Hepatocellular Carcinoma In Asia Research Articles

GALAD Score for the Diagnosis of Hepatocellular Carcinoma in Sub-Saharan Africa: A Validation Study in Ghanaian Patients.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide including sub-Saharan Africa. The GALAD score, derived from Gender, Age, Lens culinaris agglutinin-reactive fraction of alpha fetoprotein, Alpha fetoprotein, and Des-carboxy-prothrombin, has high accuracy in diagnosing HCC in Asia, Europe, and North America; however, it has not been validated in an African cohort. The aim of this study was to assess the performance of the GALAD score in the diagnosis of HCC in sub-Saharan Africa. Clinical data from patients with cirrhosis (n = 93) or HCC (n = 78) from outpatient hepatology clinics at three teaching hospitals in Ghana were abstracted, and serum samples were analyzed. A logistic regression model predicting HCC status based on the GALAD score was constructed to obtain the ROC curve for GALAD. The AUC with 95% confidence interval (CI) was calculated. The median GALAD score was higher among patients with HCC versus cirrhosis controls (8.0 vs. -4.1, P < 0.01). The AUC of the GALAD score for HCC detection was 0.86 (95% CI, 0.79-0.92). At a cut-off value of -0.37, the GALAD score had a sensitivity of 0.81 and a specificity of 0.86. The AUC (95% CI) was 0.87 (0.80-0.95) and 0.81 (0.67-0.94) in hepatitis B virus-positive and hepatitis B virus-negative patients, respectively. The GALAD score has a high accuracy for HCC detection. It has great potential to improve HCC surveillance in sub-Saharan Africa where imaging resources are limited. Significance: The GALAD score or its relevant modifications have the potential to aid in improving HCC surveillance efforts in low-resource settings in sub-Saharan Africa. This could enhance early detection rates of HCC and potentially improve survival rates in resource-limited settings.

Liver diseases and hepatocellular carcinoma in the Asia-Pacific region: burden, trends, challenges and future directions.

Globally, nearly half of deaths from cirrhosis and chronic liver diseases (CLD) and three-quarters of deaths from hepatocellular carcinoma (HCC) occur in the Asia-Pacific region. Chronic hepatitis B is responsible for the vast majority of liver-related deaths in the region. Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common form of CLD, affecting an estimated 30% of the adult population. Compared with people of European descent, people from the Asia-Pacific region carry more genetic variants associated with MASLD and its progression. Alcohol is a fast-growing cause of CLD and HCC in Asia as a result of the rising per-capita consumption of alcohol. Drug-induced liver injury is under-recognized and probably has a high prevalence in this region. The epidemiological and outcome data of acute-on-chronic liver failure are heterogeneous, and non-unified definitions across regions contribute to this heterogeneity. CLDs are severely underdiagnosed, and effective treatments and vaccinations are underutilized. In this Review, we highlight trends in the burden of CLD and HCC in the Asia-Pacific region and discuss the rapidly changing aetiologies of liver disease. We examine the multiple gaps in the care cascade and propose mitigating strategies and future directions.

Hepatocellular Carcinoma in Asia: Physician and Patient Perspectives on Surveillance, Diagnosis, and Treatment

PurposeIn several Asian countries, hepatocellular carcinoma (HCC) is a leading cause of cancer deaths. HCC risk factors in Asia differ from those elsewhere and are changing with the treatment landscape as systemic treatment options increase. This study was conducted to gain insight from physicians and patients into HCC screening, diagnosis, and treatment strategies in Indonesia, Korea, Malaysia, Singapore, Taiwan, Thailand, and Vietnam.MethodsTwo cross-sectional, anonymized, online surveys were completed between July and December 2022 by physicians diagnosing and treating HCC (55 questions on risk factors, surveillance, diagnosis, and treatment) and patients ≥ 18 years old diagnosed with HCC (36 questions on disease knowledge, quality of life, and experiences of diagnosis and treatment).ResultsResponses were received from 276 physicians in all 7 countries and 130 patients in Thailand, Taiwan, and Vietnam. From the physician’s perspective, surveillance programs are widespread but identify insufficient HCC cases; only 18% are early-stage HCC at diagnosis. From the patient’s perspective, knowledge of risk factors increases after diagnosis, but few seek support from patient associations; patients would benefit from better communication from their doctors. Treatment affordability and side effects are key issues for patients.ConclusionsAwareness of the risk factors for HCC should be raised in primary care and the general population, and surveillance should identify early-stage HCC. Because patients rely on their doctors for support, doctors should better understand their patients’ needs, and patients could be supported by trained nurses or case managers. Programs are needed to increase patients’ access to proven HCC treatments.

