Chinese Chronic Hepatitis C Patients Research Articles

Cost-Effectiveness Analysis of Oral Direct-Acting Antivirals for Chinese Patients with Chronic Hepatitis C.

All oral direct-acting antivirals (DAAs) have shown excellent efficacy and safety in Chinese patients with chronic hepatitis C (CHC). However, the cost of DAAs used to be expensive; therefore, large numbers of patients had no access to DAAs in China. Recently, prices have been greatly reduced. The objective of this study was to evaluate the cost-effectiveness of ledipasvir/sofosbuvir (LDV/SOF), sofosbuvir/velpatasvir (SOF/VEL), elbasvir/grazoprevir (EBR/GZR) and glecaprevir/pibrentasvir (GLE/PIB) in Chinese CHC patients stratified by hepatitis C virus (HCV) genotype (GT), cirrhosis status, and treatment history. On the basis of a Chinese healthcare perspective, a Markov model was constructed to estimate the lifetime costs and health outcomes of patients treated with different DAA regimens. Chinese-specific clinical, cost, and utility inputs were obtained or calculated from published sources and expert opinions. Costs, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were reported as primary outcomes. Base-case analysis and sensitivity analysis were conducted. At a willing-to-pay (WTP) threshold of US$30,081/QALY (calculated by three times the GDP per capita in China), SOF/VEL was cost-effective in patients with HCV GT 1, 3, and 6 infections, and the probabilities that SOF/VEL was cost-effective were 9.7-75.7%, 39.1-63.9%, and 35.6-88.0%, respectively. For GT2 patients, noncirrhotic patients, treatment-naïve patients, and treatment-experienced patients, LDV/SOF was the most cost-effective regimen, and the probabilities of cost-effectiveness for each of these groups was 92.1-99.8%, 89.9-99.0%, 61.6-91.2%, and 99.3-100.0%, respectively below the WTP threshold. The GLE/PIB regimen (12-week duration) was the most cost-effective in cirrhotic patients, whereas the probability of its cost-effectiveness varied with that of EBR/GZR (4.1-93.8% versus 6.2-93.3%) below the WTP threshold. Overall, SOF/VEL and LDV/SOF regimens are more likely to be cost-effective among various subgroups of Chinese patients with CHC.

IN1 - Impact of Sofosbuvir-Based Regimens for Chronic Hepatitis C Infection: A Work Productivity Model from Mainland China

Chronic Hepatitis C (CHC) imposes a considerable disease burden in China. There are approximately 10 million Chinese CHC patients, the majority of which are genotype 1 (GT1). Untreated infections are associated with a poor clinical prognosis and impairment in work productivity (WP), which has not been comprehensively evaluated in mainland China. This study models the impact of CHC infection on WP in China and estimates potential WP gains associated with ledipasvir/sofosbuvir (LDV/SOF) and sofosbuvir/velpatasvir (SOF/VEL) treatments, which are currently under review by China FDA. An economic model was developed to assess the impact of treatment with LDV/SOF on WP over a one-year period, with patients entering the model post-treatment, having achieved sustained virological response at 12 weeks (SVR12), or not. Absenteeism (absence from work) and presenteeism (reduced productivity at work) rates were extracted from the Phase III ION and ASTRAL trials as measured by the Work Productivity and Activity Index-Specific Health Problem questionnaire (WPAI-SHP); rates were assumed to be unchanged from baseline for patients not achieving SVR12. These rates were converted into hours of lost productivity, multiplied by the average working wage, total employment rate, and adult GT1 population in mainland China. We assumed universal treatment with either LDV/SOF or SOF/VEL in the model and contrasted the results relative to no treatment. Total annual work productivity loss due to not treating GT1 CHC patients was estimated to be around ¥18.11 billion. Treatment with sofobusvir-based regimens resulted in estimated productivity gains of ¥6.85 billion, primarily due to reduced presenteeism. Productivity losses due to untreated HCV infection represent a substantial indirect economic burden in China. Treatment with sofobusvir-based regimens is likely to result in substantial economic savings for society versus no treatment, which should be considered when assessing the value of CHC treatment.

