Important Risk Factor For Hepatocellular Carcinoma Research Articles

Increased plasma levels of monocyte chemoattractant protein-1 in patients with hepatitis B virus pre-S2 gene deletion mutation predict a higher risk of hepatocellular carcinoma recurrence after curative surgical resection.

Despite resection surgery as a curative therapy for hepatocellular carcinoma (HCC), the high rate of postoperative HCC recurrence remains a big challenge for patient survival. Chronic hepatitis B virus (HBV) infection is the most important risk factor for HCC. Deletion mutation in the HBV pre-S2 gene leads to expression of an essential viral oncoprotein called pre-S2 mutant and represents an independent prognostic biomarker for HCC recurrence after curative surgical resection. Additionally, cytokines are multifunctional secreted proteins and implicated in all stages of HBV-related HCC tumorigenesis. This study aimed to identify the cytokines whose plasma levels were associated with pre-S2 gene deletion mutation and HCC recurrence and evaluate their potential to be combined with pre-S2 gene deletion mutation in predicting HCC recurrence. Among a panel of 27 cytokines examined, plasma levels of monocyte chemoattractant protein-1 (MCP-1) were significantly upregulated in patients with pre-S2 gene deletion mutation or HCC recurrence. MCP-1 was validated as an independent prognostic biomarker for HCC recurrence. Moreover, patients with both the presence of pre-S2 gene deletion mutation and high levels of MCP-1 displayed a higher risk of HCC recurrence than patients with either one or none of these two biomarkers. The combination of pre-S2 gene deletion mutation and MCP-1 levels exhibited a better prognostic performance for HCC recurrence than each biomarker alone. This study discovered that MCP-1 levels had a significance to be as a combination biomarker with pre-S2 gene deletion mutation providing an improved performance in predicting HCC recurrence after curative surgical resection.

Does hepatic steatosis impact chronic hepatitis B?

Does hepatic steatosis impact chronic hepatitis B?

Poor Prognosis in HBV-associated Hepatocellular Carcinoma After Successful Viral Suppression: A Case Series Highlighting a Need for a Cure

Hepatocellular Carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide, with chronic hepatitis B virus (HBV) infection being an important risk factor for HCC. While nucleos(t)ide analog (NA) therapy has succeeded in suppressing HBV replication and decreasing the risk of HCC in patients with HBV infection, there remains a persistent risk of HCC in those patients. Furthermore, previous studies have highlighted worse survival in patients who developed HCC while on successful NA therapy compared to those who developed HCC without previous NA treatment. We conducted a long-term, retrospective case study in 5 patients observed between 10 and 25 years, to further explore the poor outcomes in patients with HBV-associated HCC with or without previous NA therapy. Our study highlights the aggression and recurrence of HCC in patients with HBV infection, well-suppressed on NA therapy. The results of our observation emphasize the need for early referral for liver transplantation in these select patients.

Dynamics of cytokines predicts risk of hepatocellular carcinoma among chronic hepatitis C patients after viral eradication.

