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The question of when to treat liver transplant patients with chronic hepatitis C virus (HCV) infection is vital. HCV is the diagnosis most commonly leading to liver transplantation, and recurrence of HCV after transplant is nearly universal. An estimated 30% of HCV liver transplant recipients experience recurrence within five years of transplantation, resulting in death or loss of the allograft because of cirrhosis or graft failure.1 Thus, if we knew when and how to treat HCV in this population, we could envision a world in which liver transplants would not be required—and certainly one in which retransplant because of HCV would never be needed.
In planning to treat HCV-positive patients who need a liver transplant, the question arises: Do we treat them preoperatively, perioperatively, or postoperatively? And if we select postoperative treatment, do we wait until the graft shows HCV recurrence, or do we treat prophylactically—knowing that recurrence is likely?
Results from multiple small studies of interferon-free treatment of HCV, both prior to and following recurrence of HCV posttransplant, have been reported. The SOLAR trial, which used ribavirin plus sofosbuvir, demonstrated a sustained viral response (SVR) rate of 70%.2 The SOLAR-1 trial of ledipasvir/sofosbuvir (Harvoni®) plus ribavirin in patients with genotype 1 or 4 who were treated following posttransplant recurrence showed an average SVR rate of 96%.3 Duration of treatment varied, depending on genotype and presence of cirrhosis, and there was differing dosing and addition of ribavirin at multiple doses. A 10% mortality rate was reported, but deaths occurred mainly in patients with severe cirrhosis.
A small trial was also conducted of genotype 3 patients treated with ledipasvir/sofosbuvir, with or without ribavirin.4 The addition of ribavirin appeared to shorten treatment, but patients in both treatment groups had excellent rates of SVR. However, further study is needed before this combination of medications can be recommended and/or FDA approved. Full details are available at http://hcvguidelines.org.
Ombitasvir/paritaprevir/ ritonavir with dasabuvir (Viekira Pak™) plus ribavirin for 24 weeks was evaluated in patients with HCV recurrence following liver transplant.5 This group of patients had very minimal fibrosis and essentially normal liver function. In this study group, an SVR rate exceeding 95% was achieved.
Continue for data on treatment of patients >>
The data on treatment of patients who need a transplant or who experience HCV recurrence posttransplant are very encouraging. If the SVR rates are maintained over time, it may be possible to significantly decrease the requirement for retransplantation—or even transplant in the first place. As transplant is not without significant morbidity and mortality, especially in the recurrence group, avoiding it would allow patients to live longer and healthier lives. More work is needed to understand the optimal time to treat and the best and safest regimens. Numerous trials evaluating these important management questions are ongoing.6-9
In the not-too-distant future, the requirement for liver transplantation in patients with chronic HCV infection is likely to decrease substantially. A recent New England Journal of Medicine editorial discussing liver allocation concluded that transplant centers now treating significant numbers of patients with HCV cirrhosis may soon be idle.10
If only we could be so lucky ...
REFERENCES
1. Watt K, Veldt B, Charlton M. A practical guide to the management of HCV infection following liver transplantation. Am J Transplant. 2009;9(8):1707-1713.
2. Charlton M, Gane E, Manns MP, et al. Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation. Gastroenterology. 2015;148(1):108-117.
3. Reddy KR, Everson GT, Flamm SL, et al. Ledipasvir/sofosbuvir with ribavirin for the treatment of HCV in patients with post transplant recurrence: preliminary results of a prospective, multicenter study. Presented at: 65th Annual Meeting of the American Association for the Study of Liver Diseases; November 7-11, 2014; Boston, MA. Abstract 8.
4. Kohler JJ, Nettles JH, Amblard F, et al. Approaches to hepatitis C treatment and cure using NS5A inhibitors. Infect Drug Resist. 2014;7:41-56.
5. Curry MP, Forns X, Chung RT, et al. Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open-label study. Gastroenterology. 2015;148(1):100-107.
6. A Phase 2 open-label study in patients with recurrent genotype 1 hepatitis C post–orthotopic liver transplant to explore the safety and efficacy of simeprevir and sofosbuvir with and without ribavirin. https://clinicaltrials.gov/ct2/show/NCT02165189?term=%22olysio%22&rank=1. Accessed February 15, 2015.