Impact of diabetes mellitus and hepatitis B virus coinfection on patients with chronic hepatitis C: A territory‐wide cohort study

Studies have demonstrated a higher prevalence of diabetes mellitus (DM) in patients with chronic hepatitis C (CHC). Furthermore, coinfection with hepatitis B virus (HBV) is common because of its endemicity in Asian-Pacific regions. The aim of the present study was to investigate the impact of DM and HBV coinfection on the clinical outcomes in Chinese CHC patients. A territory-wide cohort study was conducted using the database from Hospital Authority, the sole public medical service provider in Hong Kong. CHC patients were identified by the International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes, diagnosed between 2000 and 2012. The primary outcome was overall mortality. A total of 7149 CHC patients were included. Seven hundred twenty-two (10.1%) patients were coinfected with HBV. Their mean age was 56years; 69.0% were men. The prevalence of DM was similar in mono-infection and coinfection cohorts (22.3% and 21.3%, respectively). Multivariable analysis identified DM as an independent risk factor for death and antiviral treatment for hepatitis C virus (HCV) as an independent protective factor against death. The 5-year survival of CHC patients with mono-infection was better than that of HBV coinfected patients (62.5% vs 57.0%; P=0.001). The 5-year survival of patients who did or did not receive antiviral treatment for HCV was 94.7% and 55.2%, respectively (P<0.001). Hepatitis B virus coinfection and DM were independent risk factors for death in Hong Kong CHC patients. Antiviral treatment for HCV but not HBV was a protective factor against death.

Influence of IL28B and MxA gene polymorphisms on HCV clearance in Han Chinese population.

The high rate of chronic hepatitis C (CHC) was one of the key issues of global public health concern. Interferon (IFN)-λ relevant genes were in the antiviral treatment pathway, not only influenced hepatitis C virus (HCV) spontaneous clearance, but also affected the IFN-mediated viral clearance. The aim of this study was to identify the association of interleukin 28B (IL28B), myxovirus resistance A (MxA) gene polymorphisms with HCV spontaneous clearance and therapeutic response in Chinese CHC patients. IL28B and MxA gene genotypes were detected among 231 CHC carriers, 428 subjects with HCV spontaneous clearance and 662 CHC patients with pegylated IFN-α and ribavirin (pegIFN-α/RBV) treatment. Patients with MxA rs2071430 TT genotype were more likely to develop HCV infection chronicity (additive model: odds ratio (OR) 1.22, 95% confidence interval (CI) 1.01-1.48, P = 0.042). IL28B rs1298075 variant genotypes (additive model: OR 0.58, 95% CI 0.34-0.98, P = 0.040) and MxA rs17000900 variant genotypes (additive model: OR 0.54, 95% CI 0.30-0.99, P = 0.048) were less likely to achieve a sustained virological response. The life table indicated that patients with IL28B rs1298075 AG genotype were slower to achieve a viral load 106 copies/ml (all P < 0.05). This study illustrated that the carriage of IL28B rs12980275 AA had a positive effect on treatment response to pegIFN-α/RBV among Chinese CHC patients.

Annual Change in FIB-4, but not in APRI, was a Strong Predictor for Liver Disease Progression in Chinese Patients with Chronic Hepatitis C

Background: Previous studies showed a significant prognostic value of 3-year and 5-year evolution of noninvasive fibrosis tests in European chronic hepatitis C (CHC) patients with or without HIV. It is uncertain whether this conclusion can be extrapolated to Chinese patients and whether the assessment of noninvasive fibrosis tests in a shorter time interval still has a prognostic value. Objectives: The study aimed to assess the prognostic value of changes of aspartate aminotransferase-to-platelet ratio (APRI) and fibrosis-4 (FIB-4) in consecutive years in Chinese CHC patients. Methods: There were 173 CHC patients enrolled in 2 centers in this retrospective study. APRI and FIB-4 were calculated every 12 ± 2 months. The average difference between 2 adjacent calculations was defined as an annual change (AC). Risk factors were evaluated by Cox proportional regression models. Results: Cirrhosis, hepatic decompensation, hepatocellular carcinoma, and liver-related death developed in 29 patients during the median follow-up of 47.0 (29.5 - 72.0) months. Baseline FIB-4 and APRI, Child-Pugh class C, non-sustained virologic response (SVR) to interferon (IFN) or Pegylated IFN plus ribavirin, and AC of FIB-4 were significantly associated with liver disease progression. AC of FIB-4 (P 3.25 and AC of FIB-4 > 0.22, or non-SVR and AC of FIB-4 > 0.22 had the highest cumulative incidence of liver disease progression among the 4 groups identified according to baseline FIB-4 and AC of FIB-4, or SVR and AC of FIB-4. Conclusions: An increased FIB-4 over time is an independent risk factor of liver disease development in Chinese CHC patients. Monitoring FIB-4 annually may help physicians to predict prognosis in CHC patients.

