Clinical Significance Of Platelet-to-Lymphocyte Ratio And Neutrophil-to-Lymphocyte Ratio In Patients With HBV Or HCV Infection Related Liver Diseases

Backgrounds and Aims Platelet-to-lymphocyte ratio(PLR) and neutrophil-to-lymphocyte ratio(NLR), as indicators of systemic inflammation, are being heavily promoted by the inflammation and tumor related research. PLR and NLR, synthesis of hematological parameters including platelet count, neutrophil count and lymphocyte count, which are all main inflammation cells of human immune system, comprehensively reflect the body's inflammatory state. Existing studies have confirmed that PLR and NLR correlate not only with the prognosis of disease and treatment outcome of colorectal cancer,bladder cancer, liver cancer, lung cancer, esophageal cancer, but also with disease development and progression of heart and head blood-vessel, sudden deafness and vestibular neuritis, thrombosis disease.At the same time, studies about PLR and NLR in liver cancer have confirmed that they are closely related to the progress and treatment of hepatitis virus related/unrelated liver cancer. However, whether PLR and NLR are associated with HBV infection disease(chronic hepatitis B, HBV caused liver cirrhosis and HBV caused hepatocellular carcinoma) and HCV infection related liver diseases(chronic hepatitis C, HCV caused liver cirrhosis, and HCV caused hepatocellular carcinoma)has not yet been reported. Whether the two indicators are related with virological response of viral hepatitis patients accepting anti-viral treatment, disease progression,liver fibrosis/cirrhosis and cancerization, still needs further research.This research analyzes the changes of PLR and NLR and other closely related clinical indicators among patients with HBV and HCV infection and other related liver diseases to explore the role and significance of PLR and NLR in HBV and HCV infection and related liver disease. And the changes of PLR and NLR in chronic HCV infection are further analyzed to provide new evaluation and prediction indexes for the clinical diagnosis and treatment of HBV and HCV infection and related liver disease.Methods1. According to the inclusion and exclusion criteria standards, 309 patients with liver diseases and 40 healthy controls were analyzed in the first part; for the second part,120 patients with chronic hepatitis C and 40 healthy controls were included, and 24 CHC patients completing the regular follow-up of anti-viral treatment by peg-interferon and Ribavirin having different outcome of virological response were further analyzed.2. Testing of the indexes of hematology was using COULTER LH 755 automatic blood analyzer and the reagent of form a complete set in strict accordance with the instructions.3. The related parameters of liver function were tested by Roche Cobas E702 automatic biochemical analyzer and reagent of form a complete set in strict accordance with the instructions.4. Detection of HBV DNA and HCV RNA were by real-time fluorescent quantitative PCR.5. Indication function of PLR or NLR for virus clearance in CHC patients was conducted by receiver operator characteristic curve analysis.6. Relationship of PLR or NLR and virological response in CHC patients with antiviral treatment was tested by Friedman test, a kind analysis of variance of repeated measurement data.Results Part One: Clinical significance of platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio in patients with liver disease caused by different reasons.1. 309 patients with liver diseases and 40 healthy controls were analyzed in the first part. Patients were with an average age of(44.1±13.7) year-old and healthy controls were with an average age of(45.6±12.9) year-old.2. In patients with hepatitis, PLR and NLR of HCV infection group were obviously lower than that of HC; in patients with liver cirrhosis, PLR of patients with cirrhosis caused by HBV or HCV infection were obviously lower than that of HC; in HCC patients, PLR of patients with HCC caused by HBV or HCV infection were obviously lower than that of HC. The differences were statistically significant(p<0.05).3. In patients with virus un-related liver diseases, only NLR of UV-HCC is higher than that of HC. In patients with HBV infection related liver diseases, PLR of HBV-Cirr and HBV-HCC group were obviously lower and NLR of HBV-HCC was higher than of the HC and HBV-UT group. In patients with HCV infection related liver diseases, compared with HC, PLR of HCV-UT group, HCV-Cirr group and HCV-HCC group were significantly reduced; NLR of HCV-UT group was lower than that of HC. The differences were statistically significant(p<0.05).4. PLR of HBV-UC group and HBV-Cl group was obviously reduced; NLR of HBV-UC group was lower than that of HC. PLR of HCV-UT and HCV-UC group were lower than that of HC; PLR of HCV-Cl group was obviously higher than that ofboth HCV-UT and HCV-UC group; NLR of HCV-UT, HCV-UC and HCV-Cl group were lower than that of HC. The differences were statistically significant(p<0.05).Part Two: Clinical significance of platelet-to-lymphocytes ratio and neutrophil-to-lymphocyte ratio in different disease states and virological response in patients with chronic HCV infection.1. The study participants include 120 patients with CHC and 40 healthy controls in the second part. Patients was with an average age of(46.6±12.4) year-old and healthy controls was with an average age of(45.6±12.9) year-old.2. In patients with chronic HCV infection of different disease state, PLR of HCV-Cirr group and HCV-HCC patients were lower than that of both HC and HCV-Ht group,the differences were statistically significant(p<0.05), while only NLR of HCV-Ht group reduced compared with that of HC, which was statistically significant(p<0.05).3. Comparing PLR among HCV-UT group, HCV-UC group and HCV-Cl group, PLR of HCV-Cl group was higher than that of both HCV-UT and HCV-UC group, of wich differences all had statistical significances(p<0.05), while the changes of NLR had no statistical significance.4. The ROC analysis showed that AUC of PLR was 0.772 with a cutoff value of 124,specificity 92.3% and sensitivity 53.7%; AUC of NLR was 0.612, with a cutoff value of 1.44, specificity 76.9% and sensitivity 48.8%.5. PLR of RVR&SVR group got increased as soon as the antiviral treatment started;PLR of only SVR group got slightly lower in the fourth week, and then gradually increased; PLR of non-SVR group was almost unchanged, while some even got reduced.Conclusions1. PLR and NLR both have certain correlations with progression and prognosis of viral liver disease, especially with disease progression of HCV infection and virus clearance of CHC patient. Compared with NLR, PLR associates with disease progression of HCV infection related liver disease and with virological response outcome of CHC patients accepting antiviral treatment more closely.2. The variation trend of PLR, rather than a single time point of PLR value, show a good correlation with virological response outcome of CHC patients accepting antiviral treatment. A continuous and regular follow-up inspection of PLR will help to monitoring the progress and prognosis of the disease.