Comparison of Postoperative Prognosis Among HBV-Related, HCV-Related, and non-HBV non-HCV Hepatocellular Carcinomas: A Systematic Review and Meta-analysis

Context: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, and different hepatitis viruses might affect the prognosis of patients with HCC. Objectives: This study aimed to reveal the differences in the postoperative prognosis of patients with hepatitis B virus-related HCC (HBV-HCC), hepatitis C virus-related HCC (HCV-HCC), and non-HBV non-HCV hepatocellular carcinoma (NBNC-HCC). Methods: The databases PubMed, Embase, Cochrane, Web of Science, and Scopus were searched for articles published until April 2022. Stata software version 12 and Review Manager version 5.4 were used to conduct the meta-analysis, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was adopted in this study. Results: In the present study, 26 papers on a total of 20381 participants who met the inclusion criteria were analyzed. The 5-year overall survival in the HBV-HCC and HCV-HCC groups was lower than in the NBNC-HCC group (HBV-HCC vs. NBNC-HCC, P = 0.005; HCV-HCC vs. NBNC-HCC, P = 0.001). Patients with HBV-HCC and HCV-HCC had worse 5-year recurrence-free survival than patients with NBNC-HCC (HBV-HCC vs. NBNC-HCC, P = 0; HCV-HCC vs. NBNC-HCC, P = 0). In addition, the 5-year recurrence-free rate in the HCV-HCC group was lower than in the HBV-HCC group (P = 0). The observed association between serum alpha-fetoprotein levels and the postoperative prognosis was inconsistent in different subgroups. Conclusions: Patients with NBNC-HCC had a significantly better postoperative prognosis than those with virus-related HCC. The alpha-fetoprotein levels significantly correlated with the postoperative prognosis of patients with HCC.

[1]  M. Schwartz,et al.  Outcomes Of Transplantation For HBV- Vs. HCV-Related HCC: Impact Of DAA HCV Therapy In A National Analysis Of >20,000 Patients , 2021, HPB.

[2]  Shinya Sato,et al.  Molecular Signature and Immune Landscape of HCV-Associated Hepatocellular Carcinoma (HCC): Differences and Similarities with HBV-HCC , 2021, Journal of hepatocellular carcinoma.

[3]  A. Jemal,et al.  Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries , 2021, CA: a cancer journal for clinicians.

[4]  E. Duffell,et al.  Hospital discharges of hepatocellular carcinoma and non-alcohol related cirrhosis in the EU/EEA and United Kingdom: a descriptive analysis of 2004–2015 data , 2020, Infectious diseases.

[5]  Shusen Zheng,et al.  Systematic review: risk prediction models for recurrence of hepatocellular carcinoma after liver transplantation , 2020, Transplant international : official journal of the European Society for Organ Transplantation.

[6]  D. Pinato,et al.  The systemic inflammatory response as a source of biomarkers and therapeutic targets in hepatocellular carcinoma , 2019, Liver international : official journal of the International Association for the Study of the Liver.

[7]  M. Ho,et al.  Androgen Receptor Enhances Hepatic Telomerase Reverse Transcriptase Gene Transcription After Hepatitis B Virus Integration or Point Mutation in Promoter Region , 2019, Hepatology.

[8]  S. Anticoli,et al.  Sex-Dependent Outcome of Hepatitis B and C Viruses Infections: Synergy of Sex Hormones and Immune Responses? , 2018, Front. Immunol..

[9]  A. Singal,et al.  Hepatitis C Virus and Hepatocellular Carcinoma: A Narrative Review , 2017, Journal of clinical and translational hepatology.

[10]  S. Friedman,et al.  Risk factors and prevention of hepatocellular carcinoma in the era of precision medicine. , 2017, Journal of hepatology.

[11]  T. Gocho,et al.  Clinical Features and Outcome of Surgical Patients with Non-B Non-C Hepatocellular Carcinoma. , 2017, Anticancer Research.

[12]  V. Wong,et al.  Concurrent fatty liver increases risk of hepatocellular carcinoma among patients with chronic hepatitis B , 2017, Journal of gastroenterology and hepatology.

[13]  Y. Ohkura,et al.  Long-term prognosis after resection of cryptogenic hepatocellular carcinoma , 2015, BMC Surgery.

[14]  N. Yamanaka,et al.  Clinicopathological characteristics of hepatitis B surface antigen-negative and hepatitis C antibody-negative hepatocellular carcinoma. , 2015, Oncology letters.