Diabetes mellitus is a significant risk factor for the development of liver cirrhosis in chronic hepatitis C patients

We explored the association between diabetes mellitus (DM) and the risk of hepatitis C virus (HCV)-related liver cirrhosis in Chinese patients with chronic hepatitis C (CHC). To examine the link between DM and liver cirrhosis, we conducted a case-control study of 210 Chinese CHC patients diagnosed with liver cirrhosis, comparing them to an age- and sex-matched control group of 431 CHC patients without liver cirrhosis. We conducted logistic regression analyses adjusting for demographic features and liver cirrhosis risk factors, and found that DM increased the risk of developing liver cirrhosis 2-fold [adjusted odds ratio (AOR), 2.132; 95% confidence interval (CI), 1.344–3.382]. Furthermore, the proportion of liver cirrhosis patients and CHC-only patients with elevated serum triglycerides (>1.8 mmol/L) were 5.2% and 17.4%, respectively, yielding an AOR of 0.264 (95% CI, 0.135–0.517). Multivariate analyses that stratified the risk of developing HCV-related liver cirrhosis in DM patients by gender revealed that the estimated AOR (95% CI) for males was 0.415 (0.178–0.969). In conclusion, DM was associated with an increased risk of developing liver cirrhosis in CHC patients in China. Furthermore, among patients diagnosed with both CHC and DM, females had an increased risk of liver cirrhosis development.

Liver cirrhosis

We investigated the possible link between liver cirrhosis and gallstone risk in chronic hepatitis C (CHC) patients in China.To analyze the association between liver cirrhosis and gallstone development, we compared outcomes of 133 Chinese CHC patients with gallstones and an age-, sex-, and hepatitis C virus RNA level-matched control group of 431 CHC patients without gallstones.We found that liver cirrhosis was more prevalent in gallstone patients (40.6%) than in the control group (24.4%). Logistic regression analyses adjusting for demographic features and other gallstone risk factors revealed that liver cirrhosis increased the risk of gallstone development 2-fold (adjusted odds ratio [AOR]: 2.122; 95% confidence interval [CI]: 1.408–3.198). Moreover, multivariate analyses comparing the risk of gallstone development in liver cirrhosis patients with decompensated or compensated liver cirrhosis yielded an estimated AOR (95% CI) of 2.869 (1.277–6.450) in patients with decompensated liver cirrhosis. Gallstone risk also increased significantly with older age (>60 years) (AOR: 2.019; 95% CI: 1.017–4.009).Liver cirrhosis significantly correlates with increased risk of gallstone development in CHC patients in China. Decompensated liver cirrhosis and older age further heighten this risk in patients diagnosed with hepatitis C-related cirrhosis.

Diabetes mellitus increases the risk of hepatocellular carcinoma in treatment-naïve chronic hepatitis C patients in China.

We investigated the link between diabetes mellitus (DM) and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) risk in treatment-naïve chronic hepatitis C (CHC) patients in China.To examine the association between DM and HCC, we conducted a case–control study of 300 Chinese CHC patients with HCC, compared to an age- and sex-matched control group of 517 CHC patients not diagnosed with HCC.We found that DM was more prevalent in the HCC patient group (18.7%) than in the CHC-only patient group (10.8%). We conducted logistic regression analyses adjusting for demographics features and other HCC risk factors and found that DM increased the risk of HCC development nearly 2-fold [adjusted odds ratio (AOR), 95% confidence interval (95% CI), 1.80 (1.17–2.75)]. Meanwhile, the proportion of HCC patients and CHC-only patients with liver cirrhosis were 79.3% and 46.2%, respectively, yielding an AOR of 4.62 (95% CI, 3.31–6.46). Multivariate analyses comparing the risk of HCV-related HCC development in DM patients with and without liver cirrhosis revealed that the estimated AOR (95% CI) for those with liver cirrhosis was 5.60 (2.25–13.96). However, the HCC risk decreased significantly with a later age of diabetes onset (AOR [95% CI], 0.94 [0.89–0.99]).DM was associated with an increased risk for HCC development in treatment-naïve CHC patients in China. Furthermore, liver cirrhosis and an early DM diagnoses further increased the risks of HCC development in patients diagnosed with both CHC and DM.