7. Phase 2, open-label study to investigate the pharmacokinetics, efficacy, safety, and tolerability of the combination of simeprevir (TMC435), daclatasvir (BMS-790052) and ribavirin (RBV) in subjects with recurrent chronic hepatitis C genotype 1b infection after orthotopic liver transplantation. https://clinicaltrials.gov/ct2/show/NCT01938625?term=%22olysio%22&rank=4. Accessed February 15, 2015.
8. A Phase 3, multicenter, open-label, single-arm study to investigate the efficacy and safety of a 12-week regimen of simeprevir in combination with sofosbuvir in treatment-naïve or -experienced subjects with chronic genotype 4 hepatitis C virus infection. https://clinicaltrials.gov/ct2/show/NCT02250807?term=%22olysio%22&rank=7. Accessed February 15, 2015.
9. A Phase 2 open-label study in patients with recurrent genotype 1 hepatitis C post–orthotopic liver transplant to explore the safety and efficacy of simeprevir and sofosbuvir with and without ribavirin. https://clinicaltrials.gov/ct2/show/NCT02165189?term=%22sovaldi%22&rank=6. Accessed February 15, 2015.
10. Lamas D, Rosenbaum L. Very complicated math: reconfiguring organ allocation. N Engl J Med. 2014;371(26):2447-2450.
The question of when to treat liver transplant patients with chronic hepatitis C virus (HCV) infection is vital. HCV is the diagnosis most commonly leading to liver transplantation, and recurrence of HCV after transplant is nearly universal. An estimated 30% of HCV liver transplant recipients experience recurrence within five years of transplantation, resulting in death or loss of the allograft because of cirrhosis or graft failure.1 Thus, if we knew when and how to treat HCV in this population, we could envision a world in which liver transplants would not be required—and certainly one in which retransplant because of HCV would never be needed.
In planning to treat HCV-positive patients who need a liver transplant, the question arises: Do we treat them preoperatively, perioperatively, or postoperatively? And if we select postoperative treatment, do we wait until the graft shows HCV recurrence, or do we treat prophylactically—knowing that recurrence is likely?
Results from multiple small studies of interferon-free treatment of HCV, both prior to and following recurrence of HCV posttransplant, have been reported. The SOLAR trial, which used ribavirin plus sofosbuvir, demonstrated a sustained viral response (SVR) rate of 70%.2 The SOLAR-1 trial of ledipasvir/sofosbuvir (Harvoni®) plus ribavirin in patients with genotype 1 or 4 who were treated following posttransplant recurrence showed an average SVR rate of 96%.3 Duration of treatment varied, depending on genotype and presence of cirrhosis, and there was differing dosing and addition of ribavirin at multiple doses. A 10% mortality rate was reported, but deaths occurred mainly in patients with severe cirrhosis.
A small trial was also conducted of genotype 3 patients treated with ledipasvir/sofosbuvir, with or without ribavirin.4 The addition of ribavirin appeared to shorten treatment, but patients in both treatment groups had excellent rates of SVR. However, further study is needed before this combination of medications can be recommended and/or FDA approved. Full details are available at http://hcvguidelines.org.
Ombitasvir/paritaprevir/ ritonavir with dasabuvir (Viekira Pak™) plus ribavirin for 24 weeks was evaluated in patients with HCV recurrence following liver transplant.5 This group of patients had very minimal fibrosis and essentially normal liver function. In this study group, an SVR rate exceeding 95% was achieved.
Continue for data on treatment of patients >>
The data on treatment of patients who need a transplant or who experience HCV recurrence posttransplant are very encouraging. If the SVR rates are maintained over time, it may be possible to significantly decrease the requirement for retransplantation—or even transplant in the first place. As transplant is not without significant morbidity and mortality, especially in the recurrence group, avoiding it would allow patients to live longer and healthier lives. More work is needed to understand the optimal time to treat and the best and safest regimens. Numerous trials evaluating these important management questions are ongoing.6-9
In the not-too-distant future, the requirement for liver transplantation in patients with chronic HCV infection is likely to decrease substantially. A recent New England Journal of Medicine editorial discussing liver allocation concluded that transplant centers now treating significant numbers of patients with HCV cirrhosis may soon be idle.10
If only we could be so lucky ...
