Low Hepatitis C Viral Load Predicts Better Long-Term Outcomes in Patients Undergoing Resection of Hepatocellular Carcinoma Irrespective of Serologic Eradication of Hepatitis C Virus

Junichi Shindoh, Kiyoshi Hasegawa, Yutaka Matsuyama, Yosuke Inoue, Takeaki Ishizawa, Taku Aoki, Yoshihiro Sakamoto, Yasuhiko Sugawara, and Norihiro Kokudo, University of Tokyo
Journal of Clinical Oncology (Impact Factor: 17.88). 11/2012; 31(6). DOI: 10.1200/JCO.2012.44.3234
Source: PubMed

ABSTRACT PURPOSEHepatitis C virus (HCV) infection has been recognized as a potent risk factor for the postoperative recurrence of hepatocellular carcinoma (HCC). However, little is known about the impact of HCV viral load on surgical outcomes. The study objective was to investigate clinical significance of HCV viral load on long-term outcomes of HCC. PATIENTS AND METHODS
Three hundred seventy patients who were classified as Child-Pugh class A and underwent curative liver resections for HCV-related HCC were divided into low and high viral load groups (≤ or > 5.3 log(10)IU/mL) based on the results of a minimum P value approach to predict moderate to severe activity of hepatitis; the clinical outcomes were then compared.ResultsThe 5-year recurrence-free survival rate was 36.1% in the low viral load group and 12.4% in the high viral load group (P < .001). The 5-year overall survival rate was 76.6% in the low viral load group and 57.7% in the high viral load group (P < .001). Multivariate analysis confirmed significant correlation between high viral load and tumor recurrence with a hazard ratio of 1.87 (95% CI, 1.41 to 2.48; P < .001). Subanalysis revealed that the favorable results in the low viral load group were not attributed to whether or not serologic eradication of HCV was obtained both in primary and recurrent lesions. CONCLUSION
Low HCV viral load predicts better long-term surgical outcomes in patients with HCC regardless of the serologic eradication of HCV.

  • [Show abstract] [Hide abstract]
    ABSTRACT: The variability in the association of host innate immune response to Hepatitis C virus (HCV) infection requires ruling out the possible role of host KIR and HLA genotypes in HCV-related disorders: therefore, we therefore explored the relationships between KIR/HLA genotypes and chronic HCV infection (CHC) as they relate to the risk of HCV-related hepatocarcinoma (HCC) or lymphoproliferative disease progression. We analyzed data from 396 HCV-positive patients with CHC (n = 125), HCC (118), and lymphoproliferative diseases (153), and 501 HCV-negative patients. All were HIV and HBV negative. KIR-SSO was used to determine the KIR typing. KIR2DL5 and KIR2DS4 variants were performed using PCR and GeneScan analysis. HLA/class-I genotyping was performed using PCR-sequence-based typing. The interaction between the KIR gene and ligand HLA molecules was investigated. Differences in frequencies were estimated using Fisher's exact test, and Cochran-Armitage trend test. The non-random association of KIR alleles was estimated using the linkage disequilibrium test. We found an association of KIR2DS2/KIR2DL2 genes, with the HCV-related lymphoproliferative disorders. Furthermore, individuals with a HLA-Bw6 KIR3DL1+ combination of genes showed higher risk of developing lymphoma than cryoglobulinemia. KIR2DS3 gene was found to be the principal gene associated with chronic HCV infection, while a reduction of HLA-Bw4 + KIR3DS1+ was associated with an increased risk of developing HCC. Our data highlight a role of the innate-system in developing HCV-related disorders and specifically KIR2DS3 and KIR2D genes demonstrated an ability to direct HCV disease progression, and mainly towards lymphoproliferative disorders. Moreover the determination of KIR3D/HLA combination of genes direct the HCV progression towards a lymphoma rather than an hepatic disease. In this contest IFN-α therapy, a standard therapy for HCV-infection and lymphoproliferative diseases, known to be able to transiently enhance the cytotoxicity of NK-cells support the role of NK cells to counterstain HCV-related and lymphoproliferative diseases.
    PLoS ONE 02/2015; 10(2):e0117420. DOI:10.1371/journal.pone.0117420 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hepatitis C is a strong prognostic factor for patients with hepatocellular carcinoma (HCC). Although liver resection and liver transplantation offer the chance of a cure for HCC, adequate management of co-existing infection with hepatitis C virus (HCV) is important to enable better long-term outcomes after surgery for HCV-related HCC. For patients undergoing liver resection, perioperative anti-viral treatment is recommended, since a decreased HCV viral load itself is reportedly associated with a lower tumor recurrence rate and a longer overall survival. For patients undergoing transplanatations for HCC complicated by end-stage liver disease, the post-transplant management of HCV infection is also necessary to prevent progressive graft injury caused by active hepatitis under the immunosuppressive condition that is needed after liver transplantation. Although only a few lines of solid evidence are available for postoperative antiviral treatment because of the limited indication and frequent adverse events caused by conventional high-dose combination interferon therapy, new direct acting anti-viral agents would enable interferon-free anti-viral treatment with a higher virologic response and minimal side effects.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hepatocellular carcinoma (HCC) is a common malignancy in the world. Although resection and various locoregional therapies can achieve eradication or complete ablation of small HCC, HCC recurrence after these therapies is still common. Although candidates for medical ablation usually exhibit compensated hepatic functional status, the frequent recurrence of HCC after successful ablation contributes to short survival. Therefore, attempts to prevent HCC recurrence are essential to prolong survival. Efforts in preventing HCC recurrence after curative therapies include prevention of early recurrence by improving liver immunity and eliminating microscopic tumor foci or micrometastases, and prevention of late recurrence by reducing the hepatitis activity and using antiviral therapies based on viral suppression/eradication. In HCC with vascular invasion, adjuvant transcatheter arterial chemoembolization should be considered to provide better control. Whether the adjuvant use of sorafenib may suppress microscopic tumor foci or micrometastases may be unveiled in the near future. This review article will update the algorithms, novel medication or study drugs in the prevention of HCC after curative therapies. © 2014 S. Karger AG, Basel.
    Digestive Diseases 01/2014; 32(6):747-54. DOI:10.1159/000368017 · 1.83 Impact Factor