中国北方地区321例乙型肝炎病毒相关肝细胞癌患者的流行病学和临床特征分析

背景:我国是肝细胞癌(HCC)高发区,其中大部分HCC与乙型肝炎病毒(HBV)感染相关,有必要对其自然史和临床进程作大样本调查研究。目的:了解中国北方地区HBV相关HCC患者的流行病学和临床特征。方法:对中国北方地区321例HBV相关HCC患者作流行病学问卷调查,行肝功能、甲胎蛋白(AFP)、HBV血清标志物和HBV DNA水平检测,并进行统计分析。结果:321例HBV相关HCC患者中,仅7.2%接受过抗病毒治疗;46.4%和25.5%分别有肝硬化和肝癌家族史;38.3%有饮酒史。21.0%的患者乙型肝炎e抗原(HBeAg)阳性,62.3%乙型肝炎e抗体(HBeAb)阳性,HBeAg阳性者合并肝硬化的比例和HBV DNA水平较高。84.5%的患者HBV DNA阳性,但其中仅42.6%HBV DNA≥5.0log10,HBV DNA高水平者合并肝硬化的比例显著高于HBV DNA低水平者。无症状HBV感染、慢性乙型肝炎、代偿性和失代偿性肝硬化患者分别占4.1%、24.1%、39.0%和32.9%。71.0%的患者AFP升高,但其中仅33.8?P≥400ng/ml。结论:本组HBV相关HCC患者中,HBeAg阳性和高HBV DNA水平者不多,但病情常较重。肝硬化是HCC的重要危险因素,饮酒和肝癌家族史对HCC的发生有一定影响。血清AFP筛查有助于HCC的诊断。     

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 2000s, 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 HBV-related HCC.     

Effects of antiviral therapy on preventing liver tumorigenesis and hepatocellular carcinoma recurrence

Chronic hepatitis B virus(HBV)infection is the key driving force of liver disease progression,resulting in the development of hepatic dysfunction,cirrhosis and hepatocellular carcinoma(HCC).The primary aim of therapy is to suppress or eliminate HBV replication to reduce the activity of hepatitis,thus reducing the risk of,or slowing the progression of,liver disease.Nucleos(t)ide analogues(Nucs)may result in rapid suppression of HBV replication with normalization of serum transaminases and restore liver function,thus increasing survival in patients with hepatic decompensation.Long-term Nuc therapy may result in histological improvement or reversal of advanced fibrosis and reduction in disease progression,including the development of HCC.The long-term benefits of a finite course of interferon(IFN)-αtherapy also include a sustained and cumulative response,as well as hepatitis B surface antigen seroclearance and reduction in the development of cirrhosis and/or HCC.Pegylated IFN and newer Nucs may achieve better long-term outcomes because of improved efficacy and a low risk of drug resistance.However,treatment outcomes are still far from satisfactory.Understanding the effects of anti-HBV treatment against HCC incidence and recurrence after hepatectomy or liver transplantation is required for further improvement of outcome.     

Hepatitis B virus DNA integration in hepatocellular carcinoma after interferon-induced disappearance of hepatitis C virus

OBJECTIVES: Hepatocellular carcinoma (HCC) has been reported in patients in whom hepatitis C virus (HCV) was eliminated by interferon (IFN) therapy. We examined the pathogenesis of HCC in patients with sustained viral response. METHODS: Operable HCC developed in 7 of 342 patients cured of HCV infection by IFN monotherapy. No patient abused alcohol or had diabetes mellitus or obesity. Resected specimens of HCC were histologically evaluated. DNA extracted from HCC was examined by polymerase chain reaction (PCR) to locate hepatitis B virus (HBV) DNA. HBV integration sites in human genome were identified by cassette-ligation-mediated PCR. RESULTS: HBV DNA was not amplified in serum samples from any of the seven patients with HCC and was found in liver in four patients. In the latter four patients, HBV DNA was integrated into the human genome of HCC. In two of these patients, covalently closed circular HBV (cccHBV) was also detected. The patients with HBV DNA integration were free of HCV for more than 3 yr. In two of the three patients without HBV DNA integration, the surrounding liver showed cirrhosis. The liver of HCC with HBV DNA integration had not progressed to cirrhosis. Three of the four tumors with HBV integration had one integration site each, located at chromosomes 11q12, 11q22-23, and 22q11, respectively. The other tumor had two integration sites, situated at chromosomes 11q13 and 14q32. At chromosome 11q12, HBV DNA was integrated into protein-coding genome, the function of which remains unclear. CONCLUSION: Integrated HBV DNA may play a role in hepatocarcinogenesis after the clearance of HCV by IFN treatment.     

