22
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      A meta-analysis and systematic review: adjuvant interferon therapy for patients with viral hepatitis-related hepatocellular carcinoma

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Objective

          To evaluate the efficacy and safety of adjuvant IFN therapy for viral hepatitis-related hepatocellular carcinoma (HCC) after treatment with surgical resection or transarterial chemoembolization (TACE).

          Methods

          Controlled trials of adjuvant treatment with IFN for patients with HCC published between 2000 and 2012 were searched electronically in MEDLINE, PubMed, Cochrane Library, and EMBASE databases. According to the heterogeneity of the studies, two different models - the fixed-effect model and the random-effect model - were applied to analyze the results.

          Results

          Ten trials were screened according to inclusion and exclusion standards. Eight randomized, controlled trials and two non-randomized, controlled trials were included. These ten trials with a total of 1,029 subjects were eventually involved in the meta-analysis; 528 HCC patients were treated with adjuvant treatment with IFN and 501 patients with placebo. Compared to the control group, the recurrence rates of HCC in IFN group were significantly lower (odds ratio (OR) = 0.66; 95% confidence interval (CI) = 0.50 to 0.86; P = 0.02), especially after TACE treatment according to subgroup analysis (OR = 0.73; 95% CI = 0.52 to 1.01; P = 0.06 for surgical resection; and OR = 0.54; 95% CI = 0.33 to 0.86, P = 0.01 for TACE). The death rates in the IFN group also significantly decreased according to not only total events analysis (OR = 0.42; 95% CI = 0.32 to 0.56; P < 0.00001) but also subgroup analysis (OR = 0.51; 95% CI = 0.36 to 0.72; P = 0.0002 for surgical resection; and OR = 0.33; 95% CI = 0.21 to 0.50; P < 0.00001 for TACE).

          Conclusions

          Adjuvant IFN therapy may significantly reduce the recurrence rates of patients with viral hepatitis-related HCC and improve the survival of patients after surgical resection or TACE. The ideal dose mostly selected is 3 MIU/ml, three times per week, which can make patients tolerate the adverse reactions of IFN better and maintain effective concentrations for a long time.

          Related collections

          Most cited references22

          • Record: found
          • Abstract: found
          • Article: not found

          Resection and liver transplantation for hepatocellular carcinoma.

          Surveillance programs in cirrhotic patients enable the detection of hepatocellular carcinoma (HCC) at early stages, when the tumor is amenable to curative treatments (60% of cases in Japan; 25 to 40% in Europe and the United States). Resection is the mainstay of treatment in noncirrhotic patients and in cirrhotics with well-preserved liver function. In modern series, a perioperative mortality < or = 3% and 5-year survival rates above 50% are expected. Tumor recurrence complicates half of the cases at 3 years, but there is no unquestionable preventive treatment. Liver transplantation provides excellent outcomes applying the Milan criteria (single nodule < or = 5 cm or two or three nodules < or = 3 cm), with 5-year survival rates of 70% and low recurrence rates. Although expansion of selection criteria is appealing, it should be assessed in the setting of prospective well-designed studies. Intention-to-treat analysis has shown that wide extended indications lead to 25% 5-year survival rates. Living donor liver transplantation is having a minor impact in HCC management. Molecular markers are needed to better select the candidates for surgery.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Hepatectomy for hepatocellular carcinoma: toward zero hospital deaths.

