Association Between Hepatitis B and Hepatocellular Carcinoma Recurrence in Patients Undergoing Liver Transplantation

Kıyıcı, Murat; Yılmaz, Merve; Akyıldız, Murat; Arıkan, Çiğdem; Ünal, Aydın; Sığırlı, Deniz; Nart, Denız; Yılmaz, Funda; Özacar, Tijen; Karasu, Zeki; Kilic, Murat

doi:10.1016/j.transproceed.2008.03.156

Cited by 26 publications

(28 citation statements)

References 31 publications

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“…Previous studies had shown similar overall survival rates in post‐OLT patients with HBV reinfection with or without HCC 25. Kiyici et al26 recently found no significant effect of HBV reinfection or HCC recurrence on overall survival in OLT patients. However, our analysis herein showed decreased cumulative survival for patients with HBV reinfection and with HCC recurrence.…”

Section: Discussionmentioning

confidence: 83%

Recurrence of hepatocellular carcinoma and hepatitis B reinfection in hepatitis B surface antigen-positive patients after liver transplantation

et al. 2009

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Hepatitis B virus (HBV) reinfection and recurrence of hepatocellular carcinoma (HCC) after orthotopic liver transplantation (OLT) are associated with increased graft failure and reduced patient survival. We evaluated the effects of both HCC recurrence and HBV reinfection on the long-term survival of these patients after OLT. One hundred seventy-five patients underwent OLT for HBV-related liver diseases and were the subjects of this retrospective study. We assessed risk factors for HBV reinfection, HCC recurrence, and survival post-OLT using univariate and multivariate analyses. During a mean follow-up of 43.0 Ϯ 42.0 months, 88 of 175 (50.3%) patients transplanted for HBV-related liver disease had HCC prior to OLT. Thirteen (14.8%) of these patients had HCC recurrence after OLT. The mean time for recurrence of HCC was 26.1 Ϯ 31.9 months. Twelve of 175 (6.9%) patients developed HBV reinfection after liver transplantation. The mean time for HBV reinfection was 28.7 Ϯ 26.4 months. Ten of these 12 (83.3%) patients had HCC prior to OLT, and 5 (50%) developed recurrence of HCC. On multivariate analyses, pre-OLT HCC and recurrence of HCC post-OLT were significantly associated with HBV reinfection after transplantation (P ϭ 0.031 and P Ͻ 0.001, respectively). HCC recurrence after OLT was associated with lymphovascular invasion (P Ͻ 0.001) and post-OLT chemotherapy (P Յ 0.001). The 3-and 5-year survival rates were significantly decreased in patients with HBV reinfection (P ϭ 0.007) and in patients with HCC recurrence after OLT (P ϭ 0.03). In conclusion, pre-OLT HCC and HCC recurrence after transplantation were associated with HBV reinfection and with decreased patient survival. Hepatitis B immunoglobulin and antiviral therapy was only partially effective in preventing HBV reinfection in patients with HCC recurrence. Liver Transpl 15:1525-1534, 2009. © 2009 AASLD. Received February 11, 2009 accepted July 14, 2009. Hepatitis B virus (HBV) is the principal cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide and is responsible for at least 500,000 deaths per year. 1Prior to the availability of immunoprophylaxis and antiviral agents, the outcome of liver transplantation for hepatitis B-related liver disease was poor, and this often led to HBV reinfection rates greater than 80% and mortality rates of 50% at 2 years.2 Prophylactic use of hepatitis B immunoglobulin (HBIG) along with the nucleoside analogue lamivudine has markedly decreased the reinfection rate of HBV by suppressing HBV replication through their synergistic effect. However, despite reports demonstrating the reduced risk of hepatitis B reinfection and improved survival of patients treated with dual prophylaxis after orthotopic liver transplantation (OLT) for HBV, approximately 10% of transplanted patients develop HBV reinfection.4 Factors associated with HBV reinfection include a high pre-OLT HBV DNA level, 5 hepatitis B e antigen positivity, 4 immunosuppression from steroids and from sys-

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Section: Discussionmentioning

confidence: 83%

Recurrence of hepatocellular carcinoma and hepatitis B reinfection in hepatitis B surface antigen-positive patients after liver transplantation

et al. 2009

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“…In total, 980 articles were initially identified from the literature search, but only 53 studies fulfilled the inclusion criteria (Fig. ) . There were four studies from one single Italian center, which included patients from overlapping study periods, and it was decided to include only the first two studies , in which the impact of CNIs and/or mTORi on HCC recurrence was evaluated.…”