REFERENCES
1. Watt K, Veldt B, Charlton M. A practical guide to the management of HCV infection following liver transplantation. Am J Transplant. 2009;9(8):1707-1713.
2. Charlton M, Gane E, Manns MP, et al. Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation. Gastroenterology. 2015;148(1):108-117.
3. Reddy KR, Everson GT, Flamm SL, et al. Ledipasvir/sofosbuvir with ribavirin for the treatment of HCV in patients with post transplant recurrence: preliminary results of a prospective, multicenter study. Presented at: 65th Annual Meeting of the American Association for the Study of Liver Diseases; November 7-11, 2014; Boston, MA. Abstract 8.
4. Kohler JJ, Nettles JH, Amblard F, et al. Approaches to hepatitis C treatment and cure using NS5A inhibitors. Infect Drug Resist. 2014;7:41-56.
5. Curry MP, Forns X, Chung RT, et al. Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open-label study. Gastroenterology. 2015;148(1):100-107.
6. A Phase 2 open-label study in patients with recurrent genotype 1 hepatitis C post–orthotopic liver transplant to explore the safety and efficacy of simeprevir and sofosbuvir with and without ribavirin. https://clinicaltrials.gov/ct2/show/NCT02165189?term=%22olysio%22&rank=1. Accessed February 15, 2015.
7. Phase 2, open-label study to investigate the pharmacokinetics, efficacy, safety, and tolerability of the combination of simeprevir (TMC435), daclatasvir (BMS-790052) and ribavirin (RBV) in subjects with recurrent chronic hepatitis C genotype 1b infection after orthotopic liver transplantation. https://clinicaltrials.gov/ct2/show/NCT01938625?term=%22olysio%22&rank=4. Accessed February 15, 2015.
8. A Phase 3, multicenter, open-label, single-arm study to investigate the efficacy and safety of a 12-week regimen of simeprevir in combination with sofosbuvir in treatment-naïve or -experienced subjects with chronic genotype 4 hepatitis C virus infection. https://clinicaltrials.gov/ct2/show/NCT02250807?term=%22olysio%22&rank=7. Accessed February 15, 2015.
9. A Phase 2 open-label study in patients with recurrent genotype 1 hepatitis C post–orthotopic liver transplant to explore the safety and efficacy of simeprevir and sofosbuvir with and without ribavirin. https://clinicaltrials.gov/ct2/show/NCT02165189?term=%22sovaldi%22&rank=6. Accessed February 15, 2015.
10. Lamas D, Rosenbaum L. Very complicated math: reconfiguring organ allocation. N Engl J Med. 2014;371(26):2447-2450.
The question of when to treat liver transplant patients with chronic hepatitis C virus (HCV) infection is vital. HCV is the diagnosis most commonly leading to liver transplantation, and recurrence of HCV after transplant is nearly universal. An estimated 30% of HCV liver transplant recipients experience recurrence within five years of transplantation, resulting in death or loss of the allograft because of cirrhosis or graft failure.1 Thus, if we knew when and how to treat HCV in this population, we could envision a world in which liver transplants would not be required—and certainly one in which retransplant because of HCV would never be needed.
In planning to treat HCV-positive patients who need a liver transplant, the question arises: Do we treat them preoperatively, perioperatively, or postoperatively? And if we select postoperative treatment, do we wait until the graft shows HCV recurrence, or do we treat prophylactically—knowing that recurrence is likely?
Results from multiple small studies of interferon-free treatment of HCV, both prior to and following recurrence of HCV posttransplant, have been reported. The SOLAR trial, which used ribavirin plus sofosbuvir, demonstrated a sustained viral response (SVR) rate of 70%.2 The SOLAR-1 trial of ledipasvir/sofosbuvir (Harvoni®) plus ribavirin in patients with genotype 1 or 4 who were treated following posttransplant recurrence showed an average SVR rate of 96%.3 Duration of treatment varied, depending on genotype and presence of cirrhosis, and there was differing dosing and addition of ribavirin at multiple doses. A 10% mortality rate was reported, but deaths occurred mainly in patients with severe cirrhosis.
