Molecular targets for 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 toxins (alcohol, aflatoxin B1), androgens and estrogens, hepatitis B virus (HBV) and hepatitis C virus (HCV) infection as well as various inherited metabolic disorders, such as alpha-1-antitrypsin deficiency and hemochromatosis. The molecular pathogenesis of HCC development is very complex and involves alterations in the structure or expression of several tumor suppressor genes, oncogenes and, possibly, mechanisms leading to a genetic instability due to mismatch repair deficiency or chromosomal instability and aneuploidy due to defective chromosomal segregation. Central to the molecular pathogenesis of HCCs are mutations of various genes and a genetic instability which in most cases result from chronic liver disease and the associated enhanced liver cell regeneration and mitotic activity. The prognosis of HCC patients is generally very poor. Most studies report a five year survival rate of less than 5% in symptomatic HCC patients. Furthermore, these tumors have been shown to be quite resistant to radio- or chemotherapy. Investigations of the natural history and clinical course of HCCs revealed long-term survival of patients only with small asymptomatic HCCs that could be treated surgically or by non-surgical interventions. Apart from exploring and refining new HCC treatment strategies, the implementation of existing and the development of novel measures to prevent HCC development are most important. Primary HCC prevention includes among others universal hepatitis B vaccination, antiviral therapy of patients with chronic hepatitis B or C, reduction of food contamination with aflatoxins, elimination of excessive alcohol etc. Also for some genetic diseases there is the potential for HCC prevention by identifying affected family members at risk, such as patients with precirrhotic hemochromatosis. Reduction of iron overload by phlebotomy has been shown to eliminate the progression hemochromatosis to liver cirrhosis and HCC. Preventive measures, therefore, should have a major impact on the incidence of HCCs in patients with acquired and inherited liver diseases. Further, the prevention of a local recurrence or the development of new HCC lesions in patients after successful surgical or non-surgical HCC treatment (secondary prevention) is of paramount importance and is expected to significantly improve disease-free and overall patient survival. Based on rapid scientific advances, molecular diagnosis, gene therapy and molecular prevention are becoming increasingly part of our patient management and will eventually complement and in part replace existing diagnostic, therapeutic and preventive strategies. Overall, this should result in a reduction of the incidence of HCCs, one of the most devastating malignancies worldwide.     

Hepatozelluläres Karzinom

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in some areas of the world. The major etiologic risk factors include toxins (alcohol, aflatoxin B(1)), hepatitis B and C virus infection as well as various inherited metabolic disorders. The prognosis of HCC patients is generally very poor with a 5-year survival rate of less than 5%. The diagnosis is based on biochemical and imaging tests as well as histology. Therapeutic strategies include surgery (resection or liver transplantation) and non-surgical interventions, such as percutaneous ethanol injection or radiofrequency thermal ablation as well as transarterial embolization or chemoembolization. Radio- or chemotherapy are mostly ineffective. Therefore, the development and evaluation of novel HCC treatment strategies as well as the implementation of existing and the development of new measures to prevent HCC are of utmost importance. The better understanding of the clinical and molecular pathogenesis of HCC should lead to improved diagnostic, therapeutic and preventive strategies with the aim to reduce the incidence of HCC, one of the most devastating malignancies worldwide.     

Prevention of hepatocellular carcinoma]

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors and has the third highest mortality rate among malignancies in South Korea. Despite the continuing efforts for the early detection of HCC, the mortality rate and prognosis have not been improved yet. Its clinical behavior is quite different from other cancers. High recurrence rate after curative treatment might be the reason for poor prognosis. Several methods including chemoprevention, blocking the development of HCC, have been under investigations. The vaccine for hepatitis, in the form of primary prevention, is considered to be the most effective one inhibiting the development of liver disease. Furthermore, keeping away from hepatotoxic agents is another way for preventing liver cell injuries. Secondary prevention is to stop the development of HCC in chronic liver diseases. Since the level of DNA in hepatitis B virus (HBV) hepatitis patients is closely related with the development of HCC, it is helpful to lower the DNA level using anti-viral agents. In addition, IFN, one of the anti-viral agents, can inhibit HCV hepatitis from tumorigenesis. Cyclo-oxygenase (COX)-2 inhibitors are also alleged to have a function in interrupting the development of HCC. Tertiary prevention means the prevention of recurrence of HCC after successful treatment. Because of high recurrence rate, the prevention of recurrence should be one of the important factors affecting the prognosis of HCC. Up to now, COX inhibitors, retinoic acids, vitamin K2, glycyrrhizin epigallocatechin-3-gallate (EGCG), and ginseng had been reported to be effective for the chemoprevention of HCC. Further studies are required for an advancement in the prevention of HCC.     

