Perioperative remedial antiviral therapy in hepatitis B virus-related hepatocellular carcinoma resection:How to achieve a better outcome

BACKGROUND Although the benefits of antiviral therapy for hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC)have been proven,researchers have not con-firmed the differences in patient outcomes between patients who received preoperative antiviral therapy for a period of time(at least 24 wk)and patients who received remedial antiviral therapy just before radical resection for HBV-related HCC.AIM To investigate the efficacy of perioperative remedial antiviral therapy in patients with HBV-related HCC.METHODS A retrospective study of patients who underwent radical resection for HBV-related HCC at the First Affiliated Hospital of Xi’an Jiaotong University from January 2016 to June 2019 was conducted.Considering the history of antiviral therapy,patients were assigned to remedial antiviral therapy and preoperative antiviral therapy groups.RESULTS Kaplan–Meier analysis revealed significant differences in overall survival(P<0.0001)and disease-free survival(P=0.035)between the two groups.Multivariate analysis demonstrated that a history of preoperative antiviral treatment was independently related to improved survival(hazard ratio=0.27;95%confidence interval:0.08-0.88;P=0.030).CONCLUSION In patients with HBV-related HCC,it is ideal to receive preoperative long-term antiviral therapy,which helps patients tolerate more extensive hepatectomy;however,remedial antiviral therapy,which reduces preoperative HBV-DNA levels to less than 4 Log10 copies DNA/mL,can also result in improved outcomes.

Timing of antiviral therapy in patients with hepatitis B virus related hepatocellular carcinoma undergoing hepatectomy

Globally,hepatocellular carcinoma(HCC)is among the most prevalent and deadly cancers.Hepatitis B virus(HBV)infection is an important etiology and disease progression factor for HCC.Hepatectomy is a widely accepted curative treatment for HCC,but the long-term survival rate is still unsatisfactory due to the high recurrence rate after resection.Preoperative or postoperative antiviral therapy plays an important role in improving the prognosis for HBV-related HCC patients who underwent hepatectomy.However,many patients miss out on the chance to receive long-term preoperative antiviral medication because their HBV and HCC infections are discovered concurrently,necessitating the start of remedial antiviral therapy in the perioperative phase.Therefore,it is of great value to know when antiviral therapy is more appropriate and whether perioperative rescue antiviral therapy can achieve the effect of preoperative long-term antiviral therapy.

Association of preoperative antiviral treatment with incidences of post-hepatectomy liver failure in hepatitis B virus-related hepatocellular carcinoma

BACKGROUND Post-hepatectomy liver failure(PHLF)is a common consequence of radical partial hepatectomy in hepatocellular carcinoma(HCC).AIMS To investigate the relationship between preoperative antiviral therapy and PHLF,as well as assess the potential efficacy of hepatitis B virus(HBV)DNA level in predicting PHLF.METHODS A retrospective study was performed involving 1301 HCC patients with HBV who underwent radical hepatectomy.Receiver operating characteristic(ROC)analysis was used to assess the capacity of HBV DNA to predict PHLF and establish the optimal cutoff value for subsequent analyses.Logistic regression analyses were performed to assess the independent risk factors of PHLF.The increase in the area under the ROC curve,categorical net reclassification improvement(NRI),and integrated discrimination improvement(IDI)were used to quantify the efficacy of HBV DNA level for predicting PHLF.The P<0.05 was considered statistically significant.RESULTS Logistic regression analyses showed that preoperative antiviral therapy was independently associated with a reduced risk of PHLF(P<0.05).HBV DNA level with an optimal cutoff value of 269 IU/mL(P<0.001)was an independent risk factor of PHLF.All the reference models by adding the variable of HBV DNA level had an improvement in area under the curve,categorical NRI,and IDI,particularly for the fibrosis-4 model,with values of 0.729(95%CI:0.705-0.754),1.382(95%CI:1.341-1.423),and 0.112(95%CI:0.110-0.114),respectively.All the above findings were statistically significant.CONCLUSION In summary,preoperative antiviral treatment can reduce the incidence of PHLF,whereas an increased preoperative HBV DNA level has a correlative relationship with an increased susceptibility to PHLF.

