Risk for immune-mediated graft dysfunction in liver transplant recipients with recurrent HCV infection treated with pegylated interferon.

BACKGROUND & AIMS: Patients with recurrent hepatitis C virus infection treated with pegylated interferon (PEG) after liver transplantation can develop severe immune-mediated graft dysfunction (IGD) characterized by plasma cell hepatitis or rejection. METHODS: We conducted a multicenter case-control study of 52 liver transplant recipients with hepatitis C to assess the incidence of, risk factors for, and outcomes of PEG-IGD. Data from each patient were compared with those from 2 matched patients who did not develop PEG-IGD (n = 104). We performed a multivariate analysis of risk factors and analyzed treatment and outcomes of graft dysfunction subtypes. RESULTS: Overall incidence of PEG-IGD during a 10-year study period was 7.2%. Risk factors included no prior PEG therapy (odds ratio = 5.3; P < .0001), therapy with PEGα-2a (odds ratio = 4.7; P = .03), and immune features (mainly plasma cell hepatitis) on pre-PEG therapy liver biopsies (odds ratio = 3.9; P = .005). The PEG-IGD group had lower long-term patient (61.5% vs 91.3% of controls) and graft (38.5% vs 85.6% of controls) survival and higher rates of retransplantation (34.6% vs 6.7% of controls) (all, P < .0001), without increases in sustained virologic response. Variables associated with increased mortality included acute rejection as the PEG-IGD sub-type (hazard ratio [HR] = 2.4; P = .002), a high level of alkaline phosphatase at PEG initiation (HR = 1.003; P = .005), and lack of a sustained virologic response (HR = 3.3; P = .04). Variables associated with graft failure included a high level of alkaline phosphatase at PEG initiation (HR = 1.002; P = .04) and lack of a sustained virologic response (HR = 2.1; P = .04). CONCLUSIONS: PEG-IGD has high morbidity and mortality and is not associated with increased rates of virologic response. It is important to avoid PEG therapy in liver transplant recipients with specific clinical, biochemical, and histologic risk factors for PEG-IGD.

Self-reported oral symptoms and signs in liver transplant recipients and a control population.

Recipients of liver transplantation (LT) receive lifelong immunosuppression, which causes side effects. We investigated self-reported oral symptoms and associated risk factors with the following hypothesis: symptoms and signs would differ between LT recipients of different etiology groups and also between LT recipients and a control population. Eighty-four LT recipients (64 with chronic liver disease and 20 with acute liver disease) were recruited for clinical oral and salivary examinations (median follow-up = 5.7 years). A structured questionnaire was used to record subjective oral symptoms. Matched controls (n = 252) came from the National Finnish Health 2000 survey. The prevalence of symptoms was compared between the groups, and the risk factors for oral symptoms were analyzed. Xerostomia was prevalent in 48.4% of the chronic LT recipients and in 42.1% of the acute LT recipients. This subjective feeling of dry mouth was only partly linked to objectively measured hyposalivation. The chronic transplant recipients had significantly lower unstimulated salivary flow rates than the acute transplant recipients (0.34 ± 0.31 versus 0.61 ± 0.49 mL/minute, P = 0.005). Among the chronic transplant recipients, hyposalivation with unstimulated salivary flow was associated with fewer teeth (17.7 ± 8.2 versus 21.9 ± 8.4, P = 0.047) and more dentures (33.3% versus 12.2%, P = not significant). The chronic patients reported significantly more dysphagia than their controls (23.4% versus 11.5%, P = 0.02). Increases in the number of medications increased the symptoms in all groups. In conclusion, dysphagia was significantly more prevalent among the chronic LT recipients versus the controls. The number of medications was a risk factor for dry mouth-related symptoms for both the LT recipients and the controls. The chronic transplant recipients presented with lower salivary flow rates than the acute transplant recipients. Hyposalivation correlated with generally worse oral health among the chronic transplant recipients. These differences between the chronic and acute LT recipients may have been due to differences in their medical conditions due to the different etiologies.

Current management and perspectives for HCV recurrence after liver transplantation.

