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HCV Recurrence (hcv + recurrence)
Selected AbstractsTherapeutic management of recurrent hepatitis C after liver transplantationLIVER INTERNATIONAL, Issue 3 2007Rosāngela Teixeira Abstract Recurrent hepatitis C ranges from minimal damage to cirrhosis developing in a few months or years in a substantial proportion of transplant recipients. Different virus, host and donor factors are involved in the pathogenesis of recurrence, but many are poorly understood. Therapeutic strategies can be utilized in the pre-, peri- or posttransplantation setting. Antiviral therapy using interferon and ribavirin and modifying immunosuppression are the main strategies to prevent progression disease. The efficacy of interferon and ribavirin is limited and side effects, reduction/withdrawal are frequent. Current sustained virological response rates are approximately 28%. An optimal immunosupppression regimen has not been established. The choice of calcineurin inhibitors has not clearly been shown to affect histological hepatitis C virus (HCV) but higher cumulative exposure to corticosteroids to treat acute rejection is associated with more severe recurrence. The manner in which the doses of immunosuppression are modified has more influence on HCV recurrence than the use of a specific drug per se. Debate about the influence of immunosuppressive regimens on HCV recurrence is ongoing. Potential antifibrotic therapy and new agents targeting HCV infection and replication are emerging and are anticipated to be added to our armentarium in battling recurrent HCV post-LT. [source] Enfuvirtide: A safe and effective antiretroviral agent for human immunodeficiency virus,infected patients shortly after liver transplantationLIVER TRANSPLANTATION, Issue 10 2009Elina Teicher The aim of this study was to evaluate the impact of an enfuvirtide-based antiretroviral (ARV) regimen on the management of immunosuppression and follow-up in hepatitis C virus (HCV)/hepatitis B virus (HBV)/human immunodeficiency virus (HIV),coinfected liver transplant patients in comparison with a lopinavir/ritonavir-based ARV regimen. Tacrolimus and cyclosporine trough concentrations were determined at a steady state during 3 periods: after liver transplantation without ARV treatment (period 1), at the time of ARV reintroduction (period 2), and 2 to 3 months after liver transplantation (period 3). The findings for 22 HIV-coinfected patients were compared (18 with HCV and 4 with HBV); 11 patients were treated with enfuvirtide and were matched with 11 lopinavir/ritonavir,exposed patients. During period 1, tacrolimus and cyclosporine A doses were 8 and 600 mg/day, respectively, and the trough concentrations were within the therapeutic range in both groups. In period 2, the addition of lopinavir/ritonavir to the immunosuppressant regimen enabled a reduction in the dose of immunosuppressants required to maintain trough concentrations within the therapeutic range (to 0.3 mg/day for tacrolimus and 75 mg/day for cyclosporine). Immunosuppressant doses were not modified by the reintroduction of enfuvirtide, there being no change in the mean trough concentrations over the 3 periods. CD4 cell counts remained at about 200 cells/mm. The HIV RNA viral load remained undetectable. Both groups displayed signs of mild cytolysis and cholestasis due to the recurrence of HCV, whereas no renal insufficiency was observed. Enfuvirtide is an attractive alternative to standard ARV therapy, facilitating the management of drug-drug interactions shortly after liver transplantation. Moreover, the lack of liver toxicity renders this drug valuable in the event of a severe HCV recurrence. Liver Transpl 15:1330,1335, 2009. © 2009 AASLD. [source] Impact of immunosuppression without steroids on rejection and hepatitis C virus evolution after liver transplantation: Results of a prospective randomized studyLIVER TRANSPLANTATION, Issue 12 2008Laura Lladó The purpose of this study was to evaluate the influence of a steroid-free immunosuppression on hepatitis C virus (HCV) recurrence. A total of 198 liver transplantation (LT) patients were randomized to receive immunosuppression with basiliximab and cyclosporine, either with prednisone (steroid [St] group) or without prednisone (no steroids [NoSt] group). The group of 89 HCV-infected patients was followed up with protocol biopsies for 2 years after LT. This group of HCV patients are the patients evaluated in the present study. The rejection rate was 19% (St: 