Effect of lifestyle modification on hepatocellular carcinoma incidence and mortality among patients with chronic hepatitis B

BACKGROUND Research exploring the influence of healthier lifestyle modification(LSM)on the risk of hepatocellular carcinoma(HCC)in patients with chronic hepatitis B(CHB)is limited.AIM To emulate a target trial to determine the effect of LSM on HCC incidence and mortality among patients with CHB by large-scale population-based observational data.METHODS Among the patients with CHB enrolled in the Korean National Health Insurance Service between January 1,2009,and December 31,2017,those aged≥20 years who drank alcohol,smoked cigarettes,and were sedentary were analyzed.Exposure included at least one LSM,including alcohol abstinence,smoking cessation,and regular exercise.The primary outcome was HCC development,and the secondary outcome was liver-related mortality.We used 2:1 propensity score matching to account for covariates.RESULTS With 48766 patients in the LSM group and 103560 in the control group,the adjusted hazard ratio(HR)for incident HCC and liver-related mortality was 0.92[95%confidence interval(CI):0.87-0.96]and 0.92(95%CI:0.86-0.99)in the LSM group,respectively,compared with the control group.Among the LSM group,the adjusted HR(95%CI)for incident HCC was 0.84(0.76-0.94),0.87(0.81-0.94),and 1.08(1.00-1.16)for alcohol abstinence,smoking cessation,and regular exercise,respectively.The adjusted HR(95%CI)for liver-related mortality was 0.92(0.80-1.06),0.81(0.72-0.91),and 1.15(1.04-1.27)for alcohol abstinence,smoking cessation,and regular exercise,respectively.CONCLUSION LSM lowered the risk of HCC and mortality in patients with CHB.Thus,active LSM,particularly alcohol abstinence and smoking cessation,should be encouraged in patients with CHB.

Postoperative adjuvant antiviral therapy for hepatitis B/C virus-related hepatocellular carcinoma:A meta-analysis

AIM:To investigate the impact of postoperative antiviral treatment on tumor recurrence and survival of patients with chronic hepatitis B virus(HBV) or hepatitis C virus(HCV) infection-related primary hepatocellular carcinoma(HCC) after curative therapy.METHODS:We performed a meta-analysis of randomized and non-randomized control trials from electronic search and manual search.The fixed effect model of Mantel-Haenszel method and the random effect model of Der Simonian and Laird method were used for homogeneous and heterogeneous studies,respectively.Seven HCV-related studies,three HBV-related studies and three studies on HBV or HCV-related HCC were identified.RESULTS:A total of 1224 patients were included in this analysis.The estimated odds ratios(OR) for the 1-,2-,3-and 5-year recurrence were 0.54 [15.4% vs 24.1%,95% confidence interval(CI):0.32-0.89,P=0.02],0.42(36.9% vs 58.0%,95% CI:0.19-0.90,P=0.03),0.37(47.9% vs 63.8%,95% CI:0.19-0.71,P=0.003),and 0.32(66.7% vs 74.3%,95% CI:0.15-0.66,P=0.002),respectively;and the OR for the 1-,2-,3-,5-and 7-year mortality were 0.23(1.2% vs 9.1%,95% CI:0.07-0.71,P=0.01),0.31(6.4% vs 22.1%,95% CI:0.12-0.79,P=0.01),0.43(12.7% vs 20.8%,95% CI:0.21-0.89,P=0.02),0.42(25.1% vs 42.0%,95% CI:0.27-0.66,P=0.0002) and 0.28(31.9% vs 52.2%,95% CI:0.13-0.59,P=0.0008).CONCLUSION:This meta-analysis indicates the postoperative antiviral therapy,interferon in particular,may serve as a favorable alternative to reduce recurrence and mortality in patients with HBV/HCV related HCCs.

WJG 20^(th) Anniversary Special Issues(1): Hepatocellular carcinoma Risk prediction of hepatitis B virus-related hepatocellular carcinoma in the era of antiviral therapy

Chronic hepatitis B(CHB)-related hepatocellular carcinoma(HCC)is a major health problem in AsianPacific regions.Antiviral therapy reduces,but does not eliminate the risk of HCC.It would be a heavy financial burden in most low and middle economic countries if all CHB patients received antiviral therapy and HCC surveillance.Thus,there is a need for accurate risk prediction to assist prognostication,decisions on the need for antiviral therapy and HCC surveillance.A few wellestablished risk factors for HCC,namely advanced age,male gender,high viral load,cirrhosis etc.,are the core components of three HCC risk scores:CU-HCC,GAGHCC and REACH-B scores.These 3 scores were confirmed to be accurate in predicting HCC up to 10 years in treatment-na ve patients.Their validity and applicability have recently been demonstrated in a large cohort of entecavir treatment patients.A decrease in risk scores after antiviral therapy translates to a lower risk of HCC.These findings support the application of HCC risk scores in all CHB patients.Different levels of care and different intensities of HCC surveillance should be offered according to the risk profile of patients.Patients at risk of HCC should undergo regular HCC surveillance,even when they are receiving antiviral treatment.