Hepatitis B Virus Pre-S Gene Deletions and Pre-S Deleted Proteins: Clinical and Molecular Implications in Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the most frequent and fatal human cancers worldwide and its development and prognosis are intimately associated with chronic infection with hepatitis B virus (HBV). The identification of genetic mutations and molecular mechanisms that mediate HBV-induced tumorigenesis therefore holds promise for the development of potential biomarkers and targets for HCC prevention and therapy. The presence of HBV pre-S gene deletions in the blood and the expression of pre-S deleted proteins in the liver tissues of patients with chronic hepatitis B and HBV-related HCC have emerged as valuable biomarkers for higher incidence rates of HCC development and a higher risk of HCC recurrence after curative surgical resection, respectively. Moreover, pre-S deleted proteins are regarded as important oncoproteins that activate multiple signaling pathways to induce DNA damage and promote growth and proliferation in hepatocytes, leading to HCC development. The signaling molecules dysregulated by pre-S deleted proteins have also been validated as potential targets for the prevention of HCC development. In this review, we summarize the clinical and molecular implications of HBV pre-S gene deletions and pre-S deleted proteins in HCC development and recurrence and highlight their potential applications in HCC prevention and 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.     

Hepatocellular carcinoma in southern Germany: epidemiological and clinicopathological characteristics and risk factors

The aetiology of chronic liver disease leading to hepatocellular carcinoma (HCC) and the clinical characteristics of patients with HCC vary considerably internationally and intranationally. This study analyses the characteristics of HCC patients in southern Germany, a low endemic area of HCC. METHODS: The files of 118 consecutive patients with HCC observed in a single tertiary care hospital between 1994 and 2000 have been reviewed. Epidemiological and clinicopathological characteristics such as age at presentation, ethanol consumption, serological hepatitis virus markers, and fibrosis were studied. Additionally, serum levels of alpha-fetoprotein (AFP) were analysed at the time of diagnosis in 77 patients. RESULTS: The male:female ratio was 4:1 and the mean age at presentation was 61.8 years. Alcohol abuse (49.2%) and chronic hepatitis C infection (17.8%) were the most frequent risk factors. Histologically proven liver cirrhosis in the surrounding non-tumorous tissue was present in only 59.0% of cases. AFP levels were elevated in 78% of cases, but only 34% reached >500 ng/ml, a value considered to be significant for the diagnosis of HCC. AFP levels correlated with the stage of fibrosis. SUMMARY AND CONCLUSIONS: The sensitivity of AFP serum levels as a tumour marker is poor but might help to detect at least a minority of cases. As in other populations within Europe, chronic alcohol abuse is frequently associated with HCC in southern Germany, confirming that alcohol is still the most important risk factor for hepatocarcinogenesis in areas with low hepatitis virus prevalence. Considering the poor prognosis of HCC, prevention is of pivotal importance, particularly for patients with chronic liver disease and other risk factors for the development of HCC.     

Prediction and prevention of intrahepatic recurrence of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) has characteristic features of the coexistence of two life-threatening conditions, cancer and cirrhosis, which makes prognostic assessment difficult. In addition, the high rate of intrahepatic recurrence is a key feature that correlates with poor prognosis and its prevention is an issue for urgent investigation. Gene expression in the tumor and adjacent liver tissue for the prediction of intrahepatic recurrence of HCC has been extensively investigated. Among them, the expression of progenitor cell feature markers in the cancer cells such as epidermal cell adhesion molecule (EpCAM), cytokeratin 19 (CK19) and CD 133 have been shown to be associated with intrahepatic recurrence of HCC. Gene expression patterns from adjacent tissues were shown to predict early and overall recurrence in patients with HCC. Insulin resistance should be included in the analysis for the prevention of recurrence. To suppress or eradicate the replication of hepatitis B and C virus must be the most important issue for prevention. Supplementation by branched chain amino acid-enrichment and administration of vitamin K, acyclic retinoid and chemotherapeutic agents have been examined. There is an urgent need to develop a predictive tool and an effective treatment for prevention. It would be extremely valuable to find a useful biomarker for prediction and to develop new molecular targeting agents for the prevention of HCC recurrence in the near future.     

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.     