Hepatitis C virus (HCV) infection is one of the leading causes of end-stage liver disease and the main indication for liver transplantation (LT) in most countries. All patients who undergo LT with detectable serum HCV RNA experience graft reinfection. Between 20 and 30% of patients develop cirrhosis within 5 years post-LT. The outcome of transplant patients with cirrhosis on the graft is severe, with a rate of decompensation at 1 year of around 40%. To date, retransplantation is the only option for patients who develop decompensation. Until 2011, standard antiviral therapy, using pegylated interferon (PEG-IFN) and ribavirin (RBV), was the only effective therapy. Obtaining a sustained virological response (SVR) in the setting of LT greatly improves overall and graft survival, but this only concerns 30% of transplanted patients. Direct-acting antivirals (DAA) such as protease inhibitors, polymerase or other non-structural proteins inhibitors represent a new era in HCV-associated liver disease. Although their use in the field of liver transplantation seems to be essential, there are some limitations due to safety and tolerance. One limitation is the potential interaction with calcineurin inhibitors. We describe the preliminary results of triple therapy with boceprevir or telaprevir in terms of efficacy and safety in liver transplant recipients.

Practical management of boceprevir and immunosuppressive therapy in liver transplant recipients with hepatitis C virus recurrence.

Hepatitis C virus (HCV) recurrence is the most important complication in HCV liver transplant patients. Boceprevir with pegylated interferon and ribavirin (PegIFN/RBV) enabled improvement in sustained virological response rates of patients with genotype 1 HCV. Boceprevir interacts with immunosuppressive therapy (IT) by inhibiting the cytochrome P450 3A enzyme. Our aim was to study interactions and assess the safety of boceprevir in the context of HCV recurrence. Boceprevir (800 mg three times a day) initiated after a 4-week lead-in phase was associated with cyclosporine (three patients), tacrolimus (two patients), and everolimus (one patient) in five liver transplant patients with genotype 1 HCV infection who experienced HCV recurrence. The mean follow-up period after HCV therapy was 14.8 ± 3.1 weeks. Estimated oral clearances of IT decreased on average by 50%, requiring reduced dosing regimens. Anemia occurred in all patients, with a mean fall in hemoglobin levels between baseline and week 12 of 3.12 ± 2.27 g/dl. All patients required administration of ß-erythropoietin (n = 5), three needed ribavirin dose reduction, and one needed a blood transfusion. A virological response was observed in all patients (mean HCV viral load [HVL] decrease at week 12, 6.64 ± 0.35 log(10) IU/ml). These preliminary results in liver transplant patients with HCV recurrence demonstrate the feasibility and safety of coadministration of boceprevir and IT.

Telaprevir-based triple therapy in liver transplant patients with hepatitis C virus: a 12-week pilot study providing safety and efficacy data.

After liver transplantation (LT), the management of recurrent hepatitis C virus (HCV) infections still remains a major challenge. In HCV genotype 1 patients not undergoing transplantation, the introduction of protease inhibitor (PI)-based regimens has increased the sustained virological response rate significantly. This pilot study investigated both the safety and efficacy of telaprevir (TVR)-based triple therapy in HCV-infected LT patients with a special emphasis on drug-drug interactions between immunosuppressants and PIs. Safety and efficacy data were gathered for 12 weeks for 9 HCV-infected LT patients who were treated with a combination of TVR, pegylated interferon, and ribavirin (RBV) in parallel with immunosuppressive drugs such as tacrolimus (TAC; n = 4), cyclosporine A (CSA; n = 4), and sirolimus (SIR; n = 1). Seven of the transplant patients completed the 12 weeks of triple therapy. At week 4, 4 of the patients were found to be HCV RNA-negative, and importantly, 8 were found to be negative at week 12. During the 12-week course of triple therapy, short-term measurements of immunosuppressant trough levels required individual dose reductions in all patients (CSA, 2.5-fold; SIR, 7-fold; and TAC, 22-fold). Furthermore, two-thirds of the patients exhibited hematological side effects requiring RBV dose reductions, the administration of erythropoietin, or even blood transfusions. In conclusion, this pilot study provides evidence showing that TVR-based triple therapy is effective within the first 4 to 12 weeks in LT patients suffering from HCV genotype 1 recurrence, and it also provides evidence showing that drug-drug interactions between TVR and immunosuppressants can be handled appropriately through the close monitoring of trough levels and adequate dosage adjustments.

Murine Kupffer cells are protective in total hepatic ischemia/reperfusion injury with bowel congestion through IL-10.