Impact of antiviral therapy on post-hepatectomy outcome for hepatitis B-related hepatocellular carcinoma

The outcome after curative resection for hepatocellular carcinoma(HCC)remains unsatisfactory due to the high recurrence rate after surgery.In patients with hepatitis B virus(HBV)-related HCC,which is the majority of patients with HCC in Asia,a high viral load is a strong risk factor for HCC recurrence.It is logical to believe that antiviral therapy may improve the postoperative outcome by promoting viral clearance and hepatocyte regeneration,as well as improving residual liver volume in HCC patients with hepatitis B.However,the effect of antiviral therapy on clinical outcomes after liver resection in patients with HBV-related HCC remains to be established.There are two main groups of antiviral treatment for HBV-oral nucleos(t)ide analogues and interferon.Interferon treatment reduces the overall incidence of HBV-related HCC in sustained re-sponders.However,side effects may limit its long-term clinical application.Nucleos(t)ide analogues carry fewer side effects and are potent in terms of viral suppression when compared to interferon and are typically implemented for patients with more advanced liver diseases.They may also improve the outcome after curative resection for HBV-related HCC.There are increasing evidence to suggest that antiviral therapy could suppress HBV,decrease the perioperative reactivation of viral replication,reduce liver injury,preserve the liver function before and after operation,and may lower the risk of HCC recurrence.After all,antiviral therapy may improve the survival after liver resection by reducing recurrence and delaying the liver damage by the virus,resulting in a higher chance of receiving aggressive salvage therapy during HCC recurrence.

Long-term follow-up of cumulative incidence of hepatocellular carcinoma in hepatitis B virus patients without antiviral therapy

BACKGROUND China has a high prevalence of hepatitis B virus(HBV),but most chronic hepatitis B(CHB)patients do not receive standardized antiviral therapy.There are few relevant reports addressing the outcomes of the large number of CHB patients who do not receive antiviral therapy.AIM To observe the outcomes of long-term follow-up of patients with CHB without antiviral treatment.METHODS This study included 362 patients with CHB and 96 with hepatitis B cirrhosis without antiviral treatment and with only liver protection and anti-inflammatory treatment from 1993 to 1998.The median follow-up times were 10 and 7 years,respectively.A total of 203 CHB and 129 hepatitis B cirrhosis patients receiving antiviral therapy were selected as the control groups.The median follow-up times were 8 and 7 years,respectively.Kaplan-Meier curves were used to analyze the cumulative incidence of hepatocellular carcinoma(HCC),and the Cox regression model was used to analyze the risk factors for HCC.RESULTS Among the patients in the non-antiviral group,16.9%had spontaneous decreases(HBeAg)seroconversion.In the antiviral group,87.2%of patients had undetectable HBV DNA,and 52%showed HBeAg seroconversion.Among CHB and hepatitis B cirrhosis patients,the cumulative incidence rates of HCC were 14.9%and 53.1%,respectively,in the non-antiviral group and were 10.7%and 31.9%,respectively,in the antiviral group.There was no difference between the two groups regarding the CHB patients(P=0.842),but there was a difference between the groups regarding the hepatitis B cirrhosis patients(P=0.026).The cumulative incidence rates of HCC were 1.6%and 22.3%(P=0.022)in the groups with and without spontaneous HBeAg seroconversion,respectively.The incidence rates of HCC among patients with and without spontaneous declines in HBV DNA to undetectable levels were 1.6%and 19.1%,respectively(P=0.051).There was no difference in the cumulative incidence of HCC between the two groups regarding the patients with drug-resistant CHB(P=0.119),but there was a significant difference between the two groups regarding the patients with cirrhosis(P=0.004).The Cox regression model was used for regression of the corrected REACH-B score,which showed that alanine aminotransferase>400 U/L,history of diabetes,and family history of liver cancer were risk factors for HCC among men aged>40 years(P<0.05).Multifactorial analysis showed that a family history of HCC among men was a risk factor for HCC.CONCLUSION Antiviral therapy and non-antiviral therapy with liver protection and antiinflammatory therapy can reduce the risk of HCC.Antiviral therapy may mask the spontaneous serological response of some patients during CHB.Therefore,the effect of early antiviral therapy on reducing the incidence of HCC cannot be overestimated.

