Survival after diagnosis of hepatocellular carcinoma and potential impact of treatment in a hepatitis B or C infected cohort

Aim: Little is known about the patterns of care and the impact of hepatocellular carcinoma (HCC) treatment on health outcomes at a population level. We conducted a population-based cohort study to examine HCC survival trends among people diagnosed with hepatitis B (HBV) or hepatitis C virus (HCV) infection, to determine predictors of receiving potentially curative therapy for HCC, and to examine the impact of HCC treatment on survival in New South Wales, Australia. Methods: The Kaplan–Meier method was used to estimate survival, logistic regression to determine predictors of potentially curative therapy and Cox proportional hazards models to determine the impact of HCC treatment on survival. Years of potential life lost (YPLL) were calculated. Results: During the period 1993–2007, 1081 cases of HCC were diagnosed. Median survival increased from 10.4 months during 1993–1997 to 18.4 months during 1998–2002, with no further improvement thereafter. Younger age at diagnosis (<65 years), being Asian-born and having multiple comorbid conditions increased the odds of receiving curative therapy. The effect of HCC treatment on the risk of mortality was similar between the HBV- and HCV-related HCC groups. Tumor-specific therapies had adjusted hazard ratios ranging 0.06–0.25 and palliative/supportive therapy alone had adjusted hazard ratios ranging 0.76–1.08. The average YPLL per person was 23.3. Conclusion: The burden of viral hepatitis-related HCC is substantial. Despite treatment advances in recent years, there has been no significant improvement in HCC survival. Efforts to improve HCC screening and early diagnosis are required to deliver curative treatment which clearly has a survival advantage.     

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.     

Secondary prevention of hepatocellular carcinoma

Two decades have gone by since the earlier trials of alpha-fetoprotein (AFP) screening for hepatocellular carcinoma (HCC) were conducted in Africa and China. It is accepted that early detection, diagnosis and treatment of HCC remains an important target to be achieved before a breakthrough appears on the primary prevention of HCC. In the present study, screening investigations were performed in a high risk population of HCC, defined as persons who had hepatitis, blood transfusions, a family history of HCC, and were hepatitis B virus carriers. Ultrasonography combined with AFP serosurvey was accepted as an effective screening procedure to detect small HCC. Early diagnosis of HCC was not difficult if tumour markers and medical imaging were combined. Early resection has been proven to prolong survival of patients with small HCC. Repeated intralesional ethanol injection is an alternative treatment to surgery, while transcatheter arterial embolization is a less effective alternative. Re-resection of subclinical recurrence after curative resection has proven of merit in prolonging survival even further. Resection of small HCC remains an important approach in getting long-term HCC survival and to improving 5-year survival rates. It is more effective than treatment of large HCC. Studies on the secondary prevention of HCC have stimulated research into tumour markers, the natural history and cellular origin of HCC and oncogenes. However, the issue of ‘cost-effectiveness’ remains to be evaluated.     

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.     

Impact of diabetes on recurrence of hepatocellular carcinoma after surgical treatment in patients with viral hepatitis

OBJECTIVES: Consensus has been reached that diabetes is a risk factor for development of HCC, but the impact on postoperative recurrence is still controversial. To clarify this point, we analyzed the relationship of postoperative recurrence rate of HCC and coexistence of diabetes in the patients with viral hepatitis. METHODS: A total of 90 patients who had undergone curative resection for HCC were analyzed. They were divided into two groups with and without diabetes, and the recurrence-free survival rates after surgical treatment and the factors contributing to recurrence were examined. RESULTS: Kaplan-Meier survival analysis showed the recurrence-free survival rates in the diabetic group were significantly lower than those in the nondiabetic group (P= 0.005) and overall survival rates in the diabetic group were significantly lower than those in the nondiabetic group (P= 0.005). These results were emphasized in the analysis of patients infected with hepatitis C virus. Univariate and multivariate analyses showed diabetes was a significant factor contributing to HCC recurrence after treatment. Furthermore, multivariate analysis in HCC patients with diabetes showed Child-Pugh classification B (P= 0.001) and insulin therapy (P= 0.049) were significant factors contributing to HCC recurrence after treatment. CONCLUSIONS: The results of the present study suggest that diabetes is a risk factor for the recurrence of HCV-related HCC and decreases the overall survival rates after surgical treatment. HCV-related HCC patients with diabetes should be closely followed for postoperative recurrence.     