Efficacy and safety of combined directly acting antivirals for treatment of Chinese chronic hepatitis C patients in a real-world setting.

AIMTo assess the efficacy and safety of combined directly acting antivirals (DAAs) for the treatment of Chinese chronic hepatitis C (CHC) patients in a real-world setting.METHODSHospitalized CHC patients who were treated with DAAs at Peking University First Hospital between January 2015 and December 2016 were enrolled. Samples and clinical data were collected at 0 wk, 2 wk, 4 wk, 8 wk, 12 wk, or 24 wk during DAAs treatment and at 4 wk, 12 wk, and 24 wk after the end of treatment.RESULTSFifty-four patients who underwent DAAs treatment were included in our study, of whom 83.3% (45/54) achieved rapid virological response at 2 wk after treatment initiation (RVR 2) and 94.4% (51/54) achieved sustained virological response at 24 wk after the end of treatment (SVR 24). Serum creatinine and uric acid levels at the end of treatment were significantly increased compared with baseline levels (83.6 ± 17.9 vs 88.8 ± 19.4, P01 < 0.001; 320.8 ± 76.3 vs 354.5 ± 87.6, P01 < 0.001), and no significant improvements were observed at 24w after the end of treatment (83.6 ± 17.9 vs 86.8 ± 19.1, P02 = 0.039; 320.8 ± 76.3 vs 345.9 ± 89.4, P02 = 0.001). The total frequency of adverse events (AEs) during treatment was 33.3% (18/54), with major AEs being fatigue (16.7%), headache (7.4%), anorexia (7.4%), and insomnia (5.6%).CONCLUSIONThough based in a small cohort of patients, the abnormal changes in renal function indices and relative high frequency of AEs during combined DAAs treatment should be taken as a note of caution.

Association between ABO blood group and HCV-related hepatocellular carcinoma risk in China.

The ABO blood group has previously been reported to be associated with risk for certain malignancies; however, data about the risks for hepatocellular carcinoma (HCC) according to blood type are limited. Thus, we conducted a retrospective case–control study to investigate whether the ABO blood group contributes to hepatitis C virus (HCV) infection–induced HCC.From January 2010 to June 2016, 447 consecutive patients with chronic HCV infection were recruited. Of these patients, 217 had HCV-related HCC, and 230 had chronic hepatitis C (CHC) without HCC. We performed multivariate logistic regression to probe the association between the ABO blood group and HCC risk.Compared with subjects with blood type O, patients with blood type A had an adjusted odds ratio (AOR) of 3.301 (95% confidence interval [CI], 1.927–5.653) for HCC after adjusting for age and gender. We found statistically significant associations between blood type A and HCC risk for both men (AOR [95% CI] = 4.192 [1.959–8.973]) and women (AOR [95% CI] = 2.594 [1.231–5.466]), and for patients aged below 70 years (<60 years: AOR [95% CI] = 3.418 [1.338–8.734]; 60–69 years: AOR [95% CI] = 3.917 [1.730–8.867]).Thus, HCC risk is associated with ABO blood type in Chinese CHC patients, and CHC patients with blood type A are more susceptible to HCV-related HCC than patients with other blood types.

Sustained viral response and treatment-induced cytopenia correlate with SLCs and KLF12 genotypes in interferon/ribavirin-treated Chinese chronic hepatitis C patients.