Interferon lowers tumor recurrence rate after surgical resection or ablation of hepatocellular carcinoma: a pilot study of patients with hepatitis B virus-related cirrhosis

Background Hepatocellular carcinoma (HCC) caused by hepatitis B virus (HBV) often recurs after surgical or medical treatment. Methods Eighty consecutive patients with HBV-positive cirrhosis and HCC who underwent potentially curative ablation for HCC were analyzed. Eleven patients received long-term interferon (IFN) therapy. HBV DNA was quantified at the time of HCC treatment. A DNA value of <6.0 log copies/ml was considered low. Results Initial DNA was low in 39 and high in 41 patients. HCC recurrence rates in the low DNA group and high DNA group were 46.9% and 82.6% at the fifth year, and 73.5% and 91.3% at the tenth year, respectively (P = 0.0103). Similarly, recurrence rates after treatment of HCC in the normal aspartate aminotransferase (AST) group (<38 IU/l, n = 42) and abnormal AST group (n = 38) were 50.6% and 84.0% at the fifth year, and 71.3% and 100% at the tenth year, respectively (P = 0.0003). Six of the 38 patients with abnormal AST, and 5 of 42 patients with normal AST, received IFN after confirmation of tumor ablation. In the subgroup of abnormal AST, tumor recurrence rates in the IFN and untreated groups were 16.7% and 37.9% at the end of the first year, 16.7% and 60.1% at the second year, and 16.7% and 83.4% at the third year, respectively (P = 0.0139). Multivariate analysis revealed that IFN significantly reduced the recurrence rate (hazard ratio = 0.21, P = 0.037) even after adjusting for background characteristics. Conclusions IFN was inferred to decrease tumor recurrence after treatment of HCC in patients with HBV-related cirrhosis, especially in the subgroup with high AST.     

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 post-operative 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 responders. 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.     

Hepatitis B viral load affects prognosis of hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is a complex disease that is dually challenging to treat due to underlying chronic liver disease in addition to the cancer itself.The prognosis of patients with HCC is determined by intrahepatic tumor status and reserved hepatic function.Hepatitis B virus(HBV)is an established major risk factor of HCC development,and HBV viral load is being increasingly recognized as a prognostic factor in the presence of established HCC.High HBV viral load may affect the prognosis of HBV-related HCC patients in several ways.First,it is associated with more frequent recurrence of HBV-related HCC after treatment.Second,it is associated with more occurrence and severity of potentially life-threatening HBV reactivation.Last,it is associated with more worsened liver function,which limits the therapeutic options for HBV-related HCC.HBV,directly or indirectly,can induce hepatocarcinogenesis.In patients with a high HBV DNA level and subsequent active hepatitis,adhesion molecules expressed on the sinusoidal cells are up-regulated and may increase intrahepatic metastasis.HCC progression after treatment can lead to a poor prognosis by reducing number of normal functioning hepatocytes.Thus,high HBV viral load can affect the prognosis of patientswith HCC by frequent recurrence after treatment for HCC and deterioration of hepatic function associated with HCC progression.Recent meta-analysis showed that antiviral treatment reduces HCC recurrence and liver-related mortality after curative therapy of HCC.Given the strong relationship between high HBV DNA load and poor survival outcome of HCC patients due to cancer progression,it is expected that long-term antiviral therapy results in the sustained HBV suppression,control of inflammation,reduction in HCC progression,and eventually in improved overall survival.     

Guidelines for the treatment of chronic hepatitis and cirrhosis due to hepatitis B virus infection for the fiscal year 2008 in Japan

