Impact of immunosuppression minimization and withdrawal in long-term hepatitis C virus liver transplant recipients

AIM:To investigate the effects of different immunosuppressive regimens and avoidance on fibrosis progression in hepatitis C virus(HCV)liver transplant(LT)recipients.METHODS:We retrospectively compared the liver biopsies of well-matched HCV LT recipients under calcineurin inhibitors(CNI group,n=21)and mycophenolate(MMF group,n=15)monotherapy,with those patients who successfully withdrawn immunosuppression(IS)therapy from at least 3 years(TOL group,n=10).To perform the well-matched analysis,all HCV transplanted patients from December 1993 were screened.Only those HCV patients who reached the following criteria were considered for the analysis:(1)at least3 years of post-operative follow-up;(2)patients with normal liver graft function under low dose CNI monotherapy(CNI group);(3)patients with normal liver graft function under antimetabolite(Micophenolate Mofetil or coated mycophenolate sodium)monotherapy(MMF group);and(4)recipients with normal liver function without any IS.We excluded from the analysis recipients who were IS free or under monotherapy for<36 mo,recipients with cirrhosis or with unstable liver function tests.RESULTS:Thirty six recipients were enrolled in the study.Demographics,clinical data,time after LT and baseline liver biopsies were comparable in the three groups.After six years of follow-up,there was no worsening of hepatic fibrosis in the MMF group(2.5±1.5Ishak Units vs 2.9±1.7 Ishak Units,P=0.5)and TOL group(2.7±10.7 vs 2.5±1.2,P=0.2).In contrast,a significant increase in the fibrosis score was observed in the CNI group(2.2±1.7 vs 3.9±1.6,P=0.008).The yearly fibrosis progression rate was significantly worse in the CNI group(0.32±0.35)vs MMF group(0.03±0.31,P=0.03),and TOL group(-0.02±0.27,P=0.02).No differences have been reported in grading scores for CNI group(2.79±1.9,P=0.7),MMF group(3.2±1.5,P=0.9)and TOL group(3.1±1.4,P=0.2).Twenty four patients were treated with low dose ribavirin(8TOL,7 MMF,9 CNI).The hepatitis C titers were comparable in the three groups.No episodes of rejection have been reported despite differences of liver function test in the three groups during the observational period.CONCLUSION:IS withdrawal and MMF monotherapy is safe and seems to be associated with the slowest fibrosis progression in HCV LT recipients.

Surgical treatment of stage IV gastric cancer: is it worthwhile?

Aim:To analyze clinical features and survival outcomes of patients with surgically-treated stage IV gastric cancer,in order to evaluate the suitability of surgery in these patients.Methods:We performed a systematic literature search using PubMed,MEDLINE,and Embase on October 9th,2017.Survival outcomes data were collected.Results:The original search returned 2434 papers.Thirty-nine studies were included in the final review,of which 26 evaluated liver metastasis resection,four pulmonary metastasis resections and nine palliative gastrectomies.In total 933 patients underwent hepatectomy for liver metastasis from gastric cancer and median survival rates were 73%,37%and 27%at 1-,3-and 5-year respectively,with a median overall survival of 22 months(9-52 months).Data regarding resection of lung metastases were scarce and extremely heterogeneous.In total 1115 patients underwent palliative gastrectomy and median overall survival of patients was 12 months(8-53 months).In the only randomized controlled trial,no survival benefit of additional gastrectomy over chemotherapy alone was found,in contrast with the retrospective studies.Conclusion:Survival benefit of surgery in advanced gastric cancer is still unclear.Surgery may play an important role in highly selected patients.However,further randomized controlled trials are necessary to clarify the actual impact of surgery in these patients.