Abstract 4802: Accuracy of the GALAD serologic model in the diagnosis of hepatocellular carcinoma in Ghanaian patients

Abstract Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality worldwide. In sub-Saharan Africa, HCC is the second most common cancer in men and the sixth in women. African patients present with HCC at a young age and at advanced stage of disease. Improved surveillance can increase early HCC detection. The GALAD score has good sensitivity in the diagnosis of HCC in Asia, Europe and North America, however, it has not been validated in an African cohort. The aim of this study was to assess the performance of the GALAD score in the diagnosis of HCC in Ghanaian patients. Methods: Clinical data from patients with cirrhosis (n=93) or HCC (n=78) from out-patient hepatology clinics at 3 teaching hospitals in Ghana were abstracted, and serum samples analyzed. A logistic regression model predicting HCC status based on GALAD score was constructed to obtain the Receiver Operating Characteristics (ROC) curve for GALAD. The area under the curve (AUC) with 95% confidence interval was calculated and used to assess the performance of the GALAD score in surveillance for HCC. Results: The median AFP (5010.2 vs. 3.4), L3% (28.3 vs. 0.3) and DCP (507.6 vs. 0.2) levels were all significantly higher among HCC cases than the controls (p&amp;lt;0.0001). The median GALAD score was also higher among HCC patients (8.0 vs. -4.1, p&amp;lt;0.0001). The AUC of the GALAD score in the diagnosis of HCC was 0.86 (95% CI 0.79 - 0.92). At a cut-off value of -0.37, the GALAD score had a sensitivity of 0.81 and a specificity of 0.86. In a re-fit of the logistic regression model, the most significant factors in the GALAD model in our cohort were AFP-L3% and log(DCP). The AUC of the new GALAD model after model selection was 0.89. Conclusion: The GALAD score can be used to detect HCC in Ghana and has the potential to improve HCC surveillance in low-resource settings in sub-Saharan Africa. Citation Format: Yvonne Ayerki Nartey, Ju Dong Yang, Tyler Zemla, Joshua Ayawin, Shadrack Osei Asibey, Mohamed El-Kassas, Sally Afua Bampoh, Amoako Duah, Adwoa Agyei-Nkansah, Yaw Asante Awuku, Mary Yeboah Afihene, Hiroyuki Yamada, Jun Yin, Amelie Plymoth, Lewis Rowland Roberts. Accuracy of the GALAD serologic model in the diagnosis of hepatocellular carcinoma in Ghanaian patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4802.

Hepatocellular Carcinoma-Southeast Asia Updates.

Hepatocellular carcinoma (HCC) is one of the leading cancers worldwide. Classically, HCC develops in genetically susceptible individuals who are exposed to risk factors, especially in the presence of liver cirrhosis. Significant temporal and geographic variations exist for HCC and its etiologies. Over time, the burden of HCC has shifted from the low-moderate to the high sociodemographic index regions, reflecting the transition from viral to nonviral causes. Geographically, the hepatitis viruses predominate as the causes of HCC in Asia and Africa. Although there are genetic conditions that confer increased risk for HCC, these diagnoses are rarely recognized outside North America and Europe. In this review, we evaluate the epidemiologic trends and risk factors of HCC and discuss the prevention with surveillance and short management.

