Dual chronic hepatitis B virus and hepatitis C virus infection

Dual hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are common in HBV or HCV endemic areas. However, several clinical and pathogenetic issues remain unresolved. First, clinical and in vitro studies suggest the interactions between two viruses. The dynamics of the interaction in untreated setting versus treated setting and its influence on the long-term outcomes await further studies. A key issue regarding viral interactions is whether modulation of infection occurs in the same dually infected individual hepatocyte of the liver. Clarifying this issue may help to understand the reciprocal interference between HCV and HBV and provide clues for future immunopathogenetic studies. Second, the prevalence and clinical significance of coexisting occult HBV infection in patients with chronic HCV infection need further investigations. Third, combination therapy of peginterferon alfa-2a and ribavirin appears to be just as effective and safe for the treatment of hepatitis B surface antigen (HBsAg)-positive patients chronically infected with active chronic hepatitis C as it is in patients with HCV monoinfection. Nevertheless, one-third of dually infected patients with nondetectable serum HBV DNA-level pretreatment developed HBV reactivation posttreatment. How to prevent and treat this reactivation should be clarified. Furthermore, about 10% of the dually infected patients lost HBsAg. Underlying mechanisms await further investigations. Finally, the optimal treatment strategies for dually infected patients with hepatitis B e antigen-positive chronic hepatitis B should be identified in future clinical trials.     

Treatment of patients with dual hepatitis C virus and hepatitis B virus infection: Resolved and unresolved issues

Dual hepatitis C virus (HCV)/hepatitis B virus (HBV) infection is not uncommon in HCV or HBV endemic areas and among subjects at risk of parenteral transmission. In patients dually infected with hepatitis C and B, the disease manifestations are usually more severe than those with either virus infection. In the past decade, the following issues have been resolved. In dually infected patients with active hepatitis C, combined pegylated interferon alfa plus ribavirin was effective, the treatment outcomes being similar to patients with HCV monoinfection. During long‐term follow‐up, the HCV response was sustained in around 97% of patients; and the long‐term outcomes including the development of hepatocellular carcinoma and liver‐related mortality were improved. However, several clinical issues remain to be resolved. First, host and viral factors influencing the long‐term outcomes and treatment options in patients with dual HCV/HBV infection await further studies. Second, about 60% of dually infected patients with baseline undetectable serum HBV DNA levels develop HBV reactivation after the start of treatment. How to prevent and treat HBV reactivation should be clarified. Third, about 30% of dually infected patients lose hepatitis B surface antigen at 5 years after the end of combination therapy; the mechanisms need further investigations. Fourth, the optimal treatment strategies for dually infected patients with active hepatitis B or established cirrhosis should be explored in future clinical trials. Finally, the role of new direct‐acting antiviral‐based therapy for the treatment of patients with dual HCV/HBV infection also remains to be evaluated.     

Treatment of hepatitis C virus infection

Acute and chronic hepatitis C virus （HCV） infection remains a serious health problem worldwide, however, there has been advancement in the treatment of HCV infection due to standard treatment using pegylated interferon and ribavirin. The literature indicates that therapy for HCV is becoming more individualized. In addition to considering genotype and viral RNA levels before treatment, achievement of an early virologic response （EVR） and a rapid virologic response （RVR） is now possible during therapy. Moreover, problem patients, such as non-responders, relapsers, HIV or HBV coinfected patients, patients with liver cirrhosis, and preor post-liver transplantation patients are an increasing fraction of the patients requiring treatment. This article reviews the literature regarding standard treatments and problem patients with acute and chronic HCV infection. It also includes discussion on contraindications and side effects of treatment with interferon and ribavirin, as well as new drug development.     

MiR-122 in hepatitis B virus and hepatitis C virus dual infection

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the most common causes of chronic liver diseases and hepatocelluar carcinomas. Over the past few years, the liver-enriched microRNA-122 (miR-122) has been shown to differentially regulate viral replication of HBV and HCV. It is notable that the level of miR-122 is positively and negatively regulated by HCV and HBV, respectively. Consistent with the well-documented phenomenon that miR-122 promotes HCV accumulation, inhibition of miR-122 has been shown as an effective therapy for the treatment of HCV infection in both chimpanzees and humans. On the other hand, miR-122 is also known to block HBV replication, and HBV has recently been shown to inhibit miR-122 expression; such a reciprocal inhibition between miR-122 and HBV suggests an intriguing possibility that miR-122 replacement may represent a potential therapy for treatment of HBV infection. As HBV and HCV have shared transmission routes, dual infection is not an uncommon scenario, which is associated with more advanced liver disease than either HBV or HCV mono-infection. Thus, there is a clear need to further understand the interaction between HBV and HCV and to delineate the role of miR-122 in HBV/HCV dual infection in order to devise effective therapy. This review summarizes the current understanding of HBV/HCV dual infection, focusing on the pathobiological role and therapeutic potential of miR-122.     