BACKGROUNDChronic hepatitis C virus (HCV) infection induces profound alterations in the cytokine and chemokine signatures in peripheral blood. Clearance of HCV by antivirals results in host immune modification, which may interfere with immune-mediated cancer surveillance. Identifying HCV patients who remain at risk of hepatocellular carcinoma (HCC) following HCV eradication remains an unmet need. We hypothesized that antiviral therapy-induced immune reconstruction may be relevant to HCC development.AIMTo investigate the impact of differential dynamics of cytokine expression on the development of HCC following successful antiviral therapy.METHODSOne hundred treatment-naïve HCV patients with advanced fibrosis (F3/4) treated with direct-acting antivirals (DAAs) or peginterferon/ribavirin who achieved sustained virologic response [SVR, defined as undetectable HCV RNA throughout 12 wk (SVR12) for the DAA group or 24 wk (SVR24) for the interferon group after completion of antiviral therapy] were enrolled since 2003. The primary endpoint was the development of new-onset HCC. Standard HCC surveillance (abdominal ultrasound and α-fetoprotein) was performed every six months during the follow-up. Overall, 64 serum cytokines were detected by the multiplex immunoassay at baseline and 24 wk after end-of-treatment.RESULTSHCC developed in 12 of the 97 patients over 459 person-years after HCV eradication. In univariate analysis, the Fibrosis-4 index (FIB-4), hemoglobin A1c (HbA1c), the dynamics of tumor necrosis factor-α (TNF-α), and TNF-like weak inducer of apoptosis (TWEAK) after antiviral therapy were significant HCC predictors. The multivariate Cox regression model showed that ΔTNF-α (≤ -5.7 pg/mL) was the most important risk factor for HCC (HR = 11.54, 95%CI: 2.27-58.72, P = 0.003 in overall cases; HR = 9.98, 95%CI: 1.88-52.87, P = 0.007 in the interferon group). An HCC predictive model comprising FIB-4, HbA1c, ΔTNF-α, and ΔTWEAK had excellent performance, with 3-, 5-, 10-, and 13-year areas under the curve of 0.882, 0.864, 0.903, and 1.000, respectively. The 5-year accumulative risks of HCC were 0%, 16.9%, and 40.0% in the low-, intermediate-, and high-risk groups, respectively.CONCLUSIONDownregulation of serum TNF-α significantly increases the risk of HCC after HCV eradication. A predictive model consisting of cytokine kinetics could ameliorate personalized HCC surveillance strategies for post-SVR HCV patients.

Increasing incidence of non-HBV- and non-HCV-related hepatocellular carcinoma: single-institution 20-year study

BackgroundWe previously reported on the trends in the etiologies of hepatocellular carcinoma (HCC) diagnosed in patients between 1995 and 2009. The aims of our updated study were to evaluate the incidence, nonhepatitis B and nonhepatitis C viral (NBNC) etiologies, and clinical characteristics of HCCs occurring in patients between 1992 and 2018.MethodsThe study enrolled 2171 consecutive patients with HCC between 1992 and 2018. Their medical records were reviewed. The patients were divided into two groups, patients with early diagnoses from 1992 to 2009 and those with late diagnoses from 2010 to 2018.ResultsNBNC-HCC occurred in 514 patients (23.6%). The percentage of patients with HCC who had NBNC-HCC increased from 26.5% in 2009 to 46.3% in 2018. Patients with NBNC-HCC were older (median ages from 67 to 73 years). Type 2 diabetes mellitus (48.5–60.3%: P = 0.008), hypertension (48.5–57.4%: P = 0.047), and hyperlipidemia (39.2–53.8%: P = 0.001) increased significantly in recent years. The median FIB-4 index decreased (4.37–3.61: P = 0.026) and the median platelet count increased (15.1–17.9 × 104/μL: P = 0.013). Among the 514 patients with NBNC-HCC, 194 underwent hepatic resection for nonalcoholic steatohepatitis (NASH) (15%), alcoholic liver disease (ALD) (29%), and cryptogenic hepatitis (56%). Cirrhosis was detected in 72%, 39%, and 16% of patients with NASH, ALD, and cryptogenic hepatitis, respectively. The prevalence of cirrhosis in patients with NASH was significantly higher than the prevalence of cirrhosis in the other groups (P < 0.001). Overall, 70% of the non-malignant liver tissue of patients with NBNC-HCC was not involved with cirrhosis. On the other hand, the median FIB-4 index in patients with cryptogenic HCC was 2.56, which was a significantly lower value than those values in the other groups of patients. The FIB-4 index considered as one of useful screening of HCC.ConclusionsThe prevalence of NBNC-HCC has increased rapidly even in a regional university hospital. Metabolic syndrome may be an important risk factor for HCC. HCC was also found in patients with non-cirrhotic livers. The FIB-4 index may be a useful screening method for HCC in patients with NBNC.

