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13 pages, 6382 KiB

Open AccessArticle

Above-Standard Survival of Hepatocellular Carcinoma as the Final Outcome of Comprehensive Hepatology Care Programs in a Remote HCV-Endemic Area

by Wei-Ru Cho, Hui-Ling Huang, Nien-Tzu Hsu, Tung-Jung Huang and Te-Sheng Chang

Viruses 2023, 15(3), 786; https://doi.org/10.3390/v15030786 - 19 Mar 2023

Viewed by 1405

Abstract

Early detection and prompt linkage to care are critical for hepatocellular carcinoma (HCC) care. Chang Gung Memorial Hospital (CGMH) Yunlin branch, a local hospital in a rural area, undertakes health checkup programs in addition to its routine clinical service. Patients with HCC are [...] Read more.

Early detection and prompt linkage to care are critical for hepatocellular carcinoma (HCC) care. Chang Gung Memorial Hospital (CGMH) Yunlin branch, a local hospital in a rural area, undertakes health checkup programs in addition to its routine clinical service. Patients with HCC are referred to CGMH Chiayi branch, a tertiary referral hospital, for treatment. This study enrolled 77 consecutive patients with newly diagnosed HCCs between 2017 and 2022, with a mean age of 65.7 ± 11.1 years. The screening group included HCC patients detected through health checkups, and those detected by routine clinical service served as the control group. Compared to the 24 patients in the control group, the 53 patients in the screening group had more cases with early stage cancer (Barcelona Clinic Liver Cancer or BCLC stage 0 + A 86.8% vs. 62.5%, p = 0.028), better liver reserve (albumin–bilirubin or ALBI grade I 77.3% vs. 50%, p = 0.031) and more prolonged survival (p = 0.036). The median survival rates of the 77 patients were >5 years, 3.3 years, and 0.5 years in the BCLC stages 0 + A, B, and C, respectively, which were above the expectations of the BCLC guideline 2022 for stages 0, A, and B. This study provides a model of HCC screening and referral to high-quality care in remote viral-hepatitis-endemic areas. Full article

(This article belongs to the Special Issue Hepatitis-Associated Liver Cancer)

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15 pages, 1603 KiB

Open AccessArticle

Incidence and Risk Factors of Hepatocellular Carcinoma in Patients with Chronic Hepatitis C Treated with Direct-Acting Antivirals

by Cassia Leal, Jorge Strogoff-de-Matos, Carmem Theodoro, Rosangela Teixeira, Renata Perez, Thais Guaraná, Paulo de Tarso Pinto, Tatiana Guimarães and Solange Artimos

Viruses 2023, 15(1), 221; https://doi.org/10.3390/v15010221 - 13 Jan 2023

Cited by 3 | Viewed by 1775

Abstract

Background: Conflicting data regarding the incidence of hepatocellular carcinoma (HCC) after cure of HCV infection with direct-acting antivirals (DAAs) remains. We investigated the incidence and risk factors to HCC after treatment with DAAs followed up for five years. Methods: A total of 1075 [...] Read more.

Background: Conflicting data regarding the incidence of hepatocellular carcinoma (HCC) after cure of HCV infection with direct-acting antivirals (DAAs) remains. We investigated the incidence and risk factors to HCC after treatment with DAAs followed up for five years. Methods: A total of 1075 HCV patients ≥ 18 years were treated with DAAs from 2015 to 2019 and followed until 2022. Ultrasonography was performed before DAAs and each 6 months thereafter. Results: Of the total, 51/1075 (4.7%) developed HCC in the median of 40 (IQR 25–58) months: 26/51 (51%) male, median age 60 (IQR 54–66) years, alpha-fetoprotein (AFP) 12.2 (IQR 6.1–18.8) ng/mL, 47/51 (92.1%) cirrhotic 78.7%, 8/51 (15.7%) without sustained virological response (SVR). Seventeen percent had non-characterized nodules before DAAs. Cumulative HCC incidence was 5.9% in 5 years. Overall incidence was 1.46/100 patient-years (PY) (95% CI = 1.09–1.91), being 2.31/100 PY (95% CI = 1.70–3.06), 0.45/100 PY (95% CI = 0.09–1.32) and 0.20/100 PY (95% CI 0.01–1.01) in METAVIR F4, F3 and F2, respectively, and the main risks to HCC were non-characterized nodule, cirrhosis, high AFP values and non-SVR. Conclusion: HCV cure reduced risk for HCC, but it still occurred particularly in cirrhotic patients. Some risk factors can be identified to predict early HCC diagnosis. Full article

