Hepatitis B: overview of the burden of disease in the Asia‐Pacific region

Abstract: Hepatitis B virus (HBV) infection and its liver‐related complications are a substantial health concern in the Asia‐Pacific region. Over the last two decades, public health interventions and the implementation of universal vaccination programs have substantially reduced the incidence of HBV infections in many countries in this region. However, large proportions of individuals remain chronically infected and subject to an increased risk for serious sequelae, including cirrhosis, decompensated liver disease, and hepatocellular carcinoma. The management of HBV infection varies throughout the Asia‐Pacific region, with each country confronting different issues related to prevention, screening, and treatment. These issues include the availability of diagnostic testing and treatment, the cost of diagnosis and treatment, the availability of trained medical professionals and medical facilities, and disease awareness among primary care physicians and the public. This article reviews the epidemiology of HBV infection in the Asia‐Pacific region, explains factors influencing hepatitis B prevalence and prevention, and discusses barriers to prevention and treatment of chronic hepatitis B and its liver‐related complications.     

Antiviral therapy and primary and secondary prevention of hepatocellular carcinoma

Viral hepatitis due to chronic hepatitis B and C virus (HBV/HCV) infects more than 500 000 000 individuals worldwide. These chronic viral diseases are highly linked to the development of hepatocellular carcinoma (HCC), the fifth most common cause of cancer death worldwide. HCC is much more common in Asia and Africa than in the USA and Europe, although HCC is one of the few cancers with a rising incidence in the USA. There are 530 000 cases of HCC worldwide of which 82% are related to viral hepatitis. 316 000 cases of HCC are HBV-associated, 118 000 are HCV-associated. The most effective way to prevent HCC is to prevent viral infection through immunization. Currently there are effective vaccinesagainst hepatitis B and A, but not against HCV, the virus that accounts for most HCC in the USA. The published work supporting the use of antiviral therapy in preventing liver cancer is limited. Data supporting the use of antiviral therapy in preventing recurrence of HCC after initial anticancer approaches is even less available. Nevertheless, the weight of evidence suggests that treatment of HBV/HCV-related fibrosis will reduce the risk of developing HCC.     

Hepatocellular carcinoma in the Asia pacific region

Primary liver cancer, particularly hepatocellular carcinoma (HCC) remains a significant disease worldwide. It is among the top three causes of cancer death in the Asia Pacific region because of the high prevalence of its main etiological agents, chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections. In this region, the incidence of HCC has been static over recent decades. Older age is a major risk factor; the incidence increasing sharply after age 40 years. There is a male predilection, with male to female ratio of 3:1, except in elderly Japanese with equal sex incidence or female predominance. In most Asia‐Pacific countries, chronic HBV infection accounts for 75–80% of cases; Japan, Singapore and Australia/New Zealand are exceptions because of higher prevalence of HCV infection. In spite of advances in surgery, liver transplantation and newer pharmaco/biological therapies, the survival rate has improved only slightly over recent decades, and this could be attributable to earlier diagnosis (‘lead‐time bias’). The majority of patients present with advanced diseases, hence reducing the chance of curative treatment. The importance of HCC may decrease in two to three decades when the prevalence of chronic HBV infection decreases as a result of the universal HBV vaccination programs implemented in late 1980s in most Asia‐Pacific countries, and because of reduced incidence of medical transmission of HCV. However, transmission of HCV by injection drug use, and rising prevalence of obesity and diabetes, both independent risk factors for HCC, may partly offset this decline.     

Does antiviral therapy for hepatitis B and C prevent hepatocellular carcinoma?