interleukin 28B genetic polymorphism and hepatitis B virus infection

interleukin(iL)28B genetic polymorphism is significantly associated with the sustained virological response rate in patients with chronic hepatitis C treated with pegylated interferon-α(PEG-iFN)plus ribavirin and with spontaneous hepatitis C virus clearance.However,a consensus on the relationship between iL28B genetic polymorphism and the favorable outcome of chronic hepatitis B virus infection defined by hepatitis B e antigen seroconversion,and/or hepatitis B surface antigen seroclearance in patients treated with interferon or PEG-iFN has not been reached.Several reports failed to show a positive association,while some studies demonstrated a positive association in certain subject settings.More prospective studies including large cohorts are needed to determine the possible association between iL28B genetic polymorphism and the outcome of interferon or PEG-iFN treatment for chronic hepatitis B.     

Sustained virological response to pegylated interferon plus ribavirin leads to normalization of liver stiffness in hepatitis C virus-infected patients

Introduction

Pegylated interferon plus ribavirin (Peg-IFN/RBV) therapy leads to improvements in liver stiffness measurements (LSM) in hepatitis C virus (HCV)-infected patients. However, the rate of LSM return to normal values in response to Peg-IFN/RBV is unclear. Thus, our aim was to assess the probability and factors associated with LSM normalization in HCV-infected patients receiving Peg-IFN/RBV.

Methods

This prospective observational longitudinal study included 160 HCV-infected patients, 111 (69%) with human immunodeficiency virus and receiving Peg-IFN/RBV, with baseline LSM ≥7 kPa. The outcome variable was LSM normalization, i.e. a stable decrease in LSM below 7 kPa after starting Peg-IFN/RBV.

Results

After starting Peg-IFN/RBV, 56 [35%, 95% confidence interval (95% CI): 28–42%] patients showed LSM normalization. The probability of LSM normalization was 21% (95% CI: 13.2–32.4%) at 12 months, and 51.3% (95% CI: 39.9–63.9%) at 24 months after Peg-INF/RBV initiation for individuals with sustained virological response (SVR), and 8.3% (95% CI: 4–16.6%) at 12 months and 11.3% (95% CI: 6–20.7%) at 24 months for those without SVR (p < 0.001). For individuals with LSM ≥7 kPa 24 weeks after the pre-planned end of treatment, LSM normalizations were only observed among those with SVR. Achievement of SVR [Hazard ratio (HR, 95% CI): 6.84 (3.39–13.81)] and lack of baseline cirrhosis [HR (95% CI): 4.17 (1.69–10)] were independently associated with LSM normalization after starting Peg-IFN/RBV.

Conclusions

LSM normalizations during Peg-IFN/RBV treatment are more likely, and occur earlier among patients with SVR. In addition, LSM normalizations continue 24 weeks after the scheduled end of therapy, but only among individuals who reach SVR.     

IL28B polymorphisms associated with therapy response in Chilean chronic hepatitis C patients

AIM:To analyze the association of three IL28B single nucleotide polymorphisms with response to therapy in Chilean patients infected with hepatitis C virus CV.METHODS:We studied two groups of patients with chronic CV infection genotype 1,under standard combined treatment with pegylated interferon plus ribavirin.One group consisted of 50 patients with sustained virological response,whereas the second group consisted of 49 null responders.In order to analyze the IL28B single nucleotide polymorphisms rs12979860...     