Outcome of patients with hepatocellular carcinoma referred to a tertiary centre with availability of multiple treatment options including cadaveric liver transplantation.

Hepatocellular carcinoma (HCC) is a primary cancer of the liver with an established causal link to viral hepatitis and other forms of chronic liver disease. Aims: The aim of this study was to analyse the determinants of outcome in patients with HCC referred to a tertiary centre for management. Method: Two hundred and thirty-five prospective patients with HCC and minimum 12-month follow-up were studied. Results: The cohort was heterogeneous, with 52% Caucasian, 40% Asian and 5% of Middle-Eastern origin. Independent predictors of outcome included tumour size and number, the presence of ascites or portal vein thrombosis, alpha-foetoprotein >50 U/L and an impaired performance status. Treatment was determined on an individual case basis by a multidisciplinary tumour team. Surgical resection was primary treatment in 43 patients, liver transplantation in 40 patients, local ablation (percutaneous radiofrequency ablation or alcohol injection) in 33 patients, transarterial chemoembolisation in 33 patients, chemotherapy or other systemic therapy in 30 patients and no treatment in 56 patients. After adjustment for significant covariates, both liver transplantation (P<0.001) and surgical resection (P=0.029) had a significant effect on patient survival compared with no treatment, but local ablation (P=0.410) and chemoembolisation (P=0.831) did not. Liver transplantation resulted in superior overall and, in particular, disease-free survival compared with surgical resection (disease-free survival 84 vs 15% at 5 years). Conclusion: In conclusion, both surgical resection and liver transplantation significantly improve the survival of patients with HCC, but improvements need to be made to the delivery of loco-regional therapy to enhance its effectiveness.     

肝细胞癌诊治中的若干问题

随着肝细胞癌（HCC）肿瘤标志物和CT／MRI诊断的应用、手术切除及局部消融等治疗方法的进步,使HCC的5年生存率达到了63．4％。但是由于我国HCC早期诊断水平的不均衡,可进行手术切除的病例仅仅有20％～30％。对于高危人群定期开展血清肿瘤标志物和肝脏超声检查;提高三期动态增强CT和Gd—DTPA增强MRI等影像学诊断水平,同时积极开展多学科会诊,制定个性化治疗方案和减少术后肝功能衰竭发生等若干问题,是提高我国HCC早期诊断水平,提高治疗效果,延长生存期的有效手段。     

Evaluation of metabolic factors on the prognosis of patients undergoing resection of hepatocellular carcinoma

Background and Aim: The metabolic factors including obesity, diabetes, and hypertension have been implicated as risk factors of hepatocellular carcinoma (HCC) in patients with chronic hepatitis. The effects of metabolic factors were investigated on the prognosis of patients undergoing resection of HCC. Methods: A total of 469 HCC patients were classified into three groups; hepatitis B virus (HBV)‐, hepatitis C virus (HCV)‐, and non‐HBV/HCV (NBC)‐related HCC. Further, the patients with HCV‐related HCC were sub‐classified into three groups; the patients who did not have documented hypertension, hypertensive patients who received angiotensin II‐blocking agents (ABA), and hypertensive patients who received no ABA. Results: There were no significant difference of survival in the HBV‐HCC and NBC‐HCC patients with or without obesity, diabetes, and hypertension. In the patients with HCV‐related HCC, however, hypertensive patients were significantly worse on both disease‐free and overall survivals than non‐hypertensive patients. Among the HCV‐HCC patients with chronic hepatitis, hypertensive patients with ABA had significantly better preoperative liver function, and hypertensive patients without ABA were significantly worse on both disease‐free and overall survivals than those of hypertensive patients with ABA and non‐hypertensive patients. Conclusions: Results suggest that hypertension is a risk factor for a poor prognosis after resection of HCV‐related HCC. Angiotensin II blockade may improve the prognosis of hypertensive patients with early hepatic fibrosis after resection in HCV‐related HCC.     

