incidence and risk factors of de novo skin cancer in the liver transplant recipients

Liver transplantation [LT] increases the risk of de novo malignancies including skin cancers. However, risk factors for this type of cancers have not been well studied. To determine the incidence of skin cancer in LT recipients, and to identify the risk factors of this type of cancer. We identified all adult patients who underwent LT and developed de novo skin cancer post-LT at our institution between 1996 and 2009. We excluded the patients with history of skin cancer prior to LT. We also studied a control group of patients who underwent LT during the same period but did not develop skin cancer; the control group was matched [1:2] for age, gender and geographical place of residence. Over a median [IQR] follow-up of 41.5 [18.0, 98.6] months, 23 [2.3%] of 998 patients developed skin cancer post-LT, of whom 10 were identified with squamous cell carcinoma, 9 with basal cell carcinoma and 4 with melanoma. After adjusting the confounding variables, subjects who had combined liver/ kidney transplant had 22 [95% CI: 5.1-99] times higher hazard of skin cancer compared to subjects with LT alone. Furthermore, patients who had non-skin cancer prior to LT had 23 [95% CI: 8.6-60] times higher hazard developing skin cancer after the transplant. Patients with history of alcohol consumption, as the underlying etiology of liver disease, had 4 [95% CI: 1.2-12.9] times higher hazard of developing skin cancer after transplantation. Type or duration of immunosuppression was not associated with increased risk of skin cancer post-LT. The post-LT survival outcome was not affected by the development of de novo skin cancer post-LT. Skin cancer is relatively common in LT recipients and should be monitored, particularly in patients with a history of pretransplant malignancy, recipients of combined liver and kidney transplant or having alcoholic cirrhosis as the underlying cause of liver disease

Recurrence of disease following liver transplantation: nonalcoholic steatohepatitis vs hepatitis C virus infection

Nonalcoholic steatohepatitis [NASH] is an increasing indication for orthotopic liver transplantation [OLT] in the United States and other countries. However, the incidence of disease recurrence and natural course following OLT remains incompletely understood. To estimate the incidence of recurrent disease, outcome and identify risk factors associated with disease recurrence in patients undergoing OLT for NASH as compared to those undergoing OLT for HCV cirrhosis. We identified all patients with end-stage liver disease secondary to NASH [n=53] or HCV [n=95] cirrhosis who underwent OLT at our institution between 1998 and 2005. Protocol liver biopsies were performed [Day 7, Month 4 and yearly] after OLT, and as clinically indicated. Kaplan-Meier survival analysis was performed to assess the fibrosis progression and survival. Cox regression analysis was performed to identify factors associated with disease recurrence. Five-year survival was 90.5% in NASH vs 88.4% in HCV group [p=0.97]. The median [25%ile, 75%ile] follow-up to last available biopsy was 12.7 [5.9, 26.3] months, during which 17 [32%] of NASH patients developed persistent fatty infiltration in their graft, 8 [15%] of whom had accompanying histologic features of recurrent NASH. There was no difference in the prevalence of post-OLT steatosis between HCV and NASH patients after adjusting for time of histologic follow-up [p=0.33]. Patients with HCV infection were more likely to develop hepatic fibrosis post-OLT than those with NASH [62.1% vs 18.9%, p<0.001]. Multivariate analysis identified post-OLT diabetes [HR=2.0, 95% CI: 1.2-3.2, p=0.007] as an independent risk factor for fibrosis development. Additionally, NASH subjects who received steroids had a significantly higher risk of developing hepatic fibrosis post-OLT than NASH patients who did not receive steroids and all HCV subjects [p<0.001]. Recurrence of steatosis post-OLT is common. Corticosteroid use may contribute to fibrosis progression in this population

Characteristics of oral abnormalities in liver transplant candidates

Several oral mucosal abnormalities have been reported to occur more frequently in patients with liver disease. It has, however, not been determined if these conditions are related to the disease or are manifestations of extraneous factors not associated with the liver pathology. To identify and quantify oral abnormalities in candidate for liver transplantation and to determine whether these conditions were correlated with the type of liver disease or were the result of other patient variables. Oral examinations were performed on 300 candidates for liver transplantation to assess their oral health and to record the presence and types of oral mucosal pathologies. Abnormalities most frequently encountered were analyzed for significant associations with classification of liver disease, hyposalivation, diuretic therapy, edentulism, or smoking. Among these subjects, 175 [58%] had one or more abnormalities. The anomalies most frequently found were fissured tongue [37%], atrophy of the papillae of the tongue [18%], angular cheilitis [4%] and manifestations of clinical candidiasis [2%]. Clinical hyposalivation was found in 28.7% of all patients and 70% of those who were on diuretic therapy. Fissured tongue and atrophy of the tongue papillae were significantly associated with hyposalivation [p<0.001]; hyposalivation was correlated to diuretic therapy [p=0.028]. Pathologies suggestive of candidiasis were significantly associated with hyposalivation and total edentulism. Several oral mucosal abnormalities that have previously been linked with liver diseases were found to be primarily associated with diuretic-induced hyposalivaiton, smoking, and total edentulism

IL-2 receptor antagonist [basiliximab] is associated with rapid fibrosis progression in patients with recurrent hepatitis c after liver transplantation using serial biopsy specimens

Recurrence of hepatitis C virus [HCV] infection following orthotopic liver transplantation [OLT] is universal. There is paucity of data on the safety and efficacy of interleukin [IL]-2 receptor antagonist [IL-2RA] when added to the standard immunosuppression regimen in OLT recipients with recurrent HCV infection. To evaluate the efficacy of IL-2RA [Basiliximab] in preventing acute cellular rejection [ACR] in patients with recurrent HCV infection after OLT and to assess the impact of IL-2RA in promoting fibrosis progression in post-OLT recurrent HCV infection. Using an electronic pathology database, we identified all OLT/HCV patients with at least 2 post-OLT liver biopsies [1998-2006]. Standard immunosuppression consisted of steroids and calcineurin inhibitor with and without mycophenolate mofetil. All patients who were transplanted after May 2004 received IL- 2RA induction therapy. The Ludwig-Batts system was used to stage all biopsies [593 biopsies from 124 patients]. The first biopsy that showed post-OLT fibrosis or the last follow-up biopsy was used for time- to-progression analysis. Univariate and multivariate Cox proportional hazards regression analyses were performed to identify factors associated with the progression of fibrosis. ACR was significantly [p<0.001] lower in patients who received IL-2RA [20 of 70, 29%] compared to those who did not [33 of 54, 61%]. The median [25%ile, 75%ile] follow-up was 12.1 [6.1, 23.9] months during which 61% of patients had progression of fibrosis. Univariate analysis revealed that a higher HCV RNA load at 4 months post-OLT [p=0.002], cytomegalovirus [CMV] infection [p<0.001], use of steroid therapy for ACR [p=0.043], and use of IL-2RA [p<0.001] were associated with higher hazards for the pro- gression of fibrosis. Viral load at 4 months post-OLT was significantly [p=0.025] higher in patients who had IL-2RA therapy [median [25%ile, 75%ile]: 2.9 [1.0, 5.0] _10[6] vs. 1.4 [1.0, 2.3] _10[6]]. In multivariate analysis, patients who received IL-2RA therapy were 3.1 [95% CI: 1.8-5.3] times more likely to develop fi- brosis than those who did not treated with IL-2RA. Steroid therapy for ACR remained significantly [Hazard Ratio=2.9, p=0.002] associated with the progression of fibrosis. IL-2RA [Basiliximab] decreases the rate of ACR. However, it may be associated with more rapid histological progression of the disease in post-OLT recurrent HCV