Approximately 75% to 80% of hepatocellular carcinomas (HCC) worldwide are attributed to chronic hepatitis B virus (HBV) and chronic hepatitis C virus (HCV) infection. Thus, effective prevention of HBV and HCV infection and progression from acute HBV and HCV infection to chronic hepatitis, cirrhosis and HCC might prevent as many as 450,000 deaths from HCC each year. The most effective approach to preventing HCC is to prevent HBV and HCV infection through vaccination. Indeed HBV vaccine is the first vaccine demonstrated to prevent cancers. However, a vaccine for HCV is not available and for persons who are chronically infected with HBV or HCV, antiviral therapy is the only option for preventing HCC. Direct evidence supporting a benefit of antiviral therapy on the prevention of HCC has been shown in a few randomized controlled trials. There is abundant evidence that antiviral therapy, in patients with long-term virological response, can improve liver histology, providing indirect support that antiviral therapy may prevent HCC by slowing progression of liver disease and possibly even reversing liver damage. Nevertheless, the risk of HCC remains in patients with chronic HBV or chronic HCV infection if treatment is initiated after cirrhosis is established. These data indicate that treatment might be of greater benefit if instituted earlier in the course of chronic hepatitis B or C. Safer, more effective, and more affordable antiviral therapies are needed for both hepatitis B and hepatitis C so more patients can benefit from treatment and more HCCs can be prevented.     

Aiming for the elimination of viral hepatitis in Australia,New Zealand,and the Pacific Islands and Territories: Where are we now and barriers to meeting World Health Organization targets by 2030

Viral hepatitis affects more than 320 million people globally, leading to significant morbidity and mortality due to liver failure and hepatocellular carcinoma (HCC). More than 248 million people (3.2% globally) are chronically infected with hepatitis B virus (HBV), and an estimated 80 million people (1.1% globally) are chronically infected with hepatitis C virus (HCV). In 2015, more than 700 000 deaths were directly attributable to HBV, and nearly 500 000 deaths were attributable to HCV infection; 2–5% of HBV‐infected people develop HCC per annum irrespective of the presence of cirrhosis, whereas 1–5% HCV‐infected people with advanced fibrosis develop HCC per annum. The rapidly escalating global mortality related to HBV and HCV related viral hepatitis to be the 7th leading cause of death worldwide in 2013, from 10th leading cause in 1990. Australia, New Zealand, and Pacific Island Countries and Territories fall within the World Health Organization Western Pacific Region, which has a high prevalence of viral hepatitis and related morbidity, particularly HBV. Remarkably, in this region, HBV‐related mortality is greater than for tuberculosis, HIV infection, and malaria combined. The region provides a unique contrast in viral hepatitis prevalence, health system resources, and approaches taken to achieve World Health Organization global elimination targets for HBV and HCV infection. This review highlights the latest evidence in viral hepatitis epidemiology and explores the health resources available to combat viral hepatitis, focusing on the major challenges and critical needs to achieve elimination in Australia, New Zealand, and Pacific Island Countries and Territories.     

Risk factors for hepatocellular carcinoma in a cohort infected with hepatitis B or C

Background and Aim: The incidence of hepatocellular carcinoma ( HCC) has increased in Australia in recent decades, a large and growing proportion of which occurs among a population chronically infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). However, risk factors for HCC among these high‐risk groups require further characterization. Methods: We conducted a population‐based cohort study using HBV and HCV cases notified to the New South Wales Health Department between 2000 and 2007. These were linked to cause of death data, HIV/AIDS notifications, and hospital records. Proportional hazards regression was used to identify significant risk factors for developing HCC. Results: A total of 242 and 339 HCC cases were linked to HBV (n = 43 892) and HCV (n = 83 817) notifications, respectively. For both HBV and HCV groups, being male and increasing age were significantly associated with risk of HCC. Increasing comorbidity score indicated high risk, while living outside urban areas was associated with lower risk. Hazard ratios for males were two to three times those of females. For both HBV and HCV groups, cirrhosis, alcoholic liver disease, and the interaction between the two were associated with significantly and considerably elevated risk. Conclusion: This large population‐based study confirms known risk factors for HCC. The association with older age highlights the potential impact of HBV and HCV screening of at‐risk groups and early clinical assessment. Additional research is required to evaluate the impact of improving antiviral therapy on HCC risk.     

