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 a significant source of morbidity and mortality worldwide. The disease is usually indolent and asymptomatic early in its course while 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 represents advanced fibrosis and portal hypertension (HTN) and most non-invasive scores that predict liver fibrosis incorporate platelets as a strong risk factor. However, 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 platelet counts trajectories over time, can predict advanced liver fibrosis across the different etiologies of liver diseases.
A nested case-control study utilizing a large computerized database. Cirrhosis cases (n = 5258) were compared to controls (n = 15744) matched for age and sex at a ratio of 1:3. All participants had multiple laboratory measurements prior to enrollment. We calculated the trends of PTC, liver enzymes, bilirubin, international normalized ratio, albumin and fibrosis scores (fibrosis-4 and aspartate transaminase-to-platelet ratio index) throughout the preceding 20 years prior to cirrhosis diagnosis compared to healthy controls. The association between PTC, cirrhosis complications and fibrosis scores prior to cirrhosis diagnosis was investigated.
The mean age in both groups was 56 (SD 15.8). Cirrhotic patients were more likely to be smokers, diabetic with chronic kidney disease and had a higher prevalence of HTN. 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 group aspartate aminotransferase and alanine aminotransferase, increased from 40 U/L to 75 U/L and FIB-4 increased gradually from 1.3 to 3 prior to cirrhosis diagnosis. 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).
In the preceding years before the diagnosis of cirrhosis, there is a progressive decline in PTC, within the normal range, matched to a gradual increase in fibrosis scores.
Core tip: Cirrhosis is usually asymptomatic thus often diagnosed late when complications occur. Most non-invasive hepatic fibrosis scores (fibrosis-4, aspartate transaminase-to-platelet ratio index) incorporate platelets as a strong risk factor. However, the association between platelets average trends within the normal range and the risk of cirrhosis development is unknown. We found that up to 15 years before the diagnosis of cirrhosis, a progressive decline in platelet counts occurs, within the normal limits along with a gradual incline in FIB-4. The decline in platelet counts may alert of an early liver disease and may enable early therapeutic and preventive interventions before complications occur.