Abstract 754: Serum iron markers in relation to hepatocellular carcinoma risk among patients with non-alcoholic fatty liver disease

Abstract Background: Hepatocellular carcinoma (HCC) is the 6th most commonly diagnosed cancer and the 3rd leading cause of cancer death in the US. Around 85-90% of primary liver cancer is HCC. Besides identified risk factors for HCC including chronic infection with hepatitis B and C virus (HBV and HCV), alcohol abuse, dietary aflatoxin exposure and hereditary hemochromatosis, nonalcoholic fatty liver disease (NAFLD) is as another important risk factor for HCC. NAFLD is a spectrum of liver disease that ranges from hepatic steatosis through non-alcoholic steatohepatitis (NASH) with or without fibrosis and may progress to cirrhosis or HCC. Iron is an essential metal and hepatocytes are its main storage site. Increased body iron from the intestine due to high dietary iron or hereditary or acquired hemochromatosis may result in hepatic iron overload. NAFLD is frequently associated with elevated serum iron indices when hepatic iron in the absence of hemochromatosis. Epidemiologic data on the association between serum iron markers and risk of HCC are sparse. The aim of the study was to examine the association of iron related serum markers with risk of HCC in NAFLD patients. We hypothesized that elevated serum iron levels, which reflects hepatic iron, are associated with increased risk of HCC among NAFLD patients. Methods: 48,328 patients with NAFLD were identified in the electronic health records (EHR) of the University of Pittsburgh Medical Center (UPMC) between 1/1/2004 to 12/31/2018. Among them, 19,908 had at least one measurement of serum iron, transferrin saturation, total iron binding capacity (TIBC) and serum ferritin. After an average 4.47 years of follow-up, 363 patients with NAFLD were diagnosed with HCC at least 30 days after measurement of iron markers. Cox proportional hazard regression was used to calculate hazard ratios (HRs) and the 95% confidence intervals (CIs) for HCC incidence associated with elevated levels of the four iron markers adjusted for age, sex, race, body mass index, history of diabetes and tobacco smoking. Results: Serum iron and transferrin saturation were significantly elevated in NAFLD patients who developed HCC compared to others who remained free of HCC during the study. The HR of HCC for elevated serum iron &amp;gt;175 mcg/dl was 3.41 (95% CI 1.48 - 7.85) compared to its normal range at 75-175 mcg/dl. Similarly, the HR for HCC associated with elevated transferrin saturation &amp;gt;35% was 2.56 (95% CI 1.49-4.39) relative to the normal range at 25-35%. The associations were not statistically significant for TIBC and serum ferritin with HCC risk. Conclusions: Elevated serum iron and transferrin saturation levels, but not TIBC or serum ferritin, were significantly associated with increased risk of developing HCC in NAFLD patients. These findings support future studies evaluating serum iron level in risk stratification of NAFLD patients at risk of HCC and potential links to pathogenesis of HCC. Citation Format: Yi-Chuan Yu, Renwei Wang, Jaideep Behari, Ada Youk, Nancy W. Glynn, Jian-Min Yuan. Serum iron markers in relation to hepatocellular carcinoma risk among patients with non-alcoholic fatty liver disease [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 754.

Microbiota-Associated Therapy for Non-Alcoholic Steatohepatitis-Induced Liver Cancer: A Review.

Even though advancement in medicine has contributed to the control of many diseases to date, cancer therapy continues to pose several challenges. Hepatocellular carcinoma (HCC) etiology is multifactorial. Recently, non-alcoholic fatty liver disease (NAFLD) has been considered as an important risk factor of HCC. NAFLD can be divided into non-alcoholic simple fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH) based on histopathological features. Recently, studies have indicated that the gut microbiota is associated with NAFLD and HCC. Therefore, in this review, we have discussed the effects of gut microbiota-related mechanisms, including dysbiosis and gut barrier function, and gut microbiota-derived metabolites on NAFLD and HCC pathogenesis and the potential therapeutic strategies for NAFLD and HCC. With a better understanding of the gut microbiota composition and function, new and improved diagnostic, prognostic, and therapeutic strategies for common liver diseases can be developed.

Management of hepatocellular carcinoma: SASL expert opinion statement.

Hepatocellular carcinoma (HCC) is the most frequent primary malignancy of the liver. HCC is characterised by a heterogeneous clinical presentation. Liver cirrhosis is the most important risk factor for HCC. Regular surveillance with ultrasound examinations allows detection of HCC at an early stage, where curative treatment options such as surgical resection, liver transplantation and local ablative therapies can be applied. More advanced tumours are treated with transarterial chemo- or radiotherapy, and with systemic treatments including immunotherapies. Treatment decisions are based on tumour staging and liver function, and should be made in specialised interdisciplinary tumour boards. This expert opinion statement by the Swiss Association for the Study of the Liver reviews the current state of HCC management and provides recommendations adapted to the health care environment in Switzerland.