De novo hepatitis B virus infection in hepatocellular carcinoma following eradication of hepatitis C virus by interferon therapy

Epidemiological studies have revealed that hepatocellular carcinoma (HCC) is still observed in hepatitis C virus (HCV)‐positive patients with a sustained response to interferon (IFN) treatment, although a substantial decrease in the incidence of hepatocellular carcinoma (HCC) has been achieved in those patients. Why HCC develops in patients who have a complete clearance of HCV remains unclear. Here, we provided evidence of latent hepatitis B virus (HBV) infection in an initially HCV‐positive chronic hepatitis patient who developed HCC after the complete eradication of HCV by IFN therapy. Although he was initially negative for anti‐hepatitis B surface antigen (HBsAg) or circulating HBV DNA but positive for anti‐hepatitis B core antigen (anti‐HBc) in his sera, he developed HBsAg and HBV DNA during the course of the management of a series of cancers. HBV DNA was detectable in the liver tissues before HBV reactivation and the viral sequences derived from his anti‐HBc‐positive liver showed 100% homology to that from the serum after HBsAg appearance. These findings indicates that HCV‐positive individuals who are positive for anti‐HBc in the absence of HBsAg could have latent HBV infection in their liver tissues and intrahepatic HBV infection may play a pivotal role in the development of HCC after the IFN‐mediated eradication of HCV.     

Diabetes, hepatitis virus infection and hepatocellular carcinoma: A case-control study in hepatitis endemic area

Aim: In spite of numerous studies on the association between diabetes mellitus (DM) and hepatocellular carcinoma (HCC), the results are inconsistent and whether and how the effect of DM on the risk for HCC is modified or synergistically exerted by hepatitis virus infection are still unclear. We aimed to elucidate and quantify the effect modification and synergism between hepatitis B and C virus (HBV and HCV, respectively) and DM leading to the risk for HCC and also assess the independent contribution of DM to the risk for HCC at population level (population attributable fraction) in a high prevalence area of hepatitis virus infection. Methods: A hospital‐based case–control study was conducted from one medical center. Information on hepatitis B and C virus infection and DM status (defined by 8‐h fasting blood glucose level ≥126 mg/dL, current use of oral hyperglycemic agent or insulin injection) was collected to assess interaction of hepatitis virus infection with DM on the risk for HCC. Results: The association between DM and the risk for HCC was significant regardless of the presence of HBV infection, whereas a significant positive association was noted for HCV negativity. Synergistic interactions between DM and HBV infection were significant. In the absence of both hepatitis virus infections, the independent effect of DM accounted for 7.5% risk for HCC from the underlying population. Conclusion: The effect of DM on the risk for developing HCC is higher in HCV negative patients and synergistic with HBV infection. The independent effect of DM provides a new insight to the prevention of HCC other than virus‐related mechanism.     

Impact of previous hepatitis B infection on the clinical outcomes from chronic hepatitis C? A population‐level analysis

Chronic coinfection with hepatitis C virus (HCV) and hepatitis B virus (HBV) is associated with adverse liver outcomes. The clinical impact of previous HBV infection on liver disease in HCV infection is unknown. We aimed at determining any association of previous HBV infection with liver outcomes using antibodies to the hepatitis B core antigen (HBcAb) positivity as a marker of exposure. The Scottish Hepatitis C Clinical Database containing data for all patients attending HCV clinics in participating health boards was linked to the HBV diagnostic registry and mortality data from Information Services Division, Scotland. Survival analyses with competing risks were constructed for time from the first appointment to decompensated cirrhosis, hepatocellular carcinoma (HCC) and liver‐related mortality. Records of 8513 chronic HCV patients were included in the analyses (87 HBcAb positive and HBV surface antigen [HBsAg] positive, 1577 HBcAb positive and HBsAg negative, and 6849 HBcAb negative). Multivariate cause‐specific proportional hazards models showed previous HBV infection (HBcAb positive and HBsAg negative) significantly increased the risks of decompensated cirrhosis (hazard ratio [HR]: 1.29, 95% CI: 1.01‐1.65) and HCC (HR: 1.64, 95% CI: 1.09‐2.49), but not liver‐related death (HR: 1.02, 95% CI: 0.80‐1.30). This is the largest study to date showing an association between previous HBV infection and certain adverse liver outcomes in HCV infection. Our analyses add significantly to evidence which suggests that HBV infection adversely affects liver health despite apparent clearance. This has important implications for HBV vaccination policy and indications for prioritization of HCV therapy.     

