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, the Guidelines for the Prevention and Treatment of Hepatitis C were developed in 2004. Because multiple factors can affect the efficacy of interferon antiviral therapy for chronic hepatitis C, clinical treatment should be individualized according to the clinical and virological characteristics of the patient in order to achieve a greater cost-effectiveness ratio. In terms of the choice of therapeutic agents, the currently marketed drugs effective against hepatitis C virus are interferons, including regular 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 selected for intramuscular injection 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 improved 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 affecting the efficacy and determining the course of treatment. HCV genotype testing is required before IFN antiviral administration in primary treatment patients. For patients with genotype 1, especially those with high viral load, severe hepatic fibrosis, and