The Effects of Sustained Virological Response to Direct-Acting Anti-Viral Therapy on the Risk of Extrahepatic Manifestations of Hepatitis C Infection

Hashem B. El-Serag; Israel C. Christie; Amy Puenpatom; Diana Castillo; Fasiha Kanwal; Jennifer R. Kramer


Aliment Pharmacol Ther. 2019;49(11):1442-1447. 

In This Article


We identified 46 930 patients with active HCV infection who received DAA, fulfilled the eligibility criteria. They were mostly men (96.63%), and their racial/ethnic distribution was 53.78% white and 37.27% black (Table 1). The mean age was 61.77 years (SD: 6.54) at DAA treatment index date. SVR was detected in 92.16% of those treated with DAAs. The mean duration for follow-up after DAA index date for the cohort was 2.01 years (median: 1.99 years; SD: 1.78). The types of DAA medications used were sofosbuvir with or without ledipasvir (34 103, 81.76%), ombitasvir/paritaprevir/ritonavir (6192, 14.85%), elbasvir/grazoprevir (1018, 2.44%), simeprevir (2609, 6.25%) and daclatasvir (669, 1.60%).

There were no major differences in age, sex, race or duration of follow-up between the two groups of patients with SVR and without SVR following DAA treatment. There were also no significant differences between the SVR and no-SVR group in coinfection with HIV or HBV, or hypertension (Table 1). However, the no-SVR group had significantly greater proportions of patients with cirrhosis and history of alcohol or drug abuse, and HCV genotypes non-1a or -1b than the SVR group. Patients without SVR also had greater healthcare utilisation both before and after DAA treatment.

The prevalence of extrahepatic manifestations is shown in Table 2. The prevalence of one or more of these five conditions (all except diabetes) was 7.09% overall (7.05% in SVR vs 7.61% in no-SVR [P = 0.2234]) and 35.46% overall if including diabetes (35.14% in SVR vs 39.22% in no-SVR [P < 0.0001]). The overall incidence rates of potential extrahepatic manifestations stratified by SVR status are shown in Table 2. The incidence rates (and IRR) of all the extrahepatic manifestation outcomes were quantitatively lower among those who achieved SVR vs those who did not achieve SVR and were statistically significantly lower for mixed cryoglobulinaemia (IRR = 0.25; 95% CI 0.10-0.59), glomerulonephritis (IRR = 0.58; 95% CI 0.39-0.86), porphyria cutanea tarda (IRR = 0.32; 95% CI 0.11-0.98) and lichen planus (IRR = 0.47; 95% CI 0.31-0.71) in the SVR than the non-SVR group.

The unadjusted, minimally adjusted (age, sex and race) and fully adjusted (age, sex, race, alcohol abuse, drug abuse, HIV, hypertension, cirrhosis, cirrhosis complications, HBV, pre- and postutilisation, prior non-DAA treatment for HCV and HCV genotype) proportional hazards for each condition are shown in Table 2. Extrahepatic manifestation risk was reduced in the SVR group compared with the group treated but with no SVR for mixed cryoglobulinaemia, glomerulonephritis, porphyria cutanea tarda and lichen planus in the unadjusted and minimally adjusted analyses. The model adjustments did not change appreciably the magnitude, significance or direction of the protective associations for mixed cryoglobulinaemia (adjusted HR (aHR) = 0.23; 95% CI 0.10-0.56; P = 0.0012), glomerulonephritis (aHR = 0.61; 95% CI 0.41-0.90; P = 0.0126) and lichen planus (aHR = 0.46; 95% CI 0.30-0.70; P = 0.0003). SVR was associated with a reduction in risk of porphyria cutanea tarda, but it was only marginally statistically significant in the fully adjusted model (aHR = 0.33; 95% CI 0.11-1.03; P = 0.057) likely due to a small number of outcomes (n = 4) among those without SVR. SVR was not associated with a significant reduction in the risk of non-Hodgkin's lymphoma or diabetes. We found comparable results to the main analysis for both sensitivity analyses (ie using more specific outcome definition and using SVR12; Table S1 and Table S2).