Ruihong Wu

Replication Inhibition of Hepatitis B Virus and Hepatitis C Virus in Co-Infected Patients in Chinese Population

Background Hepatitis B virus (HBV) and hepatitis C virus (HCV) co-infections contributes to a substantial proportion of liver disease worldwide. The aim of this study was to assess the clinical and virological features of HBV-HCV co-infection. Methods Demographic data were collected for 3238 high-risk people from an HCV-endemic region in China. Laboratory tests included HCV antibody and HBV serological markers, liver function tests, and routine blood analysis. Anti-HCV positive samples were analyzed for HCV RNA levels and subgenotypes. HBsAg-positive samples were tested for HBV DNA. Results A total of 1468 patients had chronic HCV and/or HBV infections. Among them, 1200 individuals were classified as HCV mono-infected, 161 were classified as HBV mono-infected, and 107 were classified as co-infected. The HBV-HCV co-infected patients not only had a lower HBV DNA positive rate compared to HBV mono-infected patients (84.1% versus 94.4%, respectively; P<0.001). The median HCV RNA levels in HBV-HCV co-infected patients were significantly lower than those in the HCV mono-infected patients (1.18[Interquartile range (IQR) 0–5.57] versus 5.87[IQR, 3.54–6.71] Log10 IU/mL, respectively; P<0.001). Furthermore, co-infected patients were less likely to have detectable HCV RNA levels than HCV mono-infected patients (23.4% versus 56.5%, respectively; P<0.001). Those HBV-HCV co-infected patients had significantly lower median HBV DNA levels than those mono-infected with HBV (1.97[IQR, 1.3–3.43] versus 3.06[IQR, 2–4.28] Log10 IU/mL, respectively; P<0.001). The HBV-HCV co-infection group had higher ALT, AST, ALP, GGT, APRI and FIB-4 levels, but lower ALB and total platelet compared to the HBV mono-infection group, and similar to that of the HCV mono-infected group. Conclusion These results suggest that co-infection with HCV and HBV inhibits the replication of both viruses. The serologic results of HBV-HCV co-infection in patients suggests more liver injury compared to HBV mono-infected patients, but is similar to HCV mono-infection.

Low prevalence of hepatitis B virus infection in patients with autoimmune diseases in a Chinese patient population

Hepatitis B is a very common communicable disease in China but the prevalence of hepatitis B virus (HBV) infection in patients with autoimmune diseases is unknown. We retrospectively investigated the prevalence of autoimmune diseases in patients with HBV infection. The medical records of 4060 patients with autoimmune or nonautoimmune diseases were reviewed. A positive test result for hepatitis B surface antigen (HBsAg) was used to indicate the presence of HBV infection. Autoimmune diseases included autoimmune hepatitis, primary biliary cirrhosis, systemic lupus erythematosus and ulcerative colitis. Nonautoimmune conditions included inguinal hernia, appendicitis and pregnant or postpartum women. The proportion of autoimmune disease patients who were HBsAg positive (2.24%) was significantly lower than that of nonautoimmune disease patients who were HBsAg positive (4.58%; P = 0.0014). Regarding hepatic autoimmune diseases, the positivity rates for HBsAg in autoimmune hepatitis patients (0.83%) and primary biliary cirrhosis patients (1.02%) were both significantly lower than in nonautoimmune patients (4.58%; P = 0.006 and 0.004, respectively). Patients with hepatic autoimmune disease were significantly less likely to be HBsAg positive (0.93%) than patients with non‐hepatic autoimmune disease (3.99%; P = 0.002). Patients with autoimmune diseases, especially those with hepatic autoimmune disease, may more efficiently clear HBV than patients with nonautoimmune diseases.

Accuracy of M2BPGi, compared with Fibro Scan®, in analysis of liver fibrosis in patients with hepatitis C

