Prediction and analysis of COVID-19 daily new cases and cumulative cases: times series forecasting and machine learning models.

BACKGROUND: COVID-19 poses a severe threat to global human health, especially the USA, Brazil, and India cases continue to increase dynamically, which has a far-reaching impact on people's health, social activities, and the local economic situation. METHODS: The study proposed the ARIMA, SARIMA and Prophet models to predict daily new cases and cumulative confirmed cases in the USA, Brazil and India over the next 30 days based on the COVID-19 new confirmed cases and cumulative confirmed cases data set(May 1, 2020, and November 30, 2021) published by the official WHO, Three models were implemented in the R 4.1.1 software with forecast and prophet package. The performance of different models was evaluated by using root mean square error (RMSE), mean absolute error (MAE) and mean absolute percentage error (MAPE). RESULTS: Through the fitting and prediction of daily new case data, we reveal that the Prophet model has more advantages in the prediction of the COVID-19 of the USA, which could compose data components and capture periodic characteristics when the data changes significantly, while SARIMA is more likely to appear over-fitting in the USA. And the SARIMA model captured a seven-day period hidden in daily COVID-19 new cases from 3 countries. While in the prediction of new cumulative cases, the ARIMA model has a better ability to fit and predict the data with a positive growth trend in different countries(Brazil and India). CONCLUSIONS: This study can shed light on understanding the outbreak trends and give an insight into the epidemiological control of these regions. Further, the prediction of the Prophet model showed sufficient accuracy in the daily COVID-19 new cases of the USA. The ARIMA model is suitable for predicting Brazil and India, which can help take precautions and policy formulation for this epidemic in other countries.

Viral and host factors associated with outcomes of hepatitis C virus infection (Review).

Hepatitis C virus (HCV) infection is a major health issue globally. Owing to the progress made in host genetics and HCV molecular virology, emerging data have suggested that the natural course and treatment response in patients with HCV infection are largely determined by complex host­viral interactions. HCV genotype is the most important viral factor predicting the response to pegylated interferon­α plus ribavirin therapy. The subtype of HCV genotype 1 is the key viral factor that predicts the efficacy of direct­acting antiviral therapy. HCV genome heterogeneity and baseline viral load are additionally associated with the treatment response. Multiple host genetic variants localized in genes associated with the immune response have been identified as predictors of spontaneous disease course and therapy outcome in chronic HCV. However, most findings from candidate gene association studies have not been proven universal for all investigated populations and independent studies. Previous findings in independent large genome wide association studies confirmed that interferon­λ3 gene polymorphisms are associated with spontaneous clearance and treatment responsiveness. A polymorphism of the inosine triphosphatase gene has been identified as a protective factor against ribavirin­induced anemia and dose reductions. Another genetic variant in the patatin­like phospholipase domain containing 3 genes is associated with hepatic steatosis and fibrosis in patients with HCV. The present review focused on the identified viral and host factors associated with outcomes of patients with HCV, and assessed the involvement of viral and host genetics in the natural history and treatment outcomes of HCV infection. This will provide novel ideas concerning personalized prevention and individualized clinical management.

Telbivudine prevents vertical transmission of hepatitis B virus from women with high viral loads: a prospective long-term study.

BACKGROUND & AIMS: Hepatitis B virus (HBV) infection is a leading cause of liver diseases. We investigated the efficacy and safety of telbivudine in preventing transmission of HBV from hepatitis B e antigen-positive pregnant women with high viral loads to their infants in an open-label study. METHODS: We performed a prospective study of 450 hepatitis B e antigen-positive pregnant women with HBV DNA levels greater than 10(6) IU/mL; 279 women received telbivudine (600 mg/d) during weeks 24 to 32 of gestation, and 171 women who were unwilling to take antiviral drugs participated as controls. All newborns were vaccinated with a recombinant HBV vaccine and hepatitis B immune globulin, according to a standard immunoprophylaxis procedure. Mother-to-child transmission of HBV was determined by detection of hepatitis B surface antigen and HBV DNA in the infant 6 months after birth. RESULTS: None of the infants whose mothers were given telbivudine tested positive for of hepatitis B surface antigen at 6 months, compared with 14.7% of infants in the control group (P = 5.317 × 10(-8)). Levels of HBV DNA also decreased among women given telbivudine; 40 of 172 (23.2%) women given telbivudine had undetectable HBV DNA levels before delivery, compared with none of the controls. A significantly higher proportion of women given telbivudine had undetectable levels of HBV DNA in cord blood (99.1%) than controls (61.5%; P = 1.195 × 10(-22)). No severe adverse events or complications were observed in women or infants. CONCLUSIONS: Telbivudine significantly reduces vertical transmission of HBV from pregnant women to their infants; it is safe and well tolerated by women and infants. Antiretroviral Pregnancy Registry Health Care Providers ID: 26592; Government number: Natural Science Foundation of China (NSFC) 30830090, 30972598; and Third Military Medical University Key Project for Clinical Research: 2012XLC05).