(This article belongs to the Special Issue Hepatitis-Associated Liver Cancer)

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13 pages, 2845 KiB

Open AccessArticle

Secular Trends of Clinical Characteristics and Survival of Hepatocellular Carcinoma in Taiwan from 2011 to 2019

by Kwong-Ming Kee, Chien-Hung Chen, Jui-Ting Hu, Yi-Hsiang Huang, Tsang-En Wang, Gar-Yang Chau, Kuo-Hsin Chen, Yao-Li Chen, Chih-Che Lin, Chien-Fu Hung, Shiu-Feng Huang, Tsang-Wu Liu, Hsiu-Ying Ku, Bing-Shen Huang, Yi-Pin Wang, Hui-Ping Tseng, Chun-Ju Chiang and Sheng-Nan Lu

Viruses 2023, 15(1), 126; https://doi.org/10.3390/v15010126 - 31 Dec 2022

Cited by 3 | Viewed by 2284

Abstract

Hepatocellular carcinoma (HCC) is a major cause of cancer death in Taiwan, and in the past 30–40 years, Taiwan has been committed to its prevention and treatment. We aimed to investigate the secular trends of characteristics and the survival of HCC in recent [...] Read more.

Hepatocellular carcinoma (HCC) is a major cause of cancer death in Taiwan, and in the past 30–40 years, Taiwan has been committed to its prevention and treatment. We aimed to investigate the secular trends of characteristics and the survival of HCC in recent decades after making increased efforts. Between 2011 and 2019, a total of 73,817 cases were enrolled from the TCR database. The overall male-to-female ratio was 7/3. The overall, male and female mean ages increased from 63.8 to 66.1 years, 62.0 to 64.3 years and 68.3 to 70.4 years, respectively. After dividing by viral etiologies and gender, the mean age showed increasing trends in all subgroups. The proportions of HBV-HCC, HCV-HCC, HBV+HCV-HCC and Non-HBV+non-HCV-HCC were 48.3%, 25.2%, 5.3% and 21.3% in males, compared with 25.5%, 48.6%, 5.3% and 20.5% in females, respectively. The 5-year survival rates of BCLC stages 0, A, B, C and D were 70%, 58%, 34%, 11% and 4%, respectively. The proportion of BCLC stage 0 increased from 6.2% to 11.3%. Multivariate analysis showed that being female, older age, diagnostic year, BCLC stages, hospital level, body mass index, smoking, alcohol consumption, AFP, Child–Pugh classification and HBV/HCV status were independent predictors for survival. In recent decades, the overall survival of HCC in Taiwan has been improving and might be partly associated with increased BCLC 0 and Child–Pugh A patients, while with the consequent age of patients increasing over time. The proportion of viral-related HCC is decreasing, while nonviral-related HCC is increasing. Full article

(This article belongs to the Special Issue Hepatitis-Associated Liver Cancer)

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9 pages, 437 KiB

Open AccessArticle

HBcrAg Predicts Hepatocellular Carcinoma Development in Chronic B Hepatitis Related Liver Cirrhosis Patients Undergoing Long-Term Effective Anti-Viral

by Kuo-Chin Chang, Ming-Tsung Lin, Jing-Houng Wang, Chao-Hung Hung, Chien-Hung Chen, Sherry Yueh-Hsia Chiu and Tsung-Hui Hu

Viruses 2022, 14(12), 2671; https://doi.org/10.3390/v14122671 - 29 Nov 2022

Cited by 3 | Viewed by 1502

Abstract

Hepatitis B core-related antigen (HBcrAg) is a predictor of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. Studies on anti-viral therapy have shown that the use of NUC therapy in HBV patients could reduce the incidence of HCC. However, the incidence of [...] Read more.