Risk factors for hepatocellular carcinoma (HCC) in the northeast of the United States: results of a case-control study.

HCC incidence has been continuously rising in the US for the past 30years. To understand the increase in HCC risk, we conducted a case-control study in Connecticut, New Jersey and part of New York City. Through rapid case ascertainment and random digit dialing, we recruited 673 incident HCC patients and 1,166 controls. Information on demographic and anthropometric characteristics, lifestyle factors, medical and family cancer histories, were ascertained through telephone interviews using a structured questionnaire. Saliva specimens were collected for testing hepatitis C virus (HCV) antibodies. Unconditional logistic regression models were utilized to calculate odds ratio (OR) and 95% confidence interval (CI) to determine HCC associations with risk factors. The study confirmed that HCV infection and obesity were important risk factors for HCC, ORs 110 (95% CI 59.2-204) and 2.13 (95% CI 1.52-3.00), respectively. High BMI and HCV infection had synergy in association with elevated HCC risk. Patients both obese and infected with HCV had HCC detected on average nearly 10years earlier than those with neither factor. Diabetes, cigarette smoking and heavy alcohol intake were all associated with increased risk of HCC, whereas aspirin and other NSAID use were associated with reduced risk. HCC cases tended to attain less education, with lower household incomes, unmarried, and to have had more sexual partners than the controls. Individuals at risk of HCC in the US comprise a unique population with low socioeconomic status and unhealthy lifestyle choices. Given the multifactorial nature, a comprehensive approach is needed in HCC prevention.

The characteristics and risk factors of hepatocellular carcinoma in nonalcoholic fatty liver disease without cirrhosis.

We evaluated the characteristics of hepatocellular carcinoma (HCC) in patients who had non-alcoholic fatty liver disease (NAFLD) without cirrhosis. We prospectively followed NAFLD patients at our University hospital. NAFLD was diagnosed from detection of steatosis by histology or imaging, no alcohol intake, and exclusion of other liver diseases. Cirrhosis was defined by histological features, imaging data, and symptoms. We compared NAFLD-related HCC with or without cirrhosis and non-cirrhotic NAFLD with or without HCC. There were 48 non-cirrhotic HCC patients and 71 cirrhotic HCC patients. Multiple logistic regression analysis revealed that other than liver function factors, male gender (OR: 5.603, 95%CI: 1.577-19.900), light drinker (OR: 2.797, 95%CI: 1.031-7.589), and tumor size (OR: 1.031, 95%CI 1.009-1.055) differ significantly between these two groups. The recurrence rate was significantly lower in the non-cirrhotic HCC group than the cirrhotic HCC group, with risk factors being des-γ-carboxy prothrombin and the number of HCCs. The non-cirrhotic HCC group showed significantly better survival because of absence of non-cancerous liver failure. Comparison between non-cirrhotic NAFLD patients with or without HCC (n=612) revealed the following risk factors for HCC: male gender (OR: 7.774, 95%CI: 2.176-27.775), light drinker (OR: 4.893, 95%CI: 1.923-12.449), and high FIB4 index (OR 2.634, 95%CI: 1.787-3.884). In patients with non-cirrhotic NAFLD, important risk factors for HCC were male gender, alcohol consumption, and the FIB4 index. HCC recurrence and survival were only influenced by the tumor stage. We should be aware of alcohol consumption as a modifiable risk factor for HCC.

Hepatitis viruses take advantage of traditional practices to increase the burden of hepatocellular carcinoma in Tunisia.