[15]  J. Shindoh,et al.  Postoperative Outcomes for Patients with Non-B Non-C Hepatocellular Carcinoma: A Subgroup Analysis of Patients with a History of Hepatitis B Infection , 2015, Annals of Surgical Oncology.

[16]  T. Utsunomiya,et al.  A comparison of the surgical outcomes among patients with HBV-positive, HCV-positive, and non-B non-C hepatocellular carcinoma: a nationwide study of 11,950 patients. , 2015, Annals of surgery.

[17]  R. Chung,et al.  Hepatitis C virus-associated cancer. , 2015, Annual review of pathology.

[18]  Ping Yi,et al.  Analysis on Postoperative Efficacy of Radical Hepatectomy for Patients with Non-HBV/HCV Hepatocellular Carcinoma. , 2015, Asian Pacific journal of cancer prevention : APJCP.

[19]  Y. Maehara,et al.  Clinicopathologic Features and Outcomes of Non-B, Non-C Hepatocellular Carcinoma After Hepatectomy , 2015, Annals of Surgical Oncology.

[20]  Y. Maehara,et al.  Surgical Outcomes of Hepatic Resection for Hepatitis B Virus Surface Antigen-Negative and Hepatitis C Virus Antibody-Negative Hepatocellular Carcinoma , 2015, Annals of Surgical Oncology.

[21]  M. Schwartz,et al.  Differences in Surgical Outcomes Between Hepatitis B- and Hepatitis C–Related Hepatocellular Carcinoma: A Retrospective Analysis of a Single North American Center , 2014, Annals of surgery.

[22]  A. Boonstra,et al.  The role of Kupffer cells in hepatitis B and hepatitis C virus infections. , 2014, Journal of hepatology.

[23]  P. Pineau,et al.  Influence of hepatitis viruses on clinicopathological profiles and long-term outcome in patients undergoing surgery for hepatocellular carcinoma. , 2014, Hepatobiliary & pancreatic diseases international : HBPD INT.

[24]  Tomomi Yamada,et al.  Clinicopathological Factors Affecting Survival and Recurrence after Initial Hepatectomy in Non-B Non-C Hepatocellular Carcinoma Patients with Comparison to Hepatitis B or C Virus , 2014, BioMed research international.

[25]  Frcsc Paul D. Greig MD,et al.  Impact of Viral Hepatitis on Outcomes after Liver Resection for Hepatocellular Carcinoma: Results from a North American Center , 2014, Annals of Surgical Oncology.

[26]  T. Wakasa,et al.  Comparison of Clinical Characteristics and Survival after Surgery in Patients with Non-B and Non-C Hepatocellular Carcinoma and Hepatitis Virus-Related Hepatocellular Carcinoma , 2013, Journal of Cancer.

[27]  P. Balladur,et al.  Infection with Hepatitis C Virus is an Adverse Prognostic Factor after Liver Resection for Early-stage Hepatocellular Carcinoma , 2013, Annals of Surgical Oncology.

[28]  A. Kwon,et al.  Clinicopathologic characteristics of patients with non-B non-C hepatitis virus hepatocellular carcinoma after hepatectomy. , 2012, American journal of surgery.

[29]  M. Imamura,et al.  Recent trend of clinical features in patients with hepatocellular carcinoma , 2012, Hepatology research : the official journal of the Japan Society of Hepatology.

[30]  B. Li,et al.  Influence of viral hepatitis status on prognosis in patients undergoing hepatic resection for hepatocellular carcinoma: a meta-analysis of observational studies , 2011, World journal of surgical oncology.

[31]  D. Largaespada,et al.  Modeling hepatitis B virus X–induced hepatocellular carcinoma in mice with the sleeping beauty transposon system , 2011, Hepatology.

[32]  G. Chau,et al.  A Comparison of Prognosis between Patients with Hepatitis B and C Virus-related Hepatocellular Carcinoma Undergoing Resection Surgery , 2011, World Journal of Surgery.

[33]  S. Costantini,et al.  Targeting the inflammation in HCV-associated hepatocellular carcinoma: a role in the prevention and treatment , 2010, Journal of Translational Medicine.

[34]  A. Stang.  Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses , 2010, European Journal of Epidemiology.

[35]  Jiamei Yang,et al.  Repeat hepatectomy for recurrent hepatocellular carcinoma: a local experience and a systematic review , 2010, World journal of surgical oncology.