The Role of Interferon Therapy in Patients with Hepatocellular Carcinoma

Interferon (IFN) not only may have antiviral properties against hepatitis C, but also may reduce the risk of hepatocellular carcinoma (HCC) through anticarcinogenic properties or indirectly by antifibrotic effects. Because patients with chronic hepatitis C and cirrhosis are at risk for HCC, IFN was used to prevent or treat HCC in patients with hepatitis C. Studies demonstrate that the risk of HCC in hepatitis C patients who are sustained viral responders is substantially reduced but not eliminated. The Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis trial demonstrated that maintenance therapy with IFN does not reduce the risk of HCC in patients with bridging fibrosis or cirrhosis. Other studies suggest the risk of HCC is reduced with IFN maintenance therapy in older patients or in patients whose ??-fetoprotein levels decline. A randomized clinical trial demonstrated IFN therapy is not effective against HCC. Few studies suggest IFN may reduce the risk of recurrent HCC or reduce tumor burden after ablation or resection. Larger trials are needed to determine if IFN can prevent tumor recurrence after resection or locoregional therapy in patients with hepatitis C cirrhosis and HCC.     

Screening for hepatocellular carcinoma: Why,when, how?

Hepatocellular carcinoma (HCC) is a major public health concern in many areas of the world, and its incidence is increasing in the United States and other countries. Screening for HCC in patients with cirrhosis has been advocated to identify those with small lesions who would benefit from transplantation or surgical resection. Despite these recommendations, several issues regarding screening remain controversial. No randomized, controlled trials have confirmed that surveillance for HCC reduces disease-specific mortality. In addition, the most appropriate screening test and optimal screening interval have not yet been defined. Clearly, these unresolved questions have a major impact on the cost-effectiveness of a screening program either at the population or the clinic level. A few studies, however, have suggested that screening may be cost-effective because a minor survival benefit could result in a cost that is acceptable to decision makers.     

The prognostic significance of clinical and pathological features in hepatocellular carcinoma

The prognosis of patients with HCC still remains dismal. The life expectancy of HCC patients is hard to predict because of the high possibility of postoperative recurrence. Many factors, such as patient's general conditions, macroscopic tumor morphology, as well as tumor histopathology features, have been proven of prognostic significance. Female HCC patient often has a better prognosis than male patient, which might be due to the receptor of sex hormones. Younger patients often have tumors with higher invasiveness and metastatic potentials, and their survival and prognosis are worse than the older ones. Co-existing hepatitis status and hepatic functional reserve have been confirmed as risk factors for recurrence. Serum alpha-fetoprotein (AFP) is useful not only for diagnosis, but also as a prognostic indicator for HCC patients. AFP mRNA has been proposed as a predictive marker of HCC cells disseminated into the circulation and for metastatic recurrence. Many pathologic features, such as tumor size, number, capsule state, cell differentiation, venous invasion, intrahepatic spreading, and advanced pTNM stage, are the best-established risk factors for recurrence and important aspects affecting the prognosis of patients with HCC. Marked inflammatory cell infiltration in the tumor could predict a better prognosis. Clinical stage is still the most important factor influencing on the prognosis. Extratumor spreading and lymph nodal metastasis are independent predictors for poor outcome. Some new predictive systems have recently been proposed. Different strategies of treatment might have significant different effects on the patients' prognosis. To date, surgical resection is still the only potentially curative treatment for HCC, including localized postoperative recurrences. Extent of resection, blood transfusion, occlusion of porta hepatis, and blood loss affect the survival and prognosis of HCC patients. Regional therapies provide alternative ways to improve the prognosis of HCC patients who have no opportunity to receive surgical treatment or postoperative recurrence. The combination of these treatment modalities is hopeful to further improve the prognosis. The efficacies of neoadjuvant (preoperative) or adjuvant (postoperative) chemotherapy or chemoembolization in preventing recurrence and on the HCC prognosis still remain great controversy, and deserve further evaluation. Biotherapy, including IFN-alpha therapy, will play more important role in preventing recurrence and metastasis of HCC after operation.     

