Search

Recent data suggest that non-alcoholic fatty liver disease (NAFLD) has become a major public health problem in Asia, with an updated population prevalence of 34%. In parallel, NAFLD-associated hepatocellular carcinoma (HCC) is also on the rise. In this review, we describe the changing epidemiology of HCC in Asia over the past 30 years. While traditional risk factors for HCC (older age, male sex and metabolic factors) are also important in Asia, the PNPLA3 gene polymorphism is particularly prevalent in East Asia and may increase the risk of HCC. NAFLD among non-obese individuals is also commonly described in Asia. Because NAFLD is often undiagnosed, few patients receive HCC surveillance, and the target surveillance population beyond patients with cirrhosis remains poorly defined. As a result, NAFLD-associated HCC is often diagnosed at an advanced stage, rendering curative treatment impossible. Finally, despite around 20-30 years of universal vaccination, chronic HBV infection remains prevalent in Asia, and emerging evidence highlights the importance of metabolic factors and concomitant hepatic steatosis on HCC development in infected patients. Future studies should explore the role of metabolic treatments in HCC prevention among patients with hepatic steatosis and concomitant liver diseases., Competing Interests: Conflicts of interests Grace Wong has served as an advisory committee member for Gilead Sciences and Janssen, and as a speaker for Abbott, Abbvie, Bristol-Myers Squibb, Echosens, Gilead Sciences, Janssen and Roche. Vincent Wong has served as a consultant or advisory board member for 3V-BIO, AbbVie, Allergan, Boehringer Ingelheim, Echosens, Gilead Sciences, Inventiva, Merck, Novartis, Novo Nordisk, Pfizer, ProSciento, Sagimet Biosciences, TARGET PharmaSolutions, and Terns; and a speaker for Abbott, AbbVie, Echosens, Gilead Sciences, and Novo Nordisk. He has received a grant from Gilead Sciences for fatty liver research. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Objectives: To investigate risk factor patterns and the simultaneous occurrence of multiple risk factors in the viral, metabolic and lifestyle domains among Asian Americans, who have had the highest mortality rates from hepatocellular carcinoma (HCC)., Setting: Sacramento County, California, USA., Participants: Eligible participants were county residents ages 18 and older who had not been screened for chronic hepatitis B virus (HBV) and were born in a CDC-defined endemic area or whose parent was born in that area. Of 1004 enrolled, 917 were foreign-born Chinese (130 women, 94 men), Hmong (133 women, 75 men), Korean (178 women, 90 men) or Vietnamese (136 women, 81 men) with complete risk factor data., Primary and Secondary Outcome Measures: We tested participants for HBV and chronic hepatitis C virus (HCV); measured haemoglobin A1c and waist circumference; and recorded self-reported history of diabetes, hypertension, alcohol use and smoking status. We identified risk factor patterns using cluster analysis and estimated gender-specific age-standardised prevalence rates., Results: We identified four patterns: (1) viral (chronic HBV or HCV); (2) lifestyle (current smoker or alcohol user, no viral); (3) metabolic (≥2 metabolic, no lifestyle or viral); and (4) lower risk (≤1 metabolic, no lifestyle or viral). Vietnamese men (16.3%, 95% CI 7.4% to 25.3%) and Hmong women (15.1%, 95% CI 7.8% to 22.5%) had the highest viral pattern prevalence. Hmong women had the highest metabolic (37.8%, 95% CI 29.8% to 45.9%), and Vietnamese men the highest lifestyle (70.4%, 95% CI 59.1% to 81.7%) pattern prevalence. In multiple domains, Hmong men and women were most likely to have viral+metabolic risk factors (men: 14.4%, 95% CI 6.0% to 22.7%; women: 11.9%, 95% CI 5.6% to 18.3%); Vietnamese men were most likely to have lifestyle+viral (10.7%, 95% CI 2.7% to 18.8%), and lifestyle+metabolic but not viral (46.4%, 95% CI 34.4% to 58.5%) risk factors., Conclusions: Efforts to reduce HCC must comprehensively address multiple risk factors., Trial Registration Number: NCT02596438., Competing Interests: Competing interests: MSC served as a consultant to Gilead Sciences in 2016-18., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Sweden has traditionally been considered a country with a low incidence of hepatocellular carcinoma (HCC). However, the increasing number of immigrants from areas with a high incidence of HCC might affect the number of HCC patients in Sweden. Aim: To examine trends in the incidence, treatment and overall survival of patients with HCC and an underlying liver disease (ULD) from a restricted, well-defined region of Sweden, between 2000 and 2014. Patients and methods: Nine hundred and eight patients with HCC were identified. Subjects were grouped into 5-year periods, and analysed for HCC diagnosis, ULD, staging and treatment selection in populations born outside Sweden versus non-immigrants and patient survival. The regions were Africa, Asia, EU-28 together with America and the Nordic countries, eastern Europe and Sweden. Results: Over the time periods, the patients with HCC and ULD increased. More patients from Africa had HCC and ULD than what would have been expected based on the number of immigrants from this region and they were also significantly younger than Sweden-born patients. For patients from Africa, Asia and eastern Europe; viral hepatitis was dominating ULDs. Patients from Africa, Asia and eastern Europe were subjected to liver transplantation (LT) in higher proportions than patients from Sweden. The survival rate for patients from eastern Europe was significantly better. Conclusions: Immigration increased the incidence of HCC and the need for active treatment such as LT. This fact raises the question of whether immigrants from regions with a high incidence of HCC ought to be subjected to mandatory hepatitis B and C virus (HBV and HCV) diagnosis and consequent liver ultrasounds for diagnosis of occult HCC. With such strategies, the morbidity and mortality of HCC could be reduced.