21% versus NoSt: 17%; P = 0.67). Patients in the St group had a slightly higher rate of bacterial infections (59% versus 38%; P = 0.05). Almost all patients had histological HCV-recurrence (St: 39/40 (97%) versus NoSt: 40/41 (97%); P = 1). The percentage of accumulated biopsies with grade 4 portal inflammation at 6 months, 1 year, and 2 years were, 23%, 49%, and 49% in the NoSt group, compared to 33%, 55%, and 69% in the St group, respectively (P = 0.04 at 2 years). The percentage of accumulated biopsies with grade 3 or 4 fibrosis at 6 months, 1 year, and 2 years were 0%, 8%, and 22% in the NoSt group, compared to 8%, 19%, and 31% in the St group, respectively. Immunosuppression without steroids in HCV patients is safe, reduces bacterial infections and metabolic complications, and improves histological short-term evolution of HCV recurrence. Liver Transpl 14:1752,1760, 2008. © 2008 AASLD. [source] Steroid avoidance in liver transplantation: Meta-analysis and meta-regression of randomized trialsLIVER TRANSPLANTATION, Issue 4 2008Dorry L. Segev Steroid use after liver transplantation (LT) has been associated with diabetes, hypertension, hyperlipidemia, obesity, and hepatitis C (HCV) recurrence. We performed meta-analysis and meta-regression of 30 publications representing 19 randomized trials that compared steroid-free with steroid-based immunosuppression (IS). There were no differences in death, graft loss, and infection. Steroid-free recipients demonstrated a trend toward reduced hypertension [relative risk (RR) 0.84, P = 0.08], and statistically significant decreases in cholesterol (standard mean difference ,0.41, P < 0.001) and cytomegalovirus (RR 0.52, P = 0.001). In studies where steroids were replaced by another IS agent, the risks of diabetes (RR 0.29, P < 0.001), rejection (RR 0.68, P = 0.03), and severe rejection (RR 0.37, P = 0.001) were markedly lower in steroid-free arms. In studies in which steroids were not replaced, rejection rates were higher in steroid-free arms (RR 1.31, P = 0.02) and reduction of diabetes was attenuated (RR 0.74, P = 0.2). HCV recurrence was lower with steroid avoidance and, although no individual trial reached statistical significance, meta-analysis demonstrated this important effect (RR 0.90, P = 0.03). However, we emphasize the heterogeneity of trials performed to date and, as such, do not recommend basing clinical guidelines on our conclusions. We believe that a large, multicenter trial will better define the role of steroid-free regimens in LT. Liver Transpl 14:512,525, 2008. © 2008 AASLD. [source] Corticosteroid-free immunosuppression with daclizumab in HCV+ liver transplant recipients: 1-year interim results of the HCV-3 study,LIVER TRANSPLANTATION, Issue 11 2007Goran B.G. Klintmalm This work is a 1-yr interim analysis of a prospective, randomized, multicenter trial evaluating the effect of corticosteroid-free immunosuppression on hepatitis C virus,positive (HCV+) liver transplant recipients following liver transplantation (LT). Patients received tacrolimus and corticosteroids (Arm 1; n = 80); tacrolimus, corticosteroids, and mycophenolate mofetil (MMF) (Arm 2; n = 79); or daclizumab induction, tacrolimus, and MMF (Arm 3; n = 153). At 1 yr, 64.1%, 63.4%, and 69.4% of patients achieved the composite primary endpoint of freedom from rejection, freedom from HCV recurrence, and freedom from treatment failure, respectively. Excellent patient and graft survival did not differ significantly among treatment arms. Freedom from HCV recurrence at 1 yr was 61.8 ± 6.2%, 60.1 ± 6.1%, and 67.0 ± 4.3% in Arms 1, 2, and 3, respectively (P = not significant). Freedom from rejection was significantly higher in Arm 3 compared to Arm 1 (93.0 ± 2.2% vs. 81.9 ± 4.4%; P = 0.011). Multivariate analysis identified acute rejection (hazard ratio = 2.692; P = 0.001) and donor age (hazard ratio = 1.015; P = 0.001) as significant risk factors for HCV recurrence. HCV recurrence was not influenced by recipient demographics, HCV genotype, or immunosuppression. In conclusion, these results suggest that a corticosteroid-free regimen of tacrolimus and MMF following daclizumab induction is safe and effective in HCV+ liver transplant recipients. Liver Transpl 13:1521,1531, 2007. © 2007 AASLD. [source] Recurrent hepatitis C after retransplantation: Factors affecting graft and patient outcome,LIVER TRANSPLANTATION, Issue 12 2005Michal Carmiel-Haggai Retransplantation (re-LT) of patients with recurrent hepatitis C virus (HCV) carries significant