基线维生素D与慢性丙型肝炎持久病毒学应答相关性的Meta分析

目的：探讨基线维生素D水平与HCV基因1、4型感染者对标准抗病毒治疗持久病毒学应答（SVR）的关系。方法检索数据库中有关基线维生素D水平与HCV基因1、4型慢性感染者接受抗病毒治疗后SVR相关性的文献,meta分析比较SVR组和非SVR组的基线维生素D水平。结果共检索到210篇相关文献,其中符合纳入标准5篇,meta分析结果显示,基线维生素D水平在SVR组（32．9 ng/mL）与非SVR组（28．3 ng/mL）的加权均数差（WMD）为6．759（95％ CI：1．786,11．733）,两组的基线维生素D水平差异有统计学意义（Z＝2．66,P＝0．008）。结论 HCV 基因1、4型慢性感染者接受标准抗HCV治疗获得SVR者的基线维生素D水平高于未获得SVR者。     

Sustained virological response in a predominantly hepatitis C virus genotype 4 infected population

AIM： To assess sustained virological response （SVR） rates in a predominantly hepatitis C virus （HCV） genotype 4 infected population. METHODS： Between 2003-2007, 240 patients who were treated for chronic hepatitis C infection at our center were included. Epidemiological data, viral genotypes, and treatment outcomes were evaluated in all treated patients. Patients with chronic renal failure, previous non-responders, and those who relapsed after previous treatment were excluded from the study. Among all patients, 57% were treated with PEG- interferon （IFN） α-2a and 43% patients were treated with PEG-IFN α-2b; both groups received a standard dose of ribavirin. RESULTS： 89.6% of patients completed the treatment with an overall SVR rate of 58%. The SVR rate was 54% in genotype 1, 44% in genotype 2, 73% in genotype 3, and 59% in genotype 4 patients. There was no statistical difference in the SVR rate between patients treated with PEG-IFN α-2a and PEG-IFN α-2b （61.5% vs 53%）. Patients younger than 40 years had higher SVR rates than older patients （75% vs 51%, P = 0.001）. SVR was also statistically significantly higher when the HCV RNA load （pretreatment） was below 800.000 （64% vs 50%, P = 0.023）, in patients with a body mass index （BMI） less than 28 （65% vs 49%, P = 0.01）, and in patients who completed the treatment duration （64% vs 8%, P ≤ 0.00001）.CONCLUSION： The SVR rate in our study is higher than in previous studies. Compliance with the standard duration of treatment, higher ribavirin dose, younger age, lower BMI, and low pretreatment RNA levels were associated with a higher virological response.     

FibroSURE and FibroScan in relation to treatment response in chronic hepatitis C virus

AIM: To compare histological endpoint assessment using noninvasive alternatives to biopsy during treatment in a chronic hepatitis C virus (HCV) cohort.METHODS: Patients with chronic HCV were randomized to receive interferon-based therapy for 24 (genotypes 2/3) or 48 (genotype 1) wk. FibroSURE™ (FS) was assessed at baseline and at week-12 post-treatment follow-up. Baseline biopsy for METAVIR was assessed by a single pathologist. FibroScan^® transient elastography (TE) was performed during treatment in a patient subset.RESULTS: Two thousand and sixty patients (n = 253 in Asia) were classified as METAVIR F0-1 (n = 1682) or F2-4 (n = 378). For F2-4, FS (n = 2055) had sensitivity and specificity of 0.87 and 0.61, respectively, with area under the receiver-operating curve of 0.82; corresponding values for TE (n = 214) and combined FS/TE (n = 209) were 0.77, 0.88 and 0.88, and 0.93, 0.68 and 0.88. Overall FS/TE agreement for F2-4 was 71% (κ = 0.41) and higher in Asians vs non-Asians (κ = 0.86 vs 0.35; P < 0.001). Combined FS/TE had 97% accuracy in Asians (n = 33). Baseline FS (0.38 vs 0.51, P < 0.001) and TE (8.0 kPa vs 11.9 kPa, P = 0.006) scores were lower in patients with sustained virological response than in nonresponders, and were maintained through follow-up.CONCLUSION: FS and TE may reliably differentiate mild from moderate-advanced disease, with a potential for high diagnostic accuracy in Asians with chronic HCV.     

