C reactive protein levels in non-alcoholic fatty liver disease
Authors: Teoman Dogru, Halil Genc, Sait Bagci
Journal: Journal of Hepatology (2011)

C-reactive protein levels in relation to various features of non-alcoholic fatty liver disease among obese patientsJournal of HepatologyVol. 55Issue 3PreviewNon-alcoholic fatty liver disease (NAFLD) is a major hepatic consequence of obesity. It has been suggested that the high sensitivity C-reactive protein (hs-CRP) is an obesity-independent surrogate marker of severity of NAFLD, especially development of non-alcoholic steato-hepatitis (NASH), but this remains controversial. We aimed to investigate whether associations between various features of NAFLD and hs-CRP are independent of body mass index (BMI) in its broad range among obese patients. Full-Text PDF Reply to: "C-reactive protein levels in non-alcoholic fatty liver disease"Journal of HepatologyVol. 56Issue 2PreviewWe thank Dr. Dogru et al. for their comments on our paper on C-reactive protein (CRP) levels in relation to various features of non-alcoholic fatty liver disease (NAFLD) among obese patients [1]. In our study of 627 obese adults with liver histology and measures of body mass index (BMI, kg/m2), and high sensitivity (hs)-CRP, we confirmed a strong association between BMI and hs-CRP, with a 20% increase in hs-CRP level per 10% increase in BMI. Also, we observed a positive association between hs-CRP and liver steatosis, but no BMI independent association between hs-CRP and non-alcoholic steato-hepatitis (NASH), hence questioning whether CRP can be used as a marker of severity of NAFLD [1]. Full-Text PDF Open Access Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the world. It represents a wide spectrum of conditions ranging from fatty liver, which in general follows a benign, non-progressive clinical course, to nonalcoholic steatohepatitis (NASH), a more serious form of NAFLD that may progress to cirrhosis and end-stage liver disease. Accurate evaluation of liver fibrosis in patients with NAFLD is important to identify patients who may develop complications. Over time, several biological markers have been studied for evaluating the extent of steatosis, the presence of necroinflammation, and the development of fibrosis to avoid performing liver biopsy, an invasive procedure that still represents the gold standard of diagnosis. The most important parameter to be identified through non-invasive methods is inflammation, as it plays a central role in NAFLD progression. Several biomarkers of inflammation were extensively studied in relation to fatty liver disease. The C reactive protein (CRP) is an acute-phase reactant produced by the liver and has an increased serum concentration in a variety of inflammatory conditions. The assessment of circulating levels of high sensitive CRP (hsCRP) proved to be useful in differentiating between simple steatosis and NASH. Moreover, it seems that high concentrations of hsCRP are associated with extensive liver fibrosis in NASH [[1]Yoneda M. et al.High-sensitivity C-reactive protein is an independent clinical feature of nonalcoholic steatohepatitis (NASH) and also of the severity of fibrosis in NASH.J Gastroenterol. 2007; 42: 573-582Crossref PubMed Scopus (227) Google Scholar]. In a recent issue of the Journal of Hepatology, Zimmermann et al. reported the association of hsCRP with various features of NAFLD in a large obese population. The authors concluded that, based on their results, hsCRP may be a marker of steatosis, but not of severity of NAFLD in these patients [[2]Zimmermann E. et al.C-reactive protein levels in relation to various features of non-alcoholic fatty liver disease among obese patients.J Hepatol. 2011; 55: 660-665Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar]. The findings of this report are interesting and contribute to our understanding of this issue. However, we have some concerns about the data presented by the authors. Firstly, circulating hsCRP levels have been reported to be elevated in subjects with diabetes mellitus (DM) and also prediabetes [3Garcia C. et al.Diabetes and inflammation: fundamental aspects and clinical implications.Diabetes Metab. 2010; 36: 327-338Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar, 4Sabanayagam C. et al.Serum C-reactive protein level and prediabetes in two Asian populations.Diabetologia. 2011; 54: 767-775Crossref PubMed Scopus (35) Google Scholar]. Although it was stated in the article that some of the patients were diabetic at baseline, there is no information regarding the glucose tolerance status of the other subjects. It is well known that NAFLD is strongly associated with obesity, hypertension, dyslipidemia and also glucose tolerance abnormalities [[5]Yun J.W. et al.Abnormal glucose tolerance in young male patients with nonalcoholic fatty liver disease.Liver Int. 2009; 29: 525-529Crossref PubMed Scopus (44) Google Scholar]. In addition, all these metabolic problems are risk factors for DM and also prediabetes. In light of these data, we think that some of the study participants may still have overt glucose dysregulation or DM without implementation of the glucose tolerance test. Secondly, there is no data about the blood pressure and lipid profiles of the study participants. A large body of evidence shows that circulating levels of hsCRP differ according to the degree of lipid disorders [[6]Nordestgaard B.G. Zacho J. Lipids, atherosclerosis and CVD risk: is CRP an innocent bystander?.Nutr Metab Cardiovasc Dis. 2009; 19: 521-524Abstract Full Text Full Text PDF PubMed Scopus (71) Google Scholar]. This point is also true for hypertension or elevated blood pressure [[7]Schillaci G. Pirro M. C-reactive protein in hypertension: clinical significance and predictive value.Nutr Metab Cardiovasc Dis. 2006; 16: 500-508Abstract Full Text Full Text PDF PubMed Scopus (57) Google Scholar]. On the other hand, metabolic syndrome is also strongly associated with circulating hsCRP levels [[8]Ndumele C.E. Steatosis Hepatic. et al.Obesity, and the metabolic syndrome are independently and additively associated with increased systemic inflammation.Arterioscler Thromb Vasc Biol. 2011; ([Epub ahead of print])PubMed Google Scholar]. Lastly, no information about the medications could be seen in the text. We know that hsCRP levels are easily affected from the medications started for the metabolic problems mentioned above [9Dandona P. Effects of antidiabetic and antihyperlipidemic agents on C-reactive protein.Mayo Clin Proc. 2008; 83: 333-342Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar, 10Dandona P. et al.Angiotensin II and inflammation: the effect of angiotensin-converting enzyme inhibition and angiotensin II receptor blockade.J Hum Hypertens. 2007; 21: 20-27Crossref PubMed Scopus (258) Google Scholar]. Collectively, all these points raise several questions warranting discussion. We conclude that, before making certain interpretations, presence of major confounders raises some questions about the data presented. In such a case, statistical correlations may also be misleading. It would be appreciated if the authors could present some more data adjusted for topics mentioned above. This could provide the readers of the Journal clearer information regarding the relationship of hsCRP with this clinically relevant condition. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.