BackgroundMac-2 Binding Protein Glycosylation isomer (M2BPGi) is a novel serological glyco-biomarker for staging liver fibrosis. Here, we aimed to evaluate the efficiency of serum M2BPGi in identifying liver fibrosis stages in Chinese patients with chronic hepatitis C infection.MethodsSerum M2BPGi levels were evaluated in 680 patients with chronic hepatitis C and 164 healthy controls who underwent the Fibro Scan® test of liver fibrosis. The diagnostic accuracy of serum M2BPGi values was compared to that of other fibrosis markers, including Fibro Scan®, the aspartate transaminase to platelet ratio index (APRI), the fibrosis index based on four factors (FIB4), and the gamma-glutamyltranspeptidase to platelet ratio (GPR).ResultsAmong the chronic hepatitis C patients, the median serum M2BPGi level increased with increasing fibrosis score as follows: 0.88 (≤F2), 1.70 (F2/F3), and 5.68 (cirrhosis). M2BPGi concentrations could also distinguish between healthy controls (0.38 ± 0.24) and hepatitis C patients (1.57 ± 2.28). After adjusting for potential confounders, M2BPGi was the most significant factor associated with the liver stiffness measurement (effect size = 0.275, P < 0.001). The optimum cutoff values of serum M2BPGi for patients with F2 and F4 were 0.945 and 1.355, respectively. The area under the curve of serum M2BPGi for prediction of significant fibrosis (F ≥ 4) using was comparable to that of APRI (0.892 vs. 0.873), while it was superior to that of other alternative markers, including FIB4 (0.818) and GPR (0.851). Compared with other non-invasive markers, M2BPGi had the greatest specificity for diagnosing cirrhosis and cirrhosis in hepatitis C patients.ConclusionsOur results suggest that the level of serum M2BPGi would be a simple and reliable diagnostic tool for identifying liver fibrosis stage in Chinese patients with chronic hepatitis.

Red Blood Cell Distribution Width to Platelet Ratio is Related to Histologic Severity of Primary Biliary Cirrhosis.

AbstractWe aimed to investigate whether red blood cell distribution width (RDW) and RDW to platelet ratio (RPR) were related to the histologic severity of primary biliary cirrhosis (PBC).Seventy-three treatment-naïve PBC patients who had undergone a liver biopsy between January 2010 and January 2015 were enrolled in our study. The patients’ histological stages were based on the classifications of Ludwig and Scheuer. The patients were divided into early stage (Stage I) and advanced stage (Stage II, III, and IV) hepatic fibrosis according to their histological stage. All common patient demographics, clinical characteristics, hematological parameters, liver biochemistry, and antimitochondrial M2 antibody levels (AMA-M2) were retrospectively analyzed, and RDW, RPR, aspartate aminotransferase-to-platelet ratio index (APRI), and fibrosis index based on the 4 factors (FIB-4) were calculated.A total of 28 (38.4%) patients had early stage PBC, whereas 45 (62.6%) were classified as advanced stage. Regarding age, no significant differences between the early and advanced stages were observed. Patients with advanced stage PBC had significantly higher RDW (13.6 vs 14.4; P = 0.019), conjugated bilirubin (10.1 vs 23.4; P = 0.029), and significantly lower cholinesterase (7901.1 vs 6060.8; P = 0.001) and platelets (212.6 vs 167.0; P = 0.006). However, no significant differences (P > 0.05) in other routine parameters previously evaluated in PBC, including aspartate aminotransferase (AST) and mean platelet volume, were found between the groups. The sensitivity and specificity of RDW were 33.3% and 92.9%, respectively, and the area under the receiver-operating characteristic curve (AUROC) was 0.66. However, the sensitivity and specificity of RPR were 46.7% and 96.4%, respectively, and the corresponding AUROC was 0.74 (P < 0.001). Hence, compared with preexisting indicators, RPR showed a higher AUROC than APRI (0.648; P = 0.035) and FIB-4 (0.682; P = 0.009).RDW and RPR may be a new noninvasive marker for predicting histologic severity of PBC.

Red blood cell distribution width and globulin, noninvasive indicators of fibrosis and inflammation in chronic hepatitis patients.