Hepatocellular carcinoma (HCC) is a major public health issue in Africa. In Tunisia, hepatitis B virus (HBV) is known to be an important risk factor for HCC in the south of the country, but the role played by hepatitis C virus (HCV) still remains unclear. The aim of the current case-control study was to identify risk factors for HCC development in the northern part of the country. Clinical and biological data including viral hepatitis status (serological and molecular) and non-infectious risk factors from 73 patients with HCC and 70 control subjects without hepatic diseases were collected. The mean age of the patients was 63 ± 10 years, and the ratio of males to females was 1.1. HCC occurred in cirrhotic liver in 72.0% of the cases. HCV infection was the dominant risk factor (64.3% of cases); the presence of HBV was observed in 53.4% of the cases. Occult hepatitis B and C were implicated, respectively, in 30.1% and 9.6% of the cases. HCV genotype 1b was predominant. Patients originating from western Tunisia formed a homogeneous group, characterized by significantly higher rates of tattoos or scarifications (83%) and HCV infection (80%) than those from other parts of the country. Chronic HCV infection is currently the primary risk factor for HCC in Tunisia; HBV infection remains frequent in its overt or occult infection forms. Traditional esthetic practices apparently contribute to increasing the burden of terminal liver diseases in western Tunisia.

Epidemiology of Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV) Related Hepatocellular Carcinoma.

Introduction:Hepatocellular carcinoma (HCC) is one of the most prevalent primary malignant tumors and accounts for about 90% of all primary liver cancers. Its distribution varies greatly according to geographic location and it is more common in middle and low- income countries than in developed ones especially in Eastern Asia and Sub Saharan Africa (70% of all new HCCs worldwide), with incidence rates of over 20 per 100,000 individuals.Explanation:The most important risk factors for HCC are Hepatitis B Virus (HBV) infection, Hepatitis C Virus (HCV) infection, excessive consumption of alcohol and exposition to aflatoxin B1. Its geographic variability and heterogeneity have been widely associated with the different distribution of HBV and HCV infections worldwide.Chronic HBV infection is one of the leading risk factors for HCC globally accounting for at least 50% cases of primary liver tumors worldwide. Generally, while HBV is the main causative agent in the high incidence HCC areas, HCV is the major etiological factor in low incidence HCC areas, like Western Europe and North America.Conclusion:HBV-induced HCC is a complex, stepwise process that includes integration of HBV DNA into host DNA at multiple or single sites. On the contrary, the cancerogenesis mechanism of HCV is not completely known and it still remains controversial as to whether HCV itself plays a direct role in the development of tumorigenic progression.

Nonalcoholic fatty liver disease promotes hepatocellular carcinoma through direct and indirect effects on hepatocytes.

Hepatocellular carcinoma (HCC) is the sixth most frequent neoplasm and the second leading cause of cancer-related deaths worldwide. Nonalcoholic fatty liver disease (NAFLD), a common disorder in obese people, has been identified as an important risk factor for HCC. Following the increasing prevalence of obesity, it is expected that the contribution of NAFLD to HCC's incidence worldwide will grow. Recently, a number of studies have been published, which help us better understand cellular and molecular mechanisms of how NAFLD promotes hepatocarcinogensis. Inflammatory cytokines, ER stress and circadian dysregulation, which mediate hepatocyte injury and NAFLD progression, have been identified to promote malignant transformation of hepatocytes. Besides these 'intrinsic' effects, lipid dysregulation dramatically affects the liver local microenvironment. The reshaped immune environment has also been found to contribute to the NAFLD-mediated hepatocarcinogenesis. This review explores recent findings of both 'intrinsic' effects on hepatocytes and the role of the local environment in NAFLD-promoted HCC development.

Nonalcoholic fatty liver disease and hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) in patients with nonalcoholic fatty liver disease is becoming more common globally. The incidence of HCC due to nonalcoholic steatohepatitis in comparison to other etiologies is increasing. This is due to the pandemic of obesity and diabetes mellitus, two important risk factors for HCC. HCC arising in this context occurs in about 40% of the cases in a liver which is not yet cirrhotic. This has implications regarding the population which should be enrolled in an HCC surveillance program and regarding the treatment options. Surgery is more frequently contemplated in patients with HCC and no cirrhosis. However, patients with nonalcoholic steatohepatitis-induced HCC have frequent co-morbidities which have to be taken into account when developing a management strategy. Interestingly, these patients are frequently on medications which have been suggested to decrease the risk to develop HCC.