Liver cancer is the second leading cause of global cancer mortality. The major risk factors for hepatocellular carcinoma (HCC) are being addressed with success by prevention efforts. Vaccination against hepatitis B virus has reduced incidence of HCC in Taiwan and is partly responsible for lower rates in China. New infections with hepatitis C virus are low in developed countries because of prevention of posttransfusion infections and reduced exposure to HCV by drug users. Aflatoxin exposure has been reduced by better grain storage and dietary changes. Obesity, metabolic syndrome, and diabetes are increasing in developed and developing countries and will lead to more cases of HCC., (Published by Elsevier Inc.)

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death, especially in Eastern areas. With advancements in diagnosis and treatment modalities for HCC, the survival and prognosis of HCC patients are improving. However, treatment patterns are not uniform between areas despite efforts to promote a common protocol. Although many hepatologists in Asian countries may adopt the principles of the Barcelona Clinic Liver Cancer staging system, they are also independently making an effort to expand the indications of each treatment and to combine therapies for better outcomes. Several expanded criteria for liver transplantation in HCC have been developed in Asian countries. Living donor liver transplantation is much more commonly performed in these countries than deceased donor liver transplantation, and it may be preceded by other treatments such as the down-staging of tumors. Local ablation therapies are often combined with transarterial chemoembolization (TACE) and the outcome is comparable to that of surgical resection. The indications of TACE are expanding, and there are new types of transarterial therapies. Although data on drug-eluting beads, TACE, and radioembolization in Asian countries are still relatively sparse compared with Western countries, these methods are gradually gaining popularity because of better tolerability and the possibility of improved response rates. Hepatic arterial infusion chemotherapy and radiotherapy are not included in Western guidelines, but are currently being used actively in several Asian countries. For more advanced HCCs, appropriate combinations of TACE, radiotherapy, and sorafenib can be considered, and emerging data indicate improved outcomes of combination therapies compared with single therapies. To include these paradigm shifts into newer treatment guidelines, more studies may be needed, but they are certainly in progress.

Background: Hepatitis B virus (HBV) infection, the predominant cause of hepatocellular carcinoma (HCC) worldwide, disproportionately affects Asian Americans. Limited data exist on the variability and characteristics of infection that determine disease progression risk within U.S. Asian ethnic subgroups., Methods: Retrospective analyses were conducted on a large, community-based HBV screening and treatment program in New York City (NYC). From 2004 to 2008, the program enrolled 7,272 Asian-born individuals. Determinants of HBV seroprevalence were calculated and risk factors for HCC progression were compared across Asian subgroups., Results: Among newly tested individuals, 13% were HBV positive. Seroprevalence varied significantly with age, gender, education, birthplace, and family history of infection. Chinese-born individuals, particularly from the Fujian province, had the highest seroprevalence (23.2% and 33.1%, respectively). Clinical and virologic characteristics placed HBV-infected individuals at significant risk for HCC. Significant differences in HCC risk existed among Asian subgroups in bivariate analysis, including age, gender, HBV viral load, and HBeAg status. Differences in HBV genotype and family history of HCC may further HCC risk among subgroups., Conclusions: Asian immigrants in NYC have a high prevalence of HBV infection and are at significant risk of disease progression and HCC. Although heterogeneity in HBV seroprevalence was found by Asian subgroups, HCC risk among infected individuals was primarily explained by age and gender differences. Country and province of birth, age, and gender may further explain seroprevalence differences., Impact: Findings provide estimates of HBV burden in Asian ethnic subgroups and identify high-risk groups to target for screening and treatment that can prevent HCC., (©2014 American Association for Cancer Research.)