Aims We aimed to develop new simple predictive models for significant fibrosis and inflammation in chronic hepatitis patients using routine laboratory parameters. Methods A total of 218 patients who had undergone liver biopsy were enrolled in our study. Among these, 116 had chronic hepatitis B, 65 had primary biliary cirrhosis, and 37 had autoimmune hepatitis. Patients were divided into two groups: absent–mild (S0–S1, G0–G1) and moderate–severe (S2–S4, G2–G4) according to the histologic severity of liver fibrosis and inflammation. All common demographics and routine laboratory parameters were analyzed. Results Red blood cell distribution width (RDW) and globulin values increased with progressive liver fibrosis and inflammation. After adjustment for other potent predictors, liver fibrosis was associated independently with RDW and platelet (odds ratio=0.976 and 1.487, respectively), whereas significant inflammation was associated independently with globulin, alanine aminotransferase, red blood cell, and platelet (odds ratio=1.153, 1.017, 0.392, and 1.487, respectively). The sensitivity and specificity of model A were 73.4 and 79.1% for the detection of significant liver fibrosis [area under the receiver-operating characteristic curve (AUROC)=0.81, P<0.001]. The sensitivity and specificity of model B were 75.9 and 88.9% for predicting advanced liver inflammation (AUROC=0.89, P<0.001). Compared with pre-existing indicators, model A achieved the highest AUROC (0.81, P<0.001) for liver fibrosis, whereas model B showed the highest AUROC (0.89, P<0.001) for liver inflammation. Conclusion RDW may provide a useful clinical value for predicting liver fibrosis; meanwhile, globulin may provide a useful clinical value for predicting liver inflammation in chronic hepatitis patients with other markers.

Factors Associated with Spontaneous Clearance of Hepatitis C Virus in Chinese Population

Hepatitis C virus (HCV) infections spontaneously clear in approximately 15–45% of infected individuals. Factors which influence spontaneous HCV clearance remain to be identified. The purpose of the present study was to identify variables associated with spontaneous HCV clearance in a referred population of Chinese patients. The prevalence of host, viral, and environmental factors known to influence the outcome of HCV infections was compared in 92 HCV spontaneous clearance subjects and 318 HCV persistent infection subjects. Univariate and multivariate analyses were performed to identify those factors associated with spontaneous HCV clearance. In univariate analysis, female gender, a history of icteric hepatitis, serologic evidence of concurrent HBV infection, and rs12979860 CC genotype were positively associated with spontaneous HCV clearance, while alcohol consumption was negatively associated with clearance. In multivariate analysis, female gender, a history of icteric hepatitis, concurrent HBV infection, and rs12979860 CC genotype remained independent variables associated with spontaneous HCV clearance. Spontaneous HCV clearance is more likely to occur in females, subjects with a history of icteric hepatitis, HBV coinfections, and those with the rs12979860 CC genotype.

The presence of hepatitis B core antibody is associated with more advanced liver disease in alcoholic patients with cirrhosis

BACKGROUND Liver disease is more severe in patients with chronic hepatitis B virus (HBV) infections and alcohol-induced liver injury. Whether the same is true for alcoholic patients with cirrhosis who have recovered from previous HBV infections remains to be determined. OBJECTIVES To document the extent of liver disease in alcoholic patients with cirrhosis who test negative for hepatitis B surface antigen (HBsAg) and test positive for antibody to hepatitis B core antigen (anti-HBc). METHODS Two hundred fifty-four alcoholic patients with cirrhosis were divided into anti-HBc-positive (N = 171) and anti-HBc-negative (N = 83) cohorts. Demographic, clinical, and biochemical features were retrospectively analyzed. Prognostic scores and the prevalence of patients at high risk for short-term mortality were calculated. Logistic regression was used to identify factors associated with an increased risk for short-term mortality. RESULTS Jaundice was more common in the anti-HBc-positive cohort (32.2% vs. 18.1%, p = 0.02). This cohort also had higher serum bilirubin (70.9 vs. 50.4 μM/L, p = 0.03), prothrombin times (15.6 vs. 14.4 s, p = 0.01), MELD scores (8.5 vs. 4.6, p = 0.01), i-MELD scores (28.6 vs. 24.7, p = 0.03), MDF scores (14.2 vs. 6.8, p = 0.02) and ABIC scores (7.2 vs. 6.6, p = 0.01). In addition, anti-HBC-positive patients were more often at high risk for short-term mortality (40.4% vs. 26.5%, p = 0.03). Multivariate analysis identified anti-HBc-positive status (OR: 1.84; 95% CI: 1.10-3.36) and alcohol intake ≥150 g/day (OR: 2.01; 95% CI: 1.10-3.66) as independent risk factors for high risk of mortality. CONCLUSION The anti-HBc-positive state is associated with more advanced liver disease in alcoholic patients with cirrhosis. A prospective study including HBV-DNA testing and liver biopsies should be considered to validate and further elucidate these findings.

