Chronic Hepatitis C Treatment: Questions and Answers
Chronic Hepatitis C Treatment: Questions and Answers
Long-term follow-up studies have shown that the risk of virological recurrence is very low (1–8%) when the patient had successfully established SVR. In a large cohort study, 344 patients with CHC were treated with IFN-based regimens, and the patients were followed up for a median duration of 3.27 years. HCV-RNA was controlled in the sera (n = 1300), post-treatment liver tissue samples (n = 114) and peripheral blood mononuclear cells (n = 156). Serum HCV-RNA remained undetectable in all of the patients, and in none of the specimens of peripheral blood mononuclear cells. But, in just two out of 114 (1.7%) liver tissue specimens, HCV-RNA was detectable. Histological analyses of 126 paired liver biopsies revealed that the stage of fibrosis improved in 56%, was stable in 32% and deteriorated in 12%. Regression of cirrhosis was observed in 64% of cases while decompensation was seen in none. Three patients had HCC. The authors of the study concluded that these results strongly suggest that SVR may be considered as indicative eradication of HCV infection.
Giannini et al. evaluated a cohort of 231 patients with CHC, who had at least 48 weeks of follow-up after SVR to PEG-IFN and RBV treatment. Median duration of follow-up after SVR was 164 weeks and exceeded 5 years in 30% of the cohort. SVR was pertinent in 211 patients (91%) while HCV-RNA became positive in two patients (less than 1%) within 1 year after SVR, and in 18 patients (8%) serum HCV-RNA was transiently positive in at least one follow-up evaluation. Clinical outcome was not significantly different between patients with persistently negative and transiently positive serum HCV-RNA.
Polymorphism in the region of the IL-28B gene located at chromosome 19 has been associated with prediction of SVR in genotype 1 HCV and rapid virological response in genotype 2 and 3 HCV. In patients of European ancestry, as well as in African–American and Hispanic patients, the CC genotype was associated with a twofold greater SVR rate than the TT genotype, with CT being closer to TT than to CC.
Veldt et al. reported a retrospective cohort study in which SVR was achieved in 29.6% of 479 patients with CHC after IFN-based treatment. One hundred and thirty-one patients (27%) received IFN monotherapy, 130 (27%) received IFN and RBV, ten (2.1%) received PEG-IFN monotherapy, and 208 (43%) received PEG-IFN and RBV. Follow-up time was 2.1 (0.8–4.9) years for all patients. They concluded that SVR was associated with a reduction in liver failure (unadjusted hazard ratio: 0.03 [95% CI: 0.00–0.91]).
Veldt et al. reported a meta-analysis of 286 CHC patients with SVR and 50 biochemical responders (detectable virus but normal ALT levels). Before the treatment, 5.2% of patients with SVR had liver cirrhosis and 39% were genotype 1. Those patients were followed up for a mean period of 59 months. The late virological relapse rate in cases with SVR after 5 years of follow-up was 4.7% (95% CI: 2.0–7.4). In this group, decompensation was detected in only 1.0% (95% CI: 0.0–2.3) and HCC was not detected during the follow-up time. SVR was found to be associated with the improvement of liver fibrosis. For biochemical responders, the rates of development of decompensation and HCC during long-term follow-up were 9.1% (95% CI: 0.5–17.7) and 7.1% (95% CI: 0–15.0), respectively. SVR was found to be a better prognostic factor than biochemical response.
The standard mortality rate in patients with SVR was 1.4% (95% CI: 0.3–2.5) and 5.6% in biochemical responders (95% CI: 0.0–12.6). The survival in patients with SVR was compatible with the general population. On the other hand, there was a trend to a higher standard mortality ratio in biochemical responders after 5 years of follow-up. However, the difference did not reach statistical significance.
In a prospective study of 352 patients with compensated liver cirrhosis as a result of CHC, the patients were followed up for a median of 14.4 years (range: 0.9–19.5 years) in terms of annual decompensation, occurrence of HCC and liver-related mortality. One hundred and ninety-four patients were treated with a single course of IFN or a combination of PEG-IFN plus RBV. At the end, 131 had decompensation, HCC occurred in 109 patients, nine had liver transplants and 158 patients died. There was no difference in annual rates of decompensation, HCC and liver-related mortality between the patients with non-SVR and the untreated patients. The overall liver-related mortality rate was significantly reduced in patients with SVR compared with the nonresponders and the untreated group (p = 0.03). Multivariate analysis revealed the beneficial effect of SVR on mortality and survival ( Table 1 ).
The Place of the Virological Response in CHC Treatment
Does SVR Maintained With IFN Administration Point to HCV Eradication?
