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HCV Genotype 3, Hispanic Ethnicity Linked to Higher Risk of Cirrhosis, Liver Cancer


People with hepatitis C virus (HCV) genotype 3 are more likely to progress to liver cirrhosis and hepatocellular carcinoma (HCC) compared to people with other genotypes, according to a recent report. A related study found that people of Hispanic/Latino ethnicity are also more likely to develop advanced liver disease.

HCV Genotype 3

As described in the July 2014 edition of Hepatology, Fasiha Kanwal and Hashem El-Serag from Michael E. DeBakey Veterans Affairs Medical Center and colleagues looked at the effect of HCV genotypes on risk of cirrhosis and HCC after adjusting for sex, race/ethnicity, age, and period of military service (World War I/II, Vietnam era, or post-Vietnam). They also looked at other factors that can potentially influence liver disease progression, including alcohol use, HIV, hepatitis B, and diabetes status, body mass index, and hepatitis C treatment history.

The researchers identified 110,484 patients with active HCV infection, confirmed by a positive HCV RNA PCR test, and a known HCV genotype from the Veterans Administration HCV Clinical Case Registry between 2000 and 2009. Most (79.9%) had HCV genotype 1, while 11.8% had genotype 2, 7.5% had genotype 3, and <1% had genotype 4.


  • Despite being younger, people with HCV genotype 3 had a higher risk of developing cirrhosis and HCC than those with genotype 1 (unadjusted hazard ratio [HR] 1.40 and 1.66, respectively).
  • After adjusting for demographic, clinical, and treatment factors, the risk of cirrhosis and HCC was 31% higher for people with HCV genotype 3 compared with genotype 1 (adjusted HR 1.31).
  • After adjusting for the same factors, the risk of HCC among people with genotype 3 was 80% higher compared with genotype 1 (adjusted HR 1.80).

"HCV genotype 3 is associated with a significantly increased risk of developing cirrhosis and HCC compared to HCV genotype 1," the study authors concluded. "This association is independent of patients' age, diabetes, body mass index, or antiviral treatment."


In the second study, described in the September 2014 American Journal of Gastroenterology, the same researcher team looked at racial/ethnic differences in progression to cirrhosis and HCC among people with hepatitis C.

Again, they searched data from the VAHCV Clinical Case Registry for patients with confirmed detectable HCV RNA between 2000 and 2009 who had at least 1 year of follow-up, and identified cases of cirrhosis and HCC through early 2010.

In this analysis there were 149,407 patients with active HCV viremia, of whom 56.3% were non-Hispanic white, 36.1% were African-American, 6.0% were Hispanic, and 1.6% belonged to other racial/ethnic groups.


  • After an average follow-up period of 5.2 years, 13,099 patients had a recorded diagnosis of cirrhosis and 3551 had HCC.
  • Hispanic patients had the highest annual incidence rates of cirrhosis and HCC, 28.8% and 7.8% (or 28.8 and 7.8 per 100 person-years), respectively.
  • African-Americans had the lowest progression rates, at 13.3% and 3.9%, respectively.
  • Non-Hispanic white patients had intermediate progression rates, at 21.6% and 4.7%, respectively.
  • Hispanic, black, and white patients differed with regard to several factors associated with liver disease progression:

o   HIV coinfection: 6.0%, 2.5%, and 2.1%, respectively;

o   HCV genotype 1: 64.2%, 50.6%, and 50.0%, respectively;

o   Obesity: 30.9%, 25.4%, and 28.0%, respectively;

o   Diabetes: 16.1%, 16.1%, and 8.7%, respectively;

o   Lack of hepatitis C treatment: 82.1%, 89.6%, and 81.1%, respectively).

  • However, the magnitude and direction of the race/ethnicity effect remained the same after adjusting for differences in demographic and clinical factors.
  • Hispanic patients had a higher risk of having diagnosed cirrhosis and HCC compared with whites (adjusted HR 1.28 and 1.61, respectively, or 28% and 61% higher risk).
  • In contrast, African-Americans had a lower risk of cirrhosis and HCC compared with whites (adjusted HR 0.58 and 0.77, respectively, or 42% and 23% reduction in risk).

"Hispanics with HCV are at a significantly higher risk, whereas AAs are at a considerably lower risk of developing cirrhosis and HCC than are [non-Hispanic whites]," the researchers concluded. "These associations persisted even after adjusting for a range of factors including HCV genotype, HCV treatment, diabetes, and body mass index."



 F Kanwal, JR Kramer, J Ilyas, et al. HCV Genotype 3 Is Associated with an Increased Risk of Cirrhosis and Hepatocellular Cancer in a National Sample of U.S. Veterans with HCV. Hepatology 60(1):98-105. July 2014.

H El Serag, J Kramer, F Kanwal. Racial Differences in the Progression to Cirrhosis and Hepatocellular Carcinoma in HCV-Infected Veterans. American Journal of Gastroenterology 109(9):1427-1435. September 2014.