Hepatitis B core-related antigen (HBcrAg) is a predictor of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients. Studies on anti-viral therapy have shown that the use of NUC therapy in HBV patients could reduce the incidence of HCC. However, the incidence of HCC continues to increase after long-term anti-viral therapy. The relationship between HBcrAg and HCC development in CHB-related liver cirrhosis (LC) patients undergoing long-term anti-viral therapy is still unclear. This study enrolled 1108 treatment-naïve CHB patients diagnosed with HBV-related LC receiving NUC therapy from April 1999 to February 2015. The baseline biomarkers, disease history, and following results were collected by the hospital. Among the 1108 patients, 219 developed HCC within a median follow-up period of 6.85 years. A multivariable Cox regression model was used, with adjustment for age, gender, FIB-4, DM, and HBsAg-HQ. The adjusted hazard ratios for the HBcrAg tertile levels were 1.70 (95%CI: 1.21, 2.39) and 2.14 (95%CI: 1.50, 3.05) for levels 3.4–4.9 and >4.9 logU/mL, respectively, compared with levels ≤3.4. The effect of the HBcrAg level on HCC incidence was found to be significantly modified by HBsAg-HQ, where lower HBsAg-HQ (≤ 3) values were associated with a significantly higher risk, but HBsAg-HQ levels >3 were not. Our results highlight that, after adjustment for potential confounding factors, patients with CHB-related LC and higher HBcrAg levels are at significant risk for HCC development, even while undergoing long-term effective anti-viral therapy. The HBcrAg level is therefore an independent risk factor for HCC development, especially for patients with HBsAg-HQ levels <3. Full article

(This article belongs to the Special Issue Hepatitis-Associated Liver Cancer)

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9 pages, 1022 KiB

Open AccessArticle

Comparisons of Viral Etiology and Outcomes of Hepatocellular Carcinoma Undergoing Liver Resection between Taiwan and Vietnam

by Song-Huy Nguyen-Dinh, Wei-Feng Li, Yueh-Wei Liu, Chih-Chi Wang, Yen-Hao Chen, Jing-Houng Wang and Chao-Hung Hung

Viruses 2022, 14(11), 2571; https://doi.org/10.3390/v14112571 - 20 Nov 2022

Viewed by 1554

Abstract

Epidemiologic data have suggested that etiologic variations of hepatocellular carcinoma (HCC) exist in different geographic areas, and might be associated with different outcomes. We compared the viral etiology, clinicopathological characteristics and surgical outcomes between 706 Taiwanese and 1704 Vietnamese patients with HCC undergoing [...] Read more.

Epidemiologic data have suggested that etiologic variations of hepatocellular carcinoma (HCC) exist in different geographic areas, and might be associated with different outcomes. We compared the viral etiology, clinicopathological characteristics and surgical outcomes between 706 Taiwanese and 1704 Vietnamese patients with HCC undergoing liver resection. Vietnamese patients had a significantly higher ratio of hepatitis B virus (HBV) (p < 0.001) and a lower ratio of hepatitis C virus (HCV) (p < 0.001) and non-B non-C than Taiwanese patients. Among patients with HBV or non-B non-C, the mean age was younger in Vietnam than in Taiwan (p < 0.001, p = 0.001, respectively). The HCC patients in Vietnam had significantly higher serum alpha-fetoprotein (AFP) levels (p < 0.001), larger tumors (p < 0.001), and a higher ratio of macrovascular invasion (p < 0.001) and extrahepatic metastasis (p < 0.001), compared to those in Taiwan. Patients treated in Vietnam had a higher tumor recurrent rate (p < 0.001), but no difference in overall survival was found between both groups. In subgroup analysis, the recurrent rate of HCC was the highest in patients with dual HBV/HCV, followed by HCV or HBV, and non-B non-C (p < 0.001). In conclusion, although the viral etiology and clinicopathological characteristics of HCC differed, postoperative overall survival was comparable between patients in Taiwan and Vietnam. Full article

(This article belongs to the Special Issue Hepatitis-Associated Liver Cancer)

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14 pages, 1251 KiB

Open AccessArticle

Higher Risk of Tumor Recurrence in NASH-Related Hepatocellular Carcinoma Following Curative Resection

by Shih-Chieh Chien, Yih-Jyh Lin, Chun-Te Lee, Yen-Cheng Chiu, Tsung-Ching Chou, Hung-Chih Chiu, Hung-Wen Tsai, Che-Min Su, Tsung-Han Yang, Hsueh-Chien Chiang, Wei-Chu Tsai, Kai-Chun Yang and Pin-Nan Cheng

Viruses 2022, 14(11), 2427; https://doi.org/10.3390/v14112427 - 31 Oct 2022

Cited by 2 | Viewed by 1441

Abstract

Background: The outcomes for patients with NASH-related HCC after curative resection have not been clarified. This study compared the overall survival (OS), time-to-tumor recurrence (TTR), and recurrence-free survival (RFS) associated with NASH-related HCC and virus-related HCC after resection. Methods: Patients with HCC who [...] Read more.