Global Epidemiology and Genetics of Hepatocellular Carcinoma

Hepatocellular carcinoma (HCC) is one of the leading cancers worldwide. Classically, HCC develops in genetically susceptible individuals who are exposed to risk factors, especially in the presence of liver cirrhosis. Significant temporal and geographic variations exist for HCC and its etiologies. Over time, the burden of HCC has shifted from the low-moderate to the high sociodemographic index regions, reflecting the transition from viral to nonviral causes. Geographically, the hepatitis viruses predominate as the causes of HCC in Asia and Africa. Although there are genetic conditions that confer increased risk for HCC, these diagnoses are rarely recognized outside North America and Europe. In this review, we will evaluate the epidemiologic trends and risk factors of HCC, and discuss the genetics of HCC, including monogenic diseases, single-nucleotide polymorphisms, gut microbiome, and somatic mutations.

Changes in the Epidemiology of Hepatocellular Carcinoma in Asia.

Simple SummaryThe incidence and mortality of hepatocellular carcinoma (HCC) in Asia are among the world leaders. By understanding the changes in prevalence and influencing factors of HCC, we can better understand the current situation in Asia and take measures to reduce the incidence.Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with high morbidity and mortality, and the incidence is on the rise. HCC imposes a heavy healthcare burden on Asian countries due to the presence of multiple HCC risk factors in this area. Chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, non-alcoholic liver disease (NAFLD), aflatoxin and alcohol intake are the causes of HCC that cannot be ignored. Compared with the pre-vaccination era, universal vaccination of newborns reduces the incidence of HCC. Anti-viral therapy with nucleos(t)ide analogues also causes a decline in HCC incidence. Early screening and direct-acting antiviral agent are beneficial to the prevention and treatment of HCV. For HCC caused by NAFLD and other reasons, lifestyle changes are imperative. This paper introduces the epidemiological trends of HCC in Asia and highlight future efforts. Focusing on prevention may be the most effective way to improve the prognosis of this hard-to-treat cancer.

Summary of key guidelines for locoregional treatment of HCC in Asia, Europe, South and North America.

Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide accounting for over 800,000 new cases in 2018, with the highest incidence in Asia and Africa where hepatitis B is the most common risk factor. In Europe, Japan, and the United States, hepatitis C chronic alcohol abuse and non-alcoholic fatty liver disease are more common risk factors. Five-year survival is low, less than 20% worldwide. HCC is a particularly challenging disease to treat because therapeutic options and prognosis must also consider hepatitis or cirrhosis independent of the malignancy. Locoregional therapies (LRT) including ablation, arterially directed therapy and external beam radiation are the preferred treatments for patients with good performance status, unresectable disease limited to the liver and preserved liver function. In practice, patients with portal vein tumor thrombus and limited extrahepatic disease may also be considered candidates for LRT. There are several guidelines developed by expert panels provide recommendations on treating this challenging disease including the Barcelona Clinic Liver Cancer, European Association for the Study of the Liver, European Society for Medical Oncology, American Association for the Study of the Liver Diseases, and the National Comprehensive Cancer Network. The purpose of this paper is to review the guidelines as they are applied clinically in regions with high incidence of HCC.

Hepatic arterial infusion chemotherapy with oxaliplatin plus raltitrexed versus oxaliplatin plus fluorouracil in intermediate and advanced hepatocellular carcinoma: A retrospective study.