Role of autophagy in tumorigenesis,metastasis,targeted therapy and drug resistance of hepatocellular carcinoma

Autophagy is a "self-degradative" process and is involved in the maintenance of cellular homeostasis and the control of cellular components by facilitating the clearance or turnover of long-lived or misfolded proteins, protein aggregates, and damaged organelles. Autophagy plays a dual role in cancer, including in tumor progression and tumor promotion, suggesting that autophagy acts as a double-edged sword in cancer cells. Liver cancer is one of the greatest leading causes of cancer death worldwide due to its high recurrence rate and poor prognosis. Especially in China, liver cancer has become one of the most common cancers due to the high infection rate of hepatitis virus. In primary liver cancer, hepatocellular carcinoma (HCC) is the most common type. Considering the perniciousness and complexity of HCC, it is essential to elucidate the function of autophagy in HCC. In this review, we summarize the physiological function of autophagy in cancer, analyze the role of autophagy in tumorigenesis and metastasis, discuss the therapeutic strategies targeting autophagy and the mechanisms of drug-resistance in HCC, and provide potential methods to circumvent resistance and combined anticancer strategies for HCC patients.     

非酒精性脂肪性肝病相关性肝细胞癌治疗的研究进展

肝细胞癌(HCC)发病率高,乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)感染是HCC的主要病因.近年来,肥胖、2型糖尿病等代谢疾病的流行加速了非酒精性脂肪性肝病(NAFLD)的发生,导致NAFLD相关性HCC(NAFLD-HCC)的发生也逐年递增.但NAFLD-HCC与病毒相关性HCC是否有相似的发病机制、预防、监测...     

Mechanisms of hepatocellular carcinoma progression

Hepatocellular carcinoma(HCC) is the most common primary malignancy of the liver. It is the second leading cause of cancer-related deaths worldwide, with a very poor prognosis. In the United States, there has been only minimal improvement in the prognosis for HCC patients over the past 15 years. Details of the molecular mechanisms and other mechanisms of HCC progression remain unclear. Consequently, there is an urgent need for better understanding of these mechanisms. HCC is often diagnosed at advanced stages, and most patients will therefore need systemic therapy, with sorafenib being the most common at the present time. However, sorafenib therapy only minimally enhances patient survival. This review provides a summary of some of the known mechanisms that either cause HCC or contribute to its progression. Included in this review are the roles of viral hepatitis, non-viral hepatitis, chronic alcohol intake, genetic predisposition and congenital abnormalities, toxic exposures, and autoimmune diseases of the liver. Well-established molecular mechanisms of HCC progression such as epithelial-mesenchymal transition, tumor-stromal interactions and the tumor microenvironment, cancer stem cells, and senescence bypass are also discussed. Additionally, we discuss the roles of circulating tumor cells,immunomodulation, and neural regulation as potential new mechanisms of HCC progression. A better understanding of these mechanisms could have implications for the development of novel and more effective therapeutic and prognostic strategies, which are critically needed.     

Hepatocellular carcinoma, human immunodeficiency virus and viral hepatitis in the HAART era

The incidence of hepatocellular carcinoma （HCC） in patients with human immunodeficiency virus （HIV） is rising. HCC in HIV almost invariably occurs in the context of hepatitis C virus （HCV） or hepatitis B virus （HBV） co-infection and, on account of shared modes of transmission, this occurs in more than 33% and 10% of patients with HIV worldwide respectively. It has yet to be clearly established whether HIV directly accelerates HCC pathogenesis or whether the rising incidence is an epiphenomenon of the highly active antiretroviral therapy （HAART） era, wherein the increased longevity of patients with HIV allows long-term complications of viral hepatitis and cirrhosis to develop. Answering this question will have implications for HCC surveillance and the timing of HCV/HBV therapy, which in HIV co-infection presents unique challenges. Once HCC develops, there is growing evidence that HIV co-infection should not preclude conventional therapeutic strategies, including liver transplantation.     

Hepatocellular carcinoma, human immunodeficiency virus and viral hepatitis in the HAART era

The incidence of hepatocellular carcinoma (HCC) in patients with human immunodeficiency virus (HIV) is rising. HCC in HIV almost invariably occurs in the context of hepatitis C virus (HCV) or hepatitis B virus (HBV) co-infection and, on account of shared modes of transmission, this occurs in more than 33% and 10% of patients with HIV worldwide respectively. It has yet to be clearly established whether HIV directly accelerates HCC pathogenesis or whether the rising incidence is an epiphenomenon of the highly active antiretroviral therapy (HAART) era, wherein the increased longevity of patients with HIV allows long-term complications of viral hepatitis and cirrhosis to develop. Answering this question will have implications for HCC surveillance and the timing of HCV/HBV therapy, which in HIV co-infection presents unique challenges. Once HCC develops, there is growing evidence that HIV co-infection should not preclude conventional therapeutic strategies, including liver transplantation.     

