Table 2. Summary of Recommendations of 2014 KLCSG-NCC Korea Practice Guidelines for Management of Hepatocellular Carcinoma.

Topic	Recommendation
Prevention	1. Hepatitis B vaccination is recommended for all newborns (A1) and for high-risk individuals (HBsAg-negative and anti-HBs-negative) (B1).
	2. General preventive measures include the followings: prevention of HBV/HCV transmission (A1), avoidance of alcohol abuse, and control of metabolic disorders such as obesity and diabetes (C1).
	3. Antiviral therapy as secondary prevention of HCC should follow the KASL guidelines for the management of chronic hepatitis B/C (A1).
	4. Antiviral therapy should be considered after curative treatment for chronic viral hepatitis-related HCC in order to reduce the risk of recurrence (B1).
Diagnosis	1. HCC is diagnosed on the basis of either pathology or clinical criteria in case of the high-risk group (HBV/HCV positive or cirrhosis) (A1).
	2. When HCC is suspected during surveillance in the high-risk group, dynamic contrast-enhanced CT/MRI or liver-specific contrast-enhanced MRI should be performed for diagnosis (B1).
	3. In the high-risk group, HCC can be diagnosed for nodules ≥ 1 cm in diameter if one or two of the abovementioned imaging techniques show typical features of HCC (for the diagnosis of nodules 1-2 cm in diameter, two or more imaging modalities are required if a suboptimal imaging technique is used). Typical features of HCC include arterial phase enhancement with washout in the portal or delayed phase (B1).
	4. Nodules < 1 cm in diameter can be diagnosed as HCC in high-risk patients when all of the following conditions are met: typical features of HCC in two or more of the abovementioned imaging modalities and continuously rising serum α-fetoprotein with hepatitis activity under control (C1).
	5. Pathological diagnosis should be considered when the clinical criteria are not met or typical features of HCC are not present. The presence of indeterminate nodules despite imaging workup or pathologic examination needs to be followed up with repeated imaging and serum tumor marker analysis (B1).
	6. Limitation of radiation exposure in diagnosis and staging is not considered relevant in patients with HCC. CT is essential for diagnosis and follow-up in HCC patients (C1).
Staging	1. This guideline adopts the modified Union for International Cancer Control stages as a primary staging system, with the Barcelona Clinic Liver Cancer staging system serving as a complementary system (B1).
Surgical resection	1. Surgical resection is the first-line treatment for patients with intrahepatic single-nodular HCC and well-preserved liver function classified as Child-Pugh class A, without portal hypertension or hyperbilirubinemia (A1).
	2. Limited resection can be selectively applied to HCC patients with liver function of Child-Pugh class A or superb B and with mild portal hypertension or mild hyperbilirubinemia (C1).
	3. HCC resection can be considered in patients with three or fewer intrahepatic tumors without macrovascular invasion, if hepatic function is well preserved (C2).
	4. Laparoscopy-assisted resection can be considered for HCC located in the lateral section of the left lobe or in the anterolateral segment of the right lobe (B2).
Transplantation	1. Deceased donor liver transplantation is the first-line treatment for patients with single-nodular HCC < 5 cm in diameter or three or fewer nodules ≤ 3 cm in diameter (Milan criteria), which are not indicated for resection (A1).
	2. Locoregional therapies (local ablation or TACE) are recommended if the timing of transplantation is not predictable (B1).
	3. Downstaging (e.g., with TACE) can be considered for HCCs exceeding the criteria for transplantation (C2).
	4. Living donor liver transplantation is an effective alternative to deceased donor transplantation (B1).
	5. An expanded indication for transplantation beyond the Milan criteria can be considered in HCC cases without definitive vascular invasion or extrahepatic spread if other effective treatment options are inapplicable (C2).
	6. Salvage transplantation can be indicated for recurrent HCC after resection according to the same criteria as for first-line transplantation (B1).
Local ablation	1. RFA provides survival comparable to that of resection in patients with single-nodular HCCs ≤ 3 cm in diameter (A2).
	2. RFA is superior to PEIT in terms of anticancer effect and survival (A1). For HCCs ≤ 2 cm in diameter, PEIT can be considered if RFA is unfeasible, because the outcomes of both modalities are similar (A2).
	3. Survival outcome can be improved by combining TACE and RFA compared to RFA alone in patients with tumors 3-5 cm in diameter if resection is unfeasible (A2).