Kupffer cells (KCs) are thought to mediate hepatocyte injury via their production of proinflammatory cytokines and reactive oxygen species in response to stress. In this study, we depleted KCs from the liver to examine their role in total warm hepatic ischemia/reperfusion (I/R) injury with bowel congestion. We injected 8-wk-old C57BL/10J mice with liposome-encapsulated clodronate 48 h before 35 min of hepatic ischemia with bowel congestion, followed by 6 or 24 h of reperfusion. KC-depleted animals had a higher mortality rate than diluent-treated animals and a 10-fold elevation in transaminase levels that correlated with increases in centrilobular necrosis. There was extensive LPS binding to the endothelial cells, which correlated with an upregulation of endothelial adhesion molecules in the KC-depleted animals versus diluent-treated animals. There was an increase in the levels of proinflammatory cytokines in KC-depleted animals, and a concomitant decrease in IL-10 levels. When KC-depleted mice were treated with recombinant IL-10, their liver damage profile in response to I/R was similar to diluent-treated animals, and endothelial cell adhesion molecules and proinflammatory cytokine levels decreased. KCs are protective in the liver subjected to total I/R with associated bowel congestion and are not deleterious as previously thought. This protection appears to be due to KC secretion of the potent anti-inflammatory cytokine IL-10.

[Effects of HBsAg pulsed dendritic vaccination on anti-HBs production in immunosuppressed rats after liver transplantation].

OBJECTIVE: To explore the effects of HBsAg pulsed dendritic vaccination on anti-HBs production in immunosuppressed rats after liver transplantation (LT). METHODS: Brown-Norway liver allografts were transplanted into Lewis recipients. The transplanted Lewis rats were injected with EK506 (2 mg/kg) and randomly divided into two groups: rats in HBsAg-DCs group (n = 15) were intraperitoneally injected with HBsAg pulsed DCs at 14 d and 28 d after LT, and rats in the HBsAg group (n = 15) were injected with HBsAg (200 mul) once a week for 12 weeks. Rats without any immunosuppressive treatment after LT served as controls (n = 5). IL-2 and IFN-gamma mRNA expression in spleen were analyzed by RT-PCR, serum IL-2, IFN-gamma and anti-HBs were detected by ELISA. RESULTS: High dose of FK506 resulted in the immunosuppressed in LT rats, as evident by low production of IL-2 and IFN-gamma, and without liver rejection compared to rats in the control group. HBsAg-DCs induced high titer of anti-HBs antibody, however, titer of anti-HBs were seldom detectable in the HBsAg group at 1, 2 and 3 mouth after vaccination. CONCLUSION: The capacity of HBsAg-DCs to induce anti-HBs in immunosuppressed rats suggested that DC vaccine may prevent HBV recurrence in liver transplanted patients.

A practical guide to the management of HCV infection following liver transplantation.

Hepatitis C-associated liver failure is the most common indication for liver transplantation, with virological recurrence near ubiquitous. Approximately 30% of HCV-infected recipients will die or lose their allograft or develop cirrhosis secondary to hepatitis C recurrence by the fifth postoperative year, with the proportion increasing with duration of follow-up. Strategies for minimizing the frequency of severe HCV recurrence include avoidance of older donors, early diagnosis/treatment of CMV and minimization of immunosuppression, particularly T-cell depleting therapies and pulsed corticosteroid treatment of acute cellular rejection. Patients should be offered treatment with peginterferon and ribavirin before LT if MELD

Drug exposure and perceived adverse drug events reported by liver-transplant patients.

INTRODUCTION: Posttransplant patient outcome and quality of life are affected by different factors, such as post-graft context, psychological state, and polymedication. Many surveys have been carried out to study immunosuppressant ADRs, and have mainly used a questionnaire completed by patients, but few have asked patients about their drug exposure. The aim of this study is to describe drug exposure and adverse drug events (ADEs) reported by liver-transplant patients (LTP). METHODS: This observational, retrospective study assessed questionnaires from LTPs concerning demographic data, drug exposure, and ADEs. RESULTS: 118 LTPs exposed to 5.9 (+/- 2.8) drugs with immunosuppressive regimens, consisting mainly of tacrolimus (79.3%), cyclosporine (18.1%), or sirolimus (2.6%), were also exposed to antihypertensive drugs (43.2%), protonpump inhibitors (30.5%), statins (28.8%), drugs acting on bile composition (26.3%), and diuretics (19.5%). 1,389 ADEs were reported: 30.1% neurological, 13.4% cutaneous, 12.4% hematological, 11.1% digestive, 10.1% osteomuscular, 6.6% cardiovascular, and 16.3% others. Significantly more ADEs were reported by patients exposed to cyclosporine than those receiving tacrolimus (p < 0.05). Patients with a transplant for < 18 months had more tremors and those with a transplant for > 79 months reported more hirsutism, gingival hypertrophia, and arterial hypertension. CONCLUSIONS: This study shows the value of patient-reporting via structured interviews for both drug exposure and ADEs, and the importance of this approach to complement total data collection.