Genetic variations in solute carrier (SLC) genes are associated with liver diseases, and Kruppel-like factor 12 (KLF12) affects the b chain of hemoglobin. We investigated possible correlations of SLC and KLF12 polymorphisms with viral clearance (spontaneous and treatment-induced) and adverse effects in Chinese chronic hepatitis C (CHC) patients. We genotyped the single nucleotide polymorphisms in 525 CHC patients, 137 patients with spontaneous clearance, and 207 healthy controls. Three hundred fifty-seven CHC patients received recombinant interferon-alpha2b/ribavirin (IFN-α2b/RBV) treatment, and 175 patients were chosen for analysis of drug-induced cytopenia. All raw P-values were corrected by the Bonferroni method. A higher rate of sustained viral response was detected in patients with SLC4A11 rs3810560 CC variant versus TT/TC variant (76.9% vs 59.2%; OR, 2.42; 95% CI, 1.06-5.56, P = 0.037 after adjustment), but there was no significant difference among different hepatitis C virus genotypes. RBV-induced anemia was independently correlated with SLC29A1 rs760370 AA genotype (OR, 2.90; 95% CI, 1.29-6.54, P = 0.010), and the severity of IFN-induced thrombocytopenia was related to GG genotype (OR, 4.98; 95% CI, 1.27-19.61; P = 0.021); the detected effects held true for HCV-2a patients but weakened in HCV-1b patients. A reactive increase in platelet count was closely associated with KLF12 rs9543524 TT variant. SLC4A11 rs3810560 polymorphism independently affected the sustained viral response rates in CHC patients, whereas SLC29A1 rs760370 and KLF12 rs9543524 single nucleotide polymorphisms correlated with treatment-induced adverse events. Clearly, the predictive power varied with HCV genotypes and the reason for genotype-dependent discrepancy was not fully understood.

Impact of IL28B and PNPLA3 polymorphisms on treatment outcomes in patients infected with genotype 6 hepatitis C virus.

Interleukin-28B (IL28B) and patatin-like phospholipase domain containing 3 (PNPLA3) gene polymorphisms are associated with hepatitis C virus (HCV) clearance and fatty liver, respectively. We aimed to test if their polymorphisms are associated with virologic responses in Chinese chronic hepatitis C (CHC) patients. This was a retrospective-prospective cohort study. Consecutive patients infected by genotype 1 and 6 HCV received antiviral therapy were included. Host IL-28B rs12979860/rs8099917 and PNPLA3 rs738409 genotype were tested. The primary outcome was sustained virologic response (sustained virologic response [SVR]: undetectable HCV RNA 24 weeks post-treatment). From 305 patients had positive antibody to HCV, 52 and 31 patients infected by genotype 1 and 6 HCV, respectively were recruited. Mean age was 58 ± 11 years; 70% were male. Mean baseline HCV RNA was 6.8 ± 2.7 log IU/ml. The SVR for patients infected by genotype 1 and 6 HCV was 67.3% and 90.3%, respectively. The proportions of IL28B genotypes were 78%, 21%, and 1% for TT/TG/GG at rs8099917, and 81%, 18%, and 1% for CC/TC/TT at rs12979860, respectively. The proportions of PNPLA3 rs738409 genotypes were 16%, 36%, and 48% for GG/GC/CC. IL28B genotype was significantly associated with SVR in patients infected by genotype 1 but not genotype 6 HCV, with 80% versus 38% of patients infected by genotype 1 achieved SVR carried TT versus TG/GG at rs8099917, respectively (P=0.003). PNPLA3 genotype was not associated with SVR. IL28B gene with rs8099917 T allele as an independent predictor of SVR in Chinese CHC patients infected by genotype 1 but not genotype 6 HCV.

Baseline factors associated with treatment response in patients infected with hepatitis C virus 1b by stratification of IL28B polymorphisms.