morbidity and mortality, negatively impacting on an already scarce donor allograft pool. In this study, we investigated the outcome of allografts and patients after re-LT due to recurrent HCV. Between 1989 and 2002, 47 patients were retransplanted at our institution due to HCV-related graft failure. Clinical HCV recurrence after re-LT was diagnosed when patients had acute liver enzyme elevation correlated with histological recurrence. The independent influence of these variables on survival was tested using Cox regression model. Chi-squared tests were used to examine the influence of individual demographic and pre/perioperative variables on recurrence. Thirty-one (66%) patients died after re-LT (median 2.2 months). Donor age >60, clinical HCV recurrence, and graft failure due to cirrhosis were significant risk factors for mortality (risk ratios of 3.6, 3.3, and 2.4, respectively). Pre-LT MELD score was lower among survivors (22± 5 vs. 27± 8). Following re-LT, 38 patients had at least one biopsy due to acute liver dysfunction; 19 of them (50%) had recurrence within the first 3 months. High-dose solumedrol was correlated with early recurrence. No association was found between time of recurrence after the first LT and time of recurrence after re-LT. In conclusion, patients with cirrhosis due to recurrent HCV undergoing re-LT have an extremely high mortality rate; older allografts should be avoided in retransplanting these patients. The timing of clinical recurrence after initial liver transplantation is not predictive of the timing of recurrence after re-LT. Patients experiencing early graft failure due to accelerated forms of HCV should not be denied re-LT with the expectation that a similar disease course will occur after re-LT. (Liver Transpl 2005;11:1567,1573.) [source] Immunosuppression for liver transplantation in HCV-infected patients: Mechanism-based principlesLIVER TRANSPLANTATION, Issue 11 2005Bijan Eghtesad We retrospectively analyzed 42 hepatitis C virus (HCV)-infected patients who underwent cadaveric liver transplantation under two strategies of immunosuppression: (1) daily tacrolimus (TAC) throughout and an initial cycle of high-dose prednisone (PRED) with subsequent gradual steroid weaning, or (2) intraoperative antithymocyte globulin (ATG) and daily TAC that was later space weaned. After 36 ± 4 months, patient and graft survival in the first group was 18/19 (94.7%) with no examples of clinically serious HCV recurrence. In the second group, the three-year patient survival was 12/23 (52%), and graft survival was 9/23 (39%); accelerated recurrent hepatitis was the principal cause of the poor results. The data were interpreted in the context of a recently proposed immunologic paradigm that is equally applicable to transplantation and viral immunity. In the framework of this paradigm, the disparate hepatitis outcomes reflected different equilibria reached under the two immunosuppression regimens between the relative kinetics of viral distribution (systemically and in the liver) and the slowly recovering HCV-specific T-cell response. As a corollary, the aims of treatment of the HCV-infected liver recipients should be to predict, monitor, and equilibrate beneficial balances between virus distribution and the absence of an immunopathologic antiviral T-cell response. In this view, favorable equilibria were accomplished in the nonweaned group of patients but not in the weaned group. In conclusion, since the anti-HCV response is unleashed when immunosuppression is weaned, treatment protocols that minimize disease recurrence in HCV-infected allograft recipients must balance the desire to reduce immunosuppression or induce allotolerance with the need to prevent antiviral immunopathology. (Liver Transpl 2005;11:1343,1352.) [source] Factors that identify survival after liver retransplantation for allograft failure caused by recurrent hepatitis C infectionLIVER TRANSPLANTATION, Issue 12 2004Guy W. Neff Hepatitis C virus (HCV) is becoming the most common indication for liver retransplantation (ReLTx). This study was a retrospective review of the medical records of liver transplant patients at our institution to determine factors that would identify the best candidates for ReLTx resulting from allograft failure because of HCV recurrence. The patients were divided into 2 groups on the basis of indication for initial liver transplant. Group 1 included ReLTx patients whose initial indication for LTx was HCV. Group 2 included patients who received ReLTx who did