Management of hepatitis C virus infection in HIV/HCV co-infected patients： Clinical review

Nearly one fourth of individuals with human immunodeficiency virus （HIV） infection have hepatitis C virus （HCV） infection in the US and Western Europe. With the availability of highly active antiretroviral therapy and the consequent reduction in opportunistic infections, resulting in the prolongation of the life span of HIV-infected patients, HCV co-infection has emerged as a significant factor influencing the survival of HIV patients. Patients with HIV/HCV co-infection have a faster rate of fibrosis progression resulting in more frequent occurrences of cirrhosis, end-stage liver disease, and hepatocellular carcinoma. However, the mechanism of interaction between the two viruses is not completely understood. The treatment for HCV in co-infected patients is similar to that of HCV monoinfection; i.e., a combination of pegylated interferon and ribavirin. The presence of any barriers to anti- HCV therapy should be identified and eliminated in order to recruit all eligible patients. The response to treatment in co-infected patients is inferior compared to the response in patients with HCV mono-infection. The sustained virologic response rate is only 38% for genotype-1 and 75% for genotype-2 and -3 infections. Liver transplantation is no longer considered a contraindication for end-stage liver disease in coinfected patients. However, the 5 year survival rate is lower in co-infected patients compared to patients with HCV mono-infection （33% vs 72%, P = 0.07）. A betterunderstanding of liver disease in co-infected patients is needed to derive new strategies for improving outcome, and survival.     

Vitamin D in addition to peg-interferon-alpha/ribavirin in chronic hepatitis C virus infection: ANRS-HC25-VITAVIC study

AIM: To investigate if correction of hypovitaminosis D before initiation of Peg-interferon-alpha/ribavirin(Peg IFN/RBV) therapy could improve the efficacy of Peg IFN/RBV in previously null-responder patients with chronic genotype 1 or 4 hepatitis C virus(HCV) infection.METHODS:Genotype 1 or 4 HCV-infected patients with null response to previous Peg IFN/RBV treatment and with hypovitaminosis D(30 ng/m L)prospectively received cholecalciferol 100000 IU per week for 4 wk[from week-4(W-4)to W0],followed by 100000 IUper month in combination with Peg IFN/RBV for 12 mo(from W0 to W48).The primary outcome was the rate of early virological response defined by an HCV RNA12 IU/m L after 12 wk Peg IFN/RBV treatment.RESULTS:A total of 32 patients were included,19(59%)and 13(41%)patients were HCV genotype1 and 4,respectively.The median baseline vitamin D level was 15 ng/m L(range:7-28).In modified intention-to-treat analysis,29 patients who received at least one dose of Peg IFN/RBV were included in the analysis.All patients except one normalized their vitamin D serum levels.The rate of early virologic response was 0/29(0%).The rate of HCV RNA12IU/m L after 24 wk of Peg IFN/RBV was 1/27(4%).The safety profile was favorable.CONCLUSION:Addition of vitamin D to Peg IFN/RBV does not improve the rate of early virologic response in previously null-responders with chronic genotype 1or 4 HCV infection.     

Pegylated interferon alfa and ribavirin for children with chronic hepatitis C

AIM:To study current treatment options for pediatric hepatitis C infection and their associated success rates.METHODS:We retrospectively reviewed charts of thirty children who had been treated with combination therapy of pegylated interferon alfa plus ribavirin for chronic hepatitis C infection.Patients had been treated with ribavirin(15 mg/kg per day) and either pegylated interferon alfa 2a(180 mg/m 2 once weekly) or pegylated interferon alfa 2b(1.5 mg/kg once weekly).Patients’ follow-up included subjective assessment of complaints,physical examination including weight and height,as well as laboratory evaluations for viral load [before treatment,at 12 wk,and 6 mo following treatment completion,as determined by sustained viral response(SVR)],complete blood count,liver enzymes,alkaline phosphatase,bilirubin,renal function tests,and thyroid function tests.For patients not achieving a two log decrease in viral load at treatment week 12,treatment was discontinued and the patient was considered a treatment non-responder.RESULTS:Thirty children aged 3-18 years were included in the study.Twenty patients(11 males,9 females) received pegylated interferon alfa 2b and ten patients(6 males,4 females) received pegylated interferon alfa 2a.Twenty-three patients were infected with genotype 1,six patients were infected with genotype 3,and one patient was infected with genotype 2.Twenty patients(67%) achieved SVR.Treatment success rates were 90% with pegylated interferon alfa 2a vs 55% with pegylated interferon alfa 2b.Although a trend was noted for improved outcomes in the group receiving pegylated interferon alfa 2a,there were no statistically significant outcome differences between the two treatment groups(P = 0.1).Treatment success was 56.5% for patients infected with genotype 1 virus,compared to 100% for patients infected with other genotypes(P = 0.064).There was no difference in treatment response between males and females.A cut-off age of twelve years was used to dichotomize younger vs older participants;however,no diff     