            The authors report on the surgical techniques and protocol for perioperative care that have yielded a zero hospital mortality rate in 110 consecutive patients undergoing hepatectomy for hepatocellular carcinoma (HCC). The hepatectomy results are analyzed with the aim of further reducing the postoperative morbidity rate. In recent years, hepatectomy has been performed with a mortality rate of <10% in patients with HCC, but a zero hospital mortality rate in a large patient series has never been reported. At Queen Mary Hospital, Hong Kong, the surgical techniques and perioperative management in hepatectomy for HCC have evolved yearly into a final standardized protocol that reduced the hospital mortality rate from 28% in 1989 to 0% in 1996 and 1997. Surgical techniques were designed to reduce intraoperative blood loss, blood transfusion, and ischemic injury to the liver remnant in hepatectomy. Postoperative care was focused on preservation and promotion of liver function by providing adequate tissue oxygenation and immediate postoperative nutritional support that consisted of branched-chain amino acid-enriched solution, low-dose dextrose, medium-chain triglycerides, and phosphate. The pre-, intra-, and postoperative data were collected prospectively and analyzed each year to assess the influence of the evolving surgical techniques and perioperative care on outcome. Of 330 patients undergoing hepatectomy for HCC, underlying cirrhosis and chronic hepatitis were present in 161 (49%) and 108 (33%) patients, respectively. There were no significant changes in the patient characteristics throughout the 9-year period, but there were significant reductions in intraoperative blood loss and blood transfusion requirements. From 1994 to 1997, the median blood transfusion requirement was 0 ml, and 64% of the patients did not require a blood transfusion. The postoperative morbidity rate remained the same throughout the study period. Complications in the patients operated on during 1996 and 1997 were primarily wound infections; the potentially fatal complications seen in the early years, such as subphrenic sepsis, biliary leakage, and hepatic coma, were absent. By univariate analysis, the volume of blood loss, volume of blood transfusions, and operation time were correlated positively with postoperative morbidity rates in 1996 and 1997. Stepwise logistic regression analysis revealed that the operation time was the only parameter that correlated significantly with the postoperative morbidity rate. With appropriate surgical techniques and perioperative management to preserve function of the liver remnant, hepatectomy for HCC can be performed without hospital deaths. To improve surgical outcome further, strategies to reduce the operation time are being investigated.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Effects of interferon alpha on vascular endothelial growth factor gene transcription and tumor angiogenesis.

              Interferon alpha (IFN-alpha) has antiangiogenic activity, although the underlying mechanism of action is unclear. Because human neuroendocrine (NE) tumors are highly vascularized and sensitive to IFN-alpha, we investigated whether the therapeutic effects of IFN-alpha result from an inhibition of angiogenesis mediated by a decrease in vascular endothelial growth factor (VEGF) gene expression. VEGF gene and protein expression was analyzed in NE tumors by immunohistochemistry and in NE tumor cell lines by quantitative competitive reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). VEGF promoter-reporter gene constructs containing various deletions or mutations and gel shift assays were used to identify minimal promoter requirements and potential transcription factors. A xenograft nude mouse model (five mice per group) was used to determine the effect of IFN-alpha on tumor growth (NE Bon cells and pancreatic Capan-1 cells) and microvessel density. Liver metastases from eight patients with NE tumors were analyzed for microvessel density, VEGF mRNA content, and VEGF plasma levels before and after initiation of IFN-alpha therapy. NE tumors and cell lines expressed VEGF mRNA and secreted VEGF protein. In vitro, IFN-alpha decreased transcription of VEGF gene expression through an Sp1- and/or Sp3-dependent inhibition of VEGF promoter activity. Compared with vehicle treatment in mice, IFN-alpha inhibited tumor growth by 36% and reduced microvessel density from 56 (95% confidence interval [CI] = 49 to 69) to 37 per x400 Field (95% CI = 32 to 41, P =.015). Patients with NE tumors had lower VEGF plasma levels and reduced VEGF mRNA levels and microvessel density in liver metastasis biopsy material after IFN-alpha treatment. IFN-alpha confers its antitumor activity, at least in part, by its antiangiogenic activity, which results from Sp1- and/or Sp3-mediated inhibition of VEGF gene transcription.
                Bookmark

                Author and article information

                Contributors
                Journal
                World J Surg Oncol
                World J Surg Oncol
                World Journal of Surgical Oncology
                BioMed Central
                1477-7819
                2013
                24 September 2013
                : 11
                : 240
                Affiliations
                [1 ]Department of Hepatobiliary Surgery, Shenyang Military Region General Hospital, Shenhe District in Shenyang culture road no. 83, Shenyang 110015, China
                [2 ]Department of Stomatology, Shenyang Military Region General Hospital, Shenyang, Liaoning 110015, China
                [3 ]Company Five of Cadet Brigade, Third Military Medical University, Chongqing 400038, China
                [4 ]Company Two of Cadet Brigade, Third Military Medical University, Chongqing 400038, China
                Article
                1477-7819-11-240
                10.1186/1477-7819-11-240
                3851844
                24060218
                db54e84c-ab1a-49c6-a139-1f484f756261
                Copyright © 2013 Jiang et al.; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 June 2013
                : 5 September 2013
                Categories
                Review

                Surgery
                interferon,adjuvant treatment,viral hepatitis,hepatocellular carcinoma,meta-analysis
                Surgery
                interferon, adjuvant treatment, viral hepatitis, hepatocellular carcinoma, meta-analysis

                Comments

                Comment on this article