e16166 Background: Hepatic arterial infusion chemotherapy (HAIC) showed promising outcomes for advanced hepatocellular carcinoma (HCC) and was recommended in patients with advanced HCC in Asia. HAIC with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX) was most commonly used in China. However, Continuous infusion (over 46 hours) with fluorouracil was inconvenient for arterial infusion. Raltitrexed, another antimetabolic drug with long plasma concentrations half-life, could be used in short infusions. HAIC with raltitrexed plus oxaliplatin (RALOX) was reported to be effective and safe in HCC. This study aimed to compare efficacy and safety of HAIC with raltitrexed plus oxaliplatin versus oxaliplatin plus fluorouracil in intermediate and advanced HCC. Methods: Sixty-six patients with intermediated and advanced HCC were included in this retrospective study between March 2019 and November 2020. Thirty-three patients were treated with HAIC of FOLFOX (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-fluorouracilbolus 400 mg/m2 on day 1, and 5-fluorouracil infusion 2400 mg/m2 for 46 h, every 3 weeks). Another thirty-three patients received HAIC of RALOX (oxaliplatin 100 mg/m2, raltitrexed3 mg/m2, every 3 weeks). Objective response rate (ORR), diseases control rate (DCR), progression-free survival (PFS) and treatment-related adverse events were analyzed. Results: The ORR was both 33.3% in the FOLFOX group and RALOX group per RECIST 1.1 criteria ( P = 1.00). The DCR was 90.9% and 87.9% in the FOLFOX group and RALOX group, respectively ( P = 1.00). The median PFS was 10.7 months in the FOLFOX group versus 7.9 months in the RALOX group ( P= 0.251). Grade 3/4 treatment-related adverse events were comparable between the two groups, including neutropenia, thrombocytopenia, elevated aminotransferase level and nausea. Conclusions: The efficacy and safety of HAIC with raltitrexed plus oxaliplatin was comparable to HAIC with oxaliplatin plus fluorouracil in intermediate and advanced HCC.

Clinical consensus statement: Selective internal radiation therapy with yttrium 90 resin microspheres for hepatocellular carcinoma in Asia

BackgroundHepatocellular carcinoma (HCC) is subject to different management approaches and guidelines according to Eastern and Western therapeutic algorithms. Use of selective internal radiation therapy (SIRT) with resin yttrium 90 microspheres for HCC has increased in Asia in recent years, without clearly defined indications for its optimal application. The objective of this systematic review and expert consensus statement is to provide guidance and perspectives on the use of SIRT among patients with HCC in Asia. Materials and methodsA systematic literature review identified current publications on HCC management and SIRT recommendations. A group of 10 experts, representing stakeholder specialties and countries, convened between August 2020 and March 2021 and implemented a modified Delphi consensus approach to develop guidelines and indications for use of SIRT for HCC in Asia. Final recommendations were organized and adjudicated based on the level of evidence and strength of recommendation, per approaches outlined by the American College of Cardiology/American Heart Association and Oxford Centre for Evidence-Based Medicine. ResultsThe experts acknowledged a general lack of evidence relating to use of SIRT in Asia and identified as an unmet need the lack of phase 3 randomized trials comparing clinical outcomes and survival following SIRT versus other therapies for HCC. Through an iterative process, the expert group explored areas of clinical relevance and generated 31 guidance statements and a patient management algorithm that achieved consensus. ConclusionThese recommendations aim to support clinicians in their decision-making and to help them identify and treat patients with HCC using SIRT in Asia. The recommendations also highlight areas in which further clinical trials are needed to define the role of SIRT in management of HCC among Asian populations.

Epidemic characteristics of alcohol-related liver disease in Asia from 2000 to 2020: A systematic review and meta-analysis.

To systematically summarize the prevalence of alcohol-related liver disease (ALD) and the alcohol-attributable proportions of liver cirrhosis and hepatocellular carcinoma (HCC) cases in Asia. The Embase, PubMed, Web of Science, Cochrane, CINAHL, WanfangMed and China National Knowledge Infrastructure databases were searched from 01 January 2000 to 01 December 2021 for reports of ALD prevalence and alcohol-attributable proportions of liver cirrhosis/HCC in Asian populations. Study characteristics were extracted, and meta-analyses were conducted. Our literature search identified 13 studies reporting the ALD prevalence, 62 studies reporting the alcohol-attributable proportion of liver cirrhosis and 34 studies reporting the alcohol-attributable proportion of HCC. The overall prevalence of ALD was 4.81% (95% confidence interval [CI] 3.67%, 6.09%). The ALD prevalence was higher in men (7.80% [95% CI 5.70%, 10.19%]) than in women (0.88% [95% CI 0.35%, 1.64%]) and increased significantly over time from 3.82% (95% CI 2.74%, 5.07%) between 2000 and 2010 to 6.62% (95% CI 4.97%, 8.50%) between 2011 and 2020. Among 469 640 cases of liver cirrhosis, the pooled alcohol-attributable proportion was 12.57% (95% CI 10.20%, 15.16%). Among 82 615 HCC cases, the pooled alcohol-attributable proportion was 8.30% (95% CI 6.10%,11.21%). Significant regional differences were observed in alcohol-attributable proportions of liver cirrhosis and HCC. The prevalence of ALD and the proportions of alcohol-related liver cirrhosis and HCC in Asia are lower than those in western populations. However, a gradual increasing trend was observed over the last 21 years. ALD is likely to emerge as a leading cause of chronic liver disease in Asia.