[Effect of L-ornithine L-aspartate granules in treating chronic liver disease in patients with high-level serum gamma-glutamyltransferase].

OBJECTIVE: To explore the clinical effect of L-ornithine L-aspartate (LOLA) granules in treating chronic liver disease in patients with high-level serum gamma-glutamyltransferase (G-GT) using a 24-week treatment course. METHODS: Two-hundred patients with chronic liver disease and above normal G-GT were given a 12-week course of LOLA granules (9 g/d) and then classified into the following three groups according to the change in serum Gamma-GT:group I:patients with Gamma-GT level returned to normal;group II:patients with serum Gamma-GT level that was reduced during the treatment; group III:patients with serum Gamma-GT level that did not decrease or that increased to a higher level than at start of treatment.After the 12-week treatment course, the patients in group I were divided into three subgroups for receipt of a control drug (compound glycyrrhizin, 50mg/d) or an additional 12-week course of Gamma-GT at a reduced dose (LOLA granules 3 g/d) or at the original dose; groups II and III were maintained on the initial dose for an additional 12 weeks.The groups were reassessed at the end of the second 12-week course (at the end of week 24 of the study's observation period).Count data were compared using the x2 test and measurement data were compared using the t-test. RESULTS: In group I, the serum Gamma-GT level was 90.9% at the end of the first 12-week course and dropped to a mean level of 52.2% for both of the subgroups that received the reduced and original dose after the additional 12 weeks of LOLA granules treatment; the difference from week 12 to week 24 was significant (x2=8.213, P less than 0.05).The 24-week change in serum Gamma-GT levels for the group I reduced and original dose subgroups vs.the control subgroup were also significantly different from those seen in groups II and III (P less than 0.05).The percentage of patients in group I who achieved normal level serum Gamma-GT after 24 weeks of treatment (78.6%) was significantly higher than that for the control group (vs.55.0%, x2=11.452, P less than 0.05).When the patients in group 1 who had received the 12 additional weeks of LOLA granules treatment were measured again at two weeks after the treatments had been discontinued (end of week 26), the percentage of patients with normal serum Gamma-GT level was 92.7%, with only three cases showing obviously abnormal levels; in contrast, the group I patients in the control group of the second 12-week study period had on 66.7% of patients with normal-level serum Gamma-GT.The difference in change between the treated groups (both reduced and original dose) and the control group was significant (x2=14.964, P less than 0.05). CONCLUSION: Patients whose serumGamma-GT levels returned to normal after receipt of LOLA granules for 12 weeks benefitted from an additional 12 weeks of consolidation treatment, and those given the treatment at the original dose benefitted most.Compared with the compound glycyrrhizin, LOLA granules provided a better maintenance of resolved Gamma-GT level.Therefore, the effect of LOLA appears to be reliable and stable as well as safe for clinical use.

[Meta-analysis of magnesium isoglycyrrhizinate combined with nucleoside analogues in patients with chronic hepatitis B].

OBJECTIVE: To evaluate the efficacy and safety of the magnesium isoglycyrrhizinate plus nucleoside analogues (MGL + NA) combination therapy in patients with chronic hepatitis B using a meta-analysis approach. METHODS: The Chinese Biochemical literature on Disc (CBMDisc) and the Chinese Scientific Journal database, CNKI, were searched for randomized controlled trials (RCTs) of MGL+NA in patients with chronic hepatitis B published between 1995 and 2013. Data related to treatment type (combination therapy vs. mono-therapy) and outcome (markers of efficacy and safety, including levels of hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg), alanine aminotransferase (ALT) and aspartate aminotransferase (AST)). Weighted mean differences (WMD) were calculated and the Peto method was used to determine the relative risk (RR), both with 95% confidence intervals (CIs). RESULTS: Meta-analysis of the six included RCTs of MGL + NA, representing a 704 patients with chronic hepatitis B, showed WMDs for ALT of -12.98 (95% CI: -18.24 to -7.71, P less than 0.01) and for AST of -9.49 (95% CI: -14.53 to -4.45, P = 0.0002) and RRs for HBeAg of 1.79 (95% CI: 1.17 to 2.76, P = 0.008) and for HBV DNA of 1.35 (95% CI: 1.05 to 1.74, P = 0.02). The therapeutic efficacy of MGL+NA combination therapy was better than that of NA mono-therapy (P less than 0.01). CONCLUSION: For patients with chronic hepatitis B, MGL combination therapy may enhance the antiviral efficacy of NA treatment and help to improve liver function during treatment.

