Published online Oct 14, 2020. doi: 10.3748/wjg.v26.i38.5849
Peer-review started: May 21, 2020
First decision: May 29, 2020
Revised: June 10, 2020
Accepted: August 26, 2020
Article in press: August 26, 2020
Published online: October 14, 2020
Liver cirrhosis is usually asymptomatic early in its course. Many cirrhotic patients are diagnosed late when severe complications occur. A major challenge is to diagnose advanced fibrosis as early as possible, using simple and non-invasive diagnostics tools. Thrombocytopenia (platelet count < 150000/μL) on the background of chronic liver disease of any etiology represents advanced fibrosis and portal hypertension. As such, platelets have been incorporated in most non-invasive scores that predict liver fibrosis as a strong risk factor.
As opposed to thrombocytopenia which is associated with advanced fibrosis, little is known about the association between longitudinal changes in platelet counts (PTC), when still within the normal range, and the risk of cirrhosis.
To explore whether big data analysis of PTC trajectories over time, can predict advanced liver fibrosis and cirrhosis complications across the different etiologies of liver diseases.
A nested case-control study with diagnosed cirrhosis patients and matched controls, utilizing the Maccabi Health Services database was performed. The trends of PTC, liver enzymes, bilirubin, international normalized ratio, albumin and fibrosis scores [fibrosis-4 (FIB-4) and aspartate transaminase-to-platelet ratio index] throughout the preceding 20 years prior to cirrhosis diagnosis were calculated and compared to healthy controls. The association between PTC, cirrhosis complications and fibrosis scores prior to cirrhosis diagnosis was investigated.
Cirrhosis cases (n = 5258) were compared to controls (n = 15744) matched for age and sex at a ratio of 1:3. The leading cirrhosis etiologies were viral, alcoholic and fatty liver disease. The mean PTC decreased from 240000/μL to 190000/μL up to 15 years prior to cirrhosis diagnosis compared to controls who’s PTC remained stable around the values of 240000/μL. This trend was consistent regardless of sex, cirrhosis etiology and was more pronounced in patients who developed varices and ascites. Compared to controls whose values remained in the normal range, in the cirrhosis FIB-4 increased gradually from 1.3 to 3 prior to cirrhosis diagnosis. Additionally, in multivariable regression analysis, a decrease of 50 units in PTC was associated with 1.3 times odds of cirrhosis (95%CI: 1.25-1.35).
This study indicates that a progressive decline in platelet counts, within the normal range, is associated with a gradual increase in fibrosis scores, starting up to 15 years before the diagnosis of cirrhosis.
Progressive PTC decline in the preceding years before the diagnosis of liver cirrhosis, when still within the normal limits, may be identified by machine learning algorithms and alert the treating physicians of an early liver disease and may enable early therapeutic and preventive interventions before serious complications occur.