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Treatment of hepatitis C in a lung transplant recipient with sofosbuvir and daclatasvir
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CASE ANECDOTES, COMMENTS AND OPINIONS Treatment of hepatitis C in a lung transplant recipient with sofosbuvir and daclatasvir Karen Doucette, MD, MSc,a Suzanne Sumner, RN,b and Justin Weinkauf, MDc From the aDivision of Infectious Diseases University of Alberta, University of Alberta, Edmonton, Alberta, Canada; bHepatitis Support Program, Alberta Health Services, Edmonton, Alberta, Canada; and the cDivision of Pulmonary Medicine and Lung Transplant Program, University of Alberta, Edmonton, Alberta, Canada.
A 51-year-old man underwent double-lung transplant (DLT) for end-stage lung disease due to talc lung granulomatosis. He had genotype 3 chronic hepatitis C virus (HCV) infection, with relapse after 6 months of pegylated interferon and ribavirin 6 years before DLT. He underwent a complete assessment for HCV 8 months before DLT and was documented to have minimal fibrosis (liver stiffness, 5.8 kPa) by transient elastography (TE) using FibroScan (Echosens). On the basis of this result, institutional guidelines for DLT in those with HCV infection, and published guidelines for management of HCV in nonhepatic transplant candidates,1 he was listed for lung transplant. His peri-operative course was uncomplicated. He received basiliximab induction, with tacrolimus, mycophenolate mofetil, and prednisone as maintenance immunosuppression. Repeat TE 4 months after DLT documented progression to advanced fibrosis (liver stiffness, 11.5 kPa). This was confirmed with a second measurement the same day. One week later, liver stiffness was further elevated into the range of early cirrhosis (17.5 kPa). Hepatic synthetic function was within normal reference ranges, including bilirubin, 10 μmol/ liter; albumin, 33 g/liter; and international normalized ratio, 1.2. Alanine aminotransferase was mildly elevated at 57 U/ liter, aspartate aminotransferase was normal at 31 U/liter, and creatinine remained normal at 70 μmol/liter. He had no symptoms of decompensated liver disease. A complete blood count revealed hemoglobin of 100 g/liter and normal reference ranges for platelets (307 109/liter) and white blood cell (7.9 109/liter) counts. With TE evidence of rapidly progressing hepatic fibrosis, options for treatment were discussed. For a patient with genotype 3 HCV cirrhosis and prior relapse after pegylated
interferon plus ribavirin, the only Health Canada–approved therapy is sofosbuvir plus ribavirin for 24 weeks. This has an expected cure rate of 62%,2 which was felt to be suboptimal in this patient due to expected ribavirin-associated hemolytic anemia and the patient’s low baseline hemoglobin. The combination of sofosbuvir plus daclatasvir for 12 weeks has a cure rate of 69% in treatment-experienced cirrhotic patients3; however, based on expert opinion, 24 weeks, with or without ribavirin, is recommended in international guidelines.4 Compassionate access for daclatasvir was granted. He started therapy with sofosbuvir (400 mg daily) and daclatasvir (60 mg daily) at 5 months after DLT and completed 24 weeks. Moderate nausea, diarrhea, and weight loss occurred during treatment; however, he also had an intercurrent norovirus infection, and symptoms may have been due to this and/or HCV therapy. HCV RNA was negative at 12 weeks after completion, documenting virologic cure. His liver stiffness decreased into the moderate fibrosis range (8.8 kPa) at 4 months after therapy. This case highlights the efficacy and safety of the all-oral direct-acting antiviral combination therapy of sofosbuvir and daclatasvir for HCV after lung transplantation. International guidelines on selection of lung transplant candidates5 require revision in the era of direct-acting antiviral therapy, which can now be administered before or after lung transplant with few adverse effects or drug interactions.
Disclosure statement K.D. has received funding for research from Gilead, Merck, Bristol-Myers Squibb, GSK, and AbbVie, as well as speaking honoraria from Gilead and Bristol-Myers Squibb. The other authors do not have a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose. The authors thank Bristol-Myers Squibb providing compassionate access to daclatasvir (Daklinza) in this case.
References 1. Levitsky J, Doucette K. AST Infectious Diseases Community of Practice. Viral hepatitis in solid organ transplantation. Am J Transplant 2013;13(Suppl 4):147-68. 2. Zeuzem S, Dusheiko GM, Salupere R, et al. Sofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med 2014;370:1993-2001.
1053-2498/$ - see front matter r 2016 International Society for Heart and Lung Transplantation. All rights reserved. http://dx.doi.org/10.1016/j.healun.2016.01.1219
2
The Journal of Heart and Lung Transplantation, Vol ], No ], Month ]]]]
3. Nelson DR, Cooper JN, Lalezari JP, et al. All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study. Hepatology 2015;61:1127-35. 4. European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2015. J Hepatol 2015;63:199-236.
5. Weill D, Benden C, Corris PA, et al. A consensus document for the selection of lung transplant candidates: 2014—an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2015;34: 1-15.
