Pathogenesis and significance of hepatitis C virus steatosis: An update on survival strategy of a successful pathogen

Table 3 Steatosis is associated with increased hepatocellular carcinoma risk

Method and findings	Conclusion	Ref.
1818 patients with histologically proven CHC treated with IFN Cumulative incidence and HCC risk were analyzed over a mean follow-up period of 6.1 yr HCC developed in 179 study subjects	Severe steatosis, is an independent factor significantly associated with HCC	[112]
The 5-yr occurrence rate of HCC in 353 consecutive patients with histologically proven HCV cirrhosis and persistent viral replication prospectively followed and screened for HCC was 34% in genotype 3 and 17% in non-3 genotype group	For patients with HCV cirrhosis and ongoing infection, infection with genotype 3 (a potent steatogenic virus) is independently associated with an increased risk of HCC development	[113]
The steatohepatitis-HCC variant was found in 35.5% of 62 HCC cases In 14 of the 22 cases (63.6%) of SH-HCC, the non-neoplastic liver showed changes of NAFLD/NASH superimposed on otherwise typical features of HCV-C	This study suggests a possible NAFLD/NASH pathway leading to SH-HCC in the setting of HCV-C	[114]
This retrospective study investigated the features of 5 patients who developed HCC after 10 yr of achieving SVR	In 3 patients, liver tissues were obtained at the treatment of HCC. These tissues showed marked improvement in both activities and fibroses, but severe steatosis in 1 patient	[115]
Two-hundred and sixty-six patients, who achieved SVR, were enrolled in this retrospective study	Age, hepatic fibrosis, and hepatic steatosis at pre-interferon treatment might be risk factors for developing HCC after SVR	[116]
A retrospective study was conducted in 88 patients undergoing curative resection of HCV-associated HCC	Hepatic steatosis is a useful predictor of postoperative recurrence of HCV-related HCC	[117]
94 consecutive patients with cirrhosis due to HCV who underwent liver transplantation and had pathology available for review were retrospectively identified	In patients with HCV-related cirrhosis, the presence of hepatic steatosis is independently associated with the development of HCC	[118]
The histological severity of steatosis in the index liver biopsies of 25 patients with chronic hepatitis C who subsequently developed HCC was compared with matched controls who did not. As determined by percentage area of biopsy core occupied by steatosis on computer assisted morphometric evaluation, and graded semiquantitatively, steatosis was comparable among cases and controls	The odds of developing HCC among those with steatosis grades 1 and 2 did not differ significantly from those without steatosis. There was no association between increasing morphometric percentage area occupied by steatosis and the subsequent development of HCC. Neither steatosis grade or percent area of steatosis on biopsy were selected in multivariate regression analysis as independent predictors for the development of HCC	[119]
161 patients with chronic HCV infection	At multivariate analysis hepatic steatosis, (together with aging, cirrhosis, and no IFN treatment) was an independent, significant risk factor for HCC	[120]

CHC: Chronic hepatitis C; IFN: Interferon; SH-HCC: Steatohepatitis-hepatocellular carcinoma (HCC); SVR: Sustained virologic response; HCV: Hepatitis C virus.