Background and Aim: A number of studies have shown that hepatitis virus infections may be associated with cholangiocarcinoma (CC). However, the relationship between hepatitis B virus (HBV) infection and CC, especially intrahepatic cholangiocarcinoma (ICC), is still controversial., Methods: Relevant studies were identified by searching PUBMED, EMBASE and Web of Science Datebases up to September 2011. Pooled risk estimates were calculated using a random-effects model. Potential sources of heterogeneity were performed by subgroup analyses. A total of 18 papers were included in this meta-analysis., Results: The pooled risk estimate of all studies showed a statistically significant increased risk of CC among individuals with HBV infection (rate ratio [RR]: 2.66; 95% confidence interval [CI]: 1.97, 3.60). Compared with those without HBV infection, persons with HBV infection had an increased risk of intra-CC (ICC) (RR: 3.42; 95% CI: 2.46, 43.74), extrahepatic CC (OR: 1.46; 95% CI: 0.98, 2.17), and CC (OR: 2.03; 95% CI: 1.15, 3.56). In a subgroup analysis of HBV infection and risk of ICC, the pooled risk estimate of studies in Asians (RR: 3.63; 95% CI: 2.56, 5.13) was higher than that in non-Asians (RR: 1.93; 95% CI: 0.78, 4.76). A Begg funnel plot and Egger test revealed no evidence for publication bias., Conclusions: This meta-analysis shows that HBV is associated with increased risk of CC, especially for ICC. Further investigation is needed to focus on the mechanism by which HBV may be involved in the pathogenesis of CC., (© 2012 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

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.

Background and Aim: Australia has increasing immigration from hepatitis B virus (HBV) endemic countries of the Asia-Pacific region (APR). This study estimates immigration-related chronic HBV cases, chronic HBV prevalence, and HBV-related hepatocellular carcinoma (HCC) from 1960 to 2005 and projects HBV-related HCC to 2025 in Australia among people born in the APR., Methods: The populations of APR origin for the period 1960-2005 were derived from Australian census data. HBV prevalence from population-based sero surveys in the APR countries was used to estimate new chronic HBV cases (immigrant arrivals per year with chronic HBV). Age-specific incidence rates of HCC derived from a Taiwanese population-based study were used to estimate and project HBV-related HCC., Results: Chronic HBV cases among APR-born population increased rapidly from the late 1970s reaching a peak of 4182 in 1990. Chronic HBV prevalence increased to >53 000 in 2005. Estimates of HBV-related HCC increased linearly from one in 1960 to 140 in 2005, with a projected increase to 250 in 2025. Universal HBV vaccination programs in countries of origin had limited impact on projected HBV-related HCC to 2025., Conclusion: The burden of chronic HBV including HBV-related HCC among APR-born Australians has increased over the past three decades and is projected to increase further during the next two decades.

Background: The aim of this research was to determine the hepatitis B surface antigen (HBsAg) carrier prevalence among cases of hepatocellular carcinoma (HCC), and the population attributable risk of HBsAg carriage for HCC, by ethnicity in New Zealand., Methods: The hospital notes of HCC cases registered with the New Zealand Cancer Registry, for the years 1987-1994 inclusive, were viewed to determine the HBsAg status. Results The HBsAg status was determined for 193 cases of HCC. The HBsAg carrier prevalence for non-Europeans with HCC was markedly higher than that for Europeans, being 76.7% for Maori, 80.0% for Pacific Island people, and 88.5% for Asians, compared to 6.0% for Europeans. In addition to the effect of ethnicity, HCC cases aged <60 years were more likely to be HBsAg carriers than those aged > or = 60 years. The estimated population attributable risk of HBsAg for HCC, within each ethnic group, was only marginally less than the HBsAg prevalence due to the high relative risk of HBsAg carriage for HCC. The standardized incidence rate ratios of HCC for Maori, Pacific Island people and Asians compared to Europeans were 9.6, 20.4, and 22.3, respectively. Hepatocellular carcinoma attributable to HBsAg carriage explained 79%, 83%, and 92% of the excess standardized rate of HCC, compared to Europeans, for Maori, Pacific Island people, and Asians, respectively. Conclusions The HBsAg carrier prevalence in non-European cases of HCC in New Zealand is between 75% and 90%. HBsAg carriage explains the majority of the excess rate of HCC in non-Europeans compared to Europeans in New Zealand.

