Analysis of Serum Cys-C,TBA,and Routine Blood Parameters of Patients with Hepatitis B-Related Decompensated Cirrhosis

Objective:To study the levels of serum cystatin C(Cys-C),total bile acid(TBA),and other routine blood parameters on patients with decompensated hepatitis B cirrhosis.Methods:Study group 1 consisted of 30 patients with hepatitis B-related decompensated cirrhosis,and study group 2 consisted of 30 patients with hepatitis B;while the control group consisted of 30 healthy people who underwent physical examination.The blood parameters were used to evaluate the clinical treatment effect of patients.Results:The TBA,Cys-C,alanine transaminase(ALT),total bilirubin(TBIL),aspartate aminotransferase(AST),and international normalized ratio(INR)in study group 1 were significantly higher than those of study group 2 and the control group;while the platelet count(PLT),hemoglobin(Hb),albumin(ALB),and estimated glomerular filtration rate(eGFR)were significantly lower in the study group 1 compared to the control group and study group 2(P<0.05).The Cys-C,PLT,TBA,AST,TBIL,and INR of patients in study group 1 who were successfully treated were significantly lower than the patients who were not successfully treated(P<0.05).Conclusion:Serum Cys-C,TBA,and routine blood parameters are useful in predicting the condition and the prognosis of patients of hepatitis B-related decompensated cirrhosis.

Cyclooxygenase-2 promoter polymorphism -899G/C is associated with hepatitis B-related liver cancer in a Chinese population of Gansu province

Background Hepatitis B virus infection is closely related to hepatocellular carcinoma （HCC）. Cyclooxygenase-2 （COX-2） is overexpressed in HCC and considered to play a role in hepatic carcinogenesis. In this study, we analyzed the polymorphism of COX-2 promoter -899G/C in healthy controls, chronic hepatitis B （CHB） patients, liver cirrhosis patients, and hepatocellular carcinoma （HCC） patients, to investigate the relationship between COX-2 -899G/C polymorphism and the risk for hepatitis B-related liver cancer in a Chinese population from Gansu province. Methods Patients were divided into four groups： 300 patients with CHB, 300 patients with liver cirrhosis, 300 patients with HCC, and 300 healthy controls. The polymorphism of COX-2 -899G/C was detected by PCR-TaqMan probes. The results were analyzed by SPSS 17.0. Results The COX-2 -899G/C genotypes were GG, GC, and CC. Frequencies in CHB were 87.00%, 12.67%, 0.33%; in liver cirrhosis were 85.33%, 14.00%, 0.67%; in HCC were 77.00%, 21.67%, 1.33%; and in healthy controls were 90.67%, 9.00%, 0.33%, respectively. COX-2 -899C carriers may have an increased risk for hepatitis B-related liver cancer. Compared with the frequency of GG genotype, there were significant differences in the frequency of GC genotype between HCC and healthy control groups （0R=2.835, 95%C/： 1.751-4.589）; HCC and CHB groups （OR=1.933, 95%C/： 1.248-2.994）; and HCC and liver cirrhosis groups （OR=1. 175, 95%C/： 1.119-2.628）. Stratification analyses showed that COX-2 -899C allele carriers with a drinking history are more susceptible to develop HCC. Conclusion COX-2 -899C genotype may increase the susceptibility of individuals to hepatitis B-related liver cancer in Gansu province, China.

Upregulation of Toll-like Receptor 4 on T Cells in PBMCs Is Associated with Disease Aggravation of HBV-related Acute-on-chronic Liver Failure

Summary： Immune-mediated inflammatory injury is an important feature of the disease aggravation of hepatitis B virus-related acute-on-chronic liver failure （ACLF）. Toll-like receptors （TLRs） have been shown previously to play a pivotal role in the activation of innate immunity. The purpose of this study was.to characterize the TLR4 expression in peripheral blood mononuclear cells （PBMCs） of ACLF pa- tients and its possible role in the disease aggravation. Twelve healthy subjects, 15 chronic HBV-infected （CHB） patients and 15 ACLF patients were enrolled in this study. The TLR4 expression in PBMCs and T cells of all subjects was examined by real-time PCR and flow cytometry. The correlation of TLR4 ex- pression on T cells with the markers of disease aggravation was evaluated in ACLF patients. The ability of TLR4 ligands stimulation to induce inflammatory cytokine production in ACLF patients was ana- lyzed by flow cytometry. The results showed that TLR4 mRNA level was upregulated in PBMCs of ACLF patients compared to that in the healthy subjects and the CHB patients. Specifically, the expres- sion of TLR4 on CD4＋ and CD8＋ T cells of PBMCs was significantly increased in ACLF patients. The TLR4 levels on CD4＋ and CD8＋T cells were positively correlated with serum total bilirubin （TBIL）, direct bilirubin （DBIL）, international normalized ratio （INR） levels and white blood cells （WBCs）, and negatively correlated with serum albumin （ALB） levels in the HBV-infected patients, indicating TLR4 pathway may play a role in the disease aggravation of ACLF. In vitro TLR4 ligand stimulation on PBMCs of ACLF patients induced a strong TNF-α production by CD4＋ T cells, which was also posi- tively correlated with the serum markers for liver injury severity. It was concluded that TLR4 expression is upregulated on T cells in PBMCs, which is associated with the aggravation of ACLF.