Molecular characteristics of non‐cancerous liver tissue in non‐B non‐C hepatocellular carcinoma

Although chronic infection with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) are the most important risk factors for the development of hepatocellular carcinoma (HCC) worldwide, the proportion of HCC patients negative for the hepatitis B surface antigen and hepatitis C antibody, so‐called “non‐B non‐C HCC”, is rapidly increasing, especially in Japan. The background liver diseases of non‐B non‐C HCC patients can be multifactorial, including occult HBV infection and non‐alcoholic steatohepatitis. It is reasonable to investigate the non‐cancerous liver tissues to identify the potential molecular mechanisms responsible for the processes of hepatocarcinogenesis of non‐B non‐C HCC. However, to date, only a few studies have focused on this research concept based on the idea of “field cancerization”. This review highlights the potential importance of the molecular analysis of non‐cancerous liver tissues to clarify the molecular characteristics in patients with non‐B non‐C HCC. A better understanding of the molecular mechanisms underlying the individual predisposition to non‐B non‐C HCC will lead to improvements in the prevention, early diagnosis and treatment of this neoplastic disease.     

HCV HBV感染与肝细胞性肝癌

调查了肝癌高发地区不同肝病患者中丙型肝炎病毒(HCV)感染率。慢性肝病患者绝大多数已被乙型肝炎病毒(HBV)感染。HCV第二代抗体阳性率,肝癌7.3％,肝硬化6.6％,慢性肝炎6.6％和急性肝炎3.4％。两种病毒的复合感染率,肝癌5.1％,肝硬化1.7％,慢性肝炎3.9％和急性肝炎1.1％。在38例HCV抗体阳性的慢性肝病患者中,ALT异常84.2％,有输血史者占57.9％,HCV-RNA阳性率为71.1％。本研究的资料分析提示,在肝癌高发地区尽管HCV抗体阳性率较低,但HCV感染也是肝癌发生的重要病因之一。     

Significance of viral status on prognosis of hepatitis B‐related hepatocellular carcinoma after curative resection in East Asia

Tumor recurrence remains one major obstacle for further improving the prognosis of hepatitis B virus (HBV)‐related hepatocellular carcinoma (HCC) patients after curative liver resection. It has been widely reported that tumor size, positive surgical margin, macroscopic vascular invasion, tumor–node–metastasis stage and Edmondson's grade were significantly related to HCC recurrence. However, the association between HCC recurrence and important viral factors, including the HBV DNA levels, status of hepatitis B surface antigen and hepatitis B e‐antigen, levels of cccDNA and hepatitis B core‐related antigen, viral genotypes and specific viral sequence mutations remained controversial. Meanwhile, studies on the effect of postoperative adjuvant antiviral therapy on HCC recurrence have been relatively limited and have yielded conflicting results. Identification of certain viral risk factors for HCC recurrence and stratification of patient risk are very important to perform future surveillance programs. As a HBV hyperendemic region, the majority of HBV‐related HCC patients develop in East Asia. In this article, we thus systematically reviewed the risk of important viral factors involved in recurrent carcinogenesis and the role of adjuvant antiviral therapy in preventing tumor recurrence in this area.     

Do hepatitis B virus and hepatitis C virus co‐infections increase hepatocellular carcinoma occurrence through synergistically modulating lipogenic gene expression?

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections cause a wide range of liver diseases including hepatocellular carcinoma (HCC). Because of the similar modes of transmission, HBV HCV co-infections are found in approximately 7-20 million people globally. Compared with HBV or HCV mono-infections, co-infections are associated with more severe liver diseases and higher risk of HCC. Abnormal lipid biosynthesis and metabolism has been increasingly recognized as a cause for cancer. While HBV infection does not seem to significantly increase the risk of developing hepatic steatosis, steatosis is a prominent feature of chronic hepatitis C (CHC). In addition, steatosis in HBV or HCV mono-infections is a significant and independent risk factor for HCC. However, whether and how HBV HCV co-infections synergistically increase the risk of HCC development through modulating lipid metabolism is not well understood. Possible mechanisms by which steatosis causes HCC include: activation of sterol regulatory element-binding protein-mediated lipogenesis through the PI3K-Akt pathway, abnormal activation of peroxisome proliferator-activated receptors and endoplasmic reticulum stress. Here, we review the potential mechanisms by which HBV HCV co-infections may increase HCC risk through modulation of lipogenic gene expression. We begin with reviewing the impact of HBV and HCV on host lipogenic gene expression and carcinogenesis. We then discuss the potential mechanisms by which HBV and HCV can increase carcinogenesis through synergistically activating lipid biosynthesis and metabolism. We end by sharing our thoughts on future research directions in this emerging paradigm with an ultimate goal of developing effective therapeutics.     

