History

Patients with hepatocellular carcinoma (HCC) generally present with signs and symptoms of advancing cirrhosis, as follows:

Pruritus
Jaundice
Splenomegaly
Variceal bleeding
Cachexia
Increasing abdominal girth (portal vein occlusion by thrombus with rapid development of ascites)
Hepatic encephalopathy
Right upper quadrant pain (uncommon)

Physical Examination

Physical examination findings may include the following:

Jaundice
Ascites
Hepatomegaly
Alcoholic stigmata (Dupuytren contracture, spider angiomata)
Asterixis
Pedal edema
Periumbilical collateral veins
Enlarged hemorrhoidal veins

Differential Diagnoses

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Media Gallery

Large hepatocellular carcinoma. Image courtesy of Arief Suriawinata, MD, Department of Pathology, Dartmouth Medical School.
Photomicrograph of a liver demonstrating hepatocellular carcinoma. Image courtesy of Arief Suriawinata, MD, Department of Pathology, Dartmouth Medical School.
MRI of a liver with hepatocellular carcinoma.
Ultrasonographic image of hepatocellular carcinoma.
Arterial phase CT scan demonstrating enhancement of hepatocellular carcinoma.
Portal venous phase CT scan demonstrating washout of hepatocellular carcinoma.
The Barcelona-Clinic Liver Cancer (BCLC) approach to hepatocellular carcinoma management. Adapted from Llovet JM, Fuster J, Bruix J, Barcelona-Clinic Liver Cancer Group. The Barcelona approach: diagnosis, staging, and treatment of hepatocellular carcinoma. Liver Transpl. Feb 2004;10(2 Suppl 1):S115-20.
Hepatocellular carcinoma: pathobiology.
Right hepatectomy. Part 1: Dissection of portal vein. Courtesy of Memorial Sloan-Kettering Cancer Center, featuring Leslie H. Blumgart, MD. (From Blumgart LH. Video Atlas: Liver, Biliary & Pancreatic Surgery. Philadelphia, PA: Saunders; 2010.)
Right hepatectomy. Part 2: Devascularization of right liver. Courtesy of Memorial Sloan-Kettering Cancer Center, featuring Leslie H. Blumgart, MD. (From Blumgart LH. Video Atlas: Liver, Biliary & Pancreatic Surgery. Philadelphia, PA: Saunders; 2010.)
Right hepatectomy. Part 3: Suturing and dividing. Courtesy of Memorial Sloan-Kettering Cancer Center, featuring Leslie H. Blumgart, MD. (From Blumgart LH. Video Atlas: Liver, Biliary & Pancreatic Surgery. Philadelphia, PA: Saunders; 2010.)
Hepatocellular carcinoma (HCC). Dilated collateral superficial abdominal veins in a 67-year-old man with cirrhosis, HCC, and portal vein occlusion.
Hepatocellular carcinoma. Plain radiograph immediately following chemoembolization, demonstrating catheter placement and Ethiodol enhancement of tumors.

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Table 2. Serum Alpha-Fetoprotein (AFP) Determination in Liver Disease ^[40]

Alpha-Fetoprotein (ng/mL)	Interpretation
> 400-500	- HCC likely if accompanied by space-occupying solid lesion(s) in cirrhotic liver or levels are rapidly increasing. - Diffusely growing HCC, may be difficult to detect on imaging. - Occasionally in patients with active liver disease (particularly HBV or HCV infection) reflecting inflammation, regeneration, or seroconversion
Normal value to < 400	- Frequent: Regeneration/inflammation (usually in patients with elevated transaminases and HCV) - Regeneration after partial hepatectomy - If a space-occupying lesion and transaminases are normal, suspicious for HCC
Normal value	Does not exclude HCC (cirrhotic and noncirrhotic liver)

Table 3. Patient Survival Rates Following Liver Transplantation for Hepatocellular Carcinoma

Author (Year)	N	Survival Rate
Author (Year)	N	1 year	5 years
Mazzefero (1996)	48	84%	74%
Bismuth (1999)	45	82%	74%
Llovet (1999)	79	86%	75%
Jonas (2001)	120	90%	71%

Table 4. Barcelona Clinic Liver Cancer staging

Stage	Criteria
0 – Very Early	Child-Pugh class A Single < 2 cm nodule ECOG PS 0-1
A – Early	Child-Pugh class A-B Single or 2-3 nodules < 3 cm ECOG PS 0-1
B – Intermediate	Child-Pugh class A-B Multinodular ECOG PS 0-1
C - Advanced	Child-Pugh class A-B Portal vein invasion, N1, M1 ECOG PS 0-2
D - Terminal	Child-Pugh class C Any T, N, or M ECOG PS > 2
ECOG PS = Eastern Cooperative Oncology Group Performance Status

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Author

Luca Cicalese, MD, FACS Professor of Surgery, John Sealy Distinguished Chair in Transplantation Surgery, Director, Texas Transplant Center and Hepatobiliary Surgery, Department of Surgery, University of Texas Medical Branch School of Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

John Geibel, MD, MSc, DSc, AGAF Vice Chair and Professor, Department of Surgery, Section of Gastrointestinal Medicine, Professor, Department of Cellular and Molecular Physiology, Yale University School of Medicine; Director of Surgical Research, Department of Surgery, Yale-New Haven Hospital; American Gastroenterological Association Fellow; Fellow of the Royal Society of Medicine

John Geibel, MD, MSc, DSc, AGAF is a member of the following medical societies: American Gastroenterological Association, American Physiological Society, American Society of Nephrology, Association for Academic Surgery, International Society of Nephrology, New York Academy of Sciences, Society for Surgery of the Alimentary Tract

Disclosure: Nothing to disclose.

Additional Contributors

Burt Cagir, MD, FACS Associate Regional Dean and Professor of Surgery, Geisinger Commonwealth School of Medicine; Director, General Surgery Residency Program, Executive Director, Donald Guthrie Foundation for Research and Education, Guthrie Robert Packer Hospital; Medical Director, Guthrie/RPH Skills and Simulation Lab; Associate in Surgery, Guthrie Robert Packer Hospital and Corning Hospital

Burt Cagir, MD, FACS is a member of the following medical societies: American College of Surgeons, Association of Program Directors in Surgery, Society for Surgery of the Alimentary Tract

Disclosure: Nothing to disclose.

Acknowledgements

David A Axelrod, MD, MBA Assistant Professor of Surgery, Section Chief, Solid Organ Transplantation, Dartmouth-Hitchcock Medical Center

David A Axelrod, MD, MBA is a member of the following medical societies: American College of Surgeons, American Society of Transplant Surgeons, and New Hampshire Medical Society

Disclosure: Nothing to disclose.

Dirk J van Leeuwen, MD, PhD Professor of Medicine, Dartmouth Medical School; Consulting Staff, Director of Hepatology, Associate Director, Hepatopancreatico-biliary Center, Dartmouth-Hitchcock Medical Center; Consulting Gastroenterologist, White River Junction Veterans Administration Medical Center

Dirk J van Leeuwen, MD, PhD is a member of the following medical societies: American Association for the Study of Liver Diseases, American Gastroenterological Association, Dutch Society of Gastroenterology/Enterology, Dutch Society of Hepatology, European Association for the Study of the Liver, and New Hampshire Medical Society

Disclosure: Nothing to disclose.