Chronic hepatitis C virus infection is the most important cause of chronic hepatitis in China other than chronic hepatitis B virus infection, and the rate of HCV infection in the general population in China is 3.2%, and about 38 million people are infected with HCV. unlike chronic HBV virus which is difficult to be cleared in the infected liver cells, effective antiviral often can make HCV cleared from the body, thus achieving a cure, and thus in To some extent how to achieve effective treatment of chronic hepatitis C is more demanding than that of chronic hepatitis B. Since the discovery of hepatitis C virus in the early 1990s and the application of IFN for the treatment of chronic hepatitis C, especially in recent years with the development of pegylated interferon and combination therapy with ribavirin (RBV), there has been a significant increase in sustained viral response rates, raising the sustained viral response rate from less than 20% in the early 1990s with plain IFN alone to 40%-82%. The rate of sustained viral response in the early 1990s with conventional IFN alone was less than 20%, but increased to 40-82%. As research has progressed, numerous studies have shown that response rates to treatment correlate with host and viral factors, particularly genotype and viral load, as well as changes in serum viral load during the course of treatment. In order to standardize the antiviral treatment of chronic hepatitis C, China established the Guidelines for the Prevention and Treatment of Hepatitis C in 2004
. Because multiple factors can affect the efficacy of interferon antiviral therapy for chronic hepatitis C, clinical treatment should still be individualized according to the clinical and virological characteristics of the patient in order to achieve a greater efficacy-cost ratio. In terms of the choice of therapeutic agents, the currently marketed drugs effective against hepatitis C virus are interferons, including plain IFNα, compound IFN and polyethylene glycol (PEG)-based interferonα (PEG-IFNα). Since the application of combination RBV can significantly increase the efficacy, combination therapy should be used for anyone without contraindications to RBV. Although numerous studies have shown that the virological response rate of PEG-IFNα combined with RBV therapy is significantly higher than that of common IFNα combined with RBV, and even the treatment of PEG-IFNα combined with RBV therapy is considered as the standard of care, but limited to the national situation in China, there are still numerous patients who choose common IFN therapy. For patients with primary treatment, 3 MU to 5 MU can be chosen
intramuscular injections every other day or 3 times a week for 24 to 48 weeks. The results of a cohort study from Taiwan showed that increasing the amount of common IFN treatment significantly increased the rate of sustained viral response, suggesting that the dose of common IFN treatment should be increased for heavier patients. 180 mg of fixed dose of PEG-IFNα-2a can be administered subcutaneously once a week, while PEG-IFNα-2b should be applied at a dose of 1.5 mg/kg depending on body weight. Although no direct comparative studies have been conducted between PEG-IFNα-2a and PEG-IFNα-2b, the efficacy of both is similar according to different clinical trials reported. Genotype is one of the most important factors influencing the efficacy and determining the course of treatment, and HCV genotype testing is required before IFN antiviral treatment in primary patients, and for patients with genotype 1, especially those with high viral load, severe liver fibrosis, and high body weight (>75
kg), regular IFN 5MU should be administered intramuscularly every other day or 3 times a week, PEG-IFNα-2a 180μg or PEG-IFNα-2b
1.5μg/kg subcutaneously once a week, RBV 1000-1200mg (weight <75kg)/d, 10.6-13mg/kg/d if weight >75kg
Oral treatment for 48 weeks for those with early response; for those with early response and still HCV positive at 24 weeks of treatment
RNA positive, or no early response, do not simply stop the drug, but should promptly change the program, you can replace the ordinary IFN to PEG-IFN, PEG-IFN treatment, especially for high weight people, increase the amount of RBV treatment and then treatment if tolerated. In patients with genotypes 2 and 3 with early response, there is evidence that 24 weeks of PEG-IFN treatment and 800 mg of RBV daily can achieve sufficiently large SVR rates, but there is no evidence that 24 weeks of treatment with regular IFN + RBV is a sufficient course of therapy, and the course of therapy should be extended in older patients or those with significant liver fibrosis. IFN has been used in the treatment of chronic hepatitis C and in the rigorous screening of blood donors for more than 10 years, with a gradual decrease in the number of patients treated initially and an increase in the proportion of patients who do not respond to previous therapy or who relapse, for whom the choice of therapeutic agents is a major issue. Although the Guidelines recommend that for patients who relapse after initial treatment with IFNα alone, they should be retreated with PEG-IFNα-2a or regular IFNα combined with RBV; for patients who do not respond to initial IFNα alone, they should be retreated with regular IFNα or PEG-IFNα-2a combined with RBV; for patients who do not respond to initial combination therapy with regular IFNα and RBV or relapse PEG-IFNα-2a combined with RBV can be tried in patients who do not respond to the first application of the combination of normal IFNα and RBV or who relapse. For those who relapsed on IFN monotherapy, 47% of those who were retreated with IFN+RBV achieved SVR,
