Should patients with chronic hepatitis C infection be transplanted? (original) (raw)
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Saudi Journal of Gastroenterology, 2013
End stage liver disease secondary to hepatitis C virus (HCV) infection is a leading indication for liver transplantation (LT), constituting approximately 30-50% of all transplants. [1-5] HCV recurrence post-LT is universal. [3,6] Once HCV recurrence occurs, liver disease progresses at an accelerated rate. In untreated patients, acute biochemical hepatitis develops in approximately 75% of HCV recipients in the first 6 months following LT, and by the fifth postoperative year over 80% of HCV-infected liver transplant recipients will develop histologic evidence of chronic allograft injury secondary to hepatitis C, with up to 20-40% developing cirrhosis. [7,8] Nearly, 2-9% of patients with HCV recurrence will develop an aggressive cholestatic variant (i.e., fibrosing cholestatic hepatitis) that is associated with accelerated graft loss and patient death. [9,10] Overall, patients who undergo LT due to HCV have impaired patient and allograft survival compared with patients who undergo LT for other indications. [3] HCV treatment post-LT has been fraught with disappointing results with SVR rates of dual therapy (pegylated interferon
New and Evolving Management Paradigms for Hepatitis C after Liver Transplantation
Current hepatitis reports, 2011
Hepatitis-C induced liver failure is the leading indication for liver transplantation in the United States, and the burden of hepatitis C virus (HCV)-induced liver disease is not expected to peak for at least another decade. 2011 will usher in a new era of directly acting antiviral therapies and personalized medicine that will assist patients and clinicians in choosing the best drug regimen. Specific markers to predict sustained virologic response (SVR) in the posttransplant setting are under development, and the role of graft genetic markers like interleukin-28B and interferon-γ inducible protein-10 have yet to be fully defined. Lessons and experiences from treating the pretransplant population will be applied to patients with recurrent posttransplant HCV while studies specific to this population proceed. New paradigms for HCV treatment give promise to reducing the pretransplant burden of disease and improving SVR rates in the posttransplant population.
American Journal of Transplantation, 2008
Pegylated interferon (pegIFN) and ribavirin eradicates hepatitis C virus (HCV) in one third of liver recipients with recurrent disease. Side effects are frequent and potentially life threatening. Our aim was to define the long-term benefits of antiviral therapy in recurrent HCV. Eighty-nine (89) recipients (genotype 1: 86.5%) were treated with IFN (n = 31) or pegIFN (n = 58) plus ribavirin and 75 untreated contemporaneous disease-matched controls. The major end point was survival from transplantation. Survival, progression to cirrhosis and clinical decompensation since start of therapy were compared between sustained virologic responders (SVRs) and nonresponders (NRs). Results revealed 44 patients died during the follow-up (20% treated vs. 35% controls; p = 0.05). Patient survival was higher in treated compared to controls (7 years: 74% vs. 62%; p = 0.04). Among treated patients, an SVR was achieved in 37% (IFN 16% vs. peg-IFN 48%; p = 0.03). About 2/33 SVRs and 16/56 NRs died (p = 0.01) due to HCV-disease (56%), IFN-induced rejection (11%), both causes (11%) or others (22%). Five-year survival was greater in SVRs than in NRs (93% vs. 69%, p = 0.032). In patients without baseline cirrhosis, progression to cirrhosis occurred more frequently in NRs (27/42 vs. 6/16; p = 0.06). The 5-year risk of graft decompensation was higher in NRs (33% vs. 16%; p = 0.04). Antiviral therapy is associated with improved long-term outcome in recurrent HCV.
Journal of …, 2002
Background/Aims: Interferon (IFN) with ribavirin combination therapy (CT) was proposed for the treatment of hepatitis C recurring in liver transplants. We assessed the efficacy of two protocols of CT in transplanted patients with recurrent severe hepatitis C virus (HCV) hepatitis. Methods: Fifty-seven patients (68% genotype 1b) were treated with IFN alfa-2b 3 million units three times weekly and oral ribavirin 800 mg/die for 6 or 12 months. Study end-points were the end of treatment (ETVR) and the 12-month post-therapy sustained virologic response (SVR; negative HCV-RNA). Results: ETVR was induced in 9/27 (33%) and in 7/30 patients (23%) treated, respectively, for 6 and 12 months (P ¼ 0.4); a SVR was induced in six (22%) of the former and five (17%) of the latter (P ¼ 0.4). HCV genotype non-1 patients responded better than genotype 1 (SVR: 43% in genotype non-1 versus 12% in genotype 1, P: 0.02). In ETV responders the hepatitis activity index improved by .2 points in biopsies taken after therapy compared to pre-therapy biopsies. Anemia and leukopenia required reduction of therapy in 51% of the patients. Conclusions: CT is efficacious in controlling HCV disease in about 20% of transplants with recurrent hepatitis C. Six months of therapy are as efficacious as 12 months.