Clinical prognostic variables in young patients (under 40 years) with hepatitis B virus-associated hepatocellular carcinoma

OBJECTIVE: The aim of this study was to determine the impact of hepatocelluar carcinoma (HCC) screening in chronic hepatitis B patients who did not meet the current screening recommendations. METHODS: Patients who were admitted to Bellevue Hospital Center with HCC were assessed for risk factors, cirrhosis and tumor‐specific factors. Eligibility for liver transplantation or resection with favorable outcome was determined by applying Milan criteria. RESULTS: In all 93 patients were diagnosed with hepatitis B virus (HBV)‐associated HCC, 18 of whom were under 40 years. Cirrhosis was infrequently associated with HCC in this group, with most cancers occurring in non‐cirrhotic patients (12/18, 66.7%). No patient developed HCC outside the American Association for the Study of Liver Diseases (AASLD) cancer screening recommendations (young age, non‐cirrhotic) were eligible for liver transplantation or resection with favorable outcomes (within Milan criteria). However, HCC patients who were diagnosed within AASLD screening recommendations did meet Milan criteria in 17.3% (14/81) patients. CONCLUSIONS: Current guidelines for HCC screening in patients with HBV may lead to a delay in diagnosis in non‐cirrhotic patients under 40 years. Consideration should be given to modifying current recommendations to advocate entering HBV patients into a cancer‐screening program at young age.     

Clinical features and prognosis of hepatocellular carcinoma in young patients from a hepatitis B-endemic area

BACKGROUND AND AIM: Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. However, the clinical features of young HCC patients have not been fully studied. In the present study, we investigated the prevalence, clinical characteristics and prognosis of young HCC patients. METHODS: A retrospective analysis was performed for HCC patients in our center using Korean cancer registry data. Among 4234 patients enrolled, there were 38 patients younger than 30 years of age (0.9%). We compared clinical characteristics and survival data of these patients (group I) with those of sex-matched, randomly selected HCC patients aged 30-59 years (group II; n = 231) and 60 years or older (group III; n = 147). RESULTS: Group I showed distinct features compared with groups II and III as follows: low frequency of smoking history, high positive rate of hepatitis B s antigen, no association with anti-hepatitis C virus antibody, high frequency of alpha-fetoprotein > or = 400 ng/mL, well-preserved liver function, larger tumor size, more advanced tumor-node-metastasis (TNM) stage and Cancer of the Liver Italian Program (CLIP) score and more frequent application of surgical resection and chemotherapy as initial treatment. The overall survival of group I was worse than that of group II, but similar to that of group III. Multivariate analysis showed that TNM stage and CLIP score, not age itself, were independent predictive factors for survival. CONCLUSIONS: The results suggest that young HCC patients tend to have a poor prognosis owing to advanced tumor stage, despite well-preserved liver function and aggressive treatment. Further studies regarding the role of HCC screening in young people may be useful, especially in hepatitis B virus carriers from high endemic areas.     

The progression of hepatitis B- and C-infections to chronic liver disease and hepatocellular carcinoma: presentation, diagnosis, screening, prevention, and treatment of hepatocellular carcinoma

Much information has been gained in the diagnosis and treatment of HCC during the last 15 years. Ever improving imaging technology has made nonhistologic diagnostic criteria possible, albeit controversial. Liver transplantation, resection, and RFA are considered curative options. Yet,HCC incidence is steadily rising because of limited progress on disease prevention. Accurate and cost-effective screening is necessary. Presently, only 10% to 15% of HCC patients present with a curative stage of disease. Because the field of HCC is rapidly changing, patients with HCC should be referred to liver centers with a full array of services, from surgical to oncologic. The prognosis for HCC patients will surely improve with a multidisciplinary approach to care and further clinical research. Better screening and prevention of recurrence should eventually improve survival. It is hoped that antiviral treatment studies will lower the risk of HCC, and that these changes will occur soon enough to help the many patients at risk for or diagnosed with HCC over the next several years.     