Efficacy and safety of treatment of hepatitis C virus infection in renal transplant recipients

AIM: To assess the efficacy and safety of combined pegylated interferon and ribavirin therapy in hepatitis C virus (HCV) infection in renal transplant recipients.METHODS: This is a retrospective chart review of post renal transplant patients who were positive for anti-HCV and HCV-RNA, and who have received treatment with combination of pegylated interferon and ribavirin between October 2003 and December 2008. Only patients with stable graft function and absence of evidence of cirrhosis and who received the therapy for continuous 48 wk were included. Nineteen patients (13 male and 6 female) were identified and included. The patient’s complete blood count, liver and kidney profile, and calculated glomerular filtration rate (GFR) were monitored every 6-8 wk while on treatment. HCV-RNA was tested at 12 wk for early virological response, at 48 wk for end of treatment response (ETR), and then retested at 24, and 48 wk after completion of therapy for sustained virological response (SVR). Liver biopsies were obtained before treatment from all patients and graft kidney biopsies were performed as required.RESULTS: Of the entire cohort, 9 patients (47.4%) showed an ETR and 8 had SVR (42.1%). Of the 8 patients with abnormal alanine aminotransferase (ALT) levels at baseline, 78.9% had their ALT normalized (including the virological non responders). ALT was normal in all responders at the end of therapy and at 24 wk post therapy (100%). Only one patient (5.3%) developed an increase in creatinine and decline in GFR from baseline towards the end of treatment. This patient’s kidney biopsy revealed borderline rejection. There was no impact on response by HCV-genotype, initial HCV RNA load, age or sex of the patient or duration post transplant before commencement of therapy. All patients tolerated treatment in the same way as non-transplant with no unusual or increased occurrence of side effects.CONCLUSION: The combination of pegylated interferon and ribavirin is effective in suppressing HCV-RNA, with a low risk of graft rejection or failure in HCV infected renal transplant recipients.     

Is interferon-beta an alternative treatment for chronic hepatitis C？

The treatment of chronic hepatitis C (CMC) is still far from optimal, particularly for those subpopulations that do not respond to the standard combination therapy with Interferon-α(IFNα) plus ribavirin. Although in some cases the use of higher doses or longer treatment periods may be effective, these approaches are generally associated with a higher incidence of adverse events, which may either lead to a reduction in patient compliance or require drug withdrawal. IFNβcould represent an interesting alternative for treating CMC patients. Controversial data about IFNp efficacy in CMC exist, the main reason being that many results stem from pilot studies with small cohorts of patients. However, promising results have been obtained in some subgroups of patients that fail to respond to IFNa. Additionally, the good tolerability of IFNβrepresents an important advantage of the drug. The rates of dropouts in controlled clinical trials, as well as the need for dose reductions or treatment discontinuation are very low. It might be worth assessing the value of IFNβplus ribavirin in randomized studies with a larger cohort of patients, not eligible or not tolerating standard therapy, and for non-responders.     

Porphyria cutanea tarda as a complication of therapy for chronic hepatitis C

There is a strong association between porphyria cutanea tarda （PCT） and chronic viral hepatitis C. Therapy for chronic viral hepatitis C may improve PCT. However, there are only a few reports of the de novo development of PCT during therapy for chronic viral hepatitis C. We describe the development of PCT in a 56-year-old patient with chronic viral hepatitis C after 12 wk of peginterferon/ribavirin therapy. In addition, the patient was homozygous for the H63D hereditary hemochromatosis gene （HFE） mutation. The association of PCT with chronic viral hepatitis C and the possible role of hepatic iron overload and ribavirin-induced hemolytic anemia in the development of PCT during therapy for chronic viral hepatitis C are discussed.     

Peginterferon and ribavirin treatment for hepatitis C virus infection

Pegylated interferon α (IFNα) in combination with ribavirin is currently recommended as a standard-of-care treatment for chronic hepatitis C virus (HCV) infection. This combination therapy has drastically improved the rate of sustained virological response, specifically in difficult-to-treat patients. Recently, individualized treatment, such as response-guided therapy, is being developed based on host-, HCV- and treatment-related factors. Furthermore, modified regimens with currently available medications, ...     