Background: The outcomes for patients with NASH-related HCC after curative resection have not been clarified. This study compared the overall survival (OS), time-to-tumor recurrence (TTR), and recurrence-free survival (RFS) associated with NASH-related HCC and virus-related HCC after resection. Methods: Patients with HCC who underwent curative resection were retrospectively enrolled. Baseline characteristics, including disease etiologies and clinical and tumor features, were reviewed. The primary outcomes were OS, TTR, and RFS. Results: Two hundred and six patients were enrolled (HBV: n = 121, HCV: n = 54, NASH: n = 31). Of those with virus-related HCC, 84.0% achieved viral suppression. In both the overall and propensity-score-matched cohorts, those with NASH-related HCC experienced recurrence significantly earlier than those with virus-related HCC (median TTR: 1108 days vs. non-reached; p = 0.03). Through multivariate analysis, NASH-related HCC (hazard ratio (HR), 2.27; 95% confidence interval (CI), 1.25–4.12) was independently associated with early recurrence. The unadjusted RFS rate of the NASH-related HCC group was lower than the virus-related HCC group. There was no difference in the OS between the two groups. Conclusions: NASH-related HCC was associated with earlier tumor recurrence following curative resection compared to virus-related HCC. Post-surgical surveillance is crucial for detecting early recurrence in patients with NASH-related HCC. Full article

(This article belongs to the Special Issue Hepatitis-Associated Liver Cancer)

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12 pages, 2127 KiB

Open AccessArticle

Effects of Achieving SVR on Clinical Characteristics and Surgical Outcomes in Patients Who Developed Early-Stage HCV-Related Hepatocellular Carcinoma and Received Curative Resection: Preoperative versus Postoperative SVR

by Po-Yao Hsu, Po-Cheng Liang, Ching-I Huang, Meng-Hsuan Hsieh, Yi-Shan Tsai, Tzu-Chun Lin, Ming-Lun Yeh, Chung-Feng Huang, Chih-Wen Wang, Tyng-Yuan Jang, Yi-Hung Lin, Zu-Yau Lin, Wan-Long Chuang and Chia-Yen Dai

Viruses 2022, 14(11), 2412; https://doi.org/10.3390/v14112412 - 31 Oct 2022

Cited by 3 | Viewed by 1597

Abstract

The high accessibility to healthcare and increasing awareness of hepatocellular carcinoma (HCC) surveillance after sustained virologic response (SVR) to HCV treatment allow early detection of operable HCC in Taiwan. However, the effects of achieving SVR on patient characteristics and surgical outcomes after curative [...] Read more.

The high accessibility to healthcare and increasing awareness of hepatocellular carcinoma (HCC) surveillance after sustained virologic response (SVR) to HCV treatment allow early detection of operable HCC in Taiwan. However, the effects of achieving SVR on patient characteristics and surgical outcomes after curative resection remain elusive. We aimed to compare the clinical presentation and postoperative prognosis among patients with early-stage HCV-related HCC and different viral status. We retrospectively analyzed 208 patients with BCLC stage 0 or A-HCC, including 44 patients who remained HCV viremic, 90 patients who developed HCC after achieving SVR (post-SVR HCC), and 74 patients who subsequently achieved SVR after resection. Patients with post-SVR HCC had a lower degree of hepatitis and better liver function than those who achieved SVR or remained viremic after resection. Notably, 75.6% of patients with post-SVR HCC did not have cirrhosis. Patients with post-SVR HCC and those achieving SVR after resection exhibited comparable recurrence rates and recurrence-free survival, while patients with persistent viremia had the worst surgical outcomes. We concluded that patients with post-SVR HCC had a better liver function but similar surgical outcomes compared with patients who achieved SVR after resection. The low prevalence of cirrhosis in patients with post-SVR HCC highlights the importance of regular surveillance after SVR. Full article