In the 2008 guidelines for the treatment of patients with cirrhosis, who are infected with hepatitis B virus (HBV), the main goal is to normalize levels of alanine and aspartate aminotransferases by eliminating HBV or reducing viral loads. In patients with compensated cirrhosis, the clearance of HBV from serum is aimed for by entecavir, as the main resort, for histological improvement toward the prevention of hepatocellular carcinoma (HCC). In patients with decompensated cirrhosis, by contrast, meticulous therapeutic strategies are adopted for the reversal to compensation, toward the eventual goal of decreasing the risk of HCC. For maintaining liver function and preventing HCC, branched chain amino acids and nutrient supplements are applied, in addition to conventional liver supportive therapies. For patients with chronic hepatitis B, separate guidelines are applied to those younger than 35 years and those aged 35 years or older. Even for patients with chronic hepatitis who are negative for hepatitis e antigen (HBeAg), but who harbor HBV DNA in titers of 7 log copies/mL or more, a "drug-free state" is aimed for by sequential treatment with interferon (IFN) plus entecavir as the first line. For patients with chronic hepatitis B aged 35 years or older, who are HBeAg-negative and carry HBV DNA in titers of less than 7 log copies/mL, long-term IFN for 24–48 weeks is adopted anew. To HBeAg-negative patients who have either or both platelet counts of less than 150 × 10³/mm³ and less than 7 log copies of HBV DNA, also, long-term IFN for 24–48 weeks is indicated.     

Benefits of nucleos(t)ide analog treatments for hepatitis B virus-related cirrhosis

Chronic hepatitis B infection induces progressive liver disease. Before nucleos(t)ide analogs(NUCs) became established as a safe and effective treatment for hepatitis B,it was difficult to suppress the activity of the hepatitis B virus(HBV). Currently,many patients withhepatitis or cirrhosis associated with HBV are treated with NUCs for an extended period of time,and the effects,benefits,and limitations of these treatments have been apparent. This article reviews HBV-related cirrhosis,its natural course and survival,histological improvement after NUC treatments,treatment effects for decompensated cirrhosis,the incidence of hepatocellular carcinoma(HCC) after NUC treatments,and the efficacy of NUC treatments before and after the treatment of patients for HBV-related HCC. Of particular interest are the histological improvements,including regression of fibrosis,that have been achieved with NUC treatments. Liver function of patients with decompensated cirrhosis has significantly improved regardless of the type of NUC applied,and treatment with NUCs has reduced the incidence of HCC in cirrhotic patients. However,cirrhosis remains the strongest risk factor for HCC occurrence following NUC treatments,and the long-term cumulative incidence of HCC after NUC treatments remains high. When recurrence does occur,it is important to reconsider the treatment modality according to the degree of improved liver function that was achieved.     

Occult hepatitis B virus infection as a risk factor for hepatocellular carcinoma in patients with chronic hepatitis C in whom viral eradication fails.

Aim: Recent studies have suggested that an occult hepatitis B virus (HBV) infection negative for HBsAg but positive for HBV-DNA contributes to hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C. Some follow-up studies have suggested the clinical importance of occult HBV infections in HCC development even after interferon (IFN) therapy, but a recent study denies the significance of the impact of occult HBV infection. Focusing on HCC development in patients in whom hepatitis C virus (HCV) eradication by interferon (IFN) therapy had failed, we conducted this study in order to assess the impact of occult HBV infections on HCC development in these patients. Methods: We enrolled 141 patients with chronic hepatitis C (histological stage F2 or F3) who were seropositive for HCV-RNA even after IFN therapy. Serum HBV-DNA was assayed using the real-time polymerase chain reaction. During follow-up, ultrasonography and/or computed tomography (CT) were performed at least every 6 months to monitor HCC development. Results: The cumulative incidence rates of HCC were 8.9%, 25.7% and 53.7% at 5 years, 10 years and 15 years, respectively, after IFN therapy. Multivariate analysis indicated that low platelet counts (<12 x 10(4)/mm(3)), occult HBV infection, high ALT levels (>/=80 IU/L) after IFN therapy and the staging of liver fibrosis were important independent factors affecting the appearance of HCC. Conclusions: Occult HBV was a risk factor for HCC development in patients with chronic hepatitis C in whom HCV eradication had failed. Therefore, patients with chronic hepatitis C with occult HBV should be monitored carefully for HCC after IFN therapy.     