For those who relapsed with IFN+RBV treatment, SVR was 32% to 50% with PEG-IFN+RBV retreatment. In contrast, only 12%-15% of those who did not respond to IFN alone achieved SVR with IFN+RBV retreatment and only 16%-28% with PEG-IFN+RBV retreatment; those who did not respond to IFN+RBV, PEG-IFN
+
RBV on treatment had an SVR of only 6% to 15%. The results suggest that retreatment of nonresponders with only standard treatment regimens has limited improvement in efficacy. The causes of patient failure to previous therapy vary from individual to individual, and to further improve SVR rates, retreatment should be individualized according to the patient’s clinical characteristics and the presence or absence of unfavorable factors from previous therapy. Numerous studies have shown that HCV can infect tissue cells outside the liver and that HCV in these cells is the source of the virus that recurs after treatment or after liver transplantation, and that clearance of HCV from these cells requires a short and long period of time, making the course of therapy another major factor in determining whether SVR can be achieved. In patients with early response, a 48-week course of treatment is required for HCV genotype 1 and 24 weeks for genotypes 2 and 3 with PEG-IFN. clinical trials of IFN for chronic HCV hepatitis in China have shown that the relapse rate for genotypes 2 and 3 at 24 weeks with common IFN is 50%.
Therefore, the course of treatment with conventional IFN needs to be extended to 1 year. For the retreatment of relapsed patients, the factors leading to relapse should be analyzed, and for those who do relapse due to insufficient treatment course, the changes of virus in blood should be monitored in the retreatment even with the same therapeutic drugs to predict whether the patient can obtain SVR in time, and the rate of sustained viral response should be improved by extending the treatment course for those who have early response. The author’s study showed that only 28% of relapsed patients treated with conventional IFN achieved viral response at the end of 24 weeks of treatment with conventional IFN, and only 11.1% of genotype 1 patients had SVR, compared with 45.8% for PEG-IFN. It is suggested that retreatment of those treated with regular IFN is preferable to avoid the use of regular IFN, which has limited ability to improve SVR even with an extended course of therapy, and to change therapeutic agents, including treatment with PEG-IGN and combined RBV. Because RBV increases the effectiveness of IFN anti-HCV therapy by increasing the cellular immune function of IFN anti-HCV therapy and preventing the rebound of HCV viral replication during the interval between dosing with regular IFN anti-HCV therapy, the use of IFN in combination with RBV is now the standard of care for antiviral treatment of chronic hepatitis C. The antiviral efficacy of IFN+RBV within a certain range is positively correlated with the dosage of RBV, although in the anti-HCV therapy of PEG-IFN+RBV it is stated that the dosage of RBV is 1000 mg/d for genotype 1, weight <75 kg, and 1200 mg/d for weight >75 kg. The results of the study on the dosage of RBV and clinical efficacy show that the high dose (15.2 mg/kg) of RBV significantly improved SVR in genotype 1. The results suggest that for those patients who relapsed and failed with PEG-IFN+RBV treatment, the chances of obtaining SVR can be increased by increasing the dose of RBV for retreatment, except for treatment failure because the course of treatment is too short. although the high dose application of RBV has certain side effects, the drug can be applied reduce the occurrence of its side effects, and once virological response is obtained, lowering the RBV dosage after 20 weeks will not affect the occurrence of SVR. In patients who have relapsed or partially responded to the previous treatment, SVR can be achieved in 25-40% of patients by changing the treatment regimen or correcting factors unfavorable to treatment, but retreatment of patients who do not respond to PEG-IFN+RBV treatment, even with different types of PEG-IFN, is still a difficult task to achieve viral clearance. Maintenance therapy in this group of patients cannot achieve virus clearance, but it can improve liver histology, delay disease progression and reduce the incidence of HCC, which can reduce the occurrence of post-hepatitis C cirrhotic complications significantly prolong survival, so maintenance therapy with low-dose PEG-IFN can be beneficial. In addition to the application of interferon and RBV for antiviral treatment of HCV, HCV protease inhibitors currently under development can effectively inhibit viral replication, and their combined application can improve the anti-HCV effect of IFN and establish a new anti-HCV treatment platform.