Last updated: April 11, 2022
Hepatocellular carcinoma (HCC) is the most common primary liver malignancy in adults and one of the leading causes of cancer-related mortality worldwide. It primarily affects patients with preexisting liver disease (e.g., liver cirrhosis, chronic hepatitis) and often manifests as a solitary tumor. HCC is commonly asymptomatic in the early stage. Patients typically present with features of the underlying liver disease (e.g., ascites, jaundice). Advanced HCC can manifest with nonspecific features of abdominal pain, weight loss, and anorexia. Regular (6-monthly) surveillance with abdominal ultrasound, with or without serum AFP levels, is recommended for individuals at risk of developing HCC. If screening is suggestive of HCC (i..e, liver lesion ≥10 mm or AFP ≥ 20 ng/mL), the diagnosis should be confirmed with multiphase imaging and, if needed, a liver biopsy. Management is based on tumor burden, the patient's performance status, and the severity of liver dysfunction. Potentially curative treatment options include tumor resection, liver transplantation, and ablative therapy, most commonly radiofrequency ablation (RFA). Patients with advanced tumors may be treated with noncurative locoregional therapy (LRT) such as transarterial chemoembolization (TACE), or systemic chemotherapy. As HCC mostly occurs in patients with advanced underlying liver disease, the prognosis is generally poor.
Epidemiological data refers to the US, unless otherwise specified.
- Usually asymptomatic apart from symptoms of the underlying disease (mostly cirrhosis or hepatitis)
Possible symptoms of advanced disease
HCC may be detected via screening for HCC in at-risk groups (e.g., patients with known cirrhosis) or after symptoms develop.
- Initial diagnostics
- Ultrasound abdomen (preferred initial imaging modality in most cases)
- Consider serum AFP levels to increase detection rate.
Perform further imaging (typically multiphase imaging e.g., CT or MRI abdomen) if the following are detected:
- Lesion ≥10 mm
- Lesion of any size and AFP (if performed) ≥ 20 ng/mL
Perform a liver biopsy in the following cases:
Laboratory studies: to evaluate liver function and assess for underlying etiologies
- Confirmed HCC diagnosis: Perform further studies for staging of HCC.
A liver biopsy is not routinely required to confirm the diagnosis in patients with underlying liver disease and characteristic imaging findings of HCC. 
Ultrasound is typically the primary screening modality, but diagnostic confirmation requires imaging multiphase imaging using intravenous contrast.
- Initial evaluation for suspected HCC
- Screening in high-risk patients
- May be used to investigate focal lesions found on noncontrast CT or MRI
Any hepatic lesion in a patient with cirrhosis should be considered suspicious for a primary liver tumor.
Ultrasound features of HCC
- Serum AFP ≥ 20 ng/mL
Alternative initial screening modality in select patients (e.g., if the liver cannot be assessed appropriately by ultrasound because of habitus)
Findings: a lesion(s) with irregular borders and possible signs of local invasion ; 
- Without contrast
- With IV contrast
- Arterial phase hyperenhancement
- Nonperipheral washout
- Enhancing capsule
A hypodense or isodense lesion with arterial phase hyperenhancement followed by portal venous phase washout is characteristic of HCC. 
All multiphase image findings for suspected HCC are graded using the Liver Imaging Reporting and Data System to help standardize diagnostic criteria and improve data collection on treatment outcomes by imaging stage.
- See “Pathology” section.
Immunostaining can be considered for inconclusive or uncharacteristic findings.
False negatives with biopsy are possible as a result of the similarities between the early changes of HCC and dysplastic nodules or from insufficient tissue being obtained; if clinical suspicion remains high, repeat the biopsy or ensure regular surveillance of the lesion. 
| Barcelona Clinic Liver Cancer (BCLC) Staging System 
|BCLC Stage ||Criteria |
| Very early hepatocellular carcinoma (Stage 0) ||
| Early-stage hepatocellular carcinoma (Stage A) || |
- Single tumor > 2 cm or 2 to 3 tumors ≤ 3 cm
- AND Child–Pugh A or B
- AND ECOG PS 0–1
| Intermediate stage hepatocellular carcinoma (Stage B) || |
> 3 tumors OR 2–3 tumors, any > 3 cm in size
- AND Child–Pugh A or B
- AND ECOG PS 0–1
| Advanced stage hepatocellular carcinoma (Stage C) ||
| End-stage hepatocellular carcinoma (Stage D) ||
Patients with advanced liver disease (Child-Pugh class C) or a poor ECOG performance status are always classified as having end-stage HCC, regardless of tumor burden.
