RESUMO
Fibrosing cholestatic hepatitis (FCH) is a less common but well-recognized severe complication of recurrent hepatitis C virus (HCV) infection post-liver transplant. This condition is fatal without successful treatment and to date; post-transplant antiviral interferon-based antiviral therapy has been associated with guarded success. The new era of protease inhibitors in the treatment of chronic HCV infection may alter the dismal outcome of this condition. To date, however, the experience with protease inhibitors in this condition is unreported. We report a post-liver transplant recipient with HCV associated FCH treated successfully with boceprevir, peginteferon and ribavirin for severe FCH. The patient was young woman who was a null responder pre-transplant to peginterferon and ribavirin. The peak serum bilirubin 391 µmol/L normalized to 15 µmol/L by week 8 of therapy. The pre-treatment HCV viral load of > 78 million IU/mL, decreased to 78 IU/mL at week 8 of therapy and was undetectable by week 12 and at the end of 48 week of treatment. 12 weeks post treatment, the HCV viral load remains undetectable. Significant anemia and neutropenia were encountered. Tacrolimus dosage titrated to trough levels, required marked reduction to 0.5 mg three times weekly. Despite the suboptimal peginterferon and ribavirin dosing, limited by adverse effects, full boceprevir dosing was maintained, with resolution of liver dysfunction. Boceprevir was obtained on compassionate grounds from the manufacturer before its licensure in Canada and this was the first use of boceprevir in the world for post-transplant FCH.
Assuntos
Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Transplante de Fígado , Polietilenoglicóis/uso terapêutico , Prolina/análogos & derivados , Ribavirina/uso terapêutico , Carga Viral/efeitos dos fármacos , Adulto , Quimioterapia Combinada , Feminino , Hepacivirus , Humanos , Imunossupressores/uso terapêutico , Interferon alfa-2 , Prolina/uso terapêutico , RNA Viral/sangue , Proteínas Recombinantes/uso terapêutico , Tacrolimo/uso terapêutico , Resultado do TratamentoRESUMO
Recurrent hepatitis C virus (HCV) infection after liver transplantation is a significant cause of morbidity, mortality and graft loss. Spontaneous clearance of recurrent HCV after liver transplant is a rarely reported phenomenon. We report a case of a 66-year-old woman who underwent liver transplantation for HCV cirrhosis (treatment- naive genotype 2) under immunosuppression with tacrolimus, mycophenolate mofetil (MMF), and short-term corticosteroids. The patient developed histologically proved severe cholestatic recurrence of HCV hepatitis. Immunosuppression was reduced to tacrolimus monotherapy because of cytopenia. She subsequently became RNA negative at week 44 post- transplant while on tacrolimus and MMF despite no antiviral therapy. A spontaneous sustained virologic clearance was confirmed with subsequent HCV nucleotide testing. Only a few similar cases have been reported in the literature with uninterrupted immunosuppression and subsequent spontaneous clearance. Our experience, and the few other published cases in the literature, suggests that spontaneous clearance of HCV after liver transplantation is a rare but real phenomenon. Better understanding of this phenomenon may help to manage recurrent HCV disease after transplantation.
Assuntos
Hepatite C/cirurgia , Cirrose Hepática/cirurgia , Transplante de Fígado/efeitos adversos , Idoso , Biópsia , Quimioterapia Combinada , Feminino , Hepacivirus/genética , Hepatite C/complicações , Hepatite C/diagnóstico , Humanos , Imunossupressores/uso terapêutico , Cirrose Hepática/virologia , RNA Viral/sangue , Recidiva , Remissão Espontânea , Fatores de Tempo , Resultado do Tratamento , Carga ViralRESUMO
OBJECTIVE: To evaluate the survival benefit of multimodal therapy for the treatment of HCC. BACKGROUND: Orthotopic liver transplantation (OLT) is considered the treatment of choice for selected patients with hepatocellular carcinoma (HCC). However, donor organ shortages and patients whose HCCs exceed OLT criteria require consideration of alternate therapeutic options such as hepatic resection, radiofrequency ablation (RFA), ethanol injection (EI), transarterial chemoembolization (TACE), and chemotherapy (CTX). This study was performed to evaluate the survival benefit of multimodal therapy for treatment of HCC as complementary therapy to OLT. METHODS: A retrospective review was conducted of HCC patients undergoing therapy following multidisciplinary review at our institution from 1996 . 2006 with a minimum of a 2 year patient follow-up. Data were available on 247/252 patients evaluated. Relevant factors at time of diagnosis included symptoms, hepatitis B (HBV) and C (HCV) status, antiviral therapy, Child-Pugh classification, portal vein patency, and TNM staging. Patients underwent primary treatment by hepatic resection, RFA, EI, TACE, CTX, or were observed (best medical management). Patients with persistent or recurrent disease following initial therapy were assessed for salvage therapy. Survival curves and pairwise multiple comparisons were calculated using standard statistical methods. RESULTS: Mean overall survival was 76.8 months. Pairwise comparisons revealed significant mean survival benefits with hepatic resection (93.2 months), RFA (66.2 months), and EI (81.1 months), compared with TACE (47.4 months), CTX (24.9 months), or observation (31.4 months). Shorter survival was associated with symptoms, portal vein thrombus, or Child-Pugh class B or C. HCV infection was associated with significantly shorter survival compared with HBV infection. Antiviral therapy was associated with significantly improved survival in chronic HBV and HCV patients only with earlier stage disease. CONCLUSION: Multimodal therapy is effective therapy for HCC and may be used as complementary treatment to OLT.