Transarterial chemoembolization and other transarterial treatments	1. TACE is recommended for patients with good performance status without major vascular invasion or extrahepatic spread who are ineligible for surgical resection, liver transplantation, RFA, or PEIT (A1).
	2. TACE should be performed through tumor-feeding vessels using selective/superselective techniques to maximize antitumor activity and minimize hepatic damage (B1).
	3. Chemoembolization using drug-eluting beads results in less systemic adverse events and has similar therapeutic efficacy compared with conventional TACE (B2).
	4. In case of portal vein invasion, TACE can be considered for patients with localized tumor and well-preserved liver function (B2).
External-beam radiation therapy	1. EBRT can be performed in HCC patients if liver functions are Child-Pugh class A or superb B and the irradiated total liver volume receiving ≥ 30 Gy is ≤ 60% (B1).
	2. EBRT can be considered for HCC patients ineligible for surgical resection, liver transplantation, RFA, PEIT, or TACE (C1).
	3. EBRT can be considered for HCC patients who exhibit incomplete response to TACE when the dose-volume criteria in Recommendation 1 are met (B2).
	4. EBRT can be considered for HCC patients with portal vein invasion when the dose-volume criteria in Recommendation 1 are met (C1).
	5. EBRT is performed to alleviate symptoms caused by primary HCC or its metastases (B1).
Systemic therapies	1. Sorafenib is indicated for HCC patients with very well-preserved liver function (Child-Pugh class A), good performance status, and regional lymph node or extrahepatic spread or for patients with tumor progression on other therapies (A1).
	2. Sorafenib is recommended for HCC patients with very well-preserved liver function (Child-Pugh class A), good performance status, and vascular invasion (A2).
	3. Sorafenib is considered for HCC patients with liver function Child-Pugh class superb B and good performance status if the above conditions 1 and 2 are satisfied (B1).
	4. Cytotoxic chemotherapy can be considered for HCC patients with advanced tumors who have with well-preserved liver function and, with good performance status, in whom sorafenib therapy has failed (C1).
	5. Adjuvant TACE, sorafenib, or cytotoxic chemotherapy are not recommended for HCC patients treated with curative resection (B1).
Preemptive antiviral therapy	1. Patients should be tested for the HBsAg before starting cytotoxic chemotherapy or immunosuppressive therapy (A1).
	2. Preemptive antiviral therapy is recommended for HBV carriers undergoing cytotoxic chemotherapy to prevent reactivation (A1). Preemptive antiviral therapy is considered for HBV-infected patients receiving TACE (B1), hepatic arterial infusion chemotherapy (C1), surgical resection (C1), or EBRT (C1) to prevent reactivation.
	3. Antiviral treatment for HBV reactivation should follow the recommendations of the current KASL guidelines (A1).
Drug treatment for cancer pain in HCC	1. Careful consideration is required for pain management with medication in patients with HCC and underlying liver disease. The dosage and dosing intervals of analgesics should be determined on the basis of liver functions (C1).
	2. In patients with HCC and chronic liver disease, the dosage of acetaminophen should be lowered (C1) and NSAIDs should be used with caution (B1).
	3. In patients with HCC and chronic liver disease, opioid analgesics and their dosage should be selected carefully on the basis of drug metabolism and liver function (C1).
Assessment of tumor response and posttreatment follow-up	1. Assessment of tumor response should follow both the RECIST and modified RECIST criteria (B1).
	2. Patients with complete response after treatment should be followed up with imaging studies (i.e., dynamic contrast-enhanced CT/MRI or liver-specific contrast-enhanced MRI) and serum tumor markers every 2-6 months in the first 2 years; thereafter, patients should be followed by regular checkups at individualized intervals (B1).

CT = computed tomography, EBRT = external-beam radiation therapy, HBsAg = hepatitis B surface antigen, HBV = hepatitis B virus, HCC = hepatocellular carcinoma, HCV = hepatitis C virus, KASL = Korean Association for the Study of the Liver, MRI = magnetic resonance imaging, NSAIDs = nonsteroidal anti-inflammatory drugs, PEIT = percutaneous ethanol injection therapy, RECIST = Response Evaluation Criteria in Solid Tumors, RFA = radiofrequency ablation, TACE = transarterial chemoembolization