Viral hepatitis B and hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the sixth most common cancer in the world, some 630,000 new cases being diagnosed each year. 82% of cases are related to viral hepatitis, 55% to hepatitis B virus (HBV), 89% of those in regions where HBV is endemic. There is a striking parallel between the geographical distribution of the rates of chronic HBV infection and that of HCC. In the majority of HCC cases (70-90%) there is underlying liver cirrhosis. However, because HBV is an oncogenic virus, it can cause HCC in the absence of cirrhosis. The annual risk of HBV-induced HCC varies according to the presence or absence of concomitant cirrhosis. In HBV carriers without cirrhosis, the risk is 0.02-03% in Caucasians and 0.4-0.6% per year in Asians. In those with cirrhosis, the risk is 2.2% and 3.7% respectively in Caucasians and Asians. HBV likely causes HCC via both indirect (necro-inflammation and regeneration injury) and direct (by integration of its DNA in the host genome) pathways. During recent years it has become evident that HBV viral load >2000 IU/mL is associated with a high risk of malignant transformation. The most effective measure of prevention of HBV-related HCC is prevention of HBV infection by vaccination. A universal vaccination program in Taiwan was shown to be effective in reducing the rate of childhood and early adulthood HCC. In patients already infected with HBV, antiviral therapy remains the best strategy. Interferon-alfa therapy appears to be effective in preventing HCC in cirrhosis in Asia but not in Europe. Medium-term nucleos/tide-analogue therapy significantly reduces but does not eliminate the risk of HCC, especially in patients with pre-existing cirrhosis. Maintenance of virological remission is important for the reduction of HCC risk. With more potent antiviral drugs currently available (entecavir, tenofovir), long-term HBV DNA suppression is now possible with very low risk of drug resistance.     

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??Abstract??HBV-related end-stage liver disease and hepatocellular carcinoma (HCC) are the major indications for liver transplantation in China.With the introduction of hepatitis B immunoglobulin (HBIG) and oral nucleos(t)ide analogues (NAs)??new antiviral therapy has significantly improved the prognosis of liver transplantation.Pre-transplant antiviral therapy will significantly reduce the recurrence rates of HBV infection.All HBsAg-positive patients awaiting liver transplantation for HBV-related end-stage liver disease or HCC should be administered with a potent NA with high barrier to drug resistance to achieve the viral load as low as possible.Additional HBIG administration during the anhepatic phase will achieve a better control of HBV infection.HBIG should be used in combination with NAs post-transplantation to prevent HBV recurrence.As the fact that liver transplant recipients usually need life-long medication to prevent HBV recurrence??it is currently recommended that HBIG can be discontinued in patients under long-term administration of potent NAs with high barrier to drug resistance in combination with HBIG.     

The relationship between HBcrAg and HBV reinfection in HBV related post-liver transplantation patients

Background

Post-transplant hepatitis B virus (HBV) reinfection is one of the major problems facing patients who undergo HBV-related liver transplantation (LT). We analyzed the clinical impact of serum hepatitis B core-related antigen (HBcrAg) on HBV reinfection in post-LT patients with HBV-related liver diseases.

Methods

Serum hepatitis B surface antigen (HBsAg), HBV DNA, and HBcrAg were measured over time in 32 post-LT patients. Twenty-one out of 32 patients had HCC at LT. The effects of HBcrAg, hepatocellular carcinoma (HCC) recurrence, and HBs gene mutation on HBV reinfection and withdrawal from hepatitis B immune globulin (HBIG) were analyzed.

Results

Sixteen out of 32 patients (50 %) were positive for HBcrAg even though only six patients were thought to have experienced HBV reinfection based on reappearance of either HBV DNA or HBsAg during a median follow-up time of 75 months. Three of these six patients who became re-infected with HBV experienced HCC recurrence after LT. The HBV DNA reappearance rate was significantly higher in patients with HCC recurrence after LT (p < 0.001). Two HBV re-infected patients without HCC recurrence had HBs gene mutations G145R and G145A, respectively. Anti-HBs antibody development rate by HB vaccination was similar between HBcrAg-positive and negative patients (p = 0.325).

Conclusions

HBV reinfection is more common than is usually considered based on conventional measurement of HBsAg and HBV DNA. HCC recurrence and mutations in the HBV S gene were associated with HBV reinfection after LT.

     

Antiviral therapies for hepatitis B virus-related hepatocellular carcinoma

Chronic hepatitis B virus(HBV) infection is a critical risk factor for the carcinogenesis and progression of hepatocellular carcinoma(HCC). It promotes HCC development by inducing liver fibrogenesis, genetic and epigenetic alterations, and the expression of active viral-coded proteins. Effective antiviral treatments inhibit the replication of HBV, reduce serum viral load and accelerate hepatitis B e antigen serum conversion. Timely initiation of antiviral treatment is not only essential for preventing the incidence of HCC in chronic hepatitis B patients, but also important for reducing HBV reactivation, improving liver function, reducing or delaying HCC recurrence, and prolonging overall survival of HBV-related HCC patients after curative and palliative therapies. The selection of antiviral drugs, monitoring of indicators such as HBV DNA and hepatitis B surface antigen, and timely rescue treatment when necessary, are essential in antiviral therapies for HBVrelated HCC.     