not have a history of HCV. We defined chronic allograft dysfunction (AD) as patients with persistent jaundice (> 30 days) beginning 6 months after primary liver transplant in the absence of other reasons. HCV was the primary indication for initial orthotopic liver transplantation (OLT) in 491/1114 patients (44%) from July 1996 to February 2004. The number of patients with AD undergoing ReLTx in Groups 1 and 2 was 22 and 12, respectively. The overall patient and allograft survival at 1 year was 50% and 75% in Groups 1 and 2, respectively (P = .04). The rates of primary nonfunction and technical problems after ReLTx were not different between the groups. However, the incidence of recurrent AD was higher in Group 1 at 32% versus 17% in Group 2 (P = .04). Important factors that predicted a successful ReLTx included physical condition at the time of ReLTx (P = .002) and Child-Turcotte-Pugh score (P = .008). In conclusion, HCV is associated with an increased incidence of chronic graft destruction with a negative effect on long-term results after ReLTx. The optimum candidate for ReLTx is a patient who can maintain normal physical activity. As the allograft shortage continues, the optimal use of cadaveric livers continues to be of primary importance. The use of deceased donor livers in patients with allograft failure caused by HCV remains a highly controversial issue. (Liver Transpl 2004;10:1497,1503.) [source] Hepatitis C: Magnitude of the problemLIVER TRANSPLANTATION, Issue 10B 2002Jorge Rakela MD 1End-stage liver disease associated with hepatitis C virus (HCV) infection has become the leading indication for liver transplantation in the United States. 2Patients with end-stage liver disease caused by HCV may have such associated comorbidities as chronic alcoholism, steatosis, or coinfection with human immunodeficiency virus 1 or other hepatitis viruses. These comorbidities may accelerate disease progression. 3As chronic hepatitis C progresses to cirrhosis, the risk for the development of hepatocellular carcinoma increases; this poses difficult management problems. 4As patients who underwent transplantation for end-stage liver disease caused by HCV infection are followed up long term, it has become clear that patient and graft survival are decreased compared with HCV-negative patients or those with cholestatic liver disorders. 5Risk factors associated with a worse outcome after transplantation include host, viral, donor, and posttransplantation factors. 6Major challenges to be addressed in the future include delineation of the optimal antiviral therapy and how to handle the need to perform retransplantation on patients who develop graft dysfunction as a result of HCV recurrence. [source] Increased Expression of Regulatory Tr1 Cells in Recurrent Hepatitis C after Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009A. Carpentier Immune response failure during HCV infection has been associated with the activity of regulatory T cells. Hepatitis C-related cirrhosis is the main reason for liver transplantation. However, 80% of transplanted patients present an accelerated recurrence of the disease. This study assessed the involvement of regulatory T-cell subsets (CD4+CD25+ cells: ,Treg' and CD49b+CD18+ cells: ,T regulatory-1' cells), in the recurrence of HCV after liver transplantation, using transcriptomic analysis, ELISA assays on serum samples and immunohistochemistry on liver biopsies from liver recipients 1 and 5 years after transplantation. Three groups of patients were included: stable HCV-negative recipients and those with mild and severe hepatitis C recurrence. At 5 years, Treg markers were overexpressed in all HCV+ recipients. By contrast, Tr1 markers were only overexpressed in patients with severe recurrence. At 1 year, a trend toward the overexpression of Tr1 was noted in patients evolving toward severe recurrence. IL-10 production, a characteristic of the Tr1 subset, was enhanced in severe recurrence at both 1 and 5 years. These results suggest that Tr1 are enhanced during severe HCV recurrence after liver transplantation and could be predictive of HCV recurrence. High levels of IL-10 at 1 year could be predictive of severe recurrence, and high IL-10 producers might warrant more intensive management. [source] A Practical Guide to the Management of HCV Infection Following Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009K. Watt 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 , 17 or as soon as histological evidence of recurrence of HCV