Perioperative antiviral therapy for chronic hepatitis B-related hepatocellular carcinoma

BACKGROUND: After effective treatment with antiviral agent, patients with low serum hepatitis B virus (HBV) DNA level had a low incidence of hepatocellular carcinoma (HCC). HBV reactivation after HCC surgery is associated with HCC recurrence. To date, there are no universal guidelines for the perioperative antiviral treatment of patients with chronic hepatitis B, let alone antiviral therapy in patients with HBV-related HCC. The present analysis is trying to develop a perioperative anti-HBV treatment protocol. DATA SOURCES: A literature search of PubMed was performed, the key words were "perioperative" "antiviral therapy", "hepato-cellular carcinoma" and "chronic hepatitis B". All of the information was collected. RESULTS: Relevant documents showed that reactivation of HBV replication played a direct role in the late recurrence of HCC after surgical resection. The well control of viral load before and after operation significantly increased tumor-free survival. Many drugs are used in antiviral therapy including interferon alpha and nucleoside analogues. Foscarnet, two-agent or even multiagent of nucleoside analogues is necessary for perioperative antiviral treatment of patients with chronic hepatitis B related HCC. CONCLUSIONS: HBV reactivation after HCC surgery induces hepatitis flare and hepatocarcinogenesis, thus lifelong and vigorous control of HBV is very important in patients with chronic hepatitis B and HBV-related HCC. A uniform guideline is necessary to rapidly reduce HBV DNA to a lower level in perioperation.

Antiviral therapy for hepatitis B virus-related hepatocellular carcinoma after surgery: A comment for moving forward

Recurrence rate of hepatocellular carcinoma remains quite high even after surgery,and no postoperative therapies have been definitively shown to prevent hepatocellular carcinoma recurrence.A previous study showed that therapy with nucleos(t)ide analogues given to such patients after surgery significantly improved survival.However,many questions still exist about the usage of nucleos(t)ide analogues for patients with hepatocellular carcinoma after surgery.

Hepatocellular carcinoma after direct-acting antiviral hepatitis C virus therapy:A debate near the end

Direct acting antivirals(DAAs)have revolutionized the treatment of hepatitis C virus(HCV)infection,achieving high rates(≥95%)of sustained virological response,with a good safety profile and high compliance rates.Consequently,it had been expected that viral clearance will reduce morbidity and mortality rates,as well as the risk of hepatocellular carcinoma(HCC).However,since 2016,concerns have been raised over an unexpected high rate of HCC occurrence and recurrence after DAA therapy,which led to an avalanche of studies with contradictory results.We aimed to review the most recent and relevant articles regarding the risk of HCC after DAA treatment and identify the associated risk factors.

Antiviral treatment to prevent chronic hepatitis B or C-related hepatocellular carcinoma

Antiviral treatment is the only option to prevent or defer the occurrence of hepatocellular carcinoma(HCC) in patients chronically infected with hepatitis B virus(HBV) or hepatitis C virus(HCV). The approved medication for the treatment of chronic HBV infection is interferon-α(IFNα) and nucleos(t)ide analogues(NAs), including lamivudine, adefovir dipivoxil, telbivudine, entecavir and tenofovir disoproxil fumarate. IFNα is the most suitable for young patients with less advanced liver diseases and those infected with HBV genotype A. IFNα treatment significantly decreases the overall incidence of HBV-related HCC in sustained responders. However, side effects may limit its long-term clinical application. Orally administered NAs are typically implemented for patients with more advanced liver diseases. NA treatment significantly reduces disease progression of cirrhosis and therefore HCC incidence, especially in HBV e antigen-positive patients. NA-resistance due to the mutations in HBV polymerase is a major limiting factor. Of the NA resistance-associated mutants, A181 T mutant significantly increases the risk of HCC development during the subsequent course of NA therapy. It is important to initiate treatment with NAs that have a high genetic barrier to resistance, to counsel patients on medication adherence and to monitor virological breakthroughs. The recommended treatment for patients with chronic HCV infection is peg-IFN plus ribavirin that can decrease the occurrence of HCC in those who achieve a sustained virological response and have not yet progressed to cirrhosis. IFN-based treatment is reserved for patients with decompensated cirrhosis who are under evaluation of liver transplantation to reduce post-transplant recurrence of HCV. More effective therapeutic options such as direct acting antiviral agents will hopefully increase the response rate in difficult-totreat patients with HCV genotype 1. However, the risk of HCC remains in cirrhotic patients(both chronic HBV and HCV infection) if treatment is initiated after cirrhosis is established. Future research should focus on investigating new agents, especially for those patients with hepatic decompensation or post-transplantation.