Treatment for recurrent hepatitis C virus infection after liver transplantation.

Cirrhosis due to hepatitis C virus (HCV) infection is the current leading indication for orthotopic liver transplantation (OLT) in the world. This series reports our program's experience with the treatment of HCV infection after the development of histological hepatitis. Between March 2002 and June 2008, patients with recurrent HCV were selected for treatment if the liver biopsy showed at least the F2 degree of Metavir score. HCV viral load was measured at 4, 12 and 24 weeks as well as at the end of treatment and at 6 months thereafter for patients who became HCV RNA negative (sustained virological response [SVR]). In this period, we performed 287 liver transplantations in 279 patients, including 117 (42%) who had HCV cirrhosis as the indication for OLT of whom 25 were eligible for antiviral treatment. Twelve patients completed treatment, 7 remain on treatment, and 6 were discontinued. The principal collateral effect was anemia. Only 1 patient had an episode of acute cellular rejection, which responded to adjustment of immunosuppression. Antiviral treatment in transplanted patients was feasible and did not seem to induce severe immunological effects. Adjuvant therapies to reduce cytopenias are frequently required, principally erythropoietin. The best results were observed with the pegylated interferon alfa (PEG) plus ribavirin (RBV) group: 38.9% of SVR. We recommend antiviral treatment of eligible patients with confirmed HCV recurrence using PEG plus RBV.

Relative contribution of direct and indirect allorecognition in developing tolerance after liver transplantation.

The interaction of donor passenger leukocytes and host leukocytes in recipient secondary lymphoid tissues during the early posttransplantation period is crucial in directing host immune reactions toward allograft rejection or acceptance. Responsible T cell clones could be activated through the direct and indirect pathways of allorecognition. We examined the role of the indirect pathway in liver transplantation (LT) tolerance by depleting host antigen-presenting cells (APC) with phagocytic activity [e.g., cluster domain (CD)68+/CD163+ macrophages, CD11c+ dendritic cells (DC)] using liposome-encapsulating clodronate (LP-CL). After Lewis rat cell or liver graft transplantation, Brown Norway (BN) rat recipients pretreated with LP-CL showed a significantly reduced type 1 helper T cell cytokine up-regulation than control-LP-treated recipients. In the LT model, LP-CL treatment and host APC depletion abrogated hepatic tolerance; Lewis liver grafts in LP-CL-treated-BN recipients developed mild allograft rejection, failed to maintain donor major histocompatibility complex (MHC) class II+ leukocytes, and developed chronic rejection in challenged donor heart allografts, while control-LP-treated BN recipients maintained tolerance status and donor MHC class II+ hepatic leukocytes. Furthermore, in the BN to Lewis LT model, LP-CL recipient treatment abrogated spontaneous hepatic allograft acceptance, and graft survival rate was reduced to 43% from 100% in the control-LP group. In conclusion, the study suggests that host cells with phagocytic activity could play significant roles in developing LT tolerance.

Local presence of cytomegalovirus and Candida species vs oral lesions in liver and kidney transplant recipients.

BACKGROUND: Anti-CMV prophylaxis is currently a routine management in patients after organ transplantation. One of the clinical symptoms of CMV infection may be lesions in the oral cavity.The aim of this study was to determine the relationship between CMV infection, occurrence of Candida species and presence of oral mucosal ulceration in transplant recipients. MATERIAL/METHODS: Twenty fi ve patients after kidney or liver transplantation (mean age 13 years +/-4 years), receiving immunosuppression (tacrolimus, cyclosporine or sirolimus), who presented minor and major recurrent aphtous stomatitis (RAS), atypical ulcerations or focal necrosis in the oral cavity were enrolled into the study. Mean duration of post-transplant follow-up was 4 years and 3 months (+/-3 years and 5 months). Clinical dental examination (Pl I, GI), mycological tests and blood tests for CMV infection (specific IgM antibodies and/or pp65 antygenemia) were performed in all patients. Eighteen specimens of oral mucosa were evaluated for CMV presence in situ. RESULTS: CMV infection was confirmed in 13 patients with oral mucosal ulceration (46.43%); which were accompanied by gingivitis (average GI=1.34); in two cases Candida albicans was identified. DNA of HCMV was found in-situ in 5.5% of all biopsies, and in 9% of biopsies of patients with clinical CMV infection; changes did not show the presence of Candida spp. CONCLUSIONS: There is a significant correlation between CMV infection and oral lesions; in some cases, CMV may be a direct cause.

