Treatment of advanced hepatitis C with a low accelerating dosage regimen of antiviral therapy

Abstract

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 ؎ 2.3, and the mean MELD score was 11.0 ؎ 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.)

Indian National Association for Study of the Liver (INASL) Guidance for Antiviral Therapy Against HCV Infection: Update 2016

“…SVR rates even when using a low accelerating dose IFNa regimen were around 25%. 62 Importantly, only a small fraction of the HCV-infected decompensated cirrhotics were eligible for IFNa-based therapy. Peg-IFNa/RBV could be given only to patients with patients with reasonable liver functions [CTP 7, Model for End-Stage Liver Disease (MELD 18)], or in patients with HCC with good liver functions awaiting liver transplantation (LT).…”

Strategies to reduce hepatitis C virus recurrence after liver transplantation

“…Predictors of viral clearance include non-genotype 1 and an early virological response [22][23][24][25] . The absence of a ≥ 2 log10 reduction in HCV RNA between baseline and wk 4 has a strong negative predictive value [22][23][24]26,27] . This absence of an early virological response can be used as a guide to stopping treatment [26] .…”

“…To make AVT more tolerable, various dosing strategies have been used including tailoring dose to liver function, shortening the duration of therapy or using haematopoietic growth factors [22,24,25] . In decompensated cirrhotics, reported rates of neutropaenia, thrombocytopaenia, anaemia, infection or liver decompensation range from 50%-60%, 30%-50%, 30%-60%, 4%-13% and 11%-20% respectively [22][23][24][25] . Child-Turcotte-Pugh (CTP) C patients are unable to tolerate a course of treatment [23,28] .…”

Treatment of hepatitis C virus infection: Updated Swedish Consensus recommendations

“…Patients with a prior history of decompensation should only be considered for therapy under special circumstances. If treatment is conducted, this should be performed together with a liver transplant centre [39].…”