Persistent risk for new, subsequent new and recurrent hepatocellular carcinoma despite successful anti-hepatitis B virus therapy and tumor ablation: The need for hepatitis B virus cure

Hepatitis B virus(HBV) is one of the most significant hepatocarcinogens. The ultimate goal of anti-HBV treatment is to prevent the development of hepatocellular carcinoma(HCC). During the last two decades, with the use of currently available anti-HBV therapies(lamivudine, entecavir and tenofovir disoproxil fumatate), there has been a decrease in the incidence of HBVassociated HCC(HBV-HCC). Furthermore, several studies have demonstrated a reduction in recurrent or new HCC development after initial HCC tumor ablation. However, during an observation period spanning 10 to 20 years, several case reports have demonstrated the development of new, subsequent new and recurrent HCC even in patients with undetectable serum HBV DNA. The persistent risk for HCC is attributed to the presence of covalently closed circular DNA(cccDNA) in the hepatocyte nucleus which continues to work as a template for HBV replication. While a functional cure(loss of hepatitis B surface antigen and undetectable viral DNA) can be attained with nucleos(t)ide analogues, these therapies do not eliminate cccDNA. Of utmost importance is successful eradication of the transcriptionally active HBV cccDNA from hepatocyte nuclei which would be considered a complete cure. The unpredictable nature of HCC development in patients with chronic HBV infection shows the need for a complete cure. Continued support and encouragement for research efforts aimed at developing curative therapies is imperative. The aims of this minireview are to highlight these observations and emphasize the need for a cure for HBV.

Impact of oral anti-hepatitis B therapy on the survival of patients with hepatocellular carcinoma initially treated with chemoembolization

Introduction:Most hepatocellular carcinomas(HCC) develop in a background of underlying liver disease including chronic hepatitis B.However,the effect of antiviral therapy on the long-term outcome of patients with hepatitis B virus(HBV)-related HCC treated with chemoembolization is unclear.This study aimed to evaluate the survival benefits of anti-HBV therapy after chemoembolization for patients with HBV-related HCC.Methods:A total of 224 HCC patients who successfully underwent chemoembolization were identified,and their survival and other relevant clinical data were reviewed.Kaplan-Meier and Cox regression analyses were performed to validate possible effects of antiviral treatment on overall survival(OS).Results:The median survival time(MST) was 15.9(95%confidence interval[CI],9.5-27.7) months in the antiviral group and 9.6(95%CI,7.8-13.7) months in the non-antiviral group(log-rank test,P = 0.044).Cox multivariate analysis revealed that antiviral treatment was a prognostic factor for OS(P = 0.008).Additionally,a further analysis was based on the stratification of the TNM tumor stages.In the subgroup of early stages,MST was significantly longer in the antiviral-treatment group than in the non-antiviral group(61.8 months[95%CI,34.8 months to beyond the follow-up period]versus 26.2[95%CI,14.5-37.7]months,P= 0.012).Multivariate analysis identified antiviral treatment as a prognostic factor for OS in the early-stage subgroup(P = 0.006).However,in the subgroup of advanced stages,MST of the antiviral-treated group was comparable to that of the non-antiviral group(8.4[95%CI,5.2-13.5]months versus 7.4[95%CI,5.9-9.3]months,P = 0.219).Multivariate analysis did not indicate that antiviral treatment was a significant prognostic factor in this subgroup.Conclusion:Antiviral treatment is associated with prolonged OS time after chemoembolization for HCC,especially in patients with early-stage tumors.