Assuntos
Carcinoma Hepatocelular/terapia , Terapias Complementares , Neoplasias Hepáticas/terapia , Transplante de Fígado , Idoso , Carcinoma Hepatocelular/mortalidade , Ablação por Cateter , Quimioembolização Terapêutica , Terapia Combinada , Tratamento Farmacológico , Etanol/administração & dosagem , Feminino , Hepatectomia , Humanos , Injeções , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Hepatic artery thrombosis (HAT) is relatively infrequent, but possibly a devastating complication of orthotopic liver transplantation (OLT). It often requires urgent retransplantation. Two main forms of HAT are recognized as early and late HAT (diagnosis within or after 30 days following LT). Early HAT typically results in graft failure. Late HAT features biliary obstruction, cholangitis, and hepatic abscess formation. We report here the case of a patient of Wilson's disease who presented twelve years post-liver transplant symptoms typical of acute HAT and hepatic infarction. On diagnostic imaging, celiac axis and hepatic artery were thrombosed, resulting in ischemic necrosis of the left hepatic lobe. The resulting sepsis and transient hepatic insufficiency were managed conservatively, and repeat OLT was avoided. The patient remains stable more than one year later. To the best of our knowledge this case report is unique in the literature for the unusually long interval between OLT and late acute HAT, as well as celiac and portal vein occlusion. The acute presentation of sub massive hepatic necrosis is also uncharacteristic of late HAT and more typical of acute HAT. This report describes our experience in managing this and a literature review of the topic.
Assuntos
Artéria Celíaca , Artéria Hepática , Infarto/etiologia , Transplante de Fígado , Fígado/irrigação sanguínea , Veia Porta , Trombose/complicações , Adulto , Humanos , Infarto/diagnóstico , Fígado/diagnóstico por imagem , Masculino , Trombose/diagnóstico , Tomografia Computadorizada por Raios XRESUMO
The prevalence of obesity is increasing globally, with nearly half of a billion of the world's population now considered to be overweight or obese. Obesity and overweight patients are one of the major health issues in Canada, resulting in approximately 57,000 deaths related to obesity over the last 15 years. The effect of obesity on outcomes following liver transplantation remains largely unclear. To determine the effect of obesity on outcome we reviewed 167 liver transplants, performed at the Vancouver General Hospital, between February 1999 and October 2003. Severe obesity was defined as body mass index (BMI) > 35 kg/m2 and moderate obesity as BMI of 30 - 34 kg/m2. One hundred forty three transplants were performed in patients with a body mass index (BMI) < 30 kg/m2, 14 in patients with a BMI of 30 - 34 kg/m2, and 10 in patients with a BMI > 35 kg/m2. Non-weight related patient demographics were similar between the groups. A very high proportion of Hepatitic C patients (7/10) were observed in the severely obese group. In the early postoperative course severely obese patients had a higher rate of wound infection (20% vs. 4%, p = 0.0001) and wound dehiscence (40% vs. 1.2%, p = 0.0001). Within the first twelve postoperative months severely obese liver transplant recipients had a higher rate of ventral wound herniation (30% vs. 2.8%, p = 0.0001) when compared to obese or non-obese recipients. The one-year graft and patient survival were similar to non-obese patients. An increased BMI in liver transplant recipients in our centre did not increase the risk of early postoperative mortality, but did increase surgical complications, such as wound infection and wound dehiscence. The 1-year patient and graft survival however was indistinguishable from those of non-obese patients.
Assuntos
Hepatopatias/mortalidade , Hepatopatias/cirurgia , Transplante de Fígado/mortalidade , Obesidade/complicações , Obesidade/mortalidade , Adulto , Índice de Massa Corporal , Canadá/epidemiologia , Feminino , Sobrevivência de Enxerto , Humanos , Hepatopatias/complicações , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Obesidade/cirurgia , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Deiscência da Ferida Operatória/etiologia , Infecção da Ferida Cirúrgica/etiologia , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Calcineurin inhibitors (CNIs) provide effective immunosuppression after orthotopic liver transplantation (OLTx), but the associated nephrotoxicity can cause substantial morbidity and mortality among transplant patients. In this study, we retrospectively investigated the efficacy and safety of mycophenolate mofetil (MMF) in OLTx patients with CNI-induced renal impairment. PATIENTS & METHODS: A chart review was undertaken of all liver transplant recipients followed at the Vancouver General Hospital. Twenty-one (12 male) patients were converted to either MMF monotherapy (n = 18) or MMF with corticosteroids (n = 3) for CNI-induced renal dysfunction. Six were excluded because of other factors contributing to renal dysfunction. Mean time from OLTx to conversion was 11.3 years and mean age was 60. Non-parametric Wilcoxon's signed rank testing was used to determine whether there was a difference between the serum creatinine (SCr) before conversion, and 3 or 6 months after conversion. RESULTS: Median follow-up was 294 days, ranging from 35 to 1103 days. The median SCr was significantly reduced from 144 micromol/L before conversion to 129 micromol/L and 139 micromol/L at 3 and 6 months follow-up (p = 0.001 and 0.008, respectively). MMF was well tolerated. Only one patient (6.7%) had elevated liver enzymes and required addition of sirolimus while two (13.4%) experienced gastrointestinal intolerance. CONCLUSIONS: MMF appears to be safe for stable OLTx recipients with CNI-induced nephrotoxicity. Serious side effects were uncommon as only one patient required discontinuation of the medication. However, longer follow-up and larger study populations are needed in the future to better determine its efficacy and safety.