Patients with advanced hepatitis C virus (HCV) are at risk of death and are candidates for liver transplantation. After transplantation, HCV recurs and may rapidly progress to cirrhosis and graft loss. Treatment is needed to prevent progression of disease and minimize recurrence after liver transplantation. We evaluated the effectiveness, tolerability, and outcome of a low accelerating dose regimen (LADR) of antiviral therapy in the treatment of patients with advanced HCV. One hundred twenty-four patients (male/female ratio 81:43; age range 37-71 years; 70% genotype 1) were treated with LADR. Sixty-three percent had clinical complications of cirrhosis (ascites, spontaneous bacterial peritonitis, varices, variceal hemorrhage, encephalopathy). The mean Child-Turcotte-Pugh (CTP) score was 7.4 Ψ 2.3, and the mean MELD score was 11.0 Ψ 3.7. Fifty-six patients were CTP class A, 45 were class B, and 23 were class C. Forty-six percent were HCV RNA-negative at end of treatment, and 24% were HCV RNA-negative at last follow-up. Sustained virological response (SVR) was 13% in patients infected with genotype 1 HCV and 50% in patients infected with non-1 genotypes (P < .0001). Non-1 genotype, CTP class A (genotype 1 only), and ability to tolerate full dose and duration of treatment (P < .0001) were predictors of SVR. Twelve of 15 patients who were HCV RNA-negative before transplantation remained HCV RNAnegative 6 months or more after transplantation. In conclusion, in a sizeable proportion of patients with advanced HCV, LADR may render blood free of HCV RNA, stabilize clinical course, and prevent posttransplantation recurrence. (HEPATOLOGY 2005;42:255-262.)
P atients with advanced liver disease due to chronic hepatitis C virus (HCV) are at risk for death, need hepatic transplantation, and could benefit from effective antiviral therapy. Sustained virological response (SVR) in patients with Child-Turcotte-Pugh (CTP) class A cirrhosis has improved from 5% with interferon monotherapy 1,2 to a maximum of 50% with peginterferon plus ribavirin. [3][4][5] However, these results cannot be extrapolated to sicker patients, such as those on waiting lists for liver transplantation. In this study, we analyzed the effectiveness of a low accelerating dose regimen (LADR) of interferon plus ribavirin in patients with advanced chronic HCV. Seventy-three percent (n Ο 90) of these patients were listed before, during, or after LADR, and 38% (n Ο 47) underwent liver transplantation.
Patients and Methods
Patients. The analysis of our clinical experience with LADR was approved by the Health Insurance Portability and Accountability Act (HIPAA) Privacy Board and Combined Multi-Institutional Review Board at the University of Colorado Health Sciences Center. Inclusion criteria for the LADR protocol were HCV RNA positivity, advanced liver disease, and absence of active substance abuse or other serious systemic illness. Maintenance of abstinence from alcohol was monitored at each clinic visit by way of patient interview. All patients enrolled in LADR had absolute neutrophil count (ANC) ΟΎ800/L, hemoglobin ΟΎ10 g/dL, and platelets ΟΎ35,000/L before initiation of therapy. Patients with refractory ascites, renal failure, unstable clinical course related to ongoing gastrointestinal bleeding, refractory encephalopathy, extensive hepatoma (ΟΎstage II), or severe intolerance or neuropsychiatric complications with prior courses of interferon or