[36]  Haitao Zhao,et al.  Postoperative adjuvant antiviral therapy for hepatitis B/C virus-related hepatocellular carcinoma: a meta-analysis. , 2010, World journal of gastroenterology.

[37]  L. Capussotti,et al.  Role of hepatitis B virus infection in the prognosis after hepatectomy for hepatocellular carcinoma in patients with cirrhosis: a Western dual-center experience. , 2009, Archives of Surgery.

[38]  J. Ioannidis,et al.  The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration , 2009, BMJ : British Medical Journal.

[39]  S. Caldwell,et al.  The epidemiology of hepatocellular cancer: from the perspectives of public health problem to tumor biology , 2009, Journal of Gastroenterology.

[40]  T. Nagayasu,et al.  Clinicopathological characteristics of patients with hepatocellular carcinoma after hepatectomy: Relationship with status of viral hepatitis , 2007, Journal of surgical oncology.

[41]  Yu Qin,et al.  Comparison of surgical outcomes for small hepatocellular carcinoma in patients with hepatitis B versus hepatitis C: A Chinese experience , 2007, Journal of gastroenterology and hepatology.

[42]  T. Pawlik,et al.  Hepatitis serology predicts tumor and liver-disease characteristics but not prognosis after resection of hepatocellular carcinoma , 2004, Journal of Gastrointestinal Surgery.

[43]  H. Eguchi,et al.  Risk of Recurrence in a Long-term Follow-up After Surgery in 417 Patients With Hepatitis B- or Hepatitis C-Related Hepatocellular Carcinoma , 2006, Annals of surgery.

[44]  Chien-Hung Chen,et al.  Comparison of recurrence after hepatic resection in patients with hepatitis B vs. hepatitis C‐related small hepatocellular carcinoma in hepatitis B virus endemic area , 2005, Liver international : official journal of the International Association for the Study of the Liver.

[45]  Shohachi Suzuki,et al.  Clinicopathological features of hepatocellular carcinomas (HCCs) arising in patients without chronic viral infection or alcohol abuse: a retrospective study of patients undergoing hepatic resection , 2005, Journal of Gastroenterology.

[46]  Y. Shiratori,et al.  Clinical features of patients with HCC who are negative for both HBV and HCV markers. , 2003, Hepato-gastroenterology.

[47]  S. Thompson,et al.  Quantifying heterogeneity in a meta‐analysis , 2002, Statistics in medicine.

[48]  H. Asakura,et al.  High viral loads, serum alanine aminotransferase and gender are predictive factors for the development of hepatocellular carcinoma from viral compensated liver cirrhosis , 2001, Journal of gastroenterology and hepatology.

[49]  G. Chau,et al.  Clinicopathologic and prognostic differences between patients with hepatitis B- and C-related resectable hepatocellular carcinoma. , 2001, Journal of the Formosan Medical Association = Taiwan yi zhi.

[50]  Charles M. Miller,et al.  Comparison of Surgical Outcomes for Hepatocellular Carcinoma in Patients With Hepatitis B Versus Hepatitis C: A Western Experience , 2000, Annals of Surgical Oncology.

[51]  K. Matsushita,et al.  Viral serostatus and coexisting inflammatory activity affect metachronous carcinogenesis after hepatectomy for hepatocellular carcinoma. A further report , 2000, Journal of Gastroenterology.

[52]  J. Tang,et al.  Hepatitis viral status in patients undergoing liver resection for hepatocellular carcinoma , 1999, The British journal of surgery.

[53]  D. Dhar,et al.  Different intrahepatic recurrence rate after resection of hepatocellular carcinoma associated with chronic hepatitis B and C , 1998 .

[54]  L. Jeng,et al.  Surgical results in patients with dual hepatitis B- and C-related hepatocellular carcinoma compared with hepatitis B- or C-related hepatocellular carcinoma. , 1998, Surgery.

[55]  N. Yamanaka,et al.  Correlation of hepatitis virus serologic status with clinicopathologic features in patients undergoing hepatectomy for hepatocellular carcinoma , 1997, Cancer.

[56]  S. Kawasaki,et al.  Comparison of the characteristics of hepatocellular carcinoma between hepatitis B and C viral infection: Tumor multicentricity in cirrhotic liver with hepatitis C , 1996, Hepatology.

[57]  K. Shirabe,et al.  A comparison of the surgical results in patients with hepatitis B versus hepatitis C‐related hepatocellular carcinoma , 1995, Hepatology.