Hepatology, 2013
Hepatitis C virus (HCV) infection recurs in liver recipients who are viremic at transplantation. We conducted a randomized, controlled trial to test the efficacy and safety of pretransplant pegylated interferon alpha-2b plus ribavirin (Peg-IFN-a2b/RBV) for prevention of post-transplant HCV recurrence. Enrollees had HCV and were listed for liver transplantation, with either potential living donors or Model for End-Stage Liver Disease upgrade for hepatocellular carcinoma. Patients with HCV genotypes (G) 1/4/6 (n 5 44/2/ 1) were randomized 2:1 to treatment (n 5 31) or untreated control (n 5 16); HCV G2/3 (n532) were assigned to treatment. Overall, 59 were treated and 20 were not. Peg-IFN-a2b, starting at 0.75 lg/kg/week, and RBV, starting at 600 mg/day, were escalated as tolerated. Patients assigned to treatment versus control had similar baseline characteristics. Combined virologic response (CVR) included pretransplant sustained virologic response and post-transplant virologic response (pTVR), defined as undetectable HCV RNA 12 weeks after end of treatment or transplant, respectively. In intent-to-treat analyses, 12 (19%) assigned to treatment and 1 (6%) assigned to control achieved CVR (P 5 0.29); per-protocol values were 13 (22%) and 0 (0%) (P 5 0.03). Among treated G1/4/6 patients, 23 of 30 received transplant, of whom 22% had pTVR; among treated G2/3 patients 21 of 29 received transplant, of whom 29% had pTVR. pTVR was 0%, 18%, and 50% in patients treated for <8, 8-16, and >16 weeks, respectively (P 5 0.01). Serious adverse events (SAEs) occurred with similar frequency in treated versus untreated patients (68% versus 55%; P 5 0.30), but the number of SAEs per patient was higher in the treated group (2.7 versus 1.3; P 5 0.003). Conclusion: Pretransplant treatment with Peg-IFN-a2b/ RBV prevents post-transplant recurrence of HCV in selected patients. Efficacy is higher with >16 weeks of treatment, but treatment is associated with increased risk of potentially serious complications.
Liver Transplantation, 2006
Treatment of recurrent hepatitis C in liver transplant is controversial. The aim of our study was to evaluate the clinical and histological efficacy of pegylated interferon alpha 2b (PEG-IFN) and ribavirin therapy of recurrent hepatitis C after liver transplantation (LT). We prospectively included 47 liver transplant patients with: 1) a positive test for hepatitis C virus (HCV)-ribonucleic acid (RNA) in serum; 2) alanine aminotransferase (ALT) >45 UI/mL; and 3) a liver biopsy showing chronic hepatitis without rejection in the previous 2 months. Patients received PEG-IFN (1.5 μg/kg/week) and ribavirin (800-1,000 mg/day) for 12 months. Follow-up was based on biochemical (ALT), virological (RNA-HCV), and histological (liver biopsy) examinations. Follow-up lasted a minimum of 6 months after the end of antiviral therapy. Sustained virological response (SVR) was achieved in 23% of the patients. A total of 33 (70%) patients had normalized ALT levels at the end of therapy. Inflammatory portal and lobular score declined significantly in patients with SVR (P < 0.05) but not in nonresponder patients. Fibrosis did not change significantly in either group. SVR was significantly associated with low γ-glutamyltransferase GGT (P = 0.04) and HCV-RNA levels (P = 0.03), a virological response at 12 weeks (P = 0.002) and patient's compliance (P = 0.04). Ten (21%) patients were withdrawn prematurely due to adverse effects. In conclusion, Therapy with PEG-IFN and ribavirin achieved SVR and a significant histological improvement in 23% of liver transplant recipients with chronic hepatitis C. Toxicity is an important drawback of this therapy. Liver Transpl 12:1805-1812, 2006. © 2006 AASLD.
Transplantation Proceedings, 2001
H EPATITIS C virus (HCV)-related cirrhosis is currently a leading indicator for orthotopic liver transplantation (OLT) worldwide, and results of several studies have confirmed that persistence of HCV infection is almost universal in HCV-RNA ϩ recipients. In fact, about 50% of such patients suffer chronic hepatitis of some severity, and about 30% of liver recipients develop cirrhosis within 5 years. 1,2 Interferon therapy for recurrent hepatitis C after liver transplantation has shown low efficacy once histologic hepatitis is established, 3,4 whereas recent studies have pointed out that combination therapy with interferon-␣2b (IFN) and ribavirin induces a high rate of sustained response (40% to 50%) in nontransplant patients with HCV chronic hepatitis. In the present study we tested a novel approach of combination of IFN and ribavirin, starting treatment 3 weeks after liver replacement. Such a strategy is based on the hypothesis that eradication of HCV could be optimized if therapy is instituted in the early phases following liver transplantation, when the viral load in the recipient may be lower and the graft still uninjured. 7
The road map toward an hepatitis C virus-free transplant population
American Journal of Transplantation, 2018
In patients with active hepatitis C virus (HCV) infection at the time of liver transplantation (LT), recurrence is universal. 1 Moreover, since HCV-associated liver disease is a leading indication for LT, this is a common problem in clinical practice. 2,3 HCV recurrence may clinically manifest as a rapidly progressive disease 4,5 with 20% to 40% of patients developing graft cirrhosis within 5 years, 1 followed by decompensation in <1 year in 50% of these patients 6,7 resulting in impaired graft and patient survival overall. 8,9 Numerous factors are associated with more progressive disease, 10 but few can be prospectively modified. Thus prevention of severe HCV recurrence rests primarily on antiviral therapy, with the ultimate aim of eliminating HCV either before, at the time of, or post-LT. We review current data on interferon (IFN)-free therapy in the transplant setting, discuss how to optimize outcomes with directacting antiviral agents (DAAs), and consider areas of uncertainty that require further data. In preparing this opinion piece, MedLine databases were searched for data on the use of DAAs in the liver transplant setting using the search terms "hepatitis C,