The clinical utility of biomarkers and the nonalcoholic  steatohepatitis CRN liver biopsy scoring system in patients  with nonalcoholic fatty liver disease.
OBJECTIVE
We identified patients with nonalcoholic fatty liver disease (NAFLD) to determine the predictive value of serum markers to diagnose histological steatohepatitis (NASH).


METHODS
Demographic, serological, radiological and histological variables on 95 consecutive patients with NAFLD were recorded. The serum markers studied were CK18, Hyaluronic acid, TIMP 1 and YKL 40. The NAS score and the metavir score were the histological scoring systems used.


RESULTS
CK18 levels were higher in the NASH group compared to the simple steatosis group (394 +/- 53 micro/L vs 194 +/- 26 micro/L; P < 0.05). In assessing clinical effectiveness, CK18 yielded an AUC of 0.8 for NASH (cut-off value 300 micro/L gives PPV 81% and NPV 85%).The fibrosis markers showed no differences between groups. We stratified the same cohort according to liver fibrosis (F0 vs F1-F4). Fibrosis was associated with advanced age, high body mass index and type 2 diabetes. The biomarkers performed relatively poorly at identifying liver fibrosis (F1-F4), with HA performing the best (AUC 0.73); performance improved for advanced fibrosis (F3/F4) - (HA: AUC 0.77). The NAS score performed the best overall at identifying liver fibrosis (AUC 0.79).


CONCLUSIONS
CK18 is the only biomarker studied that can identify NASH. Additionally, liver biopsy should be performed in all high risk patients to determine the standardised NAS score to identify patients at high risk of disease progression.
Liver Center, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Suite 4A, Boston, Massachusetts, USA.
Raza
R
Malik
Michael
M
Chang
Killimangalam
K
Bhaskar
Imad
I
Nasser
Michael
M
Curry
Detlef
D
Schuppan
Valerie
V
Byrnes
Nezam
N
Afdhal
D054392:Adipokines; D000328:Adult; D000367:Age Factors; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D015992:Body Mass Index; D000071451:Chitinase-3-Like Protein 1; D003924:Diabetes Mellitus, Type 2 / Q000150:complications; D018450:Disease Progression; D005234:Fatty Liver / Q000097:blood / Q000150:complications / Q000175:diagnosis* / Q000000981:diagnostic imaging / Q000473:pathology; D005260:Female; D006023:Glycoproteins / Q000097:blood; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D053538:Keratin-18 / Q000097:blood*; D037102:Lectins; D008099:Liver / Q000000981:diagnostic imaging / Q000473:pathology*; D008103:Liver Cirrhosis / Q000097:blood / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D011859:Radiography; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
D054392:Adipokines; D015415:Biomarkers; C084533:CHI3L1 protein, human; D000071451:Chitinase-3-Like Protein 1; D006023:Glycoproteins; C488421:KRT18 protein, human; D053538:Keratin-18; D037102:Lectins; D019715:Tissue Inhibitor of Metalloproteinase-1; D006820:Hyaluronic Acid