Treatment of Chronic HCV in Patients With Cirrhosis
The study is a retrospective analysis of 120 consecutive patients with chronic HCV genotype 1 and cirrhosis in whom treatment with SMV and SOF was initiated at the Liver Institute of Virginia between 10 December 2013 and 15 April 2014. The various options for HCV treatment available at the time were discussed with every patient prior to prescribing SMV and SOF. Patients were informed of the data available on SMV and SOF and that this combination was not formally approved by the FDA at the time these medications were prescribed. Approval to tabulate and analyze these data was obtained from the Institutional Review Board at the Bon Secours St Mary's Hospital, Richmond, VA. The study was not supported by any pharmaceutical company or other funding agency.
After the FDA approval of SMV and SOF a treatment algorithm for patients with cirrhosis was developed by the authors. SMV and SOF were prescribed to all patients with HCV genotype 1, cirrhosis, and contraindications to PEGINF-based therapy, who were able to receive these medications from their insurance carriers or through alternative programs. Cirrhosis was documented by liver biopsy in 102 patients or on the basis of clinical criteria for cirrhosis, which included at least two of the following: a Child-Pugh score >8, a history of ascites or hepatic encephalopathy, endoscopic evidence of variceal or portal hypertension with or without previous hemorrhage, and thrombocytopenia. Contraindications to treatment with PEGINF included at least one of the following: age greater than 65 years, hepatic decompensation (Child class B or C), a platelet count <70,000/cc, a hemoglobin level <10 gm/dl, HCC treated with either ablation (transarterial chemoembolization and/or microwave ablation) or surgical resection and without recurrence for at least 6 months, symptomatic cryoglobulinemia, serum creatinine >1.5 mg/ml, and an inability to tolerate a previous course of PEGINF and RBV-based therapy. All patients were treated with SMV (150 mg every day) and SOF (400 mg every day) for only 12 weeks. RBV was not utilized. Patients were scheduled for monitoring at weeks 2, 4, 8, and 12 after treatment had been initiated and at weeks 4 and 12 after treatment had been completed. The primary end point for analysis was SVR12. Because they have cirrhosis, patients continue to be monitored at regular intervals. HCV RNA was also measured 6, 12, and 24 months after treatment in accordance with our routine standard of care for monitoring patients who have achieved SVR. An ultrasound is performed to screen for HCC at 6-month intervals prior to, during, and following HCV treatment. α-fetoprotein is evaluated at 3-month intervals in accordance with the standard of care we provide for all patients with cirrhosis. HCV genotyping, subtyping, and interleukin-28B (IL28B) genotyping were performed in standard medical laboratories. IL28B genotyping was not ordered or available for all patients because this test was not approved for payment by some insurance carriers. The vast majority of patients with IL28B genotype results had the test performed historically. The Q80K mutation was not tested for in any patient because this test was not required for preauthorization of SMV or approved for payment by the patients' insurance carriers.
Data were reported as mean and range. Single followed by multiple logistic regression analysis was performed on all baseline and on-treatment variables to define predictors of SVR. A P value <0.05 was considered significant.
Methods
The study is a retrospective analysis of 120 consecutive patients with chronic HCV genotype 1 and cirrhosis in whom treatment with SMV and SOF was initiated at the Liver Institute of Virginia between 10 December 2013 and 15 April 2014. The various options for HCV treatment available at the time were discussed with every patient prior to prescribing SMV and SOF. Patients were informed of the data available on SMV and SOF and that this combination was not formally approved by the FDA at the time these medications were prescribed. Approval to tabulate and analyze these data was obtained from the Institutional Review Board at the Bon Secours St Mary's Hospital, Richmond, VA. The study was not supported by any pharmaceutical company or other funding agency.
After the FDA approval of SMV and SOF a treatment algorithm for patients with cirrhosis was developed by the authors. SMV and SOF were prescribed to all patients with HCV genotype 1, cirrhosis, and contraindications to PEGINF-based therapy, who were able to receive these medications from their insurance carriers or through alternative programs. Cirrhosis was documented by liver biopsy in 102 patients or on the basis of clinical criteria for cirrhosis, which included at least two of the following: a Child-Pugh score >8, a history of ascites or hepatic encephalopathy, endoscopic evidence of variceal or portal hypertension with or without previous hemorrhage, and thrombocytopenia. Contraindications to treatment with PEGINF included at least one of the following: age greater than 65 years, hepatic decompensation (Child class B or C), a platelet count <70,000/cc, a hemoglobin level <10 gm/dl, HCC treated with either ablation (transarterial chemoembolization and/or microwave ablation) or surgical resection and without recurrence for at least 6 months, symptomatic cryoglobulinemia, serum creatinine >1.5 mg/ml, and an inability to tolerate a previous course of PEGINF and RBV-based therapy. All patients were treated with SMV (150 mg every day) and SOF (400 mg every day) for only 12 weeks. RBV was not utilized. Patients were scheduled for monitoring at weeks 2, 4, 8, and 12 after treatment had been initiated and at weeks 4 and 12 after treatment had been completed. The primary end point for analysis was SVR12. Because they have cirrhosis, patients continue to be monitored at regular intervals. HCV RNA was also measured 6, 12, and 24 months after treatment in accordance with our routine standard of care for monitoring patients who have achieved SVR. An ultrasound is performed to screen for HCC at 6-month intervals prior to, during, and following HCV treatment. α-fetoprotein is evaluated at 3-month intervals in accordance with the standard of care we provide for all patients with cirrhosis. HCV genotyping, subtyping, and interleukin-28B (IL28B) genotyping were performed in standard medical laboratories. IL28B genotyping was not ordered or available for all patients because this test was not approved for payment by some insurance carriers. The vast majority of patients with IL28B genotype results had the test performed historically. The Q80K mutation was not tested for in any patient because this test was not required for preauthorization of SMV or approved for payment by the patients' insurance carriers.
Data were reported as mean and range. Single followed by multiple logistic regression analysis was performed on all baseline and on-treatment variables to define predictors of SVR. A P value <0.05 was considered significant.
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