Progressive changes in platelet counts and Fib-4 scores precede the diagnosis of advanced fibrosis in NASH patients

BACKGROUND Cirrhosis and its complications develop in a subgroup of patients with nonalcoholic fatty liver disease(NASH).Early detection of liver fibrosis represents an important goal of clinical care.AIM To test the hypothesis that the development of cirrhosis in nonalcoholic fatty liver disease patients is preceded by the long-term trends of platelet counts and Fib-4 scores.METHODS We identified all patients in our healthcare system who had undergone fibrosis staging by liver biopsy or magnetic resonance elastography(MRE)for nonalcoholic fatty liver disease during the past decade(n=310).Platelet counts,serum glutamic-pyruvic transaminase and serum glutamic oxalacetic transaminase values preceding the staging tests were extracted from the electronic medical record system,and Fib-4 scores were calculated.Potential predictors of advanced fibrosis were evaluated using multivariate regression analysis.RESULTS Significant decreases in platelet counts and increases in Fib-4 scores were observed in all fibrosis stages,particularly in patients with cirrhosis.In the liver biopsy group,the presence of cirrhosis was best predicted by the combination of the Fib-4 score at the time closest to staging(P<0.0001),the presence of diabetes(P=0.0001),and the correlation coefficient of the preceding timedependent drop in platelet count(P=0.044).In the MRE group,Fib4 score(P=0.0025)and platelet drop(P=0.0373)were significant predictors.In comparison,the time-dependent rise of the Fib-4 score did not contribute in a statistically significant way.CONCLUSION Time-dependent changes in platelet counts and Fib-4 scores contribute to the prediction of cirrhosis in NASH patients with biopsy-or MRE-staged fibrosis.Their incorporation into predictive algorithms may assist in the earlier identification of high-risk patients.

Baseline neutrophil-lymphocyte ratio and platelet-lymphocyte ratio appear predictive of immune treatment related toxicity in hepatocellular carcinoma

BACKGROUND A well-recognized class effect of immune checkpoint inhibitors(ICI)is immune-related adverse events(IrAEs)ranging from low grade toxicities to life-threatening end organ damage requiring permanent discontinuation of ICI.Deaths are reported in<5%of patients treated with ICI.There are,however,no reliable markers to predict the onset and severity of IrAEs.We tested the association between neutrophil-lymphocyte ratio(NLR)and platelet-lymphocyte ratio(PLR)at baseline with development of clinically significant IrAEs(grade≥2)in hepatocellular carcinoma(HCC)patients treated with ICI.AIM To test the association between NLR and PLR at baseline with development of clinically significant IrAEs(grade≥2)in HCC patients treated with ICI.METHODS Data was extracted from an international database from a consortium of 11 tertiary-care referral centers.NLR=absolute neutrophil count/absolute lymphocyte count(ALC)and PLR=platelet count/ALC.Cutoff of 5 was used for NLR and 300 for PLR based on literature.We also tested the association between RESULTS Data was collected from 361 patients treated between 2016-2020 across the United States(67%),Asia(14%)and Europe(19%).Most patients received Nivolumab(n=255,71%).One hundred sixty-seven(46%)patients developed at least one IrAE,highest grade 1 in 80(48%),grade≥2 in 87(52%)patients.In a univariable regression model PLR>300 was significantly associated with a lower incidence of grade≥2 IrAEs(OR=0.40;P=0.044).Similarly,a trend was observed between NLR>5 and lower incidence of grade≥2 IrAEs(OR=0.58;P=0.097).Multivariate analyses confirmed PLR>300 as an independent predictive marker of grade≥2 IrAEs(OR=0.26;P=0.011),in addition to treatment with programmed cell death ligand 1(PD-1)/cytotoxic T lymphocyte-associated protein-4(OR=2.57;P=0.037)and PD-1/tyrosine kinase inhibitor(OR=3.39;P=0.01)combinations.Antibiotic use was not associated with IrAE incidence(OR=1.02;P=0.954).Patients treated with steroids had a>2-fold higher incidence of grade≥2 IrAEs(OR=2.74;P<0.001),although 74%were prescribed steroids for the treatment of IrAEs.CONCLUSION Given that high baseline NLR and PLR are associated with a decreased incidence of IrAEs,lower baseline NLR and PLR may be predictive biomarkers for the appearance of IrAEs in HCC treated with ICI.This finding is in keeping with several studies in solid tumors that have shown that baseline NLR and PLR appear predictive of IrAEs.

Hepatitis B vaccination in patients with inflammatory bowel disease

AIM:To determine the prevalence for hepatitis B virus(HBV) and HBV screening and vaccination practices for inflammatory bowel disease(IBD).METHODS:This study is a retrospective,cross-sectional observational study.A retrospective chart review was performed in 500 patients who have been consecutively treated for IBD between September 2008 and January 2013 at the Rush University Medical Center Gastroenterology section.The patients were identified through the electronic medical record with the criteria that they attended the gastroenterology clinic,and that they had a diagnosis of IBD at the time of visit discharge.Once identified,each record was analyzed to determine whether the subject had been infected with HBV in the past,already been vaccinated against HBV,or advised to get vaccinated and followed through with the recommended vaccination.RESULTS:About 254 out of 500 patients(51%) had HBV screening ordered.Among those ordered to have screening tests,86% followed through with HBV serology.Gastroenterology physicians had significantly different screening ratios from each other(P < 0.001).There were no significant differences in the ratios of HBV screening when IBD specialists were compared to other gastroenterology physicians(0.505 ± 0.023 vs 0.536 ± 0.066,P = 0.66).Of those 220 patients screened,51% of IBD patients were found not to be immune against HBV.Approximately 50% of gastroenterology physicians recommended HBV vaccinations to their patients in whom serology was negative for antibodies against HBV.IBD specialists recommended vaccinations to a higher percentage of their patients compared to other gastroenterology physicians(0.168 ± 0.019 vs 0.038 ± 0.026,P = 0.015).Present and/or past HBV infection was found in 3.6% of the patients who had serology checked.There was no statistically significant difference in the prevalence of hepatitis B surface antigen(HBsAg) between our study and that reported in previous studies done in Spain(4/220 vs 14/2076 respectively,P = 0.070); and in France(4/220 vs 3/315 respectively,P = 0.159).But,the prevalence of anti-HBcAb in this study was less than that reported in the study in Spain(7/220 vs 155/2076 respectively,P = 0.006); and was not sig-nificantly different from that reported in the study in France(7/220 vs 8/315 respectively,P = 0.313).CONCLUSION:The prevalence of HBsAg in our IBD patients was not higher than previously reported European studies.Most IBD patients are not routinely screened or vaccinated against HBV at a tertiary referral center in the United States.