Epidemiology and natural history of hepatitis C virus infection

Table 1 Seroprevalence of antibodies against hepatitis C virus in community-based studies

Study site	Study period	Study population	Population size	% with HCV antibody	% with positive HCV RNA among anti-HCV seropositives
America
United States[7]	1988-1994	National Health and Nutrition Examination Survey, subjects aged ≥ 6 yr	21241	1.8	73.9
Puerto Rico[15]	2001-2002	Individuals aged 21-64 yr residing in the municipality of San Juan	964	6.3	Not done
Europe
Greece[11]	1997-1998	Individuals over 15 yr in south western Greece	1500	0.5	Not done
Norway[9]	2000-2001	A subset of Oslo Health Study, subjects older than 30 yr	11456	0.7	79.5
France[10]	1994	Individuals aged 20-59 undergoing routine medical checkup in social security medical centers	6283	1.2	81.0
Spain[16]	1997-1998	Random sample of all ages in northern Spain	1170	1.6	63.0
Italy[12]	1996	Individuals of all ages which representative to southern Italy	1352	12.6	84.7
Asia
India[8]	1999	Individuals of all ages living in rural area and engaged in agriculture-related occupations	2973	0.9	80.8
China[18]	1992	Individuals aged 1-59 yr in 30 provinces	68000	3.2	Not done
Taiwan[17]	1991-1992	Males aged 30-65 yr participated a cancer screening project	11904	4.9	Not done
Japan[14]	1984-1995	Residents aged 20-89 yr in southern Miyazaki Prefecture	973	23	Not done
Africa
Egypt[13]	1997	Adults and children aged older than 10 yr residing in Nile Delta	3999	24.3	Non done

HCV: Hepatitis C virus.

Table 2 Follow-up studies to evaluate liver-related morbidities and mortality associated with hepatitis C virus infection

Ref.	Study population	Mean follow-up (yr)	Identification of infection	Liver-related disease		Mortality		Comments
				LC	HCC	All-cause	Liver-related
Tong et al[42], 1995United States	213 patients	3.9	Patients recalled the time of transfusion	51.1%	5.3%	15.3%	14.5%	Most participants had symptoms
								Patients from tertiary care center with a history of transfusion
								Recall bias
Seeff et al[38], 2001United States	222 patients	25	Time of transfusion			67.1%	4.1%	70% were males
Wiese et al[44], 2005Germany	683 CHC women	25	Vaccinated in 1978-1979	1.3%	0.1%			Relatively young and healthy
								CHC defined as HCV RNA (+)
Kenny-Walsh[37], 1999Ireland	376 CHC women	17	Vaccinated in 1977-1978	2%				Relatively young and healthy
								CHC defined as HCV RNA (+)
Thomas et al[41], 2000United States	1667 drug abusers	8.8	First injection use	ESLD incidence:3101				1/3 with HIV (+)
								Recall bias
Tanaka et al[40], 2004Japan	1927 blood donors	8.3	Unknown		3341			Participants from Osaka Red Cross Blood Center
								relatively healthy
Suruki et al[39], 2006Japan	667 CHC adults	7.9	Unknown		9831			Community-based
								CHC defined by at least 1 HCV RNA/core antigen result
								70% participants of age older than 60 yr
								Serial tests for serum ALT
Uto et al[43], 2009Japan	1125 adults	8.2	Unknown			25001		Community-based
								Tested for HCV RNA/core antigen

¹Per 100000 person-year. LC: Liver cirrhosis; HCC: Hepatocellular carcinoma; CHC: Chronic hepatitis C.

Table 3 Serum levels of hepatitis C virus RNA and liver-related diseases

Ref.	Study population	Study design	Serum RNA measurements	Findings	Comments
Naito et al[50]	22 HCV carriers with detectable RNA and persistently normal serum ALT levels in Japan	Cross-sectional	Competitive RT-PCR	Serum viral load were correlated with HAI score (r = 0.68, P < 0.01)	Limited number of study participants
					Temporality
					No control for confounders
De Moliner et al[45]	96 patients without antiviral treatments in Italy	Cross-sectional	First-generation bDNA assay (QuantiplexTM HCV RNA 1.0)	Serum viral load was not correlated with liver histological diagnosis (r = 0.58)	Temporality
					No control for confounders
Fanning et al[47]	77 women infected HCV genotype 1b through vaccination in Ireland	Cross-sectional	RT-PCR	Serum viral load was weakly (r = 0.26, P < 0.05) correlated with HAI score	Temporality
				Not correlated with the degree of fibrosis (r = 0.22, P > 0.05)	Homogeneous participants with defined source of infection and the same duration of infection
Lagging et al[48]	98 patients without antiviral treatments in Sweden	Cross-sectional	RT-PCR with Cobas Amplicor HCV monitor test	Serum viral load was not associated with the degree of inflammation or fibrosis	Temporality
Hisada et al[51]	385 drug users with detectable HCV RNA in United States	Case-cohort	Third-generation of bDNA assay (QuantiplexTM HCV RNA 3.0)	Elevated serum levels of HCV RNA increased the risk of ESLD death (relative hazard = 2.3 per log10 IU/mL, 95%CI: 1.5-5.9)	Coinfected with HIV or HTLV-II
					Large population with eight yr of follow-up

RT-PCR: Reverse-transcription polymerase chain reaction; HAI: Histological activity index; HCV: Hepatitis C virus; ESLD: End-stage liver disease; HTLV: Human T lymphotropic virus; HIV: Human immunodeficiency virus.

Table 4 Hepatitis C virus genotypes and liver-related diseases

Ref.	Study population	Study design	HCV genotypes determination	Findings	Comments
Martinot-Peignoux et al[53]	1872 HCV infected patients from 14 tertiary referral centers in France	Cross-sectional	Reverse hybridization with line probe assay (LiPA)	LC in genotype 1b and 4 (13% and 13%) were found more frequently than in genotype 1a, 2, or 3 (8%, 9%, and 7%), P = 0.03	Clinical patients
					temporality
					Only proportions provided, not control for other confounders
Silini et al[57]	162 LC and 162 HCC cases in Italy	Case-control	Polymerase chain reaction	Genotype 1b vs others: OR = 1.7 (1.1-2.9)	Clinical patients
					Temporality
					Matched with age, gender, child’s class
Kobayashi et al[56]	140 untreated CHC patients in Japan	Retrospective follow-up	Enzyme-linked immunosorbent assay	Deterioration of the stage of liver histology:Genotype 1, 63%Genotype 2, 39%P < 0.05	Clinical patients
					Only proportions calculated and time not taken into analytical consideration
Fattovich et al[55]	292 biopsy-proven LC patients form 7 referral centers in Europe	Prospective follow-up	Nested polymerase chain reaction	HCC risk	Clinical patients and more than 1/2 were treated with interferon
				Genotype 1b vs others
				HR = 1.0 (0.5-2.3)
Bruno et al[54]	163 liver cirrhosis patients in Italy	Prospective follow-up	INNO-LiPA HCV II (Bayer Corp., Tarrytown, NY)	HCC risk	Interferon treated patients
				Genotype 1b vs 2a/c	Incidence of HCC calculated
				HR = 3.0 (1.4-6.5)

CHC: Chronic hepatitis C; LC: Liver cirrhosis; HCC: Hepatocellular carcinoma; OR: Odds ratio; HR: Hazard ratio.