Gut 55:1650-1660 doi:10.1136/gut.2006.091454
  • Recent advances in clinical practice

Non-invasive markers associated with liver fibrosis in non-alcoholic fatty liver disease

  1. I N Guha1,
  2. J Parkes2,
  3. P R Roderick2,
  4. S Harris2,
  5. W M Rosenberg1
  1. 1Liver Group, Division of Infection, Inflammation, and Repair, University of Southampton, Southampton General Hospital, Southampton, UK
  2. 2Public Health and Medical Statistics, University of Southampton, Southampton, UK
  1. Correspondence to:
    Dr I N Guha
    Liver Group, Division of Infection, Inflammation, and Repair, University of Southampton, Mail point 811, Level D, South Academic Block, Southampton General Hospital, Southampton S016 6YD, UK; guhaneil{at}


    The diagnosis of fibrosis within liver disease is important for prognosis, stratification for treatment, and monitoring of treatment efficacy. The rising incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) has driven the search for accurate non-invasive tools of liver fibrosis within this condition. With the aid of a systematic review, we explore how the field has evolved from the discovery of simple blood parameters to panel markers of liver fibrosis. We will discuss the biological plausibility, limitations, potential uses, and emerging diagnostic techniques of non-invasive markers in this rapidly expanding field.


    NAFLD is emerging as one of the commonest causes of abnormal liver function tests, and in the Western world the estimated prevalence is reported to be as high as 30%.1 The prevalence of NAFLD is expected to rise in developed countries given the epidemic of its major underlying determinant obesity, in addition to the increasing ascertainment of this condition. Histologically, NAFLD is a spectrum of disease from simple fatty deposition (steatosis), to necroinflammation in zone 3 in association with ballooning degeneration (non-alcoholic steatohepatitis (NASH)), to periportal and/or perisinusoidal fibrosis, to cirrhosis. The natural history is varied; at the early stages of disease the majority remain stable at the same histological stage and grade, a proportion however will progress to cirrhosis (there is variation in the rate of progression), and finally some will have regression of disease.

    Liver biopsy is seen as the “gold standard”. Its value in revealing the relationship between inflammation and fibrosis and the presence and relative contribution to other aetiologies should not be underestimated. However, significant limitations to biopsy exist. In large studies, pain is a significant issue in 20% of cases and severe complications have been reported to occur in 0.57%.2 The biopsy may represent only 1/50 000th of the liver, and …