is apparent post-LT. Because of the high frequency of hemotoxicity and renal insufficiency, ribavirin should be dosed according to renal function. [source] Hepatitis C Virus Compartmentalization and Infection Recurrence after Liver TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2009S. Ramirez Hepatitis C virus (HCV) compartmentalization may have important implications in the pathogenesis of HCV infection. The aim of this study was to investigate the presence and relevance of HCV compartmentalization in the setting of liver transplantation (LT). We collected samples of serum, peripheral blood mononuclear cells (PBMC), perihepatic lymph nodes (PLN) and liver explant at the time of LT, and serum and PBMC after transplantation from 57 HCV-infected cirrhotic patients undergoing LT: 38 individuals received antiviral treatment before LT and 19 were untreated controls. HCV-RNA levels were determined by real-time PCR and the hypervariable region 1 (HVR-1) was sequenced. HCV-RNA was detected in all samples from control patients. In virological responders, recurrence after LT was associated with residual HCV-RNA in the liver explant. Within the entire cohort, 47% of patients harbored differences in direct sequences from distinct compartments. Quasispecies analysis revealed that in most cases, HVR-1 sequences recovered after infection recurrence were identical or closely related to those isolated from the liver explant and serum at the time of LT. Our study shows that a significant proportion of HCV-infected cirrhotic patients exhibit compartmentalization. Viral variants originating within the liver appear to be the main cause of HCV recurrence after LT. [source] Post-transplant reactivation of hepatitis C virus: lymphocyte infiltration and the expression of adhesion molecules and their ligands in liver allografts,APMIS, Issue 4 2006KATRI LIPSON Hepatitis C virus (HCV) recurrence after liver transplantation has been associated with chronic rejection. Biopsies from 10 patients with post-transplant HCV were examined for expression of adhesion molecules ICAM-1, VCAM-1, and ELAM-1, number of lymphocytes positive for their ligands LFA-1, VLA-4, and SLeX, and activation markers MHC class II antigens and IL2-R by immunohistochemistry. The phenotypes of the graft-infiltrating lymphocytes were determined. Results were compared to those for patients with normal graft function or rejection. Five recipients with HCV reactivation and one with de novo HCV had a biopsy available showing induction of ICAM-1 in sinusoidal endothelium (p<0.05) and hepatocytes (p<0.01), and Class II antigens in hepatocytes (p<0.01), compared to normal controls. Lymphocytes in the graft infiltrate expressed LFA-1, VLA-4, and Class II antigens, but IL2-R was not significantly expressed. CD3+, CD4+, and CD8+ cells were observed. In our study, HCV recurrence was not associated with acute or chronic rejection, and the inflammation was due to the viral infection. [source] Impact of human herpesvirus-6 on the frequency and severity of recurrent hepatitis C virus hepatitis in liver transplant recipientsCLINICAL TRANSPLANTATION, Issue 2 2002Nina Singh A role of tumor necrosis factor-alpha (TNF-,) In the immunopathogenesis of hepatitis C virus (HCV) infection has been proposed. The novel herpes virus, human herpes virus-6 (HHV-6), is amongst the most potent inducers of cytokines, including TNF-,. The impact of HHV-6 viremia on the progression of recurrent HCV hepatitis was assessed in 51 HCV-positive liver transplant recipients. The frequency of recurrent HCV hepatitis did not differ between patients with HCV viremia (47.6%, 10/21) as compared with those without HCV viremia (46.7%, 14/30, p=0.9). However, the patients with HHV-6 viremia had a significantly higher fibrosis score upon HCV recurrence than those without HHV-6 viremia (mean 1.5 vs. 0.3, p=0.01). An association between cytomegalovirus (CMV) viremia and HCV recurrence was not documented; 50% (15/30) of the patients with CMV viremia and 42.8% (9/21) of those without CMV viremia had recurrent HCV hepatitis (p > 0.5). Receipt of ganciclovir (administered upon the detection of CMV viremia) was associated with lower total Knodell score (mean 5.2 vs. 6.9, p=0.05) and a trend towards lower fibrosis score (mean 0.44 vs. 1.00, p=0.12) in patients with recurrent HCV hepatitis. Thus, HHV-6 viremia in HCV-positive liver transplant recipients identified a subgroup of patients at increased risk for early fibrosis upon HCV recurrence. [source] | ||||||||||