(This article belongs to the Special Issue Hepatitis-Associated Liver Cancer)

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11 pages, 2340 KiB

Open AccessArticle

Application and Impact of Antiviral Therapy for Patients with HBV-Related Hepatocellular Carcinoma Receiving Sorafenib and Lenvatinib Treatment

by I-Cheng Lee, Pei-Chang Lee, Yee Chao, Chen-Ta Chi, Chi-Jung Wu, Yi-Ping Hung, Chien-Wei Su, Ming-Chih Hou and Yi-Hsiang Huang

Viruses 2022, 14(11), 2355; https://doi.org/10.3390/v14112355 - 26 Oct 2022

Cited by 3 | Viewed by 1577

Abstract

Overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC) has improved in the era of multi-line sequential therapy. The application of antiviral therapy and its impact on survival for patients with HBV-related HCC needs to be reassessed. The aim of this study [...] Read more.

Overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC) has improved in the era of multi-line sequential therapy. The application of antiviral therapy and its impact on survival for patients with HBV-related HCC needs to be reassessed. The aim of this study was to evaluate the application and impact of antiviral therapy on survival for patients with HBV-related HCC receiving tyrosine kinase inhibitor (TKI) therapy. Patients with advanced HBV-related HCC treated with sorafenib or lenvatinib as first-line therapy with (n = 377) and without (n = 182) nucleos(t)ide analogue (NUC) therapy were retrospectively enrolled. Prognostic factors of OS were evaluated. Secular trends in the increased application of NUC therapy and improved survival were observed in the last decade. The HBV reactivation rate in patients without NUC therapy was 6.6%. By multivariate analysis, baseline low HBV viral load, achieving undetectable HBV DNA after TKI therapy, and ability to receive second-line therapy were found to be independent predictors of OS. In subgroup patients with NUC therapy, starting NUC before TKI was associated with a better OS. In conclusion, the application of antiviral therapy for patients with HBV-related HCC receiving TKI therapy has increased over time. Achieving complete virological suppression may contribute to a better OS in patients with advanced HBV-related HCC. Full article

(This article belongs to the Special Issue Hepatitis-Associated Liver Cancer)

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14 pages, 1867 KiB

Open AccessArticle

Next-Generation Sequencing Analysis of CpG Methylation of a Tumor Suppressor Gene SHP-1 Promoter in Stable Cell Lines and HCV-Positive Patients

by Priya Devi, Katarina Engdahl, Tanel Punga and Anders Bergqvist

Viruses 2022, 14(11), 2352; https://doi.org/10.3390/v14112352 - 26 Oct 2022

Viewed by 1871

Abstract

Hepatitis C virus (HCV) is the major causative pathogen associated with hepatocellular carcinoma and liver cirrhosis. The main virion component, the Core (C) protein, is involved in multiple aspects of HCV pathology including oncogenesis and immune evasion. In this study, we established a [...] Read more.

Hepatitis C virus (HCV) is the major causative pathogen associated with hepatocellular carcinoma and liver cirrhosis. The main virion component, the Core (C) protein, is involved in multiple aspects of HCV pathology including oncogenesis and immune evasion. In this study, we established a next-generation bisulfite sequencing (NGS-BS) protocol to analyze the CpG methylation profile at the tumor suppressor gene SHP-1 P2 promoter as a model system. Our data show that HCV C protein expression in the immortalized T cells correlated with a specific CpG methylation profile at the SHP-1 P2. The NGS-BS on HCV-positive (HCV⁺) patient-derived PBMCs revealed a considerably different CpG methylation profile compared to the HCV C protein immortalized T cells. Notably, the CpG methylation profile was very similar in healthy and HCV⁺ PBMCs, suggesting that the SHP-1 P2 CpG methylation profile is not altered in the HCV⁺ individuals. Collectively, the NGS-BS is a highly sensitive method that can be used to quantitatively characterize the CpG methylation status at the level of individual CpG position and also allows the characterization of cis-acting effects on epigenetic regulation. Full article

(This article belongs to the Special Issue Hepatitis-Associated Liver Cancer)