Decreasing incidence of hepatocellular carcinoma among children following universal hepatitis B immunization

Abstract: Hepatocellular carcinoma (HCC) is one of the 10 most common malignant tumors worldwide. Chronic infection with hepatitis B or C virus is closely related to hepatocarcinogenesis. The outcome of current therapies for HCC is not satisfactory. Prevention is the best way to control HCC. Among the various strategies of HCC prevention, immunization against hepatitis B virus infection is the most effective. Universal hepatitis B immunization has proved to be effective in reducing the incidence of HCC to 1/4–1/3 of that in children born before the hepatitis B vaccination era in Taiwan. The problems we face in achieving global control of hepatitis‐related HCC include: (1) no effective vaccine for the prevention of hepatitis C and its related HCC; (2) no immunization program for hepatitis B in areas with inadequate resources; (3) poor compliance to the immunization program as a result of ignorance, anxiety, or poverty; and (4) vaccine failure. Integration of the hepatitis B vaccination program into the expanded program of immunization for all infants throughout the world will be most urgent and important for HCC control. The reduction of the incidence of HCC will be seen in adults 30–40 years of age after the launch of the universal hepatitis B vaccination program. This concept of cancer vaccine can be applied to other infectious agents and their related cancers.     

Hepatocellular carcinoma: an Asian perspective

Hepatocellular carcinoma (HCC) is one of the most frequently occurring malignancies in Asia. The incidence exceeds 30 cases/100,000/year in the east Asian region. Worldwide, it accounts for almost 1 million deaths/year. The high incidence in Asia is due to the high prevalence of chronic viral hepatitis, mainly chronic hepatitis B. With the introduction of universal vaccination for hepatitis B in some Asian countries in the mid 1980s, some of these countries are experiencing a decline in the incidence of HCC. This probably underscores the point that HCC caused by hepatitis B is a malignancy preventable by vaccine. Due to the relative paucity of symptoms in the early stages and the rapid doubling time of the tumor, most HCCs are discovered late in advanced stages at presentation. Most Asian countries have adopted a screening program for patients at risk. Earlier and smaller HCCs are detected through such programs but these programs have yet to demonstrate improved patient survival. Physicians managing patients with HCC are faced with two main challenges, the malignancy itself and the underlying liver disease. The extent of the tumor and the existing liver function limits the therapeutic choices available. Hepatic resection remains the treatment of choice. However, the majority of patients present with nonresectable tumors. Transarterial chemoembolization, percutaneous ethanol injection and radiofrequency ablation are the other treatment modalities. In patients with small tumors (<5 cm) and poor liver function, liver transplant offers a viable treatment alternative. In summary, the risk factor for HCC in Asia is predominantly chronic hepatitis B. Universal vaccination against hepatitis B is likely to reduce the incidence. The prognosis and outcome of treatment remains poor with a 5-year survival of 35% for patients treated surgically and less than 10% for nonresectable tumors. Current management is aimed at earlier detection and more effective treatment of early HCC. In future, the challenge will be managing HCC in the premalignant stage.     

Hepatocellular carcinoma in non-alcoholic fatty liver disease: an emerging menace

Hepatocellular carcinoma (HCC) is a common cancer worldwide that primarily develops in cirrhosis resulting from chronic infection by hepatitis B virus and hepatitis C virus, alcoholic injury, and to a lesser extent from genetically determined disorders such as hemochromatosis. HCC has recently been linked to non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of obesity and related metabolic disorders such as diabetes. This association is alarming due to the globally high prevalence of these conditions and may contribute to the rising incidence of HCC witnessed in many industrialized countries. There is also evidence that NAFLD acts synergistically with other risk factors of HCC such as chronic hepatitis C and alcoholic liver injury. Moreover, HCC may complicate non-cirrhotic NAFLD with mild or absent fibrosis, greatly expanding the population potentially at higher risk. Major systemic and liver-specific molecular mechanisms involved include insulin resistance and hyperinsulinemia, increased TNF signaling pathways, and alterations in cellular lipid metabolism. These provide new targets for prevention, early recognition, and effective treatment of HCC associated with NAFLD. Indeed, both metformin and PPAR gamma agonists have been associated with lower risk and improved prognosis of HCC. This review summarizes current evidence as it pertains to the epidemiology, pathogenesis, and prevention of NAFLD-associated HCC.     

