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Liver stiffness in HCV and ALD: Fibrosis-related cut-off values depend on degree and location of inflammation
Introduction: Liver stiffness (LS) can also be drastically elevated during liver inflammation making it difficult to separate fibrosis- from inflammation-induced LS. We here performed a multicenter study both on a portal-tract pronounced (hepatitis C virus infection; HCV) and a predominantly lobular disease (alcoholic liver disease; ALD). The major aim was, first, to learn whether portal and lobular inflammation differently translate into LS elevation and, second, to calculate adapted cut-off values for concomitant inflammation.
Methods: 452 patients with ALD, and 1393 patients with HCV were enrolled from five centers (Heidelberg, Paris, Hannover, Düsseldorf, Cluj Napoca). All patients had histological-proven fibrosis stage F0-F4 (METAVIR or Kleiner), LS (Fibroscan), and lab tests. Fibrosis distribution (F0, F1 – 2, F3 and F4) were 5.4%, 61.6%, 13.1% and 19.9% for HCV and 36.8%, 22%, 12.8% and 28.3% for ALD. Data were analyzed by Spearman Rho correlation, multivariate regression analysis and iterating ROC calculation.
Results: Among the routine laboratory parameters for liver damage, GOT correlated best with LS (r = 0.54, P < 10E-90). Association between GOT and LS was both disease- and fibrosis stage-dependent. This was also the main reason why multivariate analysis did not identify satisfying algorithms to improve fibrosis stage allocation. Therefore, we next calculated the area under the receiver operating curves (AUROC) as a function of GOT levels. Interestingly, cut-off values determined at optimal sensitivity and specificity (Youden index) were almost identical for F0, F3 and F4 in the absence of elevated transaminases (HCV: 5.1, 9.0 and 11.9 kPa, ALD: 4.9, 8.1 and 10.5 kPa). These cut-off values increased exponentially as a function of GOT levels. The impact of GOT on LS was higher in lobular-pronounced inflammation (ALD) and fibrosis-stage dependent. Consideration of GOT improved AUROCs namely for low fibrosis stages in HCV.
Conclusion: Our data indicate that the side and the degree of inflammation affect LS cut-off values for fibrosis. GOT levels correspond best with inflammation-related LS. We propose novel GOT-adapted cut-off values namely for HCV were short interventions such as alcohol detoxication are not applicable.
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