Section: Resultsmentioning

confidence: 99%

“…Finally, two studies from the same center in Japan , both published in 2013, had overlapping study periods; in this case, we included the study with the longer study period (1999–2012 vs. 1999–2011). Thus, 42 studies providing data regarding immunosuppression regimen (CNIs or mTORi) and HCC recurrence were included in our analysis .…”

Section: Resultsmentioning

confidence: 99%

Mammalian target of rapamycin inhibitors are associated with lower rates of hepatocellular carcinoma recurrence after liver transplantation: a systematic review

et al. 2014

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SummaryCalcineurin inhibitors (CNIs) have been associated in a dose-dependent fashion with an increased risk of post-transplant hepatocellular carcinoma (HCC) recurrence. The mammalian target of rapamycin inhibitors (mTORi) (sirolimus/everolimus) might represent an alternative immunosuppressive regimen with antineoplastic effect. In the present systematic review, the association between mTORi and HCC recurrence after liver transplantation (LT) was evaluated and compared against that of CNIs-treated patients. In total, 3666 HCC liver transplant recipients from 42 studies met the inclusion criteria. Patients under CNIs developed HCC recurrence significantly more frequently, compared with patients under mTORi (448/3227 or 13.8% vs. 35/439 or 8%, P < 0.001), although patients treated with CNIs had a higher proportion of HCC within Milan criteria (74% vs. 69%) and lower rates of microvascular invasion, compared with mTORi-treated patients (22% vs. 44%) (P < 0.05). Patients on everolimus had significantly lower recurrence rates of HCC, compared with those on sirolimus or CNIs (4.1% vs. 10.5% vs. 13.8%, respectively, P < 0.05), but everolimus-treated recipients had shorter follow-up period (13 vs. 30 vs. 43.2 months, respectively) and more frequently been transplanted for HCC within Milan criteria (84% vs. 60.5% vs. 74%, respectively, P < 0.05). Our findings favor the use of mTORi instead of CNIs to control HCC recurrence after LT, but comparative studies with longer follow-up are needed for final conclusions.

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“…In addition to eliminating the premalignant liver before development of de novo HCC foci, liver transplantation can cure the underlying liver disease and restore normal liver function [1]. However, survival after transplantation for HCC was disappointing before the introduction of Milan criteria for selecting candidates for OLT [2].…”

Section: Introductionmentioning

confidence: 99%

High Hepatitis B Virus DNA Level in Serum before Liver Transplantation Increases the Risk of Hepatocellular Carcinoma Recurrence

Chen²,

Cai³

et al. 2011

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Aim: To analyze the relationship between hepatitis B virus (HBV) and hepatocellular carcinoma (HCC) recurrence in orthotopic liver transplantation (OLT) patients. Methods: 340 HBV patients with OLT were included in the study; among them were 148 patients with HBV-associated HCC. Results: HCC recurrence rates at 1, 3 and 5 years were 21, 29, and 46%, respectively. Exceeding Milan criteria (hazard ratio, HR = 12.35; 95% confidence interval, CI, 2.80–54.49; p = 0.001), HBV DNA level >5 log₁₀ copies/ml before transplant (HR = 2.45; 95% CI 1.10–5.45; p = 0.03) and HBV recurrence (HR = 2.27; 95% CI 1.10–4.75; p = 0.03) were significant independent predictors of HCC recurrence. HBV DNA >5 log₁₀ copies/ml before transplant (HR = 8.65; 95% CI 3.40–21.98; p < 0.001) and concomitance with HCC (HR = 2.79; 95% CI 1.33–5.87; p = 0.007) were predictors of HBV recurrence. Further stratified analysis showed that HBV recurrence was more prevalent in the HCC recurrence group (HR = 4.58; 95% CI 1.88–11.12; p = 0.001). Conclusions: There is a close relationship between HBV and HCC recurrence after transplant. High HBV DNA levels before transplant are associated with HCC recurrence after transplant.

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Association Between Hepatitis B and Hepatocellular Carcinoma Recurrence in Patients Undergoing Liver Transplantation

Cited by 26 publications

References 31 publications

Recurrence of hepatocellular carcinoma and hepatitis B reinfection in hepatitis B surface antigen-positive patients after liver transplantation

Recurrence of hepatocellular carcinoma and hepatitis B reinfection in hepatitis B surface antigen-positive patients after liver transplantation

Mammalian target of rapamycin inhibitors are associated with lower rates of hepatocellular carcinoma recurrence after liver transplantation: a systematic review

High Hepatitis B Virus DNA Level in Serum before Liver Transplantation Increases the Risk of Hepatocellular Carcinoma Recurrence

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