Changing epidemiology of hepatocellular carcinoma in Asia.

Liver cancer is the fifth most common cancer and the second leading cause of malignant death in Asia, and Asia reports 72.5% of the world's cases in 2020. As the most common histological type, hepatocellular carcinoma (HCC) accounts for the majority of incidence and mortality of liver cancer cases. This review presents the changing epidemiology of HCC in Asian countries in recent years. Globally, aged, male and Asian populations remain the group with the highest risk of HCC. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are still the leading risk factors of HCC with a slight decline in most Asian countries, which is mainly attributed to HBV vaccination of newborns, prevention of HCV horizontal transmission and treatment of chronic hepatitis. However, the prevalence of HCC caused by metabolic factors, including metabolic syndrome, obesity and non-alcoholic fatty liver diseases, is increasing rapidly in Asian countries, which may eventually become the major cause of HCC. Excessive alcohol consumption continues to be an important risk factor as the average consumption of alcohol is still growing. Hopefully, great effort has been made to better prevention and treatment of HCC in most Asian regions, which significantly prolongs the survival of HCC patients. Asian countries tend to use more aggressive intervention than European and American countries, but it remains unclear whether this preference is related to a better prognosis. In conclusion, HCC remains a major disease burden in Asia, and the management of HCC should be adjusted dynamically based on the changing epidemiology.

Treatment and the prognosis of hepatocellular carcinoma in Asia.

Hepatocellular carcinoma is the most common type of malignant tumour in Asia. Treatment is decided according to the staging system with information on tumour burden and liver function. The Barcelona Clinic Liver Cancer staging system is the most commonly used staging system for the selection of appropriate treatments worldwide, and although it is highly evidenced-base, it has very strict guidelines for treatment. In Asian countries, many efforts have been made to expand the indications of each treatment and combination therapies as well as alternative therapies for better outcomes. The guidelines in Asia are less evidence-based than those in Western countries. More aggressive treatments for hepatocellular carcinoma are generally employed in the guidelines of Asian countries. Surgical resection is frequently employed for selected hepatocellular carcinoma patients with the Barcelona Clinic Liver Cancer stages B and C, and combination therapies are sometimes selected, which are contrary to the recommendations of American and European association for the study of the liver guidelines. Recently, a paradigm shift in treatments for advanced hepatocellular carcinoma has occurred with molecular targeted agents, antibodies and immune checkpoint inhibitors in Asia. Atezolizumab+bevacizumab therapy has become the first-line systemic treatment ineligible for radical treatment or transarterial chemoembolization in Asian countries. The overall survival of patients with hepatocellular carcinoma varies substantially across Asia. Taiwan and Japan have the best clinical outcomes for patients with hepatocellular carcinoma worldwide. Intensive surveillance programmes and the development of radical and non-radical treatments are indispensable for the improvement of prognosis in patients with hepatocellular carcinoma.

Changes in therapeutic options for hepatocellular carcinoma in Asia.