Long-term follow-up studies have shown that the risk of virological recurrence is very low (1–8%) when the patient had successfully established SVR. In a large cohort study, 344 patients with CHC were treated with IFN-based regimens, and the patients were followed up for a median duration of 3.27 years. HCV-RNA was controlled in the sera (n = 1300), post-treatment liver tissue samples (n = 114) and peripheral blood mononuclear cells (n = 156). Serum HCV-RNA remained undetectable in all of the patients, and in none of the specimens of peripheral blood mononuclear cells. But, in just two out of 114 (1.7%) liver tissue specimens, HCV-RNA was detectable. Histological analyses of 126 paired liver biopsies revealed that the stage of fibrosis improved in 56%, was stable in 32% and deteriorated in 12%. Regression of cirrhosis was observed in 64% of cases while decompensation was seen in none. Three patients had HCC. The authors of the study concluded that these results strongly suggest that SVR may be considered as indicative eradication of HCV infection.
Giannini et al. evaluated a cohort of 231 patients with CHC, who had at least 48 weeks of follow-up after SVR to PEG-IFN and RBV treatment. Median duration of follow-up after SVR was 164 weeks and exceeded 5 years in 30% of the cohort. SVR was pertinent in 211 patients (91%) while HCV-RNA became positive in two patients (less than 1%) within 1 year after SVR, and in 18 patients (8%) serum HCV-RNA was transiently positive in at least one follow-up evaluation. Clinical outcome was not significantly different between patients with persistently negative and transiently positive serum HCV-RNA.
Do Human Genetic Factors Influence HCV Treatment Responses?
Polymorphism in the region of the IL-28B gene located at chromosome 19 has been associated with prediction of SVR in genotype 1 HCV and rapid virological response in genotype 2 and 3 HCV. In patients of European ancestry, as well as in African–American and Hispanic patients, the CC genotype was associated with a twofold greater SVR rate than the TT genotype, with CT being closer to TT than to CC.
Does SVR Prevent Liver Failure?
Veldt et al. reported a retrospective cohort study in which SVR was achieved in 29.6% of 479 patients with CHC after IFN-based treatment. One hundred and thirty-one patients (27%) received IFN monotherapy, 130 (27%) received IFN and RBV, ten (2.1%) received PEG-IFN monotherapy, and 208 (43%) received PEG-IFN and RBV. Follow-up time was 2.1 (0.8–4.9) years for all patients. They concluded that SVR was associated with a reduction in liver failure (unadjusted hazard ratio: 0.03 [95% CI: 0.00–0.91]).
Why are Virological or Biochemical Responses Important in CHC Therapy?
Veldt et al. reported a meta-analysis of 286 CHC patients with SVR and 50 biochemical responders (detectable virus but normal ALT levels). Before the treatment, 5.2% of patients with SVR had liver cirrhosis and 39% were genotype 1. Those patients were followed up for a mean period of 59 months. The late virological relapse rate in cases with SVR after 5 years of follow-up was 4.7% (95% CI: 2.0–7.4). In this group, decompensation was detected in only 1.0% (95% CI: 0.0–2.3) and HCC was not detected during the follow-up time. SVR was found to be associated with the improvement of liver fibrosis. For biochemical responders, the rates of development of decompensation and HCC during long-term follow-up were 9.1% (95% CI: 0.5–17.7) and 7.1% (95% CI: 0–15.0), respectively. SVR was found to be a better prognostic factor than biochemical response.
Is there any Difference in Mortality Between the Normal Population & the CHC Patients With SVR?
The standard mortality rate in patients with SVR was 1.4% (95% CI: 0.3–2.5) and 5.6% in biochemical responders (95% CI: 0.0–12.6). The survival in patients with SVR was compatible with the general population. On the other hand, there was a trend to a higher standard mortality ratio in biochemical responders after 5 years of follow-up. However, the difference did not reach statistical significance.
Does the Establishment of SVR Have an Effect on Mortality in Cirrhotic Patients?
In a prospective study of 352 patients with compensated liver cirrhosis as a result of CHC, the patients were followed up for a median of 14.4 years (range: 0.9–19.5 years) in terms of annual decompensation, occurrence of HCC and liver-related mortality. One hundred and ninety-four patients were treated with a single course of IFN or a combination of PEG-IFN plus RBV. At the end, 131 had decompensation, HCC occurred in 109 patients, nine had liver transplants and 158 patients died. There was no difference in annual rates of decompensation, HCC and liver-related mortality between the patients with non-SVR and the untreated patients. The overall liver-related mortality rate was significantly reduced in patients with SVR compared with the nonresponders and the untreated group (p = 0.03). Multivariate analysis revealed the beneficial effect of SVR on mortality and survival ( Table 1 ).