Sirolimus conversion in liver transplant recipients with renal dysfunction: a prospective, randomized, single-center trial.

This pilot trial was designed to assess the safety and efficacy of SRL in liver transplant recipients with renal dysfunction. Forty patients with renal dysfunction (24-hr CrCl 40-80 mL/min) were randomized to be withdrawn from the calcineurin inhibitor (CNI) and receive sirolimus (SRL) or to continue CNI (control arm). Improvement in 24-hour CrCl was seen in the SRL arm at 3 months (75 mL/min SRL vs. 56 mL/min control, P=0.012), whereas at 12 months there was a trend toward improvement in the SRL arm (72 mL/min SRL vs. 58 mL/min control, P=0.09). Two patients, one in each arm, developed steroid-sensitive rejection. Side effects of SRL were limited and included hyperlipidemia requiring treatment (15%), pruritus (5%), and mouth sores (25%). In this trial, SRL-based immunosuppression was a safe alternative to CNI. Although early improvements were observed, withdrawing CNI and replacing it with SRL did not result in a statistically significant improvement in renal function at 12 months of follow-up.

Early antiviral treatment of hepatitis C virus recurrence after liver transplantation in HIV-infected patients.

OBJECTIVE: To investigate the efficacy of early antiviral treatment for hepatitis C virus (HCV) recurrence in HIV/HCV-coinfected patients undergoing liver transplantation for end-stage liver disease. METHODS: Open prospective trial of early treatment of HCV recurrence in consecutive HIV/HCV-coinfected patients transplanted at a tertiary hospital in Barcelona between 2002 and 2004. All patients had indication for liver transplantation, no previous CDC class C HIV-associated opportunistic events, a CD4+ T-cell count >100cells/microl, and undetectable plasma HIV RNA on highly active antiretroviral therapy. Treatment with pegylated interferon-alpha2b (1.5 microg/kg/week) and ribavirin (800-1000 mg/day) was given for 24 to 48 weeks, as soon as HCV recurrence was histologically documented. RESULTS: Of six patients who underwent transplant, five patients surviving the early post-transplantation period developed HCV recurrence, presenting as severe cholestatic hepatitis in three, and were started on antiviral treatment a median of 12 weeks (range: 5-31) after transplantation. After a median follow-up of 24 months all treated patients were alive. Biochemical response was achieved in all patients, although only one achieved a sustained virological response. Mild rejection before HCV recurrence occurred in two cases. Treatment was well tolerated with no episodes of rejection or mitochondrial toxicity. No patient required modification of the antiretroviral regimen. Liver biopsies performed in patients without virological response, 12-34 months after transplantation, showed cirrhosis in two and moderate chronic active hepatitis in the remainder. CONCLUSIONS: Despite early antiviral treatment, severe HCV recurrence after liver transplantation may compromise long-term survival in HIV-infected patients. Improved treatment strategies for these patients are urgently required.

Candida-associated denture stomatitis in patients after immunosuppression therapy.

Patients who undergo kidney or liver transplantation receive long-lasting immunosuppressive therapy. The resultant unfavorable symptoms result from immune deficiency and the side effects of the medications. The aim of this study was to establish the frequency and intensity of denture stomatitis and oral candidiasis among denture-wearing patients who were treated with immunosuppressive drugs. The study was performed in the group of denture wearers with a transplanted kidney or liver who had been treated with immunosuppressive medications. The control group included healthy people wearing dentures. We made physical and clinical examinations in both groups. The history covered nonobjective symptoms in the oral cavity, hygienic habits in the mouth, and the time span during which the dentures had been used. We also evaluated the conditions of the oral mucosal membrane, angular cheilitis, as well as denture stabilization. In both groups mycological investigations were performed by inoculating a direct swab from the oral mucosa and the denture surface on Soborauda agar. The results of our study suggest that patients with immunosuppression were more frequently subject to Candida albicans infections and stomatitis.

Peginterferon and ribavirin in patients with HCV cirrhosis after liver transplantation.