CASE ANECDOTES, COMMENTS AND OPINIONS Treatment of hepatitis C in a lung transplant recipient with sofosbuvir and daclatasvir Karen Doucette, MD, MSc,a Suzanne Sumner, RN,b and Justin Weinkauf, MDc From the aDivision of Infectious Diseases University of Alberta, University of Alberta, Edmonton, Alberta, Canada; bHepatitis Support Program, Alberta Health Services, Edmonton, Alberta, Canada; and the cDivision of Pulmonary Medicine and Lung Transplant Program, University of Alberta, Edmonton, Alberta, Canada.
A 51-year-old man underwent double-lung transplant (DLT) for end-stage lung disease due to talc lung granulomatosis. He had genotype 3 chronic hepatitis C virus (HCV) infection, with relapse after 6 months of pegylated interferon and ribavirin 6 years before DLT. He underwent a complete assessment for HCV 8 months before DLT and was documented to have minimal fibrosis (liver stiffness, 5.8 kPa) by transient elastography (TE) using FibroScan (Echosens). On the basis of this result, institutional guidelines for DLT in those with HCV infection, and published guidelines for management of HCV in nonhepatic transplant candidates,1 he was listed for lung transplant. His peri-operative course was uncomplicated. He received basiliximab induction, with tacrolimus, mycophenolate mofetil, and prednisone as maintenance immunosuppression. Repeat TE 4 months after DLT documented progression to advanced fibrosis (liver stiffness, 11.5 kPa). This was confirmed with a second measurement the same day. One week later, liver stiffness was further elevated into the range of early cirrhosis (17.5 kPa). Hepatic synthetic function was within normal reference ranges, including bilirubin, 10 μmol/ liter; albumin, 33 g/liter; and international normalized ratio, 1.2. Alanine aminotransferase was mildly elevated at 57 U/ liter, aspartate aminotransferase was normal at 31 U/liter, and creatinine remained normal at 70 μmol/liter. He had no symptoms of decompensated liver disease. A complete blood count revealed hemoglobin of 100 g/liter and normal reference ranges for platelets (307 109/liter) and white blood cell (7.9 109/liter) counts. With TE evidence of rapidly progressing hepatic fibrosis, options for treatment were discussed. For a patient with genotype 3 HCV cirrhosis and prior relapse after pegylated
interferon plus ribavirin, the only Health Canada–approved therapy is sofosbuvir plus ribavirin for 24 weeks. This has an expected cure rate of 62%,2 which was felt to be suboptimal in this patient due to expected ribavirin-associated hemolytic anemia and the patient’s low baseline hemoglobin. The combination of sofosbuvir plus daclatasvir for 12 weeks has a cure rate of 69% in treatment-experienced cirrhotic patients3; however, based on expert opinion, 24 weeks, with or without ribavirin, is recommended in international guidelines.4 Compassionate access for daclatasvir was granted. He started therapy with sofosbuvir (400 mg daily) and daclatasvir (60 mg daily) at 5 months after DLT and completed 24 weeks. Moderate nausea, diarrhea, and weight loss occurred during treatment; however, he also had an intercurrent norovirus infection, and symptoms may have been due to this and/or HCV therapy. HCV RNA was negative at 12 weeks after completion, documenting virologic cure. His liver stiffness decreased into the moderate fibrosis range (8.8 kPa) at 4 months after therapy. This case highlights the efficacy and safety of the all-oral direct-acting antiviral combination therapy of sofosbuvir and daclatasvir for HCV after lung transplantation. International guidelines on selection of lung transplant candidates5 require revision in the era of direct-acting antiviral therapy, which can now be administered before or after lung transplant with few adverse effects or drug interactions.
Disclosure statement K.D. has received funding for research from Gilead, Merck, Bristol-Myers Squibb, GSK, and AbbVie, as well as speaking honoraria from Gilead and Bristol-Myers Squibb. The other authors do not have a financial relationship with a commercial entity that has an interest in the subject of the presented manuscript or other conflicts of interest to disclose. The authors thank Bristol-Myers Squibb providing compassionate access to daclatasvir (Daklinza) in this case.
References 1. Levitsky J, Doucette K. AST Infectious Diseases Community of Practice. Viral hepatitis in solid organ transplantation. Am J Transplant 2013;13(Suppl 4):147-68. 2. Zeuzem S, Dusheiko GM, Salupere R, et al. Sofosbuvir and ribavirin in HCV genotypes 2 and 3. N Engl J Med 2014;370:1993-2001.
1053-2498/$ - see front matter r 2016 International Society for Heart and Lung Transplantation. All rights reserved. http://dx.doi.org/10.1016/j.healun.2016.01.1219
2
The Journal of Heart and Lung Transplantation, Vol ], No ], Month ]]]]
3. Nelson DR, Cooper JN, Lalezari JP, et al. All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study. Hepatology 2015;61:1127-35. 4. European Association for the Study of the Liver. EASL recommendations on treatment of hepatitis C 2015. J Hepatol 2015;63:199-236.
5. Weill D, Benden C, Corris PA, et al. A consensus document for the selection of lung transplant candidates: 2014—an update from the Pulmonary Transplantation Council of the International Society for Heart and Lung Transplantation. J Heart Lung Transplant 2015;34: 1-15.