Systemic target therapeutic drugs, such as sorafenib, lenvatinib, or regorafenib are the only drugs that are known to be effective against advanced hepatocellular carcinoma (HCC). However, these agents show a limited efficacy in killing residual tumors. Immunotherapy is an alternative approach to this treatment and has been used to successfully treat different cancers, including HCC. HCC is an inflammation-induced cancer and represents a very interesting target for immunotherapeutics. Immunotherapies aim to reverse the immune tolerance and suppression found in tumor microenvironments and include approaches, such as adoptive cell therapy, immune checkpoint inhibition, and cancer vaccination. Adoptive cell therapy uses autologous natural killer or cytokine-induced killer cells by cultivating them ex vivo and subsequently reinfusing them into the patient. Immune checkpoint inhibitors reactivate tumor-specific T cells by suppressing checkpoint-mediated inhibitory signaling. Cancer vaccination induces a tumor-specific immune response by activating effector T lymphocytes. A wide range of potential immunotherapy-related adverse events occur; therefore, a multidisciplinary collaborative management is required across the clinical spectrum. This review summarizes the current status of immunotherapy for HCC and provides a perspective on its future applications.
Carcinoma, Hepatocellular ; Cell- and Tissue-Based Therapy ; Cytokine-Induced Killer Cells ; Homicide ; Humans ; Immune Tolerance ; Immunotherapy ; Neoplasm, Residual ; Oncolytic Viruses ; T-Lymphocytes ; Tumor Microenvironment ; Vaccination

Hepatocellular carcinoma (HCC) is highly prevalent and the third most common cause of cancer-related death in Asia. In contrast to the West, the main etiology of HCC in many Asian countries except Japan is chronic hepatitis B virus infection. Differences in the major causes of HCC lead to significant clinical and treatment differences. This review summarizes and compares guidelines on managing HCC from China, Hong Kong, Taiwan, Japan, and South Korea. From oncology and socio-economic perspectives, factors such as underlying diseases, staging methods, government policies, insurance coverage, and medical resources contribute to varying treatment strategies among countries. Furthermore, the differences in each guideline are fundamentally caused by the lack of incontrovertible medical evidence, and even existing results of clinical trials can be interpreted differently. This review will provide a complete overview of the current Asian guidelines for HCC in recommendations and in practice.

The prognosis of patients with advanced hepatocellular carcinoma (HCC) with tumor thrombus extending to the inferior vena cava (IVC) is extremely poor. Herein, we present a rare case of advanced HCC that was treated with sorafenib and radiotherapy, leading to complete remission. This patient had a 9 cm infiltrative HCC occupying almost the entire left lobe with a tumor thrombus extending through the hepatic vein, IVC, and left portal vein. The patient received 400 mg sorafenib twice daily. One year after the start of sorafenib, intensity-modulated radiation therapy for viable HCC and tumor thrombus was performed with a dose of 5,500 cGy. Twenty-seven months after the starting date of sorafenib, there was no intratumoral arterial enhancement, which suggested a complete response according to the modified RECIST criteria. This case suggests that the combination of sorafenib and radiotherapy might provide clinical benefits in patients with advanced HCC with IVC tumor thrombus.

The incidence of hepatocellular carcinoma (HCC) associated with nonalcoholic fatty liver disease (NAFLD) has been increasing worldwide, including Asia. Most patients with NAFLD-related HCC are at a much-advanced stage and older age at the time of diagnosis than those with virus-related HCC because they have not undergone HCC surveillance. This review provides an overview of the mechanism of hepatocarcinogenesis in NAFLD, preventive strategies for NAFLDrelated HCC, and strategies for the surveillance of patients with NAFLD.

BACKGROUND/AIMS: Overlap syndrome of autoimmune hepatitis (AIH) and primary biliary cirrhosis (PBC) (AIH-PBC overlap syndrome) is a rare disease that has not been clearly characterized in Korean patients. This study investigated the clinical features of AIH-PBC overlap syndrome compared with those of AIH and PBC alone. METHODS: This retrospective cohort study included 158 consecutive patients who were diagnosed as AIH (n=61), PBC (n=81), or AIH-PBC overlap syndrome (n=9) based on the Paris and the International Autoimmune Hepatitis Group (IAIHG) criteria from 2001 to 2011 in Korea. We compared the clinical features of these three groups retrospectively, including their biochemical characteristics, treatments, responses, and clinical outcomes. RESULTS: The AIH-PBC overlap syndrome patients exhibited biochemical characteristics of both AIH and PBC, and showed a similar response to ursodeoxycholic acid (UDCA) monotherapy as for the PBC patients. However, the response of AIH-PBC overlap syndrome patients to UDCA and steroid combination therapy was worse than the response of AIH patients to steroid-based therapy (P=0.024). Liver cirrhosis developed more rapidly in AIH-PBC overlap syndrome patients than in AIH patients group (P=0.013), but there was no difference between AIH-PBC overlap syndrome patients and PBC patients. The rates of developing hepatic decompensation did not differ significantly between the groups. CONCLUSIONS: The AIH-PBC overlap syndrome patients exhibited a worse response to UDCA and steroid combination therapy and a faster cirrhotic progression compared with AIH patients.
Adult ; Aged ; Cohort Studies ; Drug Therapy, Combination ; Female ; Hepatitis, Autoimmune/complications/*diagnosis ; Humans ; Liver/metabolism/pathology ; Liver Cirrhosis, Biliary/complications/*diagnosis/drug therapy ; Male ; Middle Aged ; Republic of Korea ; Retrospective Studies ; Steroids/therapeutic use ; Treatment Outcome ; Ursodeoxycholic Acid/therapeutic use

