HCV and fat: Something is missing
Authors: Edoardo G. Giannini, Vincenzo Savarino
Journal: Journal of Hepatology (2008)

We read with interest the article by Dai and Colleagues [[1]Dai C.Y. Chuang W.L. Ho C.K. Hsieh M.Y. Huang J.F. Lee L.P. et al.Associations between hepatitis C viremia and low serum triglyceride and cholesterol levels: a community-based study.J Hepatol. 2008; 49: 9-16Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar] evaluating the association of virologic status with serum lipids in hepatitis C virus (HCV) antibody positive subjects. In their study carried out in 11,239 residents in an area endemic for both hepatitis B virus (HBV) and HCV infection, the authors observed that HCV viraemia seems to be associated with both low serum total cholesterol and triglyceride levels. Furthermore, they observed that anti-HCV subjects who were positive for HCV-RNA were more likely to be affected by diabetes as compared to HCV-RNA negative ones (odds ratio = 3.592). On the basis of their results they conclude that HCV itself might play a significant role on serum lipid profiles in these patients. Although we agree with the authors that, as recently reviewed, the biology of HCV is strictly entangled with lipid homeostasis [2André P. Perlemuter G. Budkowska A. Bréchot C. Lotteau V. Hepatitis C virus particles and lipoprotein metabolism.Semin Liver Dis. 2005; 25: 93-104Crossref PubMed Scopus (157) Google Scholar, 3Ye J. Reliance of host cholesterol metabolic pathways for the life cycle of hepatitis C virus.PLoS Pathog. 2007; 3: e108Crossref PubMed Scopus (116) Google Scholar], we also acknowledge the fact that other aspects not taken into account by the authors may be responsible for low lipid serum levels in patients with supposed liver disease. Indeed, it has been clearly shown that a statistically significant trend towards lower serum cholesterol levels exists among patients with cirrhosis, chronic hepatitis and controls [[4]Cicognani C. Malavolti M. Morselli-Labate A.M. Zamboni L. Sama C. Barbara L. Serum lipid and lipoprotein patterns in patients with liver cirrhosis and chronic active hepatitis.Arch Intern Med. 1997; 157: 792-796Crossref PubMed Google Scholar], that low serum cholesterol levels are independently associated with significant fibrosis in HCV patients [5Cozzolino G. Lonardo A. Francica G. Amendola F. Cacciatore L. Differential diagnosis between hepatic cirrhosis and chronic active hepatitis: specificity and sensitivity of physical and laboratory findings in a series from the Mediterranean area.Am J Gastroenterol. 1983; 78: 442-445PubMed Google Scholar, 6Forns X. Ampurdanès S. Llovet J.M. Aponte J. Quintó L. Martı´nez-Bauer E. et al.Identification of chronic hepatitis C patients without hepatic fibrosis by a simple predictive model.Hepatology. 2002; 36: 986-992Crossref PubMed Scopus (977) Google Scholar], and that a progressive decrease in serum cholesterol has prognostic value in patients with decompensated viral cirrhosis [[7]D’Arienzo A. Manguso F. Scaglione G. Vicinanza G. Bennato R. Mazzacca G. Prognostic value of progressive decrease in serum cholesterol in predicting survival in Child-Pugh C viral cirrhosis.Scand J Gastroenterol. 1998; 33: 1213-1218Crossref PubMed Scopus (54) Google Scholar]. Thus, what is missing in the study by Dai and colleagues is the clinical status of their HCV subjects, and whether patients who were HCV-RNA negative were spontaneously so, or the condition had been induced by previous anti-viral therapy. Furthermore, since in the study population HBV surface antigen positivity was independently associated with low serum lipid levels as well it is not clear why HBV-DNA status of the patients was not investigated. Thus, it is reasonable to hypothesise that the non-viraemic anti-HCV population included in the study was made up of “subjects”, while HCV-RNA positive subjects were actually patients. This hypothesis is emphasised by the fact that patients without elevated cholesterol levels were significantly more likely to have abnormal alanine aminotransferase, a counterintuitive phenomenon in an era of positive association between altered liver enzymes, dyslipidemia, and liver steatosis [[8]Greenfield V. Cheung O. Sanyal A.J. Recent advances in nonalcholic fatty liver disease.Curr Opin Gastroenterol. 2008; 24: 320-327Crossref PubMed Scopus (78) Google Scholar]. Finally, the independent association between diabetes and HCV-RNA positivity in the study population further strengthens this hypothesis, since patients with (advanced) liver disease – not only those infected by HCV – are more likely to be affected by diabetes [[9]Lonardo A. Carulli N. Loria P. HCV and diabetes. A two-question-based reappraisal.Dig Liver Dis. 2007; 39: 753-761Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar]. Therefore, the hypotheses put forward by the authors regarding the association between serum lipids and HCV-RNA status in their population, albeit conceivable and interesting, remain largely speculative and the observed association rather spurious in the absence of deeper insights into the clinical and virologic characterisation of their population.