The incidence of primary liver cancer in Chinese, Japanese, and Filipino migrants to the United States and their descendants is compared with that of United States-born Whites. Incident liver cancer cases were ascertained between 1973 and 1986 from population-based cancer registries serving the San Francisco/Oakland (CA) metropolitan area, 13 counties of western Washington, and Hawaii. The population of these three areas, with regard to age, race, and country of birth, was estimated from a special tabulation of the 1980 US census. Rates of primary liver cancer were higher for men born in Asia than Asian men born in the US, who, in turn, had higher rates than did US Whites (respective annual rates per 100,000: Chinese, 26.5 and 9.8; Japanese, 16.5 and 6.6; Filipinos, 11.4 and 6.5; US Whites, 3.4). Among Asian American women, the trends were not as consistent (respective annual rates per 100,000: Chinese, 2.2 and 3.7; Japanese, 1.9 and 1.4; Filipino, 2.6 and 0; US Whites, 1.1). In general, liver cancer incidence among Asian Americans was lower than among residents of Asia. These findings are compatible with substantial variation among Asians in the prevalence of one or more etiologic factors for liver cancer, such as hepatitis-B infection and aflatoxin consumption, in relation to residence and place of birth.

Prospective studies of patients with cirrhosis who are at risk for developing hepatocellular carcinoma (HCC), have greatly improved our understanding of the natural history of this tumour. Despite many studies, the controversy of whether HCC originates from one or more than one clone of transformed liver cells is still unsettled. The natural history of HCC in many instances is an extension of that of the underlying cirrhosis, although the course of the tumour disease may vary from patient to patient and in different geographical areas. In Oriental and southern European patients with HCC, a longer time may elapse between diagnosis and death, than in African blacks. The information about tumour development in non-cirrhotic liver is scanty, due to the little known risk factors for this type of tumour which has impeded performing prospective cohort studies of high risk patients.

We retrospectively surveyed the clinical features of 73 cases of hepatocellular carcinoma at two hospitals over a 12-yr period. The population was heterogeneous, with 39% representing immigrants from regions of high hepatitis B and hepatocellular carcinoma prevalence. The yearly incidence of cases was constant over the 12 yr. Patient data were analyzed by grouping into three broad categories based on origin from known high, medium, or low prevalence hepatocellular carcinoma zones. In this fashion, differences in clinical presentation were observed. Asians (N = 12) were younger, invariably presented with pain; 82% had markers of hepatitis B and did not have features of chronic liver disease. In contrast, Westerners (N = 45) were older by more than a decade. One-quarter were HBV positive and almost two-thirds were alcoholic. The clinical presentation of this group was more varied, over one-third presenting with features of decompensated liver disease or variceal bleeds. Mediterranean patients (N = 16) had features intermediary between the two other groups. A logistic regression model clinically separated patients with hepatitis B-related hepatocellular carcinoma from those with alcohol-related hepatocellular carcinoma, suggesting different ongoing pathogenetic influences.

Hepatocellular carcinoma is a very malignant tumor that affects both Caucasian and Oriental populations. In the Caucasian patient, it frequently arises in a background of cirrhosis, most commonly the alcoholic type. In the present study, the alpha-feto-protein level was increased in less than half of the Caucasian patients. In comparison, hepatocellular carcinoma in Oriental patients most often occurs in livers with postinfectious cirrhosis. In the present study, both hepatitis B surface antigen and an increased alpha-fetoprotein level were present in three of four patients. If the tumor is present, however, it appears to behave similarly in both ethnic groups. Without resection, the prognosis is poor, regardless of the presence or absence of underlying cirrhosis or hepatitis B surface antigen status. A tissue diagnosis of hepatocellular carcinoma is most readily made by ultrasonographically guided fine-needle aspiration, which has an 81 percent sensitivity. The most important factor affecting survival is surgical resection. Clearly, the stage at diagnosis is also crucial, but even in more advanced disease, operation can improve survival. It also appears that an increased carcinoembryonic antigen level above normal or a markedly increased alpha-fetoprotein level or both are associated with poor survival. However, whether this is a reflection of tumor size alone, or in fact represents a more aggressive tumor is uncertain and will require further study.