A small trial was also conducted of genotype 3 patients treated with ledipasvir/sofosbuvir, with or without ribavirin.4 The addition of ribavirin appeared to shorten treatment, but patients in both treatment groups had excellent rates of SVR. However, further study is needed before this combination of medications can be recommended and/or FDA approved. Full details are available at http://hcvguidelines.org.
Ombitasvir/paritaprevir/ ritonavir with dasabuvir (Viekira Pak™) plus ribavirin for 24 weeks was evaluated in patients with HCV recurrence following liver transplant.5 This group of patients had very minimal fibrosis and essentially normal liver function. In this study group, an SVR rate exceeding 95% was achieved.
Continue for data on treatment of patients >>
The data on treatment of patients who need a transplant or who experience HCV recurrence posttransplant are very encouraging. If the SVR rates are maintained over time, it may be possible to significantly decrease the requirement for retransplantation—or even transplant in the first place. As transplant is not without significant morbidity and mortality, especially in the recurrence group, avoiding it would allow patients to live longer and healthier lives. More work is needed to understand the optimal time to treat and the best and safest regimens. Numerous trials evaluating these important management questions are ongoing.6-9
In the not-too-distant future, the requirement for liver transplantation in patients with chronic HCV infection is likely to decrease substantially. A recent New England Journal of Medicine editorial discussing liver allocation concluded that transplant centers now treating significant numbers of patients with HCV cirrhosis may soon be idle.10
If only we could be so lucky ...
REFERENCES
1. Watt K, Veldt B, Charlton M. A practical guide to the management of HCV infection following liver transplantation. Am J Transplant. 2009;9(8):1707-1713.
2. Charlton M, Gane E, Manns MP, et al. Sofosbuvir and ribavirin for treatment of compensated recurrent hepatitis C virus infection after liver transplantation. Gastroenterology. 2015;148(1):108-117.
3. Reddy KR, Everson GT, Flamm SL, et al. Ledipasvir/sofosbuvir with ribavirin for the treatment of HCV in patients with post transplant recurrence: preliminary results of a prospective, multicenter study. Presented at: 65th Annual Meeting of the American Association for the Study of Liver Diseases; November 7-11, 2014; Boston, MA. Abstract 8.
4. Kohler JJ, Nettles JH, Amblard F, et al. Approaches to hepatitis C treatment and cure using NS5A inhibitors. Infect Drug Resist. 2014;7:41-56.
5. Curry MP, Forns X, Chung RT, et al. Sofosbuvir and ribavirin prevent recurrence of HCV infection after liver transplantation: an open-label study. Gastroenterology. 2015;148(1):100-107.
6. A Phase 2 open-label study in patients with recurrent genotype 1 hepatitis C post–orthotopic liver transplant to explore the safety and efficacy of simeprevir and sofosbuvir with and without ribavirin. https://clinicaltrials.gov/ct2/show/NCT02165189?term=%22olysio%22&rank=1. Accessed February 15, 2015.
7. Phase 2, open-label study to investigate the pharmacokinetics, efficacy, safety, and tolerability of the combination of simeprevir (TMC435), daclatasvir (BMS-790052) and ribavirin (RBV) in subjects with recurrent chronic hepatitis C genotype 1b infection after orthotopic liver transplantation. https://clinicaltrials.gov/ct2/show/NCT01938625?term=%22olysio%22&rank=4. Accessed February 15, 2015.
8. A Phase 3, multicenter, open-label, single-arm study to investigate the efficacy and safety of a 12-week regimen of simeprevir in combination with sofosbuvir in treatment-naïve or -experienced subjects with chronic genotype 4 hepatitis C virus infection. https://clinicaltrials.gov/ct2/show/NCT02250807?term=%22olysio%22&rank=7. Accessed February 15, 2015.
9. A Phase 2 open-label study in patients with recurrent genotype 1 hepatitis C post–orthotopic liver transplant to explore the safety and efficacy of simeprevir and sofosbuvir with and without ribavirin. https://clinicaltrials.gov/ct2/show/NCT02165189?term=%22sovaldi%22&rank=6. Accessed February 15, 2015.
10. Lamas D, Rosenbaum L. Very complicated math: reconfiguring organ allocation. N Engl J Med. 2014;371(26):2447-2450.