Abstract B80: Multiple Risk Factors for Hepatocellular Carcinoma (HCC) among Asian Americans: Implications for Intervention

Abstract Multiple Risk Factors for Hepatocellular Carcinoma (HCC) among Asian Americans: Implications for Intervention Introduction: Asian Americans have the highest mortality rates from HCC compared to all other racial/ethnic populations. Historically, mitigating their HCC risks has been through screening for hepatitis B (HBV) and providing linkage to care to those who are chronically infected; however, HCC has multiple risk factors. Besides HBV, obesity-related metabolic factors, including diabetes, and chronic hepatitis C (HCV) are becoming important risk factors for HCC. Lifestyle factors, such as alcohol and tobacco use, also increase risk of HCC. Our study is among the first to measure seven literature-documented HCC risk factors to assess the prevalence of combined risk factors in this population. Objectives and hypothesis: We sought to measure the joint prevalence of 7 HCC risk factors in 3 domains (viral, metabolic, and lifestyle), and hypothesized that a substantial proportion of foreign-born Asian Americans are at risk in multiple domains. Methods: We focused on Asians born in HBV endemic areas (≥ 2%) and tested 967 adult foreign-born Chinese, Hmong, Korean, and Vietnamese American residents of Sacramento County, CA for HBV and HCV; measured hemoglobin A1c (HbA1c) and waist circumference; and recorded self-reported history of diabetes, hypertension, consumption of alcohol in the past 30 days, and smoking status. Metabolic risk factors included high glucose, defined as HbA1c ≥ 5.7% or self-reported diagnosis of diabetes; a large waist circumference, defined according to Asian cut-points (≥ 35 inches for men, ≥ 32 inches for women); and self-reported hypertension. We computed gender-specific age standardized prevalence rates with 95% confidence intervals (CI) for viral, metabolic, and lifestyle risk factors, alone and in combination. Results: Chronic HBV was much more common than HCV in Chinese, Hmong, and Vietnamese Americans; both HBV and HCV were very uncommon among Koreans. Vietnamese men (15.3%, 95% CI 6.9-23.7%) and Hmong women (15.0%, 95% CI 7.6%-22.3%) had the highest viral risk factor prevalence. High glucose was most common among Chinese men (56.3%, 95% CI 43.2-69.3%), followed by Korean men (49.3%, 95% CI 33.4-65.3%). A large waist circumference was most common among Hmong women (83.9%, 95% CI 75.0-92.8%) and Hmong men (66.9%, 95% CI 54.7-79.1%) and least common among Korean men (36.0% 95% CI 19.7-53.2%), Korean women (40.5%, 95% CI 31.3-49.8%), and Vietnamese men (41.8%, 95% CI 30.0-53.7%). Hmong women had the highest prevalence of hypertension (26.8%, 95% CI 18.2-35.4%), and Vietnamese men had the lowest (12.9%, 95% CI 2.7-23.1%). Hmong women had the highest prevalence of at least one metabolic risk factor (85.8%, 95% CI 78.2-93.5%), followed by Hmong men (79.5%, 95% CI 69.6-89.5%), with Korean women having the lowest (54.0%, 95% CI 46.1-62.0%). Among men, smoking was most common among Chinese (28.1%, 95% CI 15.8-40.4%) and least common among Koreans (16.6%, 95% CI 3.4%-29.8%); Vietnamese men were most likely (75.5%, 95% CI 65.6-85.3%) and Hmong least likely (27.4%, 95% CI 16.4-38.4%) to consume alcohol. Among women, smoking was very uncommon in all ethnic groups; alcohol consumption was most common among Vietnamese women (19.0%, 95% CI 11.1-26.9%) and least common among Hmong (5.8%, 95% CI 0.5-11.1%). Vietnamese men were the most likely to have risk factors in two or more domains (59.5%, 95% CI 47.0%-71.9%), followed by Hmong men (43.4%, 95% CI 30.9-55.9%), Chinese men (41.6%, 95% CI 28.2-55.1%), Korean men (31.6%, 95% CI 15.1-48.0%), Vietnamese women (19.9%, 95% CI 11.9-27.8%), Hmong women (19.4%, 95% CI 11.6-27.1%), Chinese women (13.6%, 95% CI 4.4-22.85), and Korean women (11.3%, 95% CI 3.3-19.4%). Conclusion: Considerable ethnic variation in the prevalence of viral, metabolic, and lifestyle risk factors exists. Efforts to reduce HCC need to concurrently address multiple risk factors. Citation Format: Susan L. Stewart, Julie HT Dang, Moon S. Chen, Jr. Multiple Risk Factors for Hepatocellular Carcinoma (HCC) among Asian Americans: Implications for Intervention. [abstract]. In: Proceedings of the Ninth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2016 Sep 25-28; Fort Lauderdale, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(2 Suppl):Abstract nr B80.