Hepatocellular carcinoma in non-cirrhotic liver: A comprehensive review

Hepatocellular carcinoma(HCC) is the most common type of primary liver cancer, which in turns accounts for the sixth most common cancer worldwide.Despite being the 6 th most common cancer it is the second leading cause of cancer related deaths. HCC typically arises in the background of cirrhosis, however,about 20% of cases can develop in a non-cirrhotic liver. This particular subgroup of HCC generally presents at an advanced stage as surveillance is not performed in a non-cirrhotic liver. HCC in non-cirrhotic patients is clinically silent in its early stages because of lack of symptoms and surveillance imaging; and higher hepatic reserve in this population. Interestingly, F3 fibrosis in non-alcoholic fatty liver disease, hepatitis B virus and hepatitis C virus infections are associated with high risk of developing HCC. Even though considerable progress has been made in the management of this entity, there is a dire need for implementation of surveillance strategies in the patient population at risk, to decrease the disease burden at presentation and improve the prognosis of these patients. This comprehensive review details the epidemiology, risk factors, clinical features,diagnosis and management of HCC in non-cirrhotic patients and provides future directions for research.     

Natural history of chronic hepatitis B

Chronic hepatitis B virus (HBV) infection can cause chronic hepatitis, cirrhosis, liver failure, and hepatocellular carcinoma (HCC). Chronic hepatitis B is characterized by an early replicative phase with hepatitis B e antigen (HBeAg) positivity, high serum HBV-DNA levels and disease activity (HBeAgpositive chronic hepatitis), and a late inactive phase with anti-HBe seroconversion, low or undetectable serum HBV-DNA, and liver disease remission (inactive carrier state). Another form is characterized by active disease due to HBV variants not expressing HBeAg (HBeAg-negative chronic hepatitis). Both types of chronic hepatitis B can lead to cirrhosis and its complications. The incidence of cirrhosis is two to five per 100 person-years, but may be as high as eight to 10 in HBeAg-negative cases. The incidence of HCC varies geographically and increases with the duration and severity of liver disease (0.1 to 8 per 100 person-years). The prognosis is reasonably good in compensated cirrhosis, but very poor following decompensation. Viral and environmental factors influence the natural history of chronic hepatitis B and explain the heterogeneity of its clinical outcomes.     

Viral hepatitis and hepatocellular carcinoma: From molecular pathways to the role of clinical surveillance and antiviral treatment

Hepatocellular carcinoma (HCC) is a global health challenge. Due to the high prevalence in low-income countries, hepatitis B virus (HBV) and hepatitis C virus infections remain the main risk factors for HCC occurrence, despite the increasing frequencies of non-viral etiologies. In addition, hepatitis D virus coinfection increases the oncogenic risk in patients with HBV infection. The molecular processes underlying HCC development are complex and various, either independent from liver disease etiology or etiology-related. The reciprocal interlinkage among non-viral and viral risk factors, the damaged cellular microenvironment, the dysregulation of the immune system and the alteration of gut-liver-axis are known to participate in liver cancer induction and progression. Oncogenic mechanisms and pathways change throughout the natural history of viral hepatitis with the worsening of liver fibrosis. The high risk of cancer incidence in chronic viral hepatitis infected patients compared to other liver disease etiologies makes it necessary to implement a proper surveillance, both through clinical-biochemical scores and periodic ultrasound assessment. This review aims to outline viral and microenvironmental factors contributing to HCC occurrence in patients with chronic viral hepatitis and to point out the importance of surveillance programs recommended by international guidelines to promote early diagnosis of HCC.     

Hepatocellular Carcinoma in Young Adults: The Clinical Characteristics, Prognosis, and Findings of a Patient Survival Analysis

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. However, HCC is rare in young Japanese patients and the clinical features of young patients with HCC have not yet been fully studied. This study was designed to determine the clinical characteristics and prognosis of patients with HCC who are younger than aged 40 years. A retrospective analysis was performed for patients newly diagnosed with HCC and observed from January 1990 to December 2003 at our hospitals. Patients younger than aged 40 years at the diagnosis of HCC were defined as the young group and were reviewed. There were 20 patients (16 males) with HCC who were younger than aged 40 years. The mean age at diagnosis was 33.6 (range, 20–39) years. Fifteen of 20 patients were positive for hepatitis B surface antigen (HBsAg) and 2 patients were positive for hepatitis C virus antibody. According to the Child-Pugh grading, the liver function was relatively good in all patients. Because most of the patients did not receive periodic follow-up, this disease often was discovered at an advanced stage, usually after the appearance of some symptoms. Although intensive treatment was performed for such young patients, the survival was nevertheless poor. Most patients died from this cancer within 1 year. However, one patient who received periodic follow-up and also was in relatively good physical condition had a better prognosis, and he survived for 88 months. Young patients with HCC tended to have a poor prognosis because of advanced stage of HCC, despite a well-preserved liver function and aggressive treatment. Screening for HCC and an early diagnosis is needed for such patients to demonstrate an improved prognosis, especially for HBsAg-positive patients.