- Refer the patient to specialist multidisciplinary team.
- Initiate treatment based on stage of hepatocellular carcinoma.
- Prevent further deterioration of any associated liver disease:
Despite high recurrence rates following surgical, ablative, and locoregional therapies, adjuvant treatment is not routinely recommended as it has not been shown to be effective. 
Patients should additionally undergo treatment of underlying etiologies e.g., antiviral therapy for hepatitis C infection.
Indication: resectable, early-stage HCC in patients with minimal concomitant liver disease
Technique: open or laparoscopic tumor resection
Resection is the first-line treatment option for patients with very early and early-stage HCC and good liver function.
Early stage HCC with significant concomitant liver disease
- AND tumor(s) meet Milan criteria (a set of criteria used to assess HCC patients for transplant) 
- 1 tumor measuring ≥ 2 cm and ≤ 5 cm
- OR 2–3 tumors measuring ≥ 1 cm and ≤ 3 cm
Bridge to transplant: Consider using ablative therapy or locoregional therapy to prevent tumor progression beyond the Milan criteria.
Recurrence risk 
11–18%; most commonly extrahepatic
- Monitor with abdominal and chest CT (surveillance frequency and benefit is uncertain).
- Up to 70% after 5 years
- Assess with multiphase imaging every 3 months for ≥ 1 year, then at least every 6 months 
Locoregional therapy 
Transarterial chemoembolization (TACE): catheter-directed localized application of a chemotherapeutic and an embolic agent
Transarterial radioembolization (TARE): catheter-directed selective irradiation via the injection of radioactive spheres into the tumor-feeding artery
Malignant liver tumors 
Metastatic liver disease 
- Often asymptomatic
- Can manifest with nonspecific symptoms, such as malaise, anorexia, weight loss, jaundice, ascites
- Features of the underlying primary may be present.
- Management depends on extent of disease, the underlying malignancy, and patient performance status.
- Options include:
Hepatic angiosarcoma 
Epidemiology: rare (2% of primary hepatic malignancies) 
Etiology: associated with exposure to vinyl chloride, arsenic, or thorium dioxide
- CT abdomen (with IV contrast)
- Variable appearance; single or multiple lesions, typically hypervascular
- Rapid growth on serial imaging
- Histology: endothelial cells positive for PECAM-1 (CD31)
- Surgical resection; adjuvant therapy may be considered
TACE may be beneficial in patients manifesting with acute hemorrhage.
Complications: rupture with intraabdominal hemorrhage
- Poor (∼ 6 months)
- Often metastatic at time of diagnosis, high recurrence rate
Primary hepatic lymphoma 
- Very rare 
- Typically occurs in the 5th decade with slight male preponderance 
Etiology: Risk factors include HIV, hepatitis B, hepatitis C, and chemical exposure.
Clinical features: nonspecific; abdominal pain, fatigue, anorexia, weight loss, jaundice, night sweats
- Usually performed as the initial imaging modality
- Appearance typically shows a hypoechoic lesion(s)
MRI or CT abdomen (with IV contrast) may show single or multiple lesions, or diffuse infiltration.
- Diagnostic confirmation: liver biopsy
Treatment: surgery when possible, followed by chemotherapy
See “Benign liver tumors and hepatic cysts” for details.
Liver lesions are most often benign, even in patients with preexisting malignancies. 
The differential diagnoses listed here are not exhaustive.
We list the most important complications. The selection is not exhaustive.
