The pathophysiology of thrombocytopenia in chronic liver disease

Mitchell, Oscar; Feldman, David; Diakow, Marla; Sigal, Samuel H.

doi:10.2147/hmer.s74612

Cited by 103 publications

(54 citation statements)

References 125 publications

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“…It was published previously, that intermediate FIB-4 values of 1.45–3.25 have negative predictive value of 89% for excluding advanced fibrosis and patients in this range would require a liver biopsy to assess the fibrosis stage. Thirty to forty percent of patients have an indeterminate score, and in these cases, additional testing is needed[ 35 , 46 ].…”

Section: Discussionmentioning

confidence: 99%

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

Gotlieb¹,

Schwartz²,

Zelber‐Sagi³

et al. 2020

WJG

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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.

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Section: Discussionmentioning

confidence: 99%

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

Gotlieb¹,

Schwartz²,

Zelber‐Sagi³

et al. 2020

WJG

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“…Thus, the platelet count has its own classical merits in predicting cirrhosis [ 17 , 18 ] and its outcome or in assessing the severity of fibrosis [ 19 , 20 ]. Studies have now elucidated various pathways on the platelet kinetics and its consumption in liver diseases and have broadened the understanding of thrombocytopenia in liver disease [ 21 ].…”

Section: Influence Of Platelet Countmentioning

confidence: 99%

Deciphering Platelet Kinetics in Diagnostic and Prognostic Evaluation of Hepatocellular Carcinoma

Aryal

Yamakuchi

Shimizu

et al. 2018

Canadian Journal of Gastroenterology and Hepatology

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Liver pathophysiology can, directly and indirectly, impose morphological or biochemical abnormalities of the platelets. Conversely, platelets are also able to regulate the promitogenic and profibrotic signals on liver pathobiology. Platelet contribution to the liver pathophysiology is typically facilitated by the platelet-derived growth factors that are sequestered in different subsets of alpha and dense granules, and the release of these growth factors is synchronized according to the stage and type of liver disease or injury. Thus, platelets harbor clinically relevant information with potential diagnostic and prognostic implications in liver diseases. Hepatocellular carcinoma (HCC) largely influences the platelet kinetics, and a growing body of evidence has recognized its association with HCC occurrence or prognosis. This narrative review summarizes the progress made on implicating platelet as a diagnostic and prognostic tool for HCC; the review also dissects the contradictory results from earlier studies and reflects how combining platelet-based information may enable more reliable test for diagnostic and prognostic evaluation of HCC.

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“…5 In addition, true tests of liver synthetic function can be assessed by measuring prothrombin time or albumin, and platelet production may be decreased in chronic liver disease due to hypersplenism, decreased thrombopoietin levels and bone marrow suppression. 6 Abnormal LFTs are often non-specific and can arise transiently in association with many acute illnesses or usage of medications. However, persistent derangement can indicate chronic liver disease, with associated morbidity and mortality.…”

Section: Introductionmentioning

confidence: 99%

Liver function tests and fibrosis scores in a rural population in Africa: a cross-sectional study to estimate the burden of disease and associated risk factors

et al. 2020

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ObjectivesLiver disease is a major cause of morbidity and mortality in sub-Saharan Africa, but its prevalence, distribution and aetiology have not been well characterised. We therefore set out to examine liver function tests (LFTs) and liver fibrosis scores in a rural African population.DesignWe undertook a cross-sectional survey of LFTs. We classified abnormal LFTs based on reference ranges set in America and in Africa. We derived fibrosis scores (aspartate aminotransferase (AST) to Platelet Ratio Index (APRI), fibrosis-4, gamma-glutamyl transferase (GGT) to platelet ratio (GPR), red cell distribution width to platelet ratio and S-index). We collected information about alcohol intake, and infection with HIV, hepatitis B virus (HBV) and hepatitis C virus (HCV).SettingWe studied a population cohort in South-Western Uganda.ParticipantsData were available for 8099 adults (median age 30 years; 56% female).ResultsThe prevalence of HBV, HCV and HIV infection was 3%, 0.2% and 8%, respectively. The prevalence of abnormal LFTs was higher based on the American reference range compared with the African reference range (eg, for AST 13% vs 3%, respectively). Elevated AST/ALT ratio was significantly associated with self-reported alcohol consumption (p<0.001), and the overall prevalence of AST/ALT ratio >2 was 11% (suggesting alcoholic hepatitis). The highest prevalence of fibrosis was predicted by the GPR score, with 24% of the population falling above the threshold for fibrosis. There was an association between the presence of HIV or HBV and raised GPR (p=0.005) and S-index (p<0.001). By multivariate analysis, elevated LFTs and fibrosis scores were most consistently associated with older age, male sex, being under-weight, HIV or HBV infection and alcohol consumption.ConclusionsFurther work is required to determine normal reference ranges for LFTs in this setting, to evaluate the specificity and sensitivity of fibrosis scores and to determine the aetiology of liver disease.

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The pathophysiology of thrombocytopenia in chronic liver disease

Cited by 103 publications

References 125 publications

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

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

Deciphering Platelet Kinetics in Diagnostic and Prognostic Evaluation of Hepatocellular Carcinoma

Liver function tests and fibrosis scores in a rural population in Africa: a cross-sectional study to estimate the burden of disease and associated risk factors

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