Longitudinal decrease in platelet counts as a surrogate marker of liver fibrosis

Abstract

BACKGROUND 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. AIM To explore whether platelet counts trajectories over time, can predict advanced liver fibrosis across the different etiologies of liver diseases. METHODS 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. RESULTS 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). CONCLUSION 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.

Sex differences in the associations of body size and body shape with platelets in the UK Biobank cohort

“…The inverse association of BMI with platelet count is most likely related to liver damage and fibrosis resulting from liver fat infiltration, which in more extreme cases leads to non-alcoholic fatty liver disease (NAFLD) [ 44 ] and would further be aggravated by liver damage related to older age, high alcohol consumption, and smoking. Low platelet count is, indeed, a hallmark of fibrosis associated with cirrhosis and gradually decreases for several years prior to the overt clinical presentation of the disease [ 45 ]. Correspondingly, platelet count is included in most non-invasive liver fibrosis indices [ 46 ].…”

Dynamic trajectory of platelet counts after the first cycle of induction chemotherapy in AML patients

“…However, they also play an important role in the disease prognosis. The association between PLT count trajectories and outcomes has been reported in several diseases, including severe coronavirus disease 2019 [ 23 ], liver fibrosis [ 24 ], and severe burns [ 25 ]. However, the novel finding was that the dynamic trajectory of PLT count was a significant predictor of all-cause mortality in patients with acute myeloid leukemia.…”

Frequency of Thrombocytopenia and its Severity among patients of Chronic Liver Disease presenting to a Tertiary Care Hospital

“…Moderate Thrombocytopenia (50,000/μL-75,000/μL) was noted in approximately 13% of cirrhotic patients. There was a strong association between chronic liver disease and thrombocytopenia in 58% patients coming to the OPD in all the hospitals 6 In recent study 7 published in 2020, most common cause of liver disease was observed as viral infection (48%), alcoholic liver disease (24%) followed by NAFLD (20%). In the cirrhosis group, males had a mean platelet count of 210000 decreasing to 170000/μL vs females, with a mean number of platelets 250000 decreasing to 215000/μL.…”