Telbivudine decreases proportion of peripheral blood CD4+CD25+CD127low T cells in parallel with inhibiting hepatitis B virus DNA.

Regulatory T cells (Treg) have significant roles in the immunopathology of patients with chronic hepatitis B (CHB) and exhibit an evident correlation with antiviral immunity when antiviral therapy is applied. In order to investigate how circulating Tregs are affected by telbivudine treatment and its significance in patients with CHB, peripheral blood mononuclear cells (PBMCs) were isolated and the proportions of circulating cluster of differentiation (CD)4+CD25+CD127low and CD8+CD25+ T cells of CHB patients prior to and during the three or six months of treatment were assessed and detected by flow cytometric analysis. The levels of forkhead/winged helix transcription factor (Foxp3) mRNA were also quantified using quantitative polymerase chain reaction. A significantly higher percentage of CD4+CD25+CD127low and CD8+CD25+ T cells in the PBMCs of patients with CHB were identified compared with that of healthy individuals. Patients with CHB also demonstrated significantly higher levels of Foxp3 mRNA compared with that of healthy individuals. Following six months of telbivudine treatment, the proportion of circulating CD4+CD25+CD127low and CD8+CD25+ T cells and the relative levels of Foxp3 mRNA in patients with CHB was comparable to the proportion in healthy individuals. The proportions of circulating peripheral blood CD4+CD25+CD127low T cells were paralleled with its HBV DNA inhibition. The results of the present study indicate that telbivudine treatment reduces HBV DNA levels rapidly and indirectly affects the immune system by downregulating the proportion of circulating Treg markedly, which may be beneficial to restore the antiviral immune response.

Genome-wide microarray-based analysis of miRNAs expression in patients with acute-on-chronic liver failure.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is a severe clinical syndrome that may cause a high mortality. However, the mechanism is still not clear. Characterization of the microRNA (miRNA) profiles in ACLF patients may provide new clues to the pathogenesis and management of this syndrome. METHODS: Genome-wide microarray was performed to compare the different miRNA expression profiles in peripheral blood mononuclear cells of a pair of monozygotic twins, an ACLF patient and an HBV asymptomatic carrier (AsC). The case-control miRNA profiles were compared and confirmed by quantitative reverse transcription-polymerase chain reaction in 104 ACLF patients and 96 AsCs. A combined computational prediction algorithm was used to predict the potential target genes. RESULTS: Forty-five miRNAs were increased and eight miRNAs were decreased in the ACLF group. The expressions of hsa-let-7a and hsa-miR-16 were increased by 8.58- and 8.63-fold in ACLF patients compared with that in AsCs, respectively (P<0.001). CARD8, BCL2, IL1RAPL1, LTB, FZD10 and EDA were identified as the target genes of hsa-miR-16; MAP4K3, OPRM1, IGF2BP1 and CERCAM were verified as the target genes of hsa-let-7a. CONCLUSIONS: Our results showed that there is a close relationship between specific miRNAs of peripheral blood mononuclear cells and ACLF. hsa-miR-16 and hsa-let-7a may contribute to the development of ACLF.

Efficacy and safety of low-dose peginterferon alpha-2a plus ribavirin on chronic hepatitis C.

Background. The purpose of this study was to assess the efficacy and safety of low-dose peg-IFN α-2a plus ribavirin on the treatment of patients with chronic hepatitis C virus (HCV) infection. Patients and Methods. A total of 243 HCV patients treated with different doses of peg-IFN α-2a plus ribavirin were stratified into three groups. End-of-treatment response (ETR) and sustained viral response (SVR) were evaluated for efficacy. Adverse events and laboratory abnormalities were conducted for safety. Results. ETR and SVR in group I were obtained in 83.9% and 68.9% of the patients, separately, which was similar to groups II (84.1% and 68.3%) and III (81.7% and 66.7%). The received peg-IFN α-2a dose was not the independent factor-related SVR in our population (OR, 1.31; 95% CI, 0.94-1.81; P = 0.106). The frequency of no adverse events reported in group III (24.7%) was significantly higher than that in group I (11.5%) and group II (12.7%) (P = 0.036). Conclusions. The peg-IFN α-2a 90 µg/week plus ribavirin is as effective as, and better tolerated than, peg-IFN α-2a standard dose with ribavirin in the treatment of chronic hepatitis C. This low-dose combination achieves high SVR rates and may be cost-saving.