Food is an essential component of good health and a high quality of life. This is especially true for the elderly, where health and quality of life can vary due to eating issues. This study attempts to measure the satisfaction with food-related life in the elderly of South Korea, while examining differences in social support, depression, isolation, and life satisfaction based on the level of satisfaction with food-related life. Data collection was conducted using one-on-one surveys from December 2011 to January 2012. A total of 390 elderly (aged 65 and over) who live in Korea participated in this study. The results showed that the satisfaction with food-related life was high (3.52 out of 5). The elderly who had company during a meal or a meal preparer showed a higher satisfaction with their food-related life. Social support was high (5.32 out of 7) and the feelings of isolation were low (3.85 out of 5). The average satisfaction with life was 4.42 out of 7, indicating a fair satisfaction with life, while the average depression score was relatively low (8.77 out of 26). In general, the elderly with a higher satisfaction with food-related life had a higher social support and overall satisfaction with their life. On the other hand, the elderly with a lower satisfaction with food-related life generally reported higher levels of depression and isolation. A positive correlation was observed between satisfaction with food-related life, social support, and satisfaction of life, while a negative correlation was found between satisfaction with food-related life, isolation, and depression. The results of this study indicate that managing the satisfaction with food-related life is an important component of mental health in the elderly.
Aged ; Data Collection ; Depression ; Eating ; Hand ; Humans ; Korea ; Meals ; Mental Health ; Quality of Life ; Republic of Korea ; Social Isolation

Oxidative damage is thought to be a major cause of the progression of dopamine (DA)rgic neurodegeneration as in Parkinson's disease. We have previously reported that tetrahydrobiopterin (BH4), an endogenous molecule required for DA synthesis, exerts oxidative stress to DA-producing cells and facilitates the production of DA quinone. It is known that aconitase, present in both mitochondrial and cytosolic forms, act as an reactive oxygen species (ROS) sensor, and that their inactivation leads to further generation of ROS. In the present study we investigated whether the BH4-associated vulnerability of DA cells might involve aconitase. In DArgic cell line CATH.a, BH4 treatment caused reduction of activity of both mitochondrial and cytosolic aconitases, and this appeared to be due to direct inactivation of the pre-existing enzyme molecules. Although most of the activity reduced by BH4 was increased upon reactivation reaction under a reducing condition, the restoration was not complete, suggesting that irreversible and covalent modification has occurred. The aconitase inactivation was exacerbated in the presence of DA and attenuated in the presence of tyrosine hydroxylase inhibitor a-methyl-p-tyrosine, suggesting the involvement of DA. The degree of inactivation increased when the cells were treated with the quinone reductase inhibitor dicoumarol and decreased in the presence of quinone reductase inducer sulforaphane. Taken together, BH4 appeared to lead to both reversible and irreversible inactivation of aconitase and that this is facilitated by the presence of DA and accumulation of DA quinone.
Aconitate Hydratase ; Benzoquinones ; Biopterin ; Cell Line ; Cytosol ; Dicumarol ; Dopamine ; NAD(P)H Dehydrogenase (Quinone) ; Oxidative Stress ; Parkinson Disease ; Reactive Oxygen Species ; Thiocyanates ; Tyrosine 3-Monooxygenase

PURPOSE: This study was conducted in order to analyze the dietary habits and food intake status according to the prevalence of depression in adults. METHODS: A total of 496 subjects, 224 men and 272 women aged 50 to 100 years were recruited from more than 13 cities in Korea. The questionnaires consisted of general characteristics, dietary life status, food intakes, the mean mini dietary assessment and satisfaction with food-related life questionnaire of the subjects to ask according to the degree of depression. Depression status was evaluated according to the Korean form of the Geriatric Depression Scale (K-GDS). RESULTS: All subjects were divided into depression or normal groups; the prevalence of depression was 13.8% (male) and 23.9% (female). People aged 65 or older were more likely to have higher prevalence of depression and to be bereaved. People in the depression group had poor appetite, almost never dined-out, and ate alone. The food intake of miscellaneous cereals, beans, tofu, chicken/duck meat, cabbage, carrot/amber, fungi, apple, pear, strawberry, grapes, and banana was significantly higher in the normal group compared with the depression group. In particular, significantly higher intake of vegetables and fruits was observed in the normal group. In addition, subjects in the depression group ate more fatty meat and were more dissatisfied with food-related life than those in the normal group. CONCLUSION: The results of this study imply that the prevalence of depression may affect the dietary habits, food intake, and dietary behaviors in the older adult population.
Adult* ; Appetite ; Brassica ; Edible Grain ; Depression* ; Eating ; Fabaceae ; Female ; Food Habits* ; Fragaria ; Fruit ; Fungi ; Humans ; Korea ; Male ; Meat ; Musa ; Prevalence ; Pyrus ; Surveys and Questionnaires ; Soy Foods ; Vegetables ; Vitis