Hepatitis B virus and hepatitis C virus infection in healthcare workers

Approximately 3 million healthcare workers per year receive an injury with an occupational instrument, with around 2000000 exposures to hepatitis B virus(HBV) and 1000000 to hepatitis C virus(HCV). Although an effective HBV vaccine has been available since the early eighties, and despite the worldwide application of universal vaccination programs started in the early nineties, HBV still remains a prominent agent of morbidity and mortality. There is no vaccine to limit the diffusion of HCV infection, which progresses to chronicity in the majority of cases and is a major cause of morbidity and mortality worldwide due to a chronic liver disease. Healthcare workers are frequently exposed by a mucosal-cutaneous or percutaneous route to accidental contact with human blood and other potentially infectious biological materials while carrying out their occupational duties. Mucosal-cutaneous exposure occurs when the biological material of a potentially infected patient accidentally comes in contact with the mucous membranes of the eyes or mouth or with the skin of a healthcare worker. Percutaneous exposure occurs when an operator accidentally injures himself with a sharp contaminated object, like a needle, blade or other sharp medical instrument. About 75% of the total occupational exposure is percutaneous and 25% mucosal-cutaneous, the risk of infecting a healthcare worker being higher in percutaneous than in mucosal-cutaneous exposure. All healthcare workers should be considered for HBV vaccination and should meticulously apply the universal prophylactic measures to prevent exposure to HBV and HCV.     

Current treatment indications and strategies in chronic hepatitis B virus infection

The optimal approach to the management of several marginal cases with chronic hepatitis B virus （HBV） infection is controversial. Serum HBV DNA and aminotransferase levels, and the degree of necroinflammation and fibrosis determine the therapeutic decisions. All patients with elevated aminotransferase （〉 twice the upper limit of normal） and serum HBV DNA above 20000 IU/mL should be treated. Liver biopsy is important for therapeutic decisions in cases with mild aminotransferase elevations and serum HBV DNA below 20000 IU/mL. Chronic HBV patients who do not receive treatment should be followed for life. There are seven agents licensed for chronic hepatitis B： standard and pegylated interferon-alpha, lamivudine, adefovir, entecavir, telbivudine and tenofovir. One-year courses with pegylated interferon-alpha induce sustained offtherapy remission in 30%-32% of patients with HBeAg- positive chronic hepatitis B and in a smaller proportion of patients with HBeAg-negative chronic hepatitis B. Oral antivirals achieve initial on-therapy responses in the majority of patients, but are intended as long-term therapies. Viral suppression has favourable effects on patients＇ outcome and modifies the natural course of the disease. Viral resistance, however, is the major drawback of long-term oral antiviral therapy. Lamivudine monotherapy is associated with the highest and entecavir monotherapy with the lowest resistance rate so far. There has been no resistance to tenofovir, but after only 18 mo of treatment to date. The optimal first-line anti-HBV therapy with the best long-term cost/benefit ratio remains unclear. If oral antiviral agents are used, compliance should always be ascertained and HBV DNA levels should be regularly tested.     

Molecular characteristics and stages of chronic hepatitis B virus infection

Hepatitis B virus （HBV） is a common viral pathogen that causes a substantial health burden worldwide. Remarkable progress has been made in our under- standing of the natural stages of chronic HBV infection. A dynamic balance between viral replication and host immune response is pivotal to the pathogenesis of liver disease. Knowledge of the HBV genome organization and replication cycle can unravel HBV genotypes and molecular variants, which contribute to the heterogeneity in outcome of chronic HBV infection. Most HBV infections are spontaneously resolved in immunocompetent adults, whereas they become chronic in most neonates and infants at a great risk of developing complications such as cirrhosis and hepatocellular carcinoma （HCC）. Those with chronic HBV infection may present in one of the four phases of infection： immune tolerance, immune clearance [hepatitis B e antigen （HBeAg）-positive chronic hepatitis B （CHB）], inactive carrier state, and reactivation （HBeAg-negative CHB）. Understanding the dynamic nature of chronic HBV infection is crucial in the management of HBV carriers. Long-term monitoring and optimal timing of antiviral therapy for chronic HBV infection help to prevent progression of HBV-related liver disease to its later stage, particularly in patients with higher risk markers of HCC, such as serum DNA concentration, HBeAg status, serum aminotransferase, HBV genotypes, and pre-core or core mutants.