Hepatocellular carcinoma,decompensation,and mortality based on hepatitis C treatment:A prospective cohort study

BACKGROUND Prospective studies of the long-term outcomes of patients with hepatitis C virus(HCV)infection after treatment with interferon-based therapy(IBT)or directacting antivirals(DAA)are limited in many Asian countries.AIM To elucidate the incidences of hepatocellular carcinoma(HCC)and death/transplantation based on treatment with IBT or DAA,to compare the outcomes of the sustained virologic response(SVR)to IBT and DAA,and to investigate outcome-determining factors after SVR.METHODS This cohort included 2054 viremic patients(mean age,57 years;46.5%male;27.4%with cirrhosis)prospectively enrolled at seven hospitals between 2007 and 2019.They were classified as the untreated group(n=619),IBT group(n=578),and DAA group(n=857).Outcomes included the incidences of HCC and death/transplantation.The incidences of the outcomes for each group according to treatment were calculated using an exact method based on the Poisson distribution.A multivariate Cox regression analysis was performed to determine the factors associated with HCC or death/transplantation,followed by propensity score matching to confirm the results.RESULTS During a median of 4.1 years of follow-up,HCC and death/transplantation occurred in 113 and 206 patients,respectively,in the entire cohort.Compared with the untreated group,the incidences of HCC and death/transplantation were significantly lower in the IBT group[adjusted hazard ratio(aHR)0.47,95%CI:0.28-0.80 and aHR 0.28,95%CI:0.18-0.43,respectively]and the DAA group(aHR 0.58,95%CI:0.35-0.96,and aHR 0.19,95%CI:0.20-0.68,respectively).Among 1268 patients who attained SVR with IBT(n=451)or DAA(n=816),the multivariable-adjusted analysis showed no differences in the risks of HCC(HR 2.03;95%CI:0.76-5.43)and death/transplantation(HR 1.38;95%CI:0.55-3.49)between the two groups.This was confirmed by a propensity score-matching analysis.Independent factors for HCC after SVR were age,genotype 1,and the presence of cirrhosis.CONCLUSION Treatment and achieving SVR with either IBT or DAA significantly reduced the incidences of HCC and mortality in the Asian patients with HCV infection.The risks of HCC and mortality were not significantly different regardless of whether SVR was induced by IBT or DAA.

Association of HBV DNA replication.with antiviral treatment outcomes in the patients with early-stage HBV-related hepatocellular carcinoma undergoing curative resection

Background:It remains unclear what the antiviral therapy affects disease-free survival(DFS) and overall survival(OS)of patients with hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC) at different tumor stages and baseline HBV DNA levels.In this study,we analyzed the association of antiviral treatment with DFS and OS based on the stratification of baseline HBV DNA load in early-stage(stages Ⅰ and Ⅱ) HCC patients.Methods:We included 445 patients with early-stage HBV-related HCC who underwent curative resection,and then classified them into four subgroups based on baseline HBV DNA load and antiviral therapy stratification.The KaplanMeier and Cox regression analyses were performed to determine the association of clinical characteristics with survival.Results:The median follow-up period was 74 months.For all patients,cumulative OS rates in the antiviral group were significantly higher than those in the non-antiviral group(log-rank test,P = 0.023),whereas no significant differences in DFS rates were observed.High baseline HBV DNA level was a risk factor associated with short DFS and OS in all patients.In patients with baseline HBV DNA levels ≥2000 lU/mL,antiviral treatment was significantly associated with prolonged DFS and OS(log-rank test,P = 0.041 and 0.001,respectively).In patients with HBV DNA levels <2000 lU/mL or undetectable,antiviral treatment did not show a significant benefit in prolonging DFS and OS.Conclusions:High baseline HBV DNA levels are associated with poor prognosis in the patients with early-stage HCC,and the antiviral treatment could generate survival benefits for the patients.Therefore,antiviral treatment should be given for these patients.However,the effect of antiviral treatment on the patients with low viral load remains unclear,and further investigation is warranted.

Long term outcome of antiviral therapy in patients with hepatitis B associated decompensated cirrhosis