Although the single-nucleotide polymorphism (SNP) rs12979860 in the IL28B gene is a better predictor of sustained virological response to treatment of chronic hepatitis C (CHC) than other baseline factors, some CHC patients with the favorable C allele cannot achieve a sustained virological response when treated with peginterferon plus ribavirin. The aim of this study was to examine baseline factors as predictors of rapid virological response (RVR) and complete early virological response (cEVR) to peginterferon alfa-2a plus ribavirin treatment in Chinese CHC patients with hepatitis C virus (HCV) genotype 1b, with emphasis on the difference between the rs129860 CC and CT/TT genotypes. A total of 337 treatment-naïve patients participated in this study. All patients were treated with peginterferon alfa-2a plus ribavirin at standard dosage. Serum samples from all patients were collected at baseline, week 4, and week 12 for testing of laboratory parameters, and IL28B genotypes were determined. Multivariate analysis showed that among rs12979860 CC genotype patients, glucose level and aspartate amino transferase (AST) activity were inversely associated with RVR, while abnormal platelet count and allergy inversely associated with cEVR. Among rs12979860 CT genotype patients, age below 40years and short infection duration were associated with RVR, while age below 40years, short infection duration, high body mass index (BMI), and no history of allergies were associated with cEVR. The baseline factors associated with the response to CHC treatment may depend on the IL28B genotype. Refinement of the baseline predictors based on IL28B genotypes may be useful for management of HCV infection.

The host HLA-A*02 allele is associated with the response to pegylated interferon and ribavirin in patients with chronic hepatitis C virus infection.

Human leukocyte antigen (HLA) alleles are associated with both the progression of chronic hepatitis C (CHC) and the sustained virological response (SVR) to antiviral therapy. HLA-A*02 is the most common HLA allele in people of European/Caucasian descent and the Chinese and Japanese population. Therefore, we investigated whether HLA-A*02 expression is associated with disease outcome in Chinese CHC patients. Three hundred thirty-one treatment-naïve CHC patients were recruited in this study. The expression of HLA-A*02 was tested by FACS and LABType SSO assays. All patients were treated weekly with pegylated interferon plus ribavirin (PEG-IFN/RBV) according to a standard protocol. Virological response was assessed by TaqMan assay at the 4th, 12th, 24th, and 48th week of therapy, and again at the 24th week post-therapy. By the end of the study, 293 CHC patients, including 144 HLA-A*02-positive patients and 149 HLA-A*02-negative patients, were evaluable for analysis. There were no statistical differences in clinicopathological parameters between HLA-A*02-positive and negative patients before antiviral therapy (P > 0.05). The HLA-A*02-positive patients had a higher rapid virological response (RVR, 74.3 % versus 62.4 %, P = 0.03) and SVR (78.5 % versus 64.4 %, P = 0.01) and a lower relapse rate (4.2 % versus 11.9 %, P = 0.03) than HLA-A*02-negative patients. Multivariable logistic regression analysis showed that HLA-A*02 expression, liver fibrosis stages <S3, HCV genotype 2a, IL-28B rs8099917 TT, and RVR were independent predictive factors of SVR (P < 0.05). Host HLA-A*02 allele expression is associated with SVR, highlighting the importance of considering HLA-A*02 as a predictor of the response to PEG-IFN/RBV treatment in the Chinese population with CHC.

Association of interferon-γ-induced protein-10 serum levels with virological responses to PEG-interferon-based therapy in hepatitis C virus genotype 1 or 2 chronically infected Chinese patients

Objective. Interferon (IFN)-γ-induced protein-10 (IP-10) serum level has been shown be associated with viral response in chronic hepatitis C (CHC) patients. However, little is known in Chinese population. We determined IP-10 serum levels in Chinese CHC patients undergoing PEG-IFN-based therapy. Predictive role of IP-10 level for virological responses was accessed. Material and methods. IP-10 serum levels were determined in 165 hepatitis C virus (HCV) genotype 1 and 33 genotype 2 patients. Multivariate analysis was performed to screen independent factors for sustained virological response (SVR) prediction. Predictive value of IP-10 level in combination with interleukin 28B (IL28B) genotype or rapid virological response was further investigated. Results. Our study showed that pretreatment IP-10 level was significantly higher in HCV genotype 1 patients. IP-10 levels were independently predictive for SVR with cut-off values of 250.60 pg/ml at baseline or 407.40 pg/ml at week 4. Positive predictive value (PPV) for SVR of low IP-10 level at baseline and IL28B CC genotype was 96.15% and negative predictive value (NPV) was 50.00%. PPV for SVR of low IP-10 level at week 4 and rapid viral response (RVR) was 95.24% and NPV was 50.00%. Conclusion. Together our study indicated that higher IP-10 serum levels were associated with HCV genotype 1 CHC Chinese patients. IP-10 levels at baseline and week 4 were both predictive of SVR and improved predictive performances of IL28B genotype and RVR for SVR.