Prevention of hepatocellular carcinoma

Prevention is the only realistic approach for reducing mortality rates associated with hepatocellular carcinoma (HCC) worldwide. Vaccination against hepatitis B and screening of blood donations are effective measures of primary prevention. Screening of blood donations has led to a substantial reduction in viral hepatitis transmission among the general population, and in Taiwan vaccination against hepatitis B caused a significant reduction in HCC incidence among infants. Primary prevention also includes approaches that alter epigenetic and genetic changes in hepatocytes, known to increase susceptibility to HCC, as well as treatments slowing progression to cirrhosis. The only evidence that chemoprevention reduces HCC risk is a multicenter randomized prospective study in Asian patients with advanced hepatitis B who received the oral nucleoside analogue lamivudine. Circumstantial evidence suggests that HCC risk is also reduced in patients with chronic hepatitis C who have had a sustained virological response to interferon therapy. HCC is not substantially reduced in patients with hepatitis B treated with interferon and patients with hepatitis C who did not respond to interferon. Secondary prevention, that is, prevention of tumor recurrence after hepatic resection or local ablative therapies, has been pursued with different approaches. Retinoids, hepatic embolization with (131)I lipiodol, and adoptive adjuvant immunotherapy have yielded encouraging results. Other approaches, including those based on interferon alfa or beta, provided inconclusive evidence for secondary prophylaxis of HCC, mainly because of the poor methodologies and scientific background of the studies. Dietary interventions and antiaflatoxin agents might help to prevent HCC in susceptible individuals, but the real efficacy of these approaches is far from being demonstrated.     

Prevention of hepatocellular carcinoma in the Asia–Pacific region: Consensus statements

Among approximately 650 000 people who die from hepatocellular carcinoma (HCC) each year, at least two‐thirds live in Asia. Efforts to improve early diagnosis and treatment have not yet impacted mortality. An Asia–Pacific Working Party convened in Hong Kong in June 2008 to consider ways to prevent HCC in this region. Separate reviews have summarized epidemiology of HCC, preventive approaches related to hepatitis B virus (HBV), hepatitis C virus (HCV) and non‐viral liver diseases, and the role of surveillance to detect HCC at a curative stage. We now present Consensus Statements from these deliberations and reviews. As chronic hepatitis B is the most common cause of HCC in Asia, effective hepatitis B vaccination programs are the most important strategy to reduce HCC incidence. Prevention of HCV by screening blood donors, universal precautions against blood contamination in health‐care settings and reducing HCV transmission from injection drug use are also vital. There is strong evidence that effective antiviral therapy to control HBV infection or eradicate HCV substantially reduces (but does not abolish) HCC risk. With hemochromatosis, family screening, early diagnosis and correcting iron overload to prevent liver fibrosis prevents HCC. There is currently insufficient evidence to give firm recommendations on alcohol, obesity/metabolic risk factors and other liver diseases. HCC surveillance for high‐risk groups is recommended in individual cases but cost‐effectiveness is not as high as infant hepatitis B vaccination and screening blood for HCV. Widespread application of HCC surveillance in Asia–Pacific countries depends on economic factors and health‐care priorities.     

Management of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) ranks fifth in frequency worldwide among all malignancies and causes 1 million deaths annually. The management of HCC begins with diagnostic confirmation by radiologic imaging or histology. Staging is essential, as the choice of therapy depends on the functional state of the liver and the extent of tumor growth. Surgery, in the form of either hepatic resection or orthotopic liver transplantation, is the only potentially curative treatment. Transarterial chemoembolization is commonly used as either palliative treatment or adjunctive therapy to surgery, and a survival benefit with this therapy has just recently been demonstrated in a randomized, controlled trial. Patients with inoperable HCC may benefit from local ablative therapy that may still have curative potential in those with sufficiently small lesions and adequate liver function. For patients with advanced HCC, systemic chemotherapy has been widely employed, despite low efficacy and significant complication rate. Tamoxifen did not improve survival in large clinical trials. Gene therapy is an exciting approach to treating HCC but is still largely confined to preclinical and experimental settings.     

New treatment for hepatocellular carcinoma

Abstract Although the incidence of hepatocellular carcinoma (HCC) is likely to start falling in many countries following mass vaccination programmes, large numbers of new cases are likely to be seen for many years to come. For the majority of patients, only palliative treatments can be offered. Systemic chemotherapy does not improve survival. Locoregional therapy is widely used and certainly results in a consistent decrease in tumour size, but clear evidence of any improvement in overall survival remains elusive. We have recently described the application of selective internal radiotherapy using ⁹⁰yttrium microspheres. Although response rates by conventional radiological criteria were only modest, several initially inoperable cases became operable and subsequent resection revealed complete pathological remission in some. The resection became possible, not only because of tumour shrinkage, but also because of hypertrophy of the non-tumorous liver. To date, only a small number, probably less than 15% of patients with HCC will be suitable for an attempt at surgical resection and recurrence will occur in more than half of these. We have recently shown that postoperative intra-arterial administration of Lipiodol I¹³¹ may significantly decrease this recurrence rate.     

