title: Circulating mitochondrial DNA content associated with the risk of liver cirrhosis: a nested case-control study.
abstract: OBJECTIVE
  Accumulating evidence has indicated that variations of mitochondrial DNA (mtDNA) content may affect the susceptibility to hepatocellular carcinoma (HCC). However, no study has been conducted to evaluate the association of circulating mtDNA content and the risk of liver cirrhosis, a leading cause of HCC.
  
  
  METHODS
  We conducted a nested case-control study including 136 cirrhotic hepatitis B virus (HBV) cases and 136 frequency-matched non-cirrhotic HBV controls. We determined mtDNA content in serum DNA using quantitative real-time PCR and analyzed its association with cirrhosis risk.
  
  
  RESULTS
  We found that cirrhotic HBV patients had significantly lower levels of mtDNA content than non-cirrhotic HBV controls (P = 0.0184). Compared to patients with high mtDNA content, those with low mtDNA content had a 2.25-fold increased risk of cirrhosis [odds ratio (OR) 2.25, 95 % confidence interval (CI) 1.26-4.02]. This association exhibited a significant dose relationship as evidenced in both tertile and quartile analyses (P for trend = 0.0018 and 0.0008, respectively). Stratified analyses showed that the association was prominent in younger patients (P = 0.0122), males (P = 0.0069), never smokers (P = 0.0063), never drinkers (P = 0.0078), patients with a family history of HBV infection (P = 0.0062), and patients with low values of aspartate aminotransferase to platelet ratio index (APRI), a commonly used noninvasive marker for cirrhosis (P = 0.0109). Moreover, a joint effect was observed between low mtDNA content and high APRI values on cirrhosis risk (OR 24.07, 95 % CI 6.72-86.24).
  
  
  CONCLUSIONS
  Low circulating mtDNA content may confer an increased cirrhosis risk in HBV patients. Further prospective studies are warranted to validate these findings and explore the clinical significance.
authors.affiliation: Division of Population Science, Department of Medical Oncology, Sidney Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Chun
authors.initials: C
authors.lastname: Wang
authors.forename: Hie-Won
authors.initials: HW
authors.lastname: Hann
authors.forename: Richard S
authors.initials: RS
authors.lastname: Hann
authors.forename: Shaogui
authors.initials: S
authors.lastname: Wan
authors.forename: Ronald E
authors.initials: RE
authors.lastname: Myers
authors.forename: Zhong
authors.initials: Z
authors.lastname: Ye
authors.forename: Jinliang
authors.initials: J
authors.lastname: Xing
authors.forename: Hushan
authors.initials: H
authors.lastname: Yang
mesh_terms: D001706:Biopsy; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000097:blood*; D003952:Diagnostic Imaging; D005260:Female; D019694:Hepatitis B, Chronic / Q000150:complications; D006801:Humans; D008103:Liver Cirrhosis / Q000097:blood* / Q000821:virology; D008297:Male; D008875:Middle Aged; D060888:Real-Time Polymerase Chain Reaction; D056910:Republic of Korea; D012307:Risk Factors
chemical_list: D004272:DNA, Mitochondrial