The objective of the study was to assess the efficacy of antiviral therapy in patients with hepatitis C virus (HCV) recurrence after liver transplantation (OLT). We included 30 patients of mean age 56 years, who experienced HCV recurrence after OLT. Mean time from OLT to the beginning of therapy was 57 months (median: 43 months). All of them were on monotherapy: tacrolimus (n = 21), cyclosporine (n = 6), and mycophenolate mofetil (n = 3). Fourteen had previously been diagnosed with allograft HCV cirrhosis. Patients were treated with peginterferon alpha 2b (1.5 mug/kg/weekly SC) and ribavirin (10.6 mg/kg/d) for 48 (genotypes 1, 4) or 24 weeks (genotypes 2, 3). After a mean follow-up of 20 months, two patients had died due to biliary sepsis (while on therapy) and acute myocardial infarction (7 months after the end of therapy). End of treatment virological response was achieved in 19 patients (63.3%) and sustained virological response (SUR) in 14 (46.7%). Comparing cirrhotic and noncirrhotic patients, SVR was achieved in seven patients in both groups (50% vs 43.8%; P = .732). Every patient had some adverse event; in 11 patients (36.7%) it was withdrawn (seven cirrhotic and four noncirrhotic; P < .05), and in 12 the starting dose was decreased (40%). There were neither rejection episodes nor cirrhotic complications during therapy, but infections were more common in cirrhotic patients (57% vs 25%; P < .05). In HCV cirrhotic transplanted patients the sustained virological response to combined antiviral therapy was similar to that in noncirrhotic patients, but severe adverse events including infections were much more common.

Steroid-free induction and preemptive antiviral therapy for liver transplant recipients with hepatitis C: a preliminary report from a prospective randomized study.

Recurrence of hepatitis C (HepC) has been a most difficult dilemma in liver transplantation (OLT) because the effects of immunosuppression with steroid, mycophenolate mofetil (MMF) calcineurin antagonists, and anti-interleukin-2 antibody as well as the role of preemptive antiviral therapy are uncertain. In this study, we randomized OLT recipients with HepC into two treatment arms: tacrolimus+daclizumab+MMF (study arm) versus tacrolimus+steroids+MMF (control arm). The study arm only received steroids for the treatment of biopsy-proven rejection episodes. Both arms received preemptive anti-viral therapy with Pegasys and ribavirin. The 39 enrolled patients (among 50 to be enrolled) have median follow-up of 458 days with 23 patients (8 in study arm, 15 in control arm) having reached 1 year. The incidences of rejection episodes within 0 to 3 months, 3 to 6 months, and 6 to 12 months were (study vs control): 0% vs 28%; 0% vs 6%; and 13% vs 20%; respectively (P = NS). The 1-year protocol biopsies showed advanced fibrosis (stage 3 or greater) in 20% (3 of 15) of the control arm, but none (0 of 7) of the study arm (P = NS). We compared anticipated side effects of steroids in the first 3 months (study vs control): hypertension (36% vs 58%, P = NS), PTDM (7% vs 43%, P = .02), and wound infections (14% vs 37%, P = NS). In conclusion, liver transplant recipients with HepC tolerate a steroid-free protocol. There was a trend toward reduced steroid side effects and a lower incidence of advanced fibrosis in 1-year biopsy samples among patients receiving the steroid-free protocol.

[Organ transplant patients' complex periodontal treatment]. / Szervátültetett betegek ínyhyperplasiájának komplex parodontális kezelése.

The number of organ transplant patients has increased in recent years. The Cyclosporin-A (CsA) has been used at least for 20 years to control graft rejections. As many organ transplant patients also take Ca channel blocking medication this might potentiate the CsA associated gingival hyperplasia. The outcome of the comprehensive periodontal treatment was evaluated in 14 kidney and liver transplant patients. If gingival overgrowth showed no marked reduction after thorough professional supra and subgingival plaque control either gingivectomy or flap surgery were indicated. The average age of the organ transplant patients was 38 years. 10 was man and 4 female. The daily dose of CsA ranged between 150-200 mg, and each patient took also Ca channel blocking drugs, 5-20 mg/day. S/RP alone was successful in two cases. Gingivectomy was performed in 10 cases and flap operation was indicated in two cases. Among patients with high compliance and excellent individual oral hygiene no recurrence occurred, while two patients with very low level of oral hygiene showed immediate gingival overgrowth after surgery. It is supposed that dental plaque is an important contributing factor in the development of drug induced gingival overgrowth and meticulous plaque control should be one of the most important treatment modalities in controlling drug-induced gingival changes.