The Hepatitis Viral Status in Patients With Hepatocellular Carcinoma: a Study of 3843 Patients From Taiwan Liver Cancer Network.

Hepatocellular carcinoma (HCC) is the leading cancer death in Taiwan. Chronic viral hepatitis infections have long been considered as the most important risk factors for HCC in Taiwan. The previously published reports were either carried out by individual investigators with small patient numbers or by large endemic studies with limited viral marker data. Through collaboration with 5 medical centers across Taiwan, Taiwan liver cancer network (TLCN) was established in 2005. All participating centers followed a standard protocol to recruit liver cancer patients along with their biosamples and clinical data. In addition, detailed viral marker analysis for hepatitis B virus (HBV) and hepatitis C virus (HCV) were also performed. This study included 3843 HCC patients with available blood samples in TLCN (recruited from November 2005 to April 2011). There were 2153 (56.02%) patients associated with HBV (HBV group); 969 (25.21%) with HCV (HCV group); 310 (8.07%) with both HBV and HCV (HBV+HCV group); and 411 (10.69%) were negative for both HBV and HCV (non-B non-C group). Two hundred two of the 2463 HBV patients (8.20%) were HBsAg(-), but HBV DNA (+). The age, gender, cirrhosis, viral titers, and viral genotypes were all significantly different between the above 4 groups of patients. The median age of the HBV group was the youngest, and the cirrhotic rate was lowest in the non-B non-C group (only 25%). This is the largest detailed viral hepatitis marker study for HCC patients in the English literatures. Our study provided novel data on the interaction of HBV and HCV in the HCC patients and also confirmed that the HCC database of TLCN is highly representative for Taiwan and an important resource for HCC research.

Magnetic Resonance Imaging in Diagnosis and Monitoring of Hepatocellular Carcinoma in Liver Transplantation: A Comprehensive Review.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. One of the most important risk factors of HCC is cirrhosis. The optimal treatment of HCC is liver transplantation, since it treats both the underlying cirrhosis and the cancer. Patients that have risk factors should be included in surveillance programs since HCC can be cured only during the early stages. Surveillance can be performed by ultrasonography (US), which is an inexpensive, non-invasive, and widely available technique, but it is considered to have a low sensitivity. If a suspicious lesion is detected on US exam, computerized tomography (CT) or magnetic resonance imaging (MRI) can be used to further evaluate this lesion. MRI is considered to be superior to CT because it has greater contrast resolution and tissue characterization. In this article, we present a review of MRI for HCC in liver transplantation (LT) with a focus on characteristic MR features of this tumor and current guidelines.

Nonalcoholic fatty liver disease and hepatocellular carcinoma

The fastest growing cause of cancer-related death is hepatocellular carcinoma (HCC), which is at least partly attributable to the rising prevalence of non-alcoholic fatty liver disease. Non-alcoholic fatty liver disease (NAFLD) encompasses a broad spectrum of conditions, ranging from non-progressive bland steatosis to malignant transformation into hepatocellular cancer. The estimated annual HCC incidence in the progressive form of NAFLD – non-alcoholic steatohepatitis (NASH) – is about 0.3%. The risk of HCC development is higher in men and increases with age, more advanced fibrosis, progressive obesity, insulin resistance and diabetes mellitus. Studies on the molecular mechanism of HCC development in NAFLD have shown that hepatocarcinogenesis is associated with complex changes at the immunometabolic interface. In line with these clinical risk factors, administration of a choline-deficient high-fat diet to mice over a prolonged period results in spontaneous HCC development in a high percentage of animals. The role of altered insulin signaling in tumorigenesis is further supported by the observation that components of the insulin-signaling cascade are frequently mutated in hepatocellular cancer cells. These changes further enhance insulin-mediated growth and cell division of hepatocytes. Furthermore, studies investigating nuclear factor kappa B (NF-κB) signaling and HCC development allowed dissection of the complex links between inflammation and carcinogenesis. To conclude, NAFLD reflects an important risk factor for HCC, develops also in non-cirrhotic livers and is a prototypic cancer involving inflammatory and metabolic pathways. Strengths/weaknesses and summary of the translational potential of the messages in the paperThe systematic review summarizes findings from unbiased clinical and translational studies on hepatocellular cancer in non-alcoholic fatty liver disease. This provides a concise overview on the epidemiology, risk factors and molecular pathogenesis of the NAFL-NASH-HCC sequence. One limitation in the field is that few HCC studies stratify patients by underlying etiology, although the etiology of the underlying liver disease is an important co-determinant of clinical disease course and molecular pathogenesis. Molecular profiling of NAFL and associated HCC holds great translational potential for individualized surveillance, prevention and therapy.