The incidence rate of hepatocellular carcinoma (HCC) is expected to increase, with most cases occurring in Asia. In some parts of Asia, the occurrence of HCC developing from metabolic-related liver disease has markedly increased in recent years, whereas the occurrence of HCC developing from viral-hepatitis-related liver disease has decreased. Advancements in the treatment of HCC over the past few decades has been remarkable, with most treatment strategies to remove or control liver tumours (hepatic resection, local ablation, radiation therapy, transarterial chemoembolisation, hepatic arterial infusion chemotherapy) primarily developing in Asia. In addition, recent progress in systemic therapies has prolonged the prognosis of advanced HCC. Nowadays, six regimens of systemic therapies have become available in most countries, according to phase III trials (atezolizumab plus bevacizumab, sorafenib, lenvatinib, regorafenib, cabozantinib and ramucirumab). In a global randomised phase III trial (IMbrave 150 trial), the most effective of the latest drug designs was newly emerged combination immunotherapy (atezolizumab plus bevacizumab), which has shown significantly prolonged overall survival compared with sorafenib, which was the first-line systemic therapy for more than a decade. Now, the treatment dynamics for HCC are undergoing a major transition as a result of two important changes: the replacement of viral-related HCC by metabolic-related HCC and the emergence of combination immune therapy.

Embolotherapy of unresectable hepatocellular carcinoma: Eastern perspective.

Asia suffers a particularly large prevalence of the world's hepatocellular carcinoma (HCC), accounting for nearly 72.5% of the newly diagnosed 609,596 cases and 72.4% of the 566,269 deaths. The majority of HCC patients is diagnosed at unresectable stages in Asia despite efforts to improve availability of screening. Although the Barcelona Clinic Liver Cancer (BCLC) staging algorithm is accepted worldwide, various staging systems and guidelines have been proposed in Asian regions. Embolotherapy has been endorsed by many Asian guidelines and is the most common treatment across all stages of HCC. There are considerable discrepancies of the allocation of embolotherapy for unresectable HCC in Asia. This review will focus on the indication and contraindication, technique variances, combination regimen, and when to start, repeat or stop embolotherapy for unresectable HCC with the hope to provide insights into TACE application to patients at any HCC stage.

Hepatocellular Carcinoma in Asia: A Challenging Situation.

ABSTRACTAmongst the primary tumors of the liver, hepatocellular carcinoma (HCC) is the most common. It is also one of the most prevalent types of cancers in Asia. Mostly, HCC occurs on a background of chronic liver disease and liver cirrhosis; however, de novo HCCs can also arise in apparently normal looking livers on imaging. There are multiple risk factors for HCC, including hepatitis B and C infections, diabetes mellitus, alcohol, and nonalcoholic steatohepatitis. Other common risk factors which are known to be involved in the pathogenesis of HCC are obesity, food contaminated with aflatoxin and hemochromatosis. Many of these factors are commonly found in this part of the world, hence the high burden of disease. Besides these, smoking and familial predisposition to HCC also seem to have an important role to play in its development. Majority of HCC are missed at an early stage despite the emphasis on adequate screening and surveillance strategies. Therefore, most of the time these tumors are diagnosed at a fairly advanced stage, when palliative treatment is the only therapeutic option left. Hence, prevention of HCC by controlling and minimizing the possible risk factors is the need of the hour.How to cite this article: Jafri W, Kamran M. Hepatocellular Carcinoma in Asia: A Challenging Situation. Euroasian J Hepatogastroenterol 2019; 9(1):27-33.

A concise review of current guidelines for the clinical management of hepatocellular carcinoma in Asia

Background: Hepatocellular carcinoma (HCC) has been the fifth most common malignancy worldwide and is particularly endemic in Asia, accounting for around 80% of new cases around the world. Currently, with many new studies and evidences coming into being in Asia, various HCC guidelines have been newly issued or updated. The aim of the present study is to incorporate new evidence on the management of HCC by assessing and comparing the main Asian guidelines. Methods: Electronic databases of MEDLINE, the Chinese SinoMed and the Japanese CiNii were systematically searched. AGREE II instrument was utilized for the quality assessment of guidelines. Results: A total of 11 main Asian guidelines were included. There still remain variances in guideline structures and certain contents. We briefly compared the guidelines and summarized the newly updated recommendations to help hepatobiliary surgeons to catch the latest information. Conclusions: The present review might help focus and target advocacy to improve clinical management of HCC. Further research and more straightforward guidelines are essential to improve the prognosis of HCC in the future.

