherence to lifestyle modifications and provide reinforcement. 1

3 Months

• Repeat lipid panel (total cholesterol, LDL, HDL, triglycerides, VLDL). 2
• Measure weight and calculate percentage weight loss. 1
• Recheck HbA1c if baseline was in prediabetic range. 1

12 Months

• Repeat FIB-4 calculation. 1
• Repeat VCTE or ELF if previously intermediate/high risk. 1
• Annual diabetes screening with HbA1c. 1
• Reassess alcohol consumption quantitatively. 1

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Critical Pitfalls to Avoid

• Do not discontinue pitavastatin based on ALT 107 U/L, as this represents <3× ULN and statins are safe in NAFLD; discontinuation would increase cardiovascular risk. 1, 2
• Do not attribute elevated transaminases solely to statin therapy without considering NAFLD as the primary cause, as the pattern (ALT > AST) and clinical context strongly suggest underlying fatty liver disease. 1, 3
• Do not delay fibrosis risk stratification with FIB-4, as identifying advanced fibrosis (F3-F4) changes management to include hepatology referral and consideration of investigational therapies. 1
• Do not underestimate the importance of weight loss, as 7-10% body weight reduction is the only proven intervention to resolve NASH and improve fibrosis, with placebo-controlled trials showing 31% improvement in steatosis and fibrosis. 1
• Do not ignore alcohol consumption, as even moderate intake has additive and synergistic interactions with cardiometabolic risk factors in accelerating NAFLD progression. 1