Thyroid dysfunction in chinese patients with chronic hepatitis C treated with interferon alpha: incidence, long-term outcome and predictive factors.

BACKGROUND: Thyroid dysfunction (TD) represents an extra-hepatic manifestation of chronic hepatitis C (CHC) and it may also be a side effect of interferon-alpha (IFN-α) based treatment. However, previous studies have shown a wide variation in the incidence of TD in patients with CHC. Furthermore, the long-term outcomes and the predictive factors of TD in patients who receive IFN-α based treatment have still not been fully studied. OBJECTIVES: The purpose of this study was to describe the incidence and long-term outcomes of TD in Chinese patients with CHC receiving IFN-αbased treatment. We also aimed to identify the predictive factors of TD associated with this type of therapy. PATIENTS AND METHODS: A retrospective case-series study of 592 consecutive CHC patients with normal baseline thyroid functions, who received IFN-αbased therapy, was performed. Thyroid function was assessed at baseline and every three months during treatment, as well as in the follow-up after cessation of therapy. The incidence and long-term outcomes of TD were observed. The prevalence of pretreatment thyroid peroxidase antibodies (TPOAb) were assayed in a sex- and age-matched nested case-control study. Multivariable stepwise regression analysis was used to explore the independent effects of the baseline factors, on the incidence of TD. RESULTS: At the end of the IFN-αbased therapy, 68 patients (11.5%) in the study had developed TD, 58 patients (85.3%) presented with subclinical TD, and only 10 patients (14.7%) developed overt thyroiditis. The thyroid function of 46 patients (67.8%) spontaneously returned to normal in the six months of follow-up and only three patients (4.4%) had persistent overt TD symptoms after the 24 month follow-up period. Multivariate stepwise analysis suggested that gender and pretreatment TPOAb were the independent factors related to the incidence of TD. Both female patients (OR, 4.31; 95%CI, 2.06-7.31; P = 1.26×10-4) and participants with a positive pretreatment TPOAb (OR = 3.9, 95%CI, 1.72-8.54, P = 0.008) had an increased risk for the development of TD. CONCLUSIONS: The incidence of TD in Chinese patients with CHC during IFN-αbased therapy was 11.5%, the majority of which was subclinical, while only a very small group had long-term overt TD requiring ongoing medical therapy. Female gender and pretreatment TPOAb positivity are risk factors for the development of TD during IFN-αbased therapy.

Relationship between HLA-DR gene polymorphisms and outcomes of hepatitis B viral infections: a meta-analysis.

AIM: To assess the rigorous relationship between human leukocyte antigens (HLA)-DR alleles and outcomes of hepatitis B virus (HBV) infections by means of meta-analysis. METHODS: Medline/PubMed, EMBASE, CNKI and VIP were searched to identify relevant studies. Study quality was evaluated using the Newcastle-Ottawa Scale. Odds ratios (OR) and 95% confidence interval (95% CI) were pooled using Stata 11.0. Subgroup analyses were performed by ethnicity. Heterogeneity and publication bias analyses were performed to validate the credibility. RESULTS: A total of 2609 patients with chronic hepatitis B and 2606 controls spontaneously recovering from prior HBV infection were included. Meta-analysis showed that HLA-DR*04 (OR = 0.72, 95% CI: 0.60-0.85) and DR*13 (OR = 0.27, 95% CI: 0.19-0.37) alleles were significantly associated with HBV clearance while patients carrying HLA-DR*03 (OR = 1.47, 95% CI: 1.16-1.87) or DR*07 (OR = 1.59, 95% CI: 1.24-2.03) alleles had a significantly increased risk of chronic HBV persistence. For the HLA-DR*01 polymorphism, a significantly association with HBV clearance was found in Chinese Han group (OR = 0.48, 95% CI: 0.26-0.86), but not found in other ethnic groups (P = 0.191). For other polymorphisms, no association with the HBV infection outcome was found. CONCLUSION: HLA-DR*04 and DR*13 alleles may be the protective factors for HBV clearance and HLA-DR*03, and DR*07 alleles may be the risk factors for HBV persistence.