A concise review of current guidelines for the clinical management of hepatocellular carcinoma in Asia

A concise review of current guidelines for the clinical management of hepatocellular carcinoma in Asia

The changing epidemiology of hepatocellular carcinoma in Asia versus United States and Europe

&lt;p&gt;Hepatocellular carcinoma (HCC) is a major disease worldwide. There were 782,000 estimated new cases globally&lt;br /&gt;in 2012 with the majority (76%) occurring in Asia, especially China. Although the etiologies are similar, the prevalence of&lt;br /&gt;each HCC risk factor varies in different geographic regions. In China, hepatitis B virus (HBV) infection is the major cause&lt;br /&gt;of HCC, whereas in Japan, US and Europe, hepatitis C virus (HCV) infection predominates. With the epidemic of obesity&lt;br /&gt;and diabetes, non-alcoholic fatty liver disease (NAFLD), especially its more aggressive form non-alcoholic steatohepatitis&lt;br /&gt;(NASH), has now become a major contributor to HCC. It is anticipated that NAFLD/NASH is likely to overtake viral&lt;br /&gt;hepatitis as the leading contributor to HCC in the future. Prior success in reducing HCC cases through hepatitis B&lt;br /&gt;immunization program and effective HBV treatments is likely to be offset by rising significance of NASH-associated HCC.&lt;br /&gt;In view of this, appropriate measures such as aggressive monitoring clinical course and prognoses of patients with HCC&lt;br /&gt;from NASH, studying pathogenesis and mechanism by which NASH promotes HCC, and developing novel intervention and&lt;br /&gt;treatment strategy for these patients would be important to address this important public health challenge.&lt;/p&gt;

Glucose-regulated protein 78 demonstrates antiviral effects but is more suitable for hepatocellular carcinoma prevention in hepatitis B

BackgroundHepatitis B virus (HBV) is the leading cause of liver cirrhosis and hepatocellular carcinoma in Asia and Africa. Existing antivirals cannot cure HBV or eliminate risk of hepatocellular carcinoma. Glucose-regulated protein 78 (GRP78) can inhibit HBV replication, but promote virion secretion and hepatocellular cancer cell invasion. For these reasons, the overall effect of GRP78 on HBV production and whether to utilize the HBV replication-inhibitory effect of GRP78 up-regulation or the hepatocellular cancer cell invasion-inhibitory effect of its down-regulation were further investigated in order to improve the efficacy of current antiviral therapy.MethodsGRP78 regulations in HepG2.2.15 cells were conducted by transfections of expressing vector and small interfering RNA, respectively. The changes in HBV replication, hepatitis B e antigen (HBeAg) synthesis and hepatoma cell motility were monitored.ResultsGRP78 overall decreased HBV production due to its HBV replication-inhibitory effect time-dependently overwhelming virion secretion-promoting effect in HepG2.2.15 cells. Unlike the parental cells (HepG2), HepG2.2.15 cells demonstrated decreased expressions of the major genes in the interferon-β1-dependent pathway. Moreover, the expressions of these genes were not affected by GRP78 regulations. However, GRP78 was found to inhibit HBeAg secretion and to increase the retro-transportation of capsid assembly-interfering HBeAg precursor from the endoplasmic reticulum into the cytosol where new viral nucleocapsids formed. Furthermore, GRP78 overexpression promoted wound healing process (the motility) of HepG2.2.15 cells. In contrast, GRP78 knockdown enhanced HBV replication and HBeAg secretion, but they were abolished by entecavir and furin inhibitor, respectively.ConclusionsGRP78 mainly demonstrates anti-HBV effects, reducing HBV production and HBeAg secretion. With due regard to the hepatocellular cancer invasion risk of the overexpression and the rectifiability of the unpleasant effects of the knockdown, GRP78 down-regulation may be more suitable to serve as an additive strategy to cover the hepatocellular cancer prevention shortage of current antiviral therapy in the future.