IFNL4 ss469415590 Polymorphism Contributes to Treatment Decisions in Patients with Chronic Hepatitis C virus Genotype 1b but not 2a Infection

Recently, the dinucleotide variant ss469415590 (TT/ΔG) in a novel gene, interferon lambda 4 (IFNL4), was identified as a stronger predictor of hepatitis C virus (HCV) clearance in individuals of African ancestry compared with rs12979860. We aimed to determine whether this variant contributes to treatment decisions in a Chinese population. A total of 447 chronic hepatitis C (CHC) patients (including 328 treated with interferon alpha-2b and ribavirin), 129 individuals who had spontaneously cleared HCV (SHC), and 169 healthy controls were retrospectively investigated. ss469415590 genotyping was performed using a mass spectrometry method (SEQUENOM). A higher proportion of SHC individuals carried the TT/TT genotype compared with CHC patients (95.3% vs. 88.8%, P=0.027). In patients with HCV genotype 1b, the ss469415590 variant was independently associated with sustained virologic response (SVR) (odds ratio [OR]=3.247, 95% confidence interval [CI]=1.038-10.159, P=0.043) and on-treatment virological responses, including rapid (RVR), complete early (cEVR), early (EVR), and end-of-treatment (ETVR), with a minimal OR of 3.73. Especially for patients with high viral load (≥4×10(5) IU/ml), ΔG allele carriers had a lower chance of achieving SVR compared with those carrying the TT/TT genotype (7.1% vs. 36.0%, P=0.034, OR [95% CI]=7.24 [1.02-318.45], negative predictive value=92.9%). In patients with HCV genotype 2a, no significant association between the ss154949590 variant and the virological response was identified (P>0.05). Additionally, we found that ss154949590 was in complete linkage disequilibrium with rs12979860. In conclusion, the IFNL4 ss154949590 TT/TT genotype favors spontaneous clearance of HCV. This same variant is associated with treatment-induced clearance in patients with genotype 1b, but not 2a. ss469415590 (or rs12979860) genotyping should be considered for patients with HCV genotype 1b and high viral load when making a choice between standard dual therapy and an IFN-free direct-acting antiviral regimen.

CD24 Ala57Val polymorphism is associated with spontaneous viral clearance in the HCV‐infected Chinese population

Host immune response to hepatitis C virus (HCV) is a vital factor involved in both viral clearance and liver disease pathogenesis. CD24 plays an important role in inflammation and immune response and CD24 polymorphisms are associated with risk and progression of chronic hepatitis B virus infection. Our study evaluated whether CD24 polymorphisms affect HCV clearance.

Use of parenteral caffeinum natrio-benzoicum: an underestimated risk factor for HCV transmission in China

BackgroundFuyu city in China has a high prevalence of hepatitis C virus (HCV) infection resulting in a high morbidity and mortality from chronic liver disease and hepatocellular carcinoma. This study was conducted to identify the risk factors for HCV infection in Fuyu city.MethodsRecruitment of study subjects involved a cross-sectional survey using non-random, convenience sampling. Information on demographic variables, risk factors for HCV infection, clinical manifestations, behavioral practices and family history was collected by administering a questionnaire. Anti-HCV antibody was detected using Abbott ARCHITECT i2000SR. HCV infection was confirmed by HCV-RNA testing by the Roche Taqman HCV test. Univariate and multivariate analyses were performed to identify the factors associated with HCV infection.ResultsOut of 3,228 persons that participated in the survey, 3,219 were enrolled in the study. The prevalence of HCV infection was 42.1 % (1355/3219). Among 734 patients with chronic HCV infection whose HCV-RNA genotyping was performed, genotype 1b was the most common (58.0 %), followed by genotype 2a (40.2 %), while co-infection with genotypes 1b and 2a was detected in 1.8 % of the subjects. On univariate analysis, male gender, older age, parenteral caffeinum natrio-benzoicum and share syringes (PCNBSS), and nine other factors were significantly associated with HCV infection. After adjusting for potential confounders, male gender, old age, cigarette smoking, lower education level, history of blood transfusion, blood donation, prior dental surgery, and PCNBSS were found to be independently associated with HCV infection.ConclusionsThe prevalence of HCV infection is likely to be high among residents in Fuyu and we observed that genotypes 1b and 2a dominated in the city. Our findings support the hypothesis that PCNBSS which became endemic in Fuyu city during 1970s-1980s is strongly associated with HCV positivity.