Prevention of hepatocellular carcinoma in hepatitis B virus infection

Chronic hepatitis B is the main risk factor for hepatocellular carcinoma (HCC) in Asia. The most important preventive strategy's adoption of the universal hepatitis B vaccination program is now in its third decade. There is a clear reduction in both chronic hepatitis B virus (HBV) infection (hepatitis B surface antigen "carriage") but also in childhood HCC in Taiwan. An outstanding concern is variability in vaccine coverage between countries. For patients with chronic hepatitis B, serum HBV DNA levels have emerged as the key risk factor for development of HCC. The initial treatment for chronic hepatitis B was interferon. One randomized control trial, and several case–control or cohort studies have shown benefits for preventing HCC, particularly in cirrhotic patients who responded to therapy. With nucleos(t)ide analogs, the most important study has been the Asian Cirrhosis Lamivudine multicenter randomized controlled trial. This showed that lamivudine can reduce disease progression in HBV-related cirrhosis, including an approximately 50% decrease in HCC incidence. Such efficacy was achieved despite emergence of drug resistance in approximately 50% of cases. Case–control studies have suggested that hepatitis B cases without cirrhosis may also benefit. In conclusion, it is now possible to prevent HBV-related HCC. The most effective method is hepatitis B vaccination, which prevents chronic HBV infection and chronic liver disease resulting therefrom. Interferon therapy appears to confer benefit but the evidence is weaker. First-generation oral antiviral (lamivudine) reduces HCC risk, particularly in cirrhotics. Long-term outcome data with newer, more potent HBV antivirals that have a higher genetic barrier to drug resistance are eagerly awaited.     

Influence of serum HBV DNA load on recurrence of hepatocellular carcinoma after treatment with percutaneous radiofrequency ablation

Background

High serum load of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) is a strong risk factor of hepatocellular carcinoma (HCC) development, independent of hepatitis B e antigen, serum alanine aminotransferase level, and liver cirrhosis. We evaluated whether serum HBV DNA load is associated with the risk of recurrence of HBV-related HCC treated with radiofrequency ablation (RFA).

Methods

The study population was 69 consecutive patients with HBV-related HCC treated locally completely with RFA between January 2000 and September 2007. The risk factors for HCC recurrence were analyzed based on laboratory data, including serum HBV DNA load, together with tumor size and number using univariate and multivariate proportional hazard regression analyses.

Results

HCC recurrence was observed in 42 of 69 patients during the median observation period of 1.5 years. Cumulative recurrence rates at 1, 3, and 5 years were 26.5, 57.8, and 74.3%, respectively. In univariate analysis, albumin (<3.5 g/dl), platelet count (<150 × 10³/mm³), prothrombin activity (PT) (<70%), Child-Pugh class B, serum HBV DNA load (>4.0 log10 copies/ml), and tumor number (>3) were associated with the recurrence at p ≤ 0.15. Multivariate Cox regression analysis with stepwise variable selection showed that the tumor number (risk ratio, 4.63; 95% CI, 1.50–14.25, P = 0.0076), low PT (3.39, 1.52–5.78, P = 0.0029), and high HBV DNA load (2.67, 1.16–6.14, P = 0.021) were independent risk factors for HCC recurrence.

Conclusion

Serum HBV DNA load is associated with the risk of recurrence of HBV-related HCC after RFA.     

Interferon therapy in HBeAg positive chronic hepatitis reduces progression to cirrhosis and hepatocellular carcinoma

BACKGROUND/AIMS: The long-term outcomes of interferon-alpha (IFN-alpha) therapy in hepatitis B e antigen (HBeAg) seropositive patients remain controversial. This study was conducted to address this issue. METHODS: The long-term outcomes were compared in 233 IFN-treated patients and 233 well-matched untreated controls. RESULTS: The cumulative incidence at the end of 15 years of follow-up (median 6.8 years, range 1.1-16.5 years) in the IFN-treated patients and controls was: HBeAg seroconversion 74.6% vs. 51.7% (P=0.031); hepatitis B surface antigen (HBsAg) seroclearance 3% vs. 0.4% (P=0.03); cirrhosis 17.8% vs. 33.7% (P=0.041); and hepatocellular carcinoma (HCC) 2.7% vs. 12.5% (P=0.011). Significant reduction of HCC was only observed in patients with pre-existing cirrhosis (P<0.01). Compared with untreated controls with persistent HBeAg, HBeAg seroconverters in untreated and IFN-treated group showed significantly lower incidence of cirrhosis and HCC (P=0.003-0.031), while non-seroconverters of IFN-treated group had marginally significant lower incidence of cirrhosis (P=0.065). Multivariate analysis showed that IFN therapy, HBeAg seroconversion and genotype B HBV infection are independent factors for better long-term outcomes. CONCLUSIONS: IFN therapy reduces cirrhosis and HCC development.     

