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HCV Genotype 3 and Fatty Liver

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Infection with Hepatitis C genotype 3 carries a greater chance of a fatty liver than other genotypes. Although this relationship is likely due to the strain’s molecular structure, successful treatment can erase this extra burden.

All of Hepatitis C’s genotypes are not created equally. Aside from differences in treatment response, one Hepatitis C strain carries a concern above and beyond damage from the virus itself. According to researchers, Hepatitis C genotype 3 (HCV3) is most likely to be accompanied by steatosis, or fatty liver.

Steatosis

As the most common liver disease in the United States, non-alcoholic fatty liver disease often accompanies Hepatitis C infection. Liver steatosis describes the accumulation of fat in liver cells. For those with Hepatitis C, steatosis is associated with more severe fibrosis progression.

Past studies have shown that various Hepatitis C virus (HCV) genotypes are associated with different forms of steatosis. In patients with genotype 1 and 4, steatosis is primarily due to metabolic factors such as obesity and diabetes. For those with genotype 3, the viral strain itself is suspected to cause fat accumulation in the liver cells.

The prevalence of steatosis is reported by a broad range of people, affecting anywhere from 34 to 81 percent of people with HCV. Variables predisposing someone with HCV to develop steatosis include:

  • Alcohol consumption
  • Obesity
  • Diabetes
  • Hyperlipidemia (high cholesterol)
  • Viral type

Genotype 3 Dominance

By pooling together various bodies of research collectively examining over 6,400 people with HCV, those infected with HCV3 have a much higher chance of developing steatosis. Some statistics relating hepatitis with steatosis include:

  • Overall, approximately 56 percent of those with HCV have steatosis.
  • Approximately 17 percent of those with autoimmune hepatitis have steatosis.
  • Approximately 27 percent of those with Hepatitis B have steatosis.
  • Approximately 48 percent of those with HCV of a genotype other than 3 have steatosis.
  • Approximately 74 percent of those with HCV3 have steatosis.

In the March 2004 issue of Gut, French researchers reported on the relationship between steatosis and HCV clearance after antiviral treatment. This study examined the liver biopsies before and after antiviral treatment of 151 participants. According to the authors:

  • Steatosis improvement was seen significantly more often in patients who achieved HCV clearance from treatment.
  • Among those who were successful in eliminating the virus with treatment, steatosis improvement occurred more often in those with HCV3 than those with other genotypes.
  • Among those who were not successful in eliminating the virus with treatment, steatosis improvement did not differ by genotype.

Also published in the March 2004 issue of Gut, an internationally-based group of researchers confirmed that Hepatitis C genotype affects steatosis. By analyzing data from 755 people with chronic HCV, the authors advised that those with HCV3 and diagnosed steatosis should receive antiviral treatment.

As published in the March 2004 issue of the Journal of Hepatology, researchers from Scripps Clinic reported on the impact of steatosis on liver disease progression and treatment response in patients with chronic Hepatitis C. The researchers evaluated liver biopsies from 574 patients, and found the following:

  • Steatosis severity was associated with body mass index, HCV3, older age and longer duration of infection.
  • Among those with genotype 3, higher HCV viral load was associated with more severe steatosis.
  • Steatosis improved markedly in genotype 3 patients who achieved viral clearance from treatment.

From a laboratory perspective, scientists agree about the association between HCV3 and liver steatosis. In an in vitro model published in the January 2007 issue of Gut, Hourioux and colleagues compared lipid levels in sections of cells producing genotype 1a or genotype 3 core proteins. They found that the cumulative lipid droplet area was significantly greater in cells producing genotype 3 core proteins; lending this strain more amenable to fat accumulation. Another study comparing HCV proteins found that the genotype 3a core protein induced significantly greater enzyme activity that is required for the development of hepatic steatosis.

To further understand this pathological difference between HCV genotypes, scientists have been closely examining each genotype’s molecular structure variances. One possible explanation may involve HCV3’s obstruction of the liver’s release of very low density lipoprotein (VLDL) particles to the bloodstream. This theory rests on the foundation that dietary fat becomes trapped in the liver of those with HCV3.

When cumulatively examined, the evidence supports the premise that Hepatitis C genotype 3 exerts a specific effect on the genesis of hepatic steatosis independent of metabolic risk factors such as obesity. Although linking steatosis to genotype 3, the evidence also shows that those with this strain who are successful with antiviral treatment have a greater chance of liver recovery. It is clearer now than ever that the divergence between HCV genotypes exert more disparities than previously thought, and is likely due to the virus’ molecular structure.

References:

C Hourioux, et al., The genotype 3-specific hepatitis C virus core protein residue phenylalanine 164 increases steatosis in an in vitro cellular model, Gut, January 2007.

Hissar SS, et al., Hepatitis C virus genotype 3 predominates in North and Central India and is associated with significant histopathologic liver disease, Journal of Medical Virology, April 2006.

http://clinicaloptions.com, Insulin Resistance and Hepatic Steatosis in Patients With Chronic Hepatitis C, Stephen A. Harrison, MD, LTC, MC, Clinical Care Options LLC, 2007.

J. Westin, et al., Impact of Hepatic Steatosis on Viral Kinetics and Treatment Outcome During Antiviral Treatment of Chronic HCV Infection, Journal of Viral Hepatology, March 2007.

Sharma, Pratina, et al., Hepatic Steatosis in Hepatitis C Virus Genotype 3 Infection: Does It Correlate with Body Mass Index, Fibrosis, and HCV Risk Factors?, Digestive Diseases and Sciences, October 2004.

www.hcvadvocate.org, Liver Steatosis, Liz Highleyman, Hepatitis Journal Review, March 2004.

www.hivandhepatitis.com, Liver Steatosis in Genotype 4 Patients Is Mainly Due to Metabolic Factors, Liz Highleyman, hivandhepatitis.com, 2007.

www.medscape.com, Hepatitis C and Steatosis: A Reappraisal, A. Lonardo, et al, Journal of Viral Hepatology, March 2006.

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