Estrogen receptor alpha gene polymorphisms and risk of HBV-related acute liver failure in the Chinese population.

BACKGROUND: The sexual dimorphism of hepatitis B virus (HBV) -related liver diseases is related with estrogen and its receptors. Recent reports indicate that abnormal expression of estrogen receptor alpha (ESR1) may be a hallmark for the progression of liver disease and HBV carriers presenting variant ESR1 have an extremely aggressive clinical course. Here we examine whether the ESR1 polymorphisms or its haplotypes are related to HBV-related acute liver failure (ALF) risk among chronic HBV carriers in a Chinese population. METHODS: A total of 1216 unrelated Han Chinese HBV carriers were recruited in this hospital-based case-control study, including 359 HBV surface antigen (HBsAg) carriers affected with ALF and 857 asymptomatic HBsAg carriers. Two ESR1 haplotype tagging polymorphisms, c.30 T > C (rs2077647) and c.453-397 T > C (rs2234693), were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. RESULTS: We observed a significantly increased susceptibility to HBV-ALF associated with the c.30 C allele (P = 8.65 × 10-4), c.453-397 C allele (5.37 × 10-4) and [c.30 C; c.453-397 C] haplotype (Dominant model, P =0.0004, odds ratio = 1.53, 95% CI 1.23 ~ 1.96) compared with the T alleles and [c.30 T; c.453-397 T] haplotype of c.30 T > C and c.453-397 T > C polymorphisms, respectively. CONCLUSIONS: Our study suggests that [c.30 C; c.453-397 C] haplotype may be a risk factor for genetic susceptibility to HBV-related ALF in the Chinese population. It also emphasizes the importance of ESR1 in the pathophysiology of HBV-related ALF on the population level.

Relationship between HLA-DP gene polymorphisms and clearance of chronic hepatitis B virus infections: case-control study and meta-analysis.

Hepatitis B virus (HBV) infection is a serious public health problem worldwide. Two common genetic variants (rs3077 and rs9277535) of human leukocyte antigen DP (HLA-DP) have been reported to be associated with persistent HBV infection in populations of Japan and Thailand. To confirm whether the association can be replicated in Chinese populations, an independent case-control study were conducted, and two polymorphisms (rs3077 and rs9277535) were genotyped using the TaqMan SNP genotyping assay in 282 persistent chronic HBV carriers and 64 spontaneously HBV recovered carriers. To provide a more definitive conclusion, a meta-analysis combining and summarizing five studies was performed by random-effects model using the DerSimonian and Laird's method. By using logistic regression analysis with adjustment for covariates, including age, sex, and alcohol consumption, the results of our independent case-control study showed that the minor allele's homozygote (AA genotype) of rs3077 and rs9277535 was significantly associated with decreasing risk/protection of HBV persistent chronic infection (for rs3077: P=0.0017, OR=0.29, 95% CI=0.13-0.62; for rs9277535, P=0.0004, OR=0.26, 95% CI=0.12-0.54). The results of meta-analysis pooling all eligible studies also showed that rs3077-A and rs9277535-A alleles were associated with an increased clearance rate to HBV infection (rs3077: OR=0.57, 95% CI=0.44-0.75; rs9277535: OR=0.56, 95% CI=0.47-0.63). These results further confirmed the strong influence of HLA-DP gene variants on risk of spontaneous HBV clearance from persistent HBV infection. Both A alleles of HLA-DP SNP rs3077 and rs9277535 showed strong protective effects for spontaneous HBV clearance from persistent HBV infection in the Han Chinese population.

Changing pattern of clinical epidemiology on hepatitis C virus infection in southwest china.