5-year survival rate of early-stage HCC: > 70% 
5-year survival rate for advanced HCC: ∼20% (median survival ∼1–1.5 years) 
Cirrhosis from any cause
Chronic hepatitis B
- With active infection
- With a family history of HCC
- In Asian men > 40 years of age or Asian women > 50 years of age
- African individuals ≥ 20 years (not applicable for US-born African-Americans)
Patients at high-risk for HCC are advised to attend regular screenings every 6 months.
Patients with Child-Pugh class C cirrhosis should only undergo screening if they are on the transplant waiting list as life expectancy in decompensated liver cirrhosis is limited.
Screening modalities and intervals
- Abdominal ultrasound is the preferred screening modality.
- Screening intervals depend on imaging findings.
- No lesion: Repeat US in 6 months.
- Lesion < 10 mm: Repeat US in 3–6 months. 
- Lesion ≥ 10 mm: Perform further imaging (typically multiphase imaging).
- Consider measuring serum AFP level: perform multiphase imaging if AFP ≥ 20 ng/mL in a patient with a liver lesion of any size 
Concerning features for malignancy (i.e., liver lesion ≥ 10 mm or AFP ≥ 20 ng/mL) should be evaluated further by multiphase imaging (see “Diagnostics of HCC” for details).
Llovet JM, Kelley RK, Villanueva A, et al. Hepatocellular carcinoma. Nature Reviews Disease Primers. 2021; 7
doi: 10.1038/s41572-020-00240-3 . | Open in Read by QxMD
Brar G, Greten TF, Graubard BI, et al. Hepatocellular Carcinoma Survival by Etiology: A SEER‐Medicare Database Analysis. Hepatology Communications. 2020; 4
doi: 10.1002/hep4.1564 . | Open in Read by QxMD
Hassanipour S, Vali M, Gaffari-Fam S, et al. The survival rate of hepatocellular carcinoma in Asian countries: a systematic review and meta-analysis. EXCLI journal. 2020; 19
doi: 10.17179/excli2019-1842 . | Open in Read by QxMD
Galle PR, Forner A, Llovet JM, et al. EASL Clinical Practice Guidelines: Management of hepatocellular carcinoma. J Hepatol. 2018; 69
doi: 10.1016/j.jhep.2018.03.019 . | Open in Read by QxMD
Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nature Reviews Gastroenterology & Hepatology. 2019; 16
doi: 10.1038/s41575-019-0186-y . | Open in Read by QxMD
Marrero JA, Kulik L, et al. Diagnosis, Staging, and Management of Hepatocellular Carcinoma: 2018 Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2018
doi: 10.1002/hep.29913 . | Open in Read by QxMD
Kanwal F, Singal AG. Surveillance for Hepatocellular Carcinoma: Current Best Practice and Future Direction. Gastroenterology. 2019; 157
doi: 10.1053/j.gastro.2019.02.049 . | Open in Read by QxMD
McGlynn KA, Petrick JL, London WT. Global epidemiology of hepatocellular carcinoma: an emphasis on demographic and regional variability. Clin Liver Dis. 2015; 19
doi: 10.1016/j.cld.2015.01.001 . | Open in Read by QxMD
Global Burden of Disease Liver Cancer Collaboration., Akinyemiju T, Abera S, et al. The Burden of Primary Liver Cancer and Underlying Etiologies From 1990 to 2015 at the Global, Regional, and National Level: Results From the Global Burden of Disease Study 2015.. JAMA oncology. 2017; 3
doi: 10.1001/jamaoncol.2017.3055 . | Open in Read by QxMD
Mak LY, Cruz-Ramón V, Chinchilla-López P, et al. Global Epidemiology, Prevention, and Management of Hepatocellular Carcinoma. American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting. 2018; 38
doi: 10.1200/EDBK_200939 . | Open in Read by QxMD
Kasper DL, Fauci AS, Hauser SL, Longo DL, Lameson JL, Loscalzo J. Harrison's Principles of Internal Medicine.