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10 pages, 849 KiB

Open AccessArticle

Direct-Acting Antiviral Therapy for Hepatitis C Virus in Patients with BCLC Stage B/C Hepatocellular Carcinoma

by Shou-Wu Lee, Li-Shu Chen, Sheng-Shun Yang, Yi-Hsiang Huang and Teng-Yu Lee

Viruses 2022, 14(11), 2316; https://doi.org/10.3390/v14112316 - 22 Oct 2022

Cited by 1 | Viewed by 1506

Abstract

Background: The benefits of hepatitis C virus (HCV)eradication for hepatocellular carcinoma (HCC) patients in Barcelona Clinic Liver Cancer (BCLC) stage B/C remain uncertain. Methods: In this hospital-based cohort study, all HCV-infected patients with BCLC stage B/C HCC during the period January 2017 to [...] Read more.

Background: The benefits of hepatitis C virus (HCV)eradication for hepatocellular carcinoma (HCC) patients in Barcelona Clinic Liver Cancer (BCLC) stage B/C remain uncertain. Methods: In this hospital-based cohort study, all HCV-infected patients with BCLC stage B/C HCC during the period January 2017 to March 2021 were retrospectively screened, with 97 patients who had completed direct-acting antiviral (DAA) therapy being enrolled for final analysis. Results: In total, the sustained virological response (SVR) rate was 90.7%. In logistic regression analysis, progressive disease (PD) to prior tumor treatments was significantly associated with SVR failure (odds ratio 5.59, 95% CI 1.30–24.06, p = 0.021). Furthermore, the overall survival (OS) rate was significantly higher in the SVR group than that in the non-SVR group (1-year OS: 87.5% vs. 57.1%, p = 0.001). SVR was found to be an independent factor related to OS (hazard ratio 8.42, 95% CI 2.93–24.19, p = 0.001). However, even upon achieving SVR, the OS rates in BCLC stage C or Child–Pugh stage B patients remained poor. Conclusions: In BCLC stage B/C HCC, DAA could achieve a high SVR rate except in those patients with PD to prior HCC treatments. SVR was related to improvements in OS; therefore, DAA therapy should be encouraged for patients diagnosed without a short life expectancy. Full article

(This article belongs to the Special Issue Hepatitis-Associated Liver Cancer)

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13 pages, 752 KiB

Open AccessArticle

Non-B, Non-C Hepatocellular Carcinoma in an HBV- and HCV-Endemic Area: A Community-Based Prospective Longitudinal Study

by Te-Sheng Chang, Nien-Tzu Hsu, Shu-Chuan Chen, I-Lin Hsu, Mei-Hsuan Lee and Sheng-Nan Lu

Viruses 2022, 14(5), 984; https://doi.org/10.3390/v14050984 - 07 May 2022

Cited by 4 | Viewed by 1878

Abstract

A large community cohort of adults who participated in a health screening program from 2003 to 2013 were prospectively analyzed for the risk factors of non-B, non-C (NBNC) hepatocellular carcinoma (HCC). The serostatus of hepatitis B and C of 52,642 participants was linked [...] Read more.

A large community cohort of adults who participated in a health screening program from 2003 to 2013 were prospectively analyzed for the risk factors of non-B, non-C (NBNC) hepatocellular carcinoma (HCC). The serostatus of hepatitis B and C of 52,642 participants was linked to the mortality and cancer registration data of the Health and Welfare Data Science Center, Ministry of Health and Welfare, Taiwan. During a median follow-up of 6 years, 35 of the 43,545 participants who were negative for both HBsAg and anti-HCV antibody developed HCC. Multivariate Cox regression analysis revealed that old age (hazard ratio, 95% CI: 1.058, 1.019–1.098, p = 0.003); male sex (2.446, 1.200–4.985, p = 0.014); high aspartate aminotransferase levels (6.816, 2.945–15.779, p < 0.001); fibrosis index based on four factor score (1.262, 1.154–1.381, p < 0.001); blood sugar (1.009, 1.002–1.015, p = 0.006); and alpha-fetoprotein ≥15 ng/mL (143.938, 43.094–480.760, p < 0.001) were independent risk factors for HCC. By contrast, triglyceride >150 mg/dL was associated with a decreased risk of HCC (0.216, 0.074–0.625, p = 0.005). This prospective community-based study provided insights into the potential HCC risk factors which may shed some light in HCC prevention and screening. Full article

