Surveillance for hepatocellular carcinoma in chronic liver disease: Evidence and controversies

Table 1 Characteristics and results of studies on risk of hepatocellular carcinoma in patients with autoimmune hepatitis,  1-antitrypsin deficiency and Wilson’s disease

Ref.	Study design	Study period	Patient No.	Duration follow-up	Results
Autoimmune hepatitis
Yeoman et al[110]	Prospective cohort study	1971-2007	243	median: 11 yr (range 1-36)	Annual HCC incidence: 1.1%
					HCC occurred more often in cirrhotic patients (9.3% vs 3.4%, P = 0.048)
Wang et al[111]	Prospective cohort study	Unknown	124	mean: 111	HCC incidence: 1 per 350 patient-year
				± 6 mo	HCC incidence in cirrhotics: 1 per 182 patient-year
Werner et al[112]	Retrospective cohort study	1990-2003	473	median: 8.8 yr (range 1-45)	23-fold increased HCC risk compared to the general population. Only HCC in cirrhotics
Wong et al[113]	Retrospective cohort study	1999-2009	322	mean: 6.25 yr	HCC incidence all patients: 459 per 100000 patient-year (0.5%/yr)
					In cirrhotics: 1920 per 100000 patient-year (1.9%/yr)
Park et al[114]	Retrospective cohort study	Unknown	212 (88 cirrhotics)	mean: 123	HCC incidence in cirrhotics: 1 per 1002 patient-year. (0.1%/yr)
				± 9 mo
Teufel et al[115]	Retrospective cohort study	1970-2009	278 (89 cirrhotics)	mean: 4.8 yr (in cirrhotic pts)	No HCC observed in 431 cirrhotic patient-year
α 1-antitrypsin deficiency
Eriksson et al[116]	Autopsy study	1963-1982	38250	NA	Increased HCC risk in patients with A1AD compared to controls. (OR = 20, 95%CI: 3.5-114.3)
			(17 pts with A1AD)
Elzouki et al[117]	Autopsy study	1963-1994	50333	NA	Increased HCC risk in patients with A1AD compared to controls (OR = 5.0, 95%CI: 1.6-15.8; P = 0.008). Only significant in males
			(31 pts with A1AD)
Propst et al[118]	Retrospective cohort study	1990-1992	Group 1: 240 cirrhotics with different etiologies (25% A1AD)	Unknown	No significant differences in HCC prevalence between cirrhotic A1AD patients and cirrhotic subjects due to other causes
			Group 2: 130 non-cirrhotic A1AD pts		No HCC in non-cirrhotic A1AD patients
Wilson’s disease
Walshe et al[119]	Retrospective cohort study	1955-1987 1987-2000 1966-2002	159	range: 10-45 yr	9 patients (6%) developed abdominal malignancies (2 × HCC). Higher incidence compared to the general population
Thattil et al[120]	Case report and review	No limitation	NA	NA	19 published case reports of HCC in patients with Wilson’s disease

HCC: Hepatocellular carcinoma; A1AD: α 1-antitrypsin deficiency; NA: Not applicable; pts: Patients.

Table 2 Comparison of recommendations regarding hepatocellular carcinoma surveillance in guidelines

Characteristics	AASLD guideline[19]	EASL guideline[20]	APASL guideline[21]
Recommended target population	Cirrhotic HBV and HCV patients	Cirrhotic patients with Child-Pugh stage A and B	Cirrhotic HBV and HCV patients
	Alcoholic cirrhosis	Cirrhotic patients with Child-Pugh stage C awaiting liver transplantation
	Stage 4 primary biliary cirrhosis	Non-cirrhotic HBV carriers with active hepatitis or family history of HCC
	Cirrhosis due to genetic hemochromatosis	Non-cirrhotic patients with chronic hepatitis C and advanced liver fibrosis F3
	Cirrhosis due to α 1-antitrypsin deficiency
	HBV carriers of Asian origin (male > 40 yr, female > 50 yr)
	African/North American Blacks with hepatitis B
	HBV carriers with family history of HCC
Surveillance benefit uncertain	HBV carriers younger than 40 (males) or
	50 (females)
	Hepatitis C and stage 3 fibrosis
	Non-cirrhotic NAFLD
Surveillance modality	US	US	US and AFP
Interval (mo)	6	6	6

AASLD: American Association for Study of Liver Disease; APASL: Asian Pacific Association for the Study of the Liver; HBV: Hepatitis B virus; HCV: Hepatitis C virus; NAFLD: Non-alcoholic fatty liver disease; US: Ultrasound, AFP: α-fetoprotein; HCC: Hepatocellular carcinoma; EASL: European Association for the Study of the Liver.