Summary

AASLD 2023 Practice Guidance on prevention, diagnosis, and treatment of hepatocellular carcinoma updates prior recommendations to reflect ultrasound plus AFP for surveillance, expanded surgical indications (including selected BCLC-B and minimally invasive resection with mild portal hypertension), incorporation of immune checkpoint inhibitor-based combinations (atezolizumab/bevacizumab, durvalumab/tremelimumab) as preferred first-line systemic therapy, and explicit recommendations for multidisciplinary care and advance care planning. The BCLC 2022 framework is endorsed for staging, and LI-RADS is the recommended imaging diagnostic algorithm in at-risk patients.

Key Recommendations

Perform HCC surveillance in all patients with cirrhosis (Child-Pugh A/B, or C if listed for transplant) and in select high-risk chronic HBV using ultrasound plus AFP every 6 months.
Do not perform surveillance in Child-Pugh C patients not eligible for transplant or in patients with life expectancy <1–2 years from comorbidities.
Do not perform routine surveillance in noncirrhotic NAFLD or in post-SVR HCV patients without cirrhosis; continue indefinite surveillance in HCV cirrhosis after SVR.
Diagnose HCC noninvasively using LI-RADS on multiphase CT or contrast-enhanced MRI in at-risk patients; biopsy LR-M, LR-TIV, and noncharacteristic lesions, and biopsy any nodule in patients without cirrhosis/HBV.
Do not use AFP alone for HCC diagnosis; biopsy is required when imaging is noncharacteristic regardless of AFP level.
Use BCLC 2022 staging and discuss all patients at a multidisciplinary tumor board.
Reserve surgical resection for Child-Pugh A, single tumor, without clinically significant portal hypertension, with adequate future liver remnant; MIS may extend criteria to patients with mild portal hypertension for minor resection.
Liver transplantation is indicated within Milan criteria or after successful downstaging from UNOS-DS criteria; expanded criteria (e.g., UCSF) and LDLT may be considered.
First-line systemic therapy for advanced HCC (Child-Pugh A, ECOG 0–1) is atezolizumab plus bevacizumab (after EGD to screen varices) or durvalumab plus tremelimumab; use sorafenib or lenvatinib if immunotherapy contraindicated.
Do not use ICIs in post-liver-transplant patients; discontinue ICIs ≥3 months prior to LT if used as bridge therapy.
Adjuvant atezolizumab plus bevacizumab for 12 months may be offered after resection/ablation in high-risk patients (tumor >5 cm, >3 tumors, vascular invasion, or poor differentiation) based on IMbrave050.
Offer advance care planning to patients with larger tumor burden or those receiving palliative-intent therapy regardless of transplant eligibility.

Thresholds & Doses

Surveillance interval: ultrasound + AFP every 6 months.
Cost-effectiveness threshold for surveillance: annual HCC incidence ≥1.0% in cirrhosis (lowered from 1.5%).
AFP cutoff for diagnostic workup: ≥20 ng/mL; significantly elevated ≥200 ng/mL (or ≥400 ng/mL) warrants further workup.
Subcentimeter lesion (US-2): repeat ultrasound + AFP in 3–6 months.
LI-RADS thresholds: nodules ≥2 cm require APHE + 1 additional feature; 10–19 mm require APHE + washout or threshold growth.
LR probability of HCC: LR-5 95–99%, LR-4 ~75%, LR-3 ~30%; LR-M 93–100% malignant but only 29–44% HCC.
Future liver remnant: >30% in noncirrhotic, >40% in cirrhotic patients for resection.
CSPH surrogate: platelets <100,000/µL, varices, splenomegaly, or HVPG ≥10 mmHg.
Milan criteria: 1 lesion 1–5 cm OR 2–3 lesions each 1–3 cm.
UNOS-DS criteria: 1 lesion 5.1–8 cm; OR 2–3 lesions <5 cm with total ≤8 cm; OR 4–5 lesions each <3 cm with total ≤8 cm.
AFP for transplant: if baseline ≥1000 ng/mL, must decrease to <500 ng/mL before LT to be eligible for MELD exception.
MELD exception: granted 6 months after listing at MMaT-3 for Milan/downstaged candidates.
Wait period bypass: salvage LT after resection with Milan-criteria recurrence eligible for immediate MELD exception.
Ablation: preferred for HCC ≤3 cm; resection superior for larger tumors.
TARE personalized dosimetry target: >205 Gy to tumor.
Post-LT HCC recurrence rate: 10–15% within Milan criteria; RETREAT score stratifies 5-year recurrence from <3% (score 0) to 75% (score ≥5).
Avoid EBRT if Child-Pugh score ≥8, uncontrolled ascites, or uncontrolled encephalopathy.
Atezolizumab/bevacizumab median OS 19.2 months (IMbrave150); durvalumab/tremelimumab median OS 16.4 months (HIMALAYA).
Ramucirumab indicated second-line only if AFP ≥400 ng/mL.
Staging bone scan/pelvic CT considered if AFP >1000 ng/mL, macrovascular invasion, or multifocal bilobar disease.

Citations

Surveillance section — ultrasound + AFP every 6 months, target populations, and HCV/NAFLD subgroup recommendations.
Recall and Management of Surveillance Results / Figure 5 — US LI-RADS recall algorithm and AFP thresholds.
Diagnosis section / Figure 6 / LI-RADS algorithm — noninvasive imaging diagnostic criteria.
Staging section / Figure 9 — BCLC 2022 staging system endorsement.
Surgical Resection / Figure 10 — patient selection, FLR thresholds, CSPH surrogates, MIS indications.
Liver Transplantation / Table 3 / Figure 12 — Milan, expanded criteria, UNOS-DS, AFP requirements.
Systemic Therapy / Figure 16 / Tables 7–8 — first- and second-line therapy selection.
Advance Care Planning section — ACP recommendations for patients with HCC.