BACKGROUND: The changing pattern of hepatitis C virus (HCV) infection could have a significant impact on future medical prevention practices and therapies. OBJECTIVES: The purpose of this study was to describe the changing pattern of HCV infection in southwest China using clinical epidemiology, and to assess the association between the genotypes distribution and certain potential risk factors. PATIENTS AND METHODS: A retrospective analysis which included 1208 subjects with chronic HCV registered at the Southwest Hospital (Chongqing, Southwest China) was performed. The information was reviewed and the data collected from clinical records and short telephone interviews when necessary. HCV genotypes were determined by nucleotide sequencing of the CE1 regions followed by phylogenic analysis with the published HCV genotype. HCV genotype distribution was analyzed according to the patients' age, gender, risk exposure, and the initial risk exposure. RESULTS: Among the 1 208 patients, the HCV subtype 1b was the most prevalent (32.9%), followed by subtype 3b (18.9%), 6a (18.0%), 3a (12.8%) and 2a (10.4%), while subtypes 1a and 6k accounted for cases of HCV infection in only 9 and 3 cases respectively. Individuals older than 40 years were mainly infected with subtypes 1b and 2a, whereas younger patients were predominantly infected with genotypes 3 and 6. Subtypes 1b and 2a were observed more frequently among 44.4% and 16.0% patients respectively, with a history of invasive operations. Subtypes 3b and 6a constituted the majority of HCV infections among intravenous drug users (IDUs) (28.7% and 34.9%, respectively). A significant difference (P < 0.001) was observed between the HCV genotype distributions, according to the potential route of infection. CONCLUSION: In southwest China, the most common remaining subtype is the 1b genotype, but this has declined significantly among young patients. This is followed by subtype 3b and 6a which has increased significantly, especially among young patients. The distribution of such genotypes was also variable according to gender and age. The changing pattern of HCV infection was associated with changes in the modes of HCV acquisition, which raises an alarm signal concerning the major steps that need to be taken in order to reduce such infections in southwest China.

A cis-acting regulatory variation of the estrogen receptor α (ESR1) gene is associated with hepatitis B virus-related liver cirrhosis.

The hepatic fibrogenesis and sexual dimorphism of hepatitis B virus-related liver cirrhosis (HBV-LC) are related to estrogen and its receptors. Abnormal expression of estrogen receptor α (ESR1) is implicated in the development of cirrhosis in both animal models and humans. Here, we examine whether the ESR1 polymorphisms are related to HBV-LC risk among chronic HBV carriers, and we investigate the functional significance of positively associated polymorphisms. A total of 2,404 unrelated Chinese HBV carriers were recruited to conduct the two-stage designed case-control study. Two ESR1 haplotype tagging polymorphisms, c.30T>C (rs2077647) and c.453-397T>C (rs2234693), were genotyped in 1,285 patients with HBV-LC and in 1,119 asymptomatic HBV carriers. We observed a significantly increased susceptibility to HBV-LC associated with the c.30C allele (P = 4.2 × 10(-8) ), c.453-397C allele (P = 2.0 × 10(-8) ), and [c.30C; c.453-397C] haplotype (Dominant model, P = 8.85 × 10(-10) , odds ratio = 1.50, 95% CI 1.32∼1.71) compared with the T alleles and (c.30T; c.453-397T) haplotype of c.30T>C and c.453-397T>C polymorphisms, respectively. Functional analyses were conducted to verify the biological functions of the associated genetic variations and showed that the c.453-397T>C polymorphism is a novel c.453-397C allele-specific and c-myb-dependent enhancer-like cis-acting regulatory variation and could be part of the genetic variations underlying the susceptibility of individuals to HBV-LC.

Regulatory polymorphisms in the promoter of CXCL10 gene and disease progression in male hepatitis B virus carriers.

BACKGROUND & AIMS: The importance of expression of interferon gamma-inducible protein of 10 kilodaltons (IP-10, CXCL10) during chronic hepatitis B virus (HBV) infection has been recently emphasized. In this report, we investigated whether the naturally occurred sequence variations in the CXCL10 gene impact liver damage and disease progression of chronic HBV infection. METHODS: A hospital-based case-control study was conducted, and a total of 613 and 1787 unrelated Han Chinese HBV carriers were recruited from Beijing and Chongqing, respectively. We systematically screened sequence variations in the CXCL10 gene and examined the association between the variations in this gene and susceptibility to disease progression of chronic HBV infection in Chinese populations from Beijing and Chongqing. Functional analyses were conducted to verify the biological significances of the associated genetic variation. RESULTS: We identified that the polymorphism G-201A, located in the promoter region of CXCL10, was associated with susceptibility to disease progression in male HBV carriers (dominant model; odds ratio, 1.53; P = .001). Functional analyses show that the G-201A polymorphism alters the binding affinity of nuclear protein and regulates CXCL10 expression. We observed higher CXCL10 transcription in interferon gamma-stimulated peripheral blood mononuclear cells with the disease-susceptible genotypes. Enzyme-linked immunosorbent assay and immunohistochemical analysis showed augmented CXCL10 production in serum and liver tissues of progressed HBV carriers. CONCLUSIONS: The novel regulatory polymorphism G-201A [corrected] in the promoter of CXCL10 gene could be a part of the genetic variation underlying the susceptibility of individuals to disease progression of chronic HBV infection.