Molecular therapy and prevention of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world with an extremely poor prognosis. The major etiologic risk factors for HCC development include hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, toxins (alcohol, aflatoxin B1) and various inherited metabolic liver diseases, such as hemochromatosis and alpha-1-antitrypsin deficiency. Central to the molecular pathogenesis of HCC are mutations of various genes and genetic/chromosomal instability that result from chronic liver disease and the associated enhanced liver cell regeneration and mitotic activity. Alterations in the structure or expression of several tumor suppressor genes and oncogenes have been described. In addition, mechanisms leading to genetic instability due to mismatch repair deficiency or chromosomal instability and aneuploidy due to defective chromosomal segregation appear to be involved. The prognosis of HCC patients is generally very poor. Most studies have shown a five-year survival rate of less than 5% in symptomatic patients. HCC has been found to be quite resistant to radio- or chemotherapy. Investigations of the natural history and clinical course of HCC revealed a long-term survival of patients only with small asymptomatic HCC that could be treated surgically or nonsurgically. For patients with advanced symptomatic HCC, novel therapeutic strategies such as gene therapy are urgently needed. Apart from exploring and refining new HCC treatment strategies, the implementation of the existing measures or the development of novel measures to prevent HCC is most important. Primary HCC prevention could have a major impact on the incidence of HCC. Further, secondary prevention of a local recurrence or of new HCC lesions in patients after successful surgical or nonsurgical HCC treatment is of paramount importance and is expected to significantly improve disease-free and overall survival rates of patients. Based on rapid scientific advances, molecular diagnosis, gene therapy and molecular prevention are becoming increasingly part of our patient management and will eventually complement or in part replace the existing diagnostic, therapeutic and preventive strategies. Overall, this should result in a reduced HCC incidence and an improved clinical outcome for patients with HCC, one of the most devastating malignancies worldwide.     

Predictors and survival in hepatitis B-related hepatocellular carcinoma in New South Wales, Australia

Background and Aim: Incidence and mortality of hepatocellular carcinoma (HCC) has increased markedly over the last three decades in Australia. An increasing proportion of HCC cases is related to chronic viral hepatitis including hepatitis B virus (HBV) infection. However, there is very limited data on HBV‐related HCC survival. Methods: Data on HBV‐related HCC cases was obtained from a community‐based linkage study. HCC cases notified to the New South Wales (NSW) Central Cancer Registry (CCR) during the period 1994–2002 were linked to HBV notifications from the NSW Health Department. Age, sex, country of birth, year of diagnosis, tumor stage were extracted from the CCR database. Survival analysis was conducted to determine median survival and identify predictors of survival. Results: Over the 9‐year study period, 278 HCC cases were linked to chronic HBV infection. The majority of cases were male (83.5%) and overseas‐born (93.6%); Asian‐born cases accounted for 72.1%. Median survival following HCC diagnosis was 15.0 months. HCC survival was poorer among older age groups (P < 0.0001), and among cases with regional spread (hazard ratio, 3.23; 95% confidence interval, 1.83–5.69; P < 0.0001) and distant metastases (hazard ratio, 3.85; 95% confidence interval, 2.44–6.08; P < 0.0001). Sex, region of birth and study period (1994–1997 vs 1998–2002) were not associated with HCC survival. Conclusion: The vast majority of HBV‐related HCC were overseas‐born, however, region of birth was unrelated to HCC survival. The continued extremely poor HCC survival, including lack of improvement in HCC survival in more recent years, suggests low uptake of HCC screening programs. Public health strategies including early diagnosis and appropriate referral for antiviral therapy assessment and increased HCC screening among high‐risk populations are required to reduce HCC incidence and improve HCC survival.