HIV and coinfected patients

HIV, hepatitis C virus (HCV), and hepatitis B virus (HBV) infections are major public health problems. Patients at risk for HIV infection are likely also at risk for HCV and HBV because of shared routes of transmission. HIV and antiretroviral therapy (ART) have a significant impact on HCV and HBV. HIV coinfection accelerates HCV and HBV natural history, leading to an increased incidence of cirrhosis, development of hepatocellular carcinoma (HCC), and death. Universal screening for HCV and HBV infections in HIV-infected patients is essential. Proper screening combined with up-to-date treatment strategies can prevent these complications. This review focuses on important aspects and recent developments in the rapidly evolving field of coinfection.     

Hepatocellular carcinoma in Korea: introduction and overview]

Hepatocellular carcinoma (HCC) is a highly malignant, generally fatal neoplasm arising from hepatocytes. HCC accounts for over 80% of all primary liver cancers which ranks fourth among the organ-specific causes of cancer-related deaths worldwide. HCC is particularly prevalent in Korea where the age standardized incidence rate is 46.5 per 100,000 population. Infection with hepatitis B virus (HBV) or hepatitis C virus (HCV) or presence of liver cirrhosis are important risk factors for HCC development globally. Infection with HBV is the most important risk for HCC in Asia except Japan. The high incidence rate of HCC in Korea is thought to be related to the high carrier rate (5-6%) of HBV, which is currently being fought via a nationwide vaccination program. Although progress has been made in the management of HCC including chemoembolization and local ablation therapy, there has been little overall reduction in HCC mortality during the past 20 years. Recently, five year survival rate of primary liver cancer is 9.6% in Korea. Such poor prognosis of HCC results from the late detection of cancer, an aggressive tumor biology and underlying chronic liver diseases. Only a limited proportion of patients are candidates for potentially curative forms of treatment. Therefore efforts should be directed toward an effective surveillance program. The early detection of HCC is the important approach in reducing HCC mortality in the short term. Because almost eighty percent of HCC is diagnosed in late stage, we launched a nationwide surveillance program to screen high risk groups (HBV or HCV carriers or liver cirrhosis, over 40 years old) and formulated the Korean practice guideline for the diagnosis and treatment of HCC with special emphasis on advanced stage of HCC.     

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.     

Care quality and outcomes among US veterans with chronic hepatitis B in the hepatitis C direct‐acting antiviral era

Adherence to guideline‐recommended hepatitis B virus (HBV) care is suboptimal. We hypothesized that national hepatitis C eradication efforts during the era from 2015 to 2017 would improve the quality of care for cHBV given increased recognition and specialty referrals for liver disease. The study described herein is a retrospective cohort study of veterans with at least one positive HBsAg (HBsAg+) result from 1 January 2003 to 31 December 2017 using the VA Corporate Data Warehouse (CDW) analysed by era (2003‐2004, 2005‐2009, 2010‐2014, 2015‐2017). Relevant covariates such as HCV co‐infection, demographics, cirrhosis and baseline laboratory testing were obtained through previously validated approaches. We evaluated completion of process measures within 2 years of the index HBsAg + result: specialty care referral; testing of ALT, HBV‐DNA, HBeAg and anti‐HBe; testing for co‐infection and/or vaccination for HAV, HCV, HDV and HIV; and hepatocellular carcinoma (HCC) surveillance among those meeting criteria. We also measured use of antiviral therapy in appropriate candidates (ALT ≥ 2 × ULN, HBV‐DNA ≥ 2000 IU/mL). Of the 16 673 individuals with HBsAg + test results, 9,521 were confirmed as chronic HBV. Era‐related (Era 3:2010‐2014 vs Era 4:2015‐2017) increases in guideline‐recommended process measures included the following: outpatient visits with GI/ID specialists (78%‐89%), HBV‐DNA testing (73%‐79%), HDV testing (27%‐35%), appropriate HBV antiviral utilization (55%‐70%) and HCC surveillance (40%‐43%); all P < .0001. In the subset of HBV/HCV‐co‐infected patients, HCV DAA therapy was associated with a trend towards improved overall survival. In conclusion, the overall quality of care for HBV has significantly improved in the era of widespread HCV DAA therapy in an integrated health system possibly due to increased recognition and referral for liver disease.     