Heimbach JK, Kulik LM, Finn RS, et al. AASLD guidelines for the treatment of hepatocellular carcinoma. Hepatology. 2017; 67
doi: 10.1002/hep.29086 . | Open in Read by QxMD
Marrero JA, Ahn J, Reddy RK. ACG Clinical Guideline: The Diagnosis and Management of Focal Liver Lesions. Am J Gastroenterol. 2014; 109
doi: 10.1038/ajg.2014.213 . | Open in Read by QxMD
Chernyak V, Horowitz JM, Kamel IR, et al. ACR Appropriateness Criteria® Liver Lesion-Initial Characterization. J Am Coll Radiol. 2020; 17
doi: 10.1016/j.jacr.2020.09.005 . | Open in Read by QxMD
Chernyak V, Fowler KJ, Kamaya A, et al. Liver Imaging Reporting and Data System (LI-RADS) Version 2018: Imaging of Hepatocellular Carcinoma in At-Risk Patients. Radiology. 2018; 289
doi: 10.1148/radiol.2018181494 . | Open in Read by QxMD
Arslanoglu A, Seyal AR, Sodagari F, et al. Current Guidelines for the Diagnosis and Management of Hepatocellular Carcinoma: A Comparative Review. AJR Am J Roentgenol. 2016; 207
doi: 10.2214/ajr.15.15490 . | Open in Read by QxMD
Shah S, Shukla A, Paunipagar B. Radiological Features of Hepatocellular Carcinoma. J Clin Exp Hepatol. 2014; 4
doi: 10.1016/j.jceh.2014.06.009 . | Open in Read by QxMD
Kwo PY, Cohen SM, Lim JK. ACG Clinical Guideline: Evaluation of Abnormal Liver Chemistries. Am J Gastroenterol. 2017; 112
doi: 10.1038/ajg.2016.517 . | Open in Read by QxMD
Kim SR, Kim HJ, Kim YJ. The role of alpha-fetoprotein (AFP) in monitoring of treatment and prediction of survival in patients with hepatocellular carcinoma (HCC). J Clin Oncol. 2005; 23
doi: 10.1200/jco.2005.23.16_suppl.4190 . | Open in Read by QxMD
Kew MC. Paraneoplastic Phenomena in Patients with Hepatocellular Carcinoma. JLRDT. 2016; 2
doi: 10.15406/jlrdt.2016.02.00017 . | Open in Read by QxMD
Bruix J, Reig M, Sherman M. Evidence-Based Diagnosis, Staging, and Treatment of Patients With Hepatocellular Carcinoma. Gastroenterology. 2016; 150
doi: 10.1053/j.gastro.2015.12.041 . | Open in Read by QxMD
Duseja A. Staging of Hepatocellular Carcinoma. J Clin Exp Hepatol. 2014; 4
doi: 10.1016/j.jceh.2014.03.045 . | Open in Read by QxMD
Hennedige T, Venkatesh SK. Imaging of hepatocellular carcinoma: diagnosis, staging and treatment monitoring. Cancer Imaging. 2012; 12
doi: 10.1102/1470-7330.2012.0044 . | Open in Read by QxMD
Reig M, Forner A, Rimola J, et al. BCLC strategy for prognosis prediction and treatment recommendation: The 2022 update. J Hepatol. 2022; 76
doi: 10.1016/j.jhep.2021.11.018 . | Open in Read by QxMD
Tsilimigras DI, Brodt P, Clavien PA, et al. Liver metastases. Nat Rev Dis Primers. 2021; 7
doi: 10.1038/s41572-021-00261-6 . | Open in Read by QxMD
Kaur H, Hindman NM, Al-Refaie WB, et al. ACR Appropriateness Criteria® Suspected Liver Metastases. J Am Coll Radiol. 2017; 14
doi: 10.1016/j.jacr.2017.01.037 . | Open in Read by QxMD
Sica GT, Ji H, Ros PR. CT and MR Imaging of Hepatic Metastases. Am J Roentgenol. 2000; 174
doi: 10.2214/ajr.174.3.1740691 . | Open in Read by QxMD
Massarweh NN, El-Serag HB. Epidemiology of Hepatocellular Carcinoma and Intrahepatic Cholangiocarcinoma. Cancer Control. 2017; 24