Clinical efficacy of antiviral therapy in patients with hepatitis Brelated cirrhosis after transjugular intrahepatic portosystemic shunt

BACKGROUND As a country with a high burden of hepatitis B,China has about 86 million cases of hepatitis B virus infection,ranking the first in the world.Currently,there are about 390000 deaths due to hepatitis B-related complications such as liver cirrhosis and liver cancer every year.Consequently,how to control portal hypertension,improve liver functional reserve,and reduce the incidence of hepatic failure and liver cancer in such patients is the focus of current clinical attention.Previous clinical study in our center suggested that at 24 mo after transjugular intrahepatic portosystemic shunt(TIPS),the liver functional reserve of patients with hepatitis B cirrhosis was better than that of patients with alcoholinduced and immune cirrhosis,which may be related to the effective etiological treatment.AIM To investigate the clinical efficacy of three first-line antiviral drugs recommended by the guidelines of prevention and treatment for chronic hepatitis B in China(2019)in the treatment of patients with hepatitis B-related cirrhosis who had received a TIPS.METHODS The clinical data of 137 patients with hepatitis B-related cirrhosis with portal hypertension after receiving TIPS at our centre between March 2016 and December 2020 were analysed retrospectively.According to different anti-viral drugs,the patients were divided into entecavir(ETV)(n=70),tenofovir alafenamide fumarate(TAF)(n=32),and tenofovir disoproxil fumarate(TDF)(n=35)groups.The cumulative incidence of hepatic encephalopathy and hepatocellular carcinoma,survival,and changes in hepatic reserve function and glomerular filtration rate in patients treated with different antiviral drugs within 24 mo after surgery were investigated.RESULTS At 24 mo after surgery,the Child-Pugh score in the TAF group(6.97±0.86)was lower than that in the TDF(7.49±0.82;t=-2.52,P=0.014)and ETV groups(7.64±1.17;t=-2.92,P=0.004).The model for end-stage liver disease score in the TAF group at 24 mo after surgery was 9.72±1.5,which was lower than that in the TDF(10.74±2.33;t=-2.09,P=0.040)and ETV groups(10.97±2.17;t=-2.93,P=0.004).At 24 mo after surgery,the estimated glomerular filtration rate(eGFR)in the TAF group(104.41±12.54)was higher than that in the TDF(93.54±8.97)and ETV groups(89.96±9.86)(F=21.57,P<0.001).CONCLUSION At 24 mo after surgery,compared with TDF and ETV,TAF has significant advantages in the improvement of liver functional reserve and eGFR.

Detection of carboxyhemoglobin in patients with hepatic encephalopathy due to hepatitis B virus-related cirrhosis

Background The heme oxygenase/carbon monoxide （HO/CO） system plays an important role in the development of hepatic fibrosis. The level of the HO/CO can be directly obtained by determining the carboxyhemoglobin （COHb） level. The aims of this study were to reveal the significance of COHb in patients with hepatitis B virus-related cirrhosis （HBC） complicated by hepatic encephalopathy （HE）, and to further investigate the influence of the HO/CO pathway on the end-stage cirrhosis, hoping to find a reliable indicator to evaluate the course of HBC. Methods According to the diagnostic criteria, 63 HBC inpatients with HE were enrolled in group H. Patients regaining awareness with current therapies were categorized into group P-H. Comparisons were made with a control group （group N） consisting of 20 health volunteers. The levels of COHb, partial pressure of oxygen （PaO2） and oxygen saturation （SaO2） were determined by arterial blood gas analysis method. The incidences of hepatorenal syndrome （HRS）, upper gastrointestinal bleeding, esophagogastric varices and spontaneous bacterial peritonitis （SBP） in group H were recorded. COHb levels in different groups were compared, and the correlations of COHb levels with HE grades （I, II, III, and IV）, PaO2, SaO2 and hypoxemia were analyzed. Results The COHb level in group P-H （（1.672＋0.761）%） was significantly higher than that in group N （（0.983±0.231）%） （P 〈0.01 ）, and the level in group H （（2.102±1.021）%） was significantly higher than groups P-H and N （P 〈0.01 ）. A positive correlation was observed between the COHb concentration and the grade of HE （rs=0.357, P=-0.004）. There were no significant differences of COHb levels between HE patients with and without complications such as esophagogastric varices （（2.302±1.072）% vs. （1.802±1.041）%, P 〉0.05） or the occurrence of SBP （（2.960±0.561）% vs. （2.030±1.021）%, P 〉0.05）. Compared with HE patients with HRS, the level of COHb was significantly higher in HE patients without HRS （（2.502±1.073）% vs. （1.981＋1.020）%, P=0.029）. The COHb level had a negative correlation with PaO2 （r=-0.335, P=0.007） while no statistically significant relationship was found with SaO2 （r=-0.071, P 〉0.05）. However, when the above two parameters met the diagnostic criteria of hypoxemia, the COHb concentration increased （（2.621±0.880）% vs. （1.910±0.931）%, P=0.011 ）. Conclusions COHb is a potential candidate to estimate the severity and therapeutic effect of HE. The levels of COHb may be tissue-specific in cirrhotic patients with different complications.