Hepatitis B and C virus infection as risk factors for liver cirrhosis and cirrhotic hepatocellular carcinoma: a case-control study

To investigate whether hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are risk factors for liver cirrhosis and hepatocellular carcinoma (HCC), a case-control study of 102 cirrhotic HCC patients, 102 sex-matched and age-matched patients with liver cirrhosis, and 102 matched patients with non-hepatic disease controls was performed. The prevalences of hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV) in HCC (70.5%, 39.2%) and liver cirrhosis (74.5%, 27.4%) were higher than controls (16.6%, 10.5%) (P = 0.0001). In HBsAg-negative patients, the prevalence of anti-HCV in cirrhotic HCC (66.6%) and liver cirrhosis (46.1%) was higher than in controls (10.5%; P = 0.0001). There was no such difference in HBsAg-positive patients. Multivariate analysis revealed that both HBsAg and anti-HCV were important risk factors for HCC (odds ratio, 6.52 and 4.59, respectively) and liver cirrhosis (odds ratio, 4.22 and 2.29, respectively). There was no difference in odds ratio when HCC and liver cirrhosis were compared. Our result implies that both HBV and HCV are independent risk factors for cirrhotic HCC and liver cirrhosis in Taiwan.     

Current status and clinical course of hepatitis C virus in Korea

The mortality due to chronic liver disease, including liver cirrhosis and hepatocellular carcinoma (HCC), ranks as one of the highest in Korea. The prevalence rates of hepatitis C virus (HCV) and hepatitis B virus (HBV) infections in the general Korean population are approximately 1 and 5%, respectively. Blood transfusion was the strongest risk factor for the transmission of HCV infection. Therefore, the evaluation of risk factors for HCV infection including blood transfusion, intravenous drug user, hemophilia, and hemodialysis, is important. The most prevalent HCV genotype is 1b followed by 2a. The annual incidence of HCC among HCV-related liver cirrhosis has been estimated at 5%, and approximately 12% of HCC is attributable to HCV and 68% to HBV in Korea. HCV infection is more closely associated with HCC in elderly patients than HBV-related HCC. Even though the prevalence of anti-HCV in Korea has been reduced and the risk of HCV transmission through blood transfusion has markedly decreased, public-health programs to prevent de novo infections should be developed. This review describes the HCV prevalence and risk factors among the general population, and the distribution of HCV genotypes as well as the clinical course of HCV in Korea.     

Hepatocellular carcinoma in an Australian tertiary referral hospital 1975-2002: change in epidemiology and clinical presentation

AIM: We compared the epidemiology and clinical features of hepatocellular carcinoma (HCC) cases diagnosed between 1975 and 2002. METHODS: Retrospective and prospective analysis was performed of HCC cases diagnosed at The Alfred during the time periods 1975-1983 and 1995-2002. Demographic, epidemiological, clinical and laboratory data were recorded and compared between the two periods. RESULTS: Comparing the 1995-2002 cohort to the 1975-1983 cohort, patients were older (64 years vs 60 years; P = 0.02), and were more likely to be non-Caucasian (25%vs 9%; P = 0.003) and born overseas (57%vs 40%; P = 0.03) particularly from Asia. In addition, hepatitis C virus (HCV) (35%), hepatitis B virus (HBV) (22%), and alcoholic liver disease (29%) were the major etiological factors for HCC with alcohol less likely the cause of underlying liver disease (33%vs 55%; P < 0.01). Among the 1995-2002 cohort, overseas-born patients were more likely to be infected with HBV (P < 0.001) and HCV (P = 0.01), while alcohol was more likely to be the etiological factor in Australian-born cases (P = 0.02), particularly among males. Detection of HCC by screening was the initial presentation in 38% of patients, and diagnosis of HCC was often by non-invasive means. CONCLUSIONS: The epidemiology of HCC has changed in Australia over the past 20 years with hepatitis C and hepatitis B now major etiological factors, and an increase in cases born overseas particularly from areas where HCV and HBV are endemic. This suggests the recent increase in incidence and death rates due to HCC in Australia relate to HCV and HBV infection.