(This article belongs to the Special Issue Hepatitis-Associated Liver Cancer)

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Review

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20 pages, 345 KiB

Open AccessReview

Genetic Susceptibility to Hepatocellular Carcinoma in Patients with Chronic Hepatitis Virus Infection

by Tsai-Hsuan Yang, Chi Chan, Po-Jiun Yang, Yu-Han Huang and Mei-Hsuan Lee

Viruses 2023, 15(2), 559; https://doi.org/10.3390/v15020559 - 17 Feb 2023

Cited by 6 | Viewed by 2226

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. The risk factors for HCC include chronic hepatitis B and C virus infections, excessive alcohol consumption, obesity, metabolic disease, and aflatoxin exposure. In addition to these viral and environmental risk [...] Read more.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths globally. The risk factors for HCC include chronic hepatitis B and C virus infections, excessive alcohol consumption, obesity, metabolic disease, and aflatoxin exposure. In addition to these viral and environmental risk factors, individual genetic predisposition is a major determinant of HCC risk. Familial clustering of HCC has been observed, and a hereditary factor likely contributes to the risk of HCC development. The familial aggregation may depend on a shared environment and genetic background as well as the interactions of environmental and genetic factors. Genome-wide association studies (GWASs) are one of the most practical tools for mapping the patterns of inheritance for the most common form of genomic variation, single nucleotide polymorphisms. This approach is practical for investigating genetic variants across the human genome, which is affected by thousands of common genetic variants that do not follow Mendelian inheritance. This review article summarizes the academic knowledge of GWAS-identified genetic loci and their association with HCC. We summarize the GWASs in accordance with various chronic hepatitis virus infection statuses. This genetic profiling could be used to identify candidate biomarkers to refine HCC screening and management by enabling individual risk-based personalization and stratification. A more comprehensive understanding of the genetic mechanisms underlying individual predisposition to HCC may lead to improvements in the prevention and early diagnosis of HCC and the development of effective treatment strategies. Full article

(This article belongs to the Special Issue Hepatitis-Associated Liver Cancer)

13 pages, 1738 KiB

Open AccessReview

Unraveling the Molecular Mechanisms Involved in HCV-Induced Carcinogenesis

by Tania Guadalupe Heredia-Torres, Ana Rosa Rincón-Sánchez, Sonia Amelia Lozano-Sepúlveda, Kame Galan-Huerta, Daniel Arellanos-Soto, Marisela García-Hernández, Aurora de Jesús Garza-Juarez and Ana María Rivas-Estilla

Viruses 2022, 14(12), 2762; https://doi.org/10.3390/v14122762 - 11 Dec 2022

Cited by 5 | Viewed by 2261

Abstract

Cancer induced by a viral infection is among the leading causes of cancer. Hepatitis C Virus (HCV) is a hepatotropic oncogenic positive-sense RNA virus that leads to chronic infection, exposing the liver to a continuous process of damage and regeneration and promoting hepatocarcinogenesis. [...] Read more.

Cancer induced by a viral infection is among the leading causes of cancer. Hepatitis C Virus (HCV) is a hepatotropic oncogenic positive-sense RNA virus that leads to chronic infection, exposing the liver to a continuous process of damage and regeneration and promoting hepatocarcinogenesis. The virus promotes the development of carcinogenesis through indirect and direct molecular mechanisms such as chronic inflammation, oxidative stress, steatosis, genetic alterations, epithelial-mesenchymal transition, proliferation, and apoptosis, among others. Recently, direct-acting antivirals (DAAs) showed sustained virologic response in 95% of cases. Nevertheless, patients treated with DAAs have reported an unexpected increase in the early incidence of Hepatocellular carcinoma (HCC). Studies suggest that HCV induces epigenetic regulation through non-coding RNAs, DNA methylation, and chromatin remodeling, which modify gene expressions and induce genomic instability related to HCC development that persists with the infection’s clearance. The need for a better understanding of the molecular mechanisms associated with the development of carcinogenesis is evident. The aim of this review was to unravel the molecular pathways involved in the development of carcinogenesis before, during, and after the viral infection’s resolution, and how these pathways were regulated by the virus, to find control points that can be used as potential therapeutic targets. Full article

(This article belongs to the Special Issue Hepatitis-Associated Liver Cancer)

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