doi: 10.1177/1073274817729245 . | Open in Read by QxMD
Joo I, Lee JM, Yoon JH. Imaging Diagnosis of Intrahepatic and Perihilar Cholangiocarcinoma: Recent Advances and Challenges. Radiology. 2018; 288
doi: 10.1148/radiol.2018171187 . | Open in Read by QxMD
Amjad W, Nassar Y, Saade R, Batool A. S2508 Primary Hepatic Angiosarcoma Presenting as Decompensated Cirrhosis. Am J Gastroenterol. 2020; 115
doi: 10.14309/01.ajg.0000712080.70398.a8 . | Open in Read by QxMD
Flabouris K, McKeen S, Chaves Gomes D, Chaudhuri D, Russell P. Hepatic angiosarcoma: Pitfalls in establishing a diagnosis. SAGE open medical case reports. 2021; 9
doi: 10.1177/2050313X211046726 . | Open in Read by QxMD
Molina E, Hernandez A. Clinical manifestations of primary hepatic angiosarcoma. Dig Dis Sci. 2003; 48
doi: 10.1023/a:1022868221670 . | Open in Read by QxMD
Chien C-Y, Hwang C, Yeh C, et al. Liver angiosarcoma, a rare liver malignancy, presented with intraabdominal bleeding due to rupture- a case report. World J Surg Oncol. 2012; 10
doi: 10.1186/1477-7819-10-23 . | Open in Read by QxMD
Ugurluer G, Miller RC, Li Y, et al. Primary Hepatic Lymphoma: A Retrospective, Multicenter Rare Cancer Network Study. Rare Tumors. 2016; 8
doi: 10.4081/rt.2016.6502 . | Open in Read by QxMD
Zentar A, Tarchouli M, Elkaoui H, et al. Primary hepatic lymphoma. J Gastrointest Cancer. 2014; 45
doi: 10.1007/s12029-013-9505-7 . | Open in Read by QxMD
Shirai D, Shinkawa H, Takemura S, et al. Impact of alcohol abstinence on survival after hepatic resection for hepatocellular carcinoma in patients with alcohol-related liver disease. Ann Med Surg. 2021; 68
doi: 10.1016/j.amsu.2021.102644 . | Open in Read by QxMD
Balogh J, Victor D, Asham EH, et al. Hepatocellular carcinoma: a review. J Hepatocell Carcinoma. 2016; Volume 3
doi: 10.2147/jhc.s61146 . | Open in Read by QxMD
Villanueva A. Hepatocellular Carcinoma. N Engl J Med. 2019; 380
doi: 10.1056/nejmra1713263 . | Open in Read by QxMD
Lingiah VA, Niazi M, Olivo R, Paterno F, Guarrera JV, Pyrsopoulos NT. Liver Transplantation Beyond Milan Criteria. J Clin Transl Hepatol. 2020; 8
doi: 10.14218/jcth.2019.00050 . | Open in Read by QxMD
El-Serag HB. Hepatocellular Carcinoma. N Engl J Med. 2011; 365
doi: 10.1056/nejmra1001683 . | Open in Read by QxMD
Makary MS, Khandpur U, Cloyd JM, Mumtaz K, Dowell JD. Locoregional Therapy Approaches for Hepatocellular Carcinoma: Recent Advances and Management Strategies. Cancers (Basel). 2020; 12
doi: 10.3390/cancers12071914 . | Open in Read by QxMD
Gbolahan OB, Schacht MA, Beckley EW, LaRoche TP, O’Neil BH, Pyko M. Locoregional and systemic therapy for hepatocellular carcinoma. J Gastrointest Oncol. 2017; 8
doi: 10.21037/jgo.2017.03.13 . | Open in Read by QxMD
Gordan JD, Kennedy EB, Abou-Alfa GK, et al. Systemic Therapy for Advanced Hepatocellular Carcinoma: ASCO Guideline. J Clin Oncol. 2020; 38
doi: 10.1200/jco.20.02672 . | Open in Read by QxMD
Su GL, Altayar O, O’Shea R, et al. AGA Clinical Practice Guideline on Systemic Therapy for Hepatocellular Carcinoma. Gastroenterology. 2022; 162
doi: 10.1053/j.gastro.2021.12.276 . | Open in Read by QxMD