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. We genotyped 544 chronic hepatitis C (CHC) patients, 78 spontaneous hepatitis C clearance (SHC) patients and 215 healthy controls for CD24 gene variants at positions -P534, P170, P1527 and IFNL3 rs12979860 by pyrosequencing. In CHC patients, 362 individuals were treated with a recombinant IFN-α2b/ribavirin combination for 48weeks and were followed up for an additional 24weeks. Lymphocyte CD24 expression was analysed by flow cytometry. We show that P170 CT and CT/TT genotypes were over-represented in the SHC group compared to CHC patients (62.8% vs. 47.2% and 75.6% vs. 60.3%, for respective polymorphisms). In multivariate logistic analysis, P170 (CD24 Ala57Val) polymorphism was an independent predictor of SHC (adjusted OR=2.11, 95%CI=1.19-3.73, P=0.010 for CT genotype; OR=2.01, 95%CI=1.15-3.49, P=0.014 for CT/TT genotype). No significant associations were found between the CD24 polymorphisms and treatment-induced viral clearance in log-rank analysis and Cox regression analysis. Patients with the CT/TT genotype had greater T-cell CD24 expression than patients with the CC genotype. Our findings suggest that CD24 Ala57Val polymorphism and associated variations in CD24 expression may be an important predictor for SHC, but have no effect on antiviral drug treatment response in Chinese CHC patients.

Preliminary study of the level of visfatin and the relationship with insulin resistance in Chinese patients with chronic hepatitis C.

Many studies have suggested that visfatin expression is closely related to the occurrence of insulin resistance (IR), while the precise role of visfatin in the regulation of IR in chronic hepatitis C (CHC) is not clear. We investigated fasting glucose, fasting insulin (FINS), C peptide, visfatin, visfatin mRNA, interleukin (IL)-6, tumor necrosis factor (TNF)-α, C-reactive protein (CRP) and other parameters of 315 patients with CHC and 150 control cases in China. Meanwhile we collected clinical and other laboratory data for further analysis. Compared with the control group, the CHC group had a significant increase in alanine aminotransferase (ALT), aspartate aminotransferase (AST), the AST to platelet ratio index (APRI), ratio of AST to ALT (AAR), gammaglutamyl trans-peptidase, IL-6, TNF-α, visfatin, visfatin mRNA, FINS, fasting C peptide, and IR index. The visfatin, visfatin mRNA, insulin, IR index, Homaβ cell function index (HBCI), and fasting β-cell function index (FBCI) of the subjects with high body mass index (BMI) from the CHC sub-group were significantly higher than the normal BMI sub-group of CHC patients. We found a positive correlation between visfatin, visfatin mRNA and BMI, IL-6, TNF-α, and IR index. Our data suggest that visfatin may be related to IR in Chinese CHC patients.

Treatment with peginterferon versus interferon in Chinese patients with chronic hepatitis C

Higher sustained virological response (SVR) rates after treating with peginterferon than after treating with interferon have been obtained in some randomized clinical trials (RCTs) in Chinese patients with chronic hepatitis C (CHC). However, the numbers of patients included in these clinical trials were too small to draw a clear conclusion. Therefore, a new meta-analysis including a large number of patients was needed to compare peginterferon with interferon in the treatment of Chinese CHC patients. A search of Medline, the China National Knowledge Infrastructure, the Wanfang Database, and the China Biomedical Database for relevant articles published between 1966 and 2009 was performed. RCTs comparing the use of peginterferon and interferon for the treatment of Chinese patients with CHC were assessed. Of the 236 studies screened, 18 RCTs including 1,148 patients (659 treated with peginterferon therapy and 489 treated with interferon therapy) were analyzed. The total SVR rates obtained in patients treated with peginterferon were significantly higher than those obtained in patients treated with interferon (64% vs. 40%; relative risk, 1.56; 95% confidence interval: 1.28-1.91; p < 0.01), but the difference between the peginterferon α-2b and interferon α-2b treatments was not significant. Withdrawal rates were similar between patients treated with peginterferon and interferon. Chinese patients with CHC have a greater likelihood of achieving an SVR with peginterferon α-2a.