AIM To investigate survival rate and incidence of hepatocellular carcinoma(HCC) in patients with decompensated cirrhosis in the antiviral era.METHODS We used the Korean Health Insurance Review and Assessment. Korea's health insurance system is a public single-payer system. The study population consisted of 286871 patients who were prescribed hepatitis B antiviral therapy for the first time between 2007 and 2014 in accordance with the insurance guidelines.Overall, 48365 antiviral treatment-na?ve patients treated between 2008 and 2009 were included, and each had a follow-up period ≥ 5 years. Data were analyzed for the 1 st decompensated chronic hepatitis B(CHB) and treatment-na?ve patients(n = 7166). RESULTS The mean patient age was 43.5 years. The annual mortality rates were 2.4%-19.1%, and 5-year cumulative mortality rate was 32.6% in 1^(st) decompensated CHB treatment-na?ve subjects. But the annual mortality rates sharply decreased to 3.4%(2.4%-4.9%, 2-5 year) after one year of antiviral treatment. Incidence of HCC at first year was 14.3%, the annual incidence of HCC decreased to 2.5%(1.8%-3.7%, 2-5 year) after one year. 5-year cumulative incidence of HCC was 24.1%. Recurrence rate of decompensated event was 46.9% at first year, but the annual incidence of second decompensation events in decompensated CHB treatment-na?ve patients was 3.4%(2.1%-5.4%, 2-5 year) after one year antiviral treatment. 5-year cumulative recurrence rate of decompensated events was 60.6%. Meanwhile, 5-year cumulative mortality rate was 3.1%, and 5-year cumulative incidence of HCC was 11.5% in compensated CHB treatment-na?ve patients.CONCLUSION Long term outcome of decompensated cirrhosis treated with antiviral agent improved much, and incidence of hepatocellular carcinoma and mortality sharply decreased after one year treatment.

Resection of hepatitis B virus-related hepatocellular carcinoma:Evolving strategies and emerging therapies to improve outcome

The incidence of hepatocellular carcinoma(HCC) is increasing worldwide,largely due to hepatitis B virus(HBV),hepatitis C virus and liver cirrhosis.Chronic HBV infection is estimated to cause 55%-60% of the cases of HCC worldwide and over 70% in Asian countries.Liver resection is currently the mainstay of treatment due to the low surgical mortality,a wider treatment indication,and simplicity of post-treatment follow-up.There is an ever-increasing demand on surgeons to perform curative liver resection in HCC,with the hope of avoiding tumor recurrences.Hepatitis B-related-HCC has distinct clinicopathological features,which should be considered when treating the disease.The author presents a review of the recently evolving strategies and emerging therapies to improve HCC postresectional outcomes and focus on perioperative measures to improve patient outcome,with particular reference to the current status of adjuvant therapies in HCC patients after liver resection.

Management of hepatitis B virus infection during treatment for hepatitis B virus-related hepatocellular carcinoma

Although liver resection is considered the most effective treatment for hepatocellular carcinoma(HCC), treatment outcomes are unsatisfactory because of the high rate of HCC recurrence. Since we reported hepatitis B e-antigen positivity and high serum hepatitis B virus(HBV) DNA concentrations are strong risk factors for HCC recurrence after curative resection of HBV-related HCC in the early 2000 s, many investigators have demonstrated the effects of viral status on HCC recurrence and post-treatment outcomes. These findings suggest controlling viral status is important to prevent HCC recurrence and improve survival after curative treatment for HBV-related HCC. Antiviral therapy after curative treatment aims to improve prognosis by preventing HCC recurrence and maintaining liver function. Therapy with interferon and nucleos(t)ide analogs may be useful for preventing HCC recurrence and improving overall survival in patients who have undergone curative resection for HBV-related HCC. In addition, reactivation of viral replication can occur after liver resection for HBV-related HCC. Antiviral therapy can be recommended for patients to prevent HBV reactivation. Nevertheless, further studies are required to establish treatment guidelines for patients with HBVrelated HCC.

Nucleos(t)ide analogues to treat hepatitis B virus-related hepatocellular carcinoma after radical resection

Significant advances have been made in nucleos(t)ideanalogue(NA) therapy to treat chronic hepatitis B,and this therapy reduces the risk of hepatitis B virus(HBV)-related hepatocellular carcinoma(HCC) in somepatients.However,whether NAs can also prevent recurrence after radical resection of HBV-related HCC remains controversial and is an important question,giventhat most patients will experience recurrence within afew years of curative surgery.Here we systematicallyreviewed the literature since 2004 on outcomes afteradministering NAs to patients with HBV-related HCCfollowing radical resection.We focused on treatmentindications,duration,effects on recurrence-free survivaland overall survival,and the management of NA resistance.We find that patients with HCC should stronglyconsider NA therapy if they are positive for HBV-DNA,and that the available evidence suggests that postoperative NA therapy can increase both recurrence-free andoverall survival.To minimize drug resistance,cliniciansshould opt for potent analogues with higher resistancebarriers,and they should monitor the patient carefully for emergence of NA-resistant HBV.