Effects of lamivudine on outcome after liver resection for hepatocellular carcinoma in patients with active replication of hepatitis B virus

Aim:  Patients with high serum hepatitis B virus (HBV) DNA concentrations are at high risk of tumor recurrence after liver resection for HBV-related hepatocellular carcinoma (HCC).
Methods:  Among 24 patients with high serum HBV DNA concentrations who underwent liver resection for HBV-related HCC, postoperative lamivudine therapy was chosen by 14 (lamivudine group). The other 10 patients were controls.
Results:  Clinicopathologic findings did not differ between the groups. Tumor-free survival rate after surgery was significantly higher in the lamivudine than the control group ( P  = 0.0086). By univariate analysis, multiple tumors were also a risk factor for a short tumor-free survival. By multivariate analysis, lack of lamivudine therapy and multiple tumors were independent risk factors for a short tumor-free survival. In four patients YMDD mutant viruses were detected after beginning lamivudine administration; in two of them, adefovir dipivoxil was administered because of sustained serum alanine aminotransferase elevations.
Conclusion:  Lamivudine therapy improved tumor-free survival rate after curative resection of HBV-related HCC in patients with high serum concentrations of HBV DNA, although careful follow up proved necessary for the detection of YMDD mutant viruses.     

Lower serum viral loads in young patients with hepatitis-B-virus-related hepatocellular carcinoma

Advanced age and high hepatitis B virus (HBV) DNA level are risk factors associated with the development of HBV-related hepatocellular carcinoma (HCC). However, little is known about the role of viral load in the carcinogenesis of HCC in young people. A total of 183 HBV-related HCC patients and 202 HBV carriers were therefore enrolled to compare serum viral loads in young (40 years of age) age groups. Other factors associated with the development of HCC were also analysed. The results showed that serum alanine aminotransferase (38.7 +/- 24.1 vs 58.4 +/- 65.4 IU/L, P = 0.006) and HBV DNA levels (log(10) titre: 4.20 +/- 1.33 vs 4.80 +/- 1.39, P = 0.053) were lower in young HCC patients than in old HCC patients. There was a positive correlation between age and serum HBV DNA level in HCC patients but a negative correlation in HBV carriers. Young HCC patients with HBV genotype B infection had higher viral loads than those with genotype C infection (log(10) titre: 4.79 +/- 1.34 vs 3.27 +/- 0.60, P = 0.001). By multivariate logistic regression analyses, high serum HBV DNA level was associated with the development of HCC in old patients [odds ratio (OR) 1.584, 95% confidence interval (CI) 1.075-2.333] rather than in young patients (OR 0.848, 95% CI 0.645-1.116). In conclusion, viral factors in association with the development of HBV-related HCC in young patients may be different from their old counterparts. The complicated interplay between host and virus could be responsible for the emergence and aggressive outcome of early-onset HCC.     

Clinicopathological differences between hepatitis B viral genotype B- and C-related resectable hepatocellular carcinoma

Clinical and pathogenic differences exist between hepatitis B viral (HBV) genotypes B and C, and genotype C has a higher risk of hepatocellular carcinoma (HCC) development than genotype B. The aim of this study was to investigate whether HBV genotypes B and C influence the clinicopathological features of patients with resectable HCC. Stored serum samples from 193 patients with resectable HBV-related HCC were tested for HBV genotypes by a molecular method. Of 193 patients undergoing resection of HCC, 107 (55%) and 86 (45%) were infected with genotypes B and C, respectively. Compared with genotype C patients, genotype B patients were less likely to be associated with liver cirrhosis (33%vs 51%, P = 0.01). Pathologically, genotype B patients had a higher rate of solitary tumour (94%vs 86%, P = 0.048) and more satellite nodules (22%vs 12%, P = 0.05) than genotype C patients. Our results indicate that genotype B-related HCC is less associated with liver cirrhosis and has a higher frequency of solitary tumour as well as more satellite nodules than genotype C-related HCC. These characteristics may contribute to the recurrence patterns and prognosis of HBV-related HCC in patients with genotype B or C infection.