Effects of interactions between environmental factors and KIF1B genetic variants on the risk of hepatocellular carcinoma in a Chinese cohort.

To examine the effect of the potential interaction between KIF1B variants (rs17401966 and rs3748578) and environmental factors on the risk of hepatocellular carcinoma (HCC) in a high-risk region in China. Three hundred and six patients with HCC and 306 hospital-based control participants residing in the Shunde region of Guangdong Province, China were enrolled. Clinical characteristics were collected by reviewing the complete medical histories from the patient archives, and epidemiological data were collected using a questionnaire and clinical examination. Two single nucleotide polymorphisms (SNPs) of KIF1B (rs17401966 and rs3748578) were chosen for the current study. All subjects were genotyped using a TaqMan real-time polymerase chain reaction. Multiplicative and additive logistic regression models were used to evaluate various gene-environment interactions. Smoking, frequent consumption of raw freshwater fish, hepatitis B virus (HBV) infection, and a family history of HCC were important risk factors for HCC in this population. Chronic infection with HBV was the most important environmental risk factor for HCC [odds ratio (OR) = 12.02; 95% confidence interval (95%CI): 6.02-24.00]. No significant association was found between the KIF1B variants alone and the risk of HCC. Nevertheless, a significant additive effect modification was observed between rs17401966 and alcohol consumption (P for additive interaction = 0.0382). Compared with non-drinkers carrying either the AG or GG genotype of rs17401966, individuals classified as alcohol consumers with the AA genotype of rs17401966 had a significantly increased risk of HCC (OR = 2.36; 95%CI: 1.49-3.74). The gene-environment interaction between the KIF1B rs17401966 variant and alcohol consumption may contribute to the development of HCC in Chinese individuals.

Predictors of hepatocellular carcinoma in patients with liver cirrhosis

Abstract Background and aim: Hepatocellular carcinoma (HCC) is one of the most important health problem, with an increasing incidence worldwide. The aim of the present study was to determine the factors that predict HCC occurrence in a group of patients with liver cirrhosis developed on various etiologies. Material and Methods: A total of 282 consecutive patients with liver cirrhosis seen between January 1, 2013 and July 31, 2014 were enrolled in a prospective study. Data from patient’s history, physical exams, laboratory tests and abdominal ultrasound were collected. Results: 282 patients were included in the study with a median age of 59.6 and a male/female ratio of 1.38/1; 12.41% (35) were diagnosed with HCC. Alcohol consumption was documented in 19 cases (54.28%), without statistical association (p=0.621), and 7 (20%) were smokers (p=0.403). According to etiological factors of liver cirrhosis: 7 (20%) had background B virus infection, 15 (42.85%) HCV infection and 11 (31.42%) cases incriminated other causes of cirrhosis (alcohol). Chi2 test identified a statistically significant association between the occurrence of HCC and viral etiology of cirrhosis (p = 0.001, r = 18,830). No statistical association was found between Child Pugh scoring of cirrhosis and HCC (p=0.774) and a statistically significant association but inversely proportional was identified between neoplasia and obesity (p=0.008, r= -0.157). Conclusion: In conclusion the viral etiology of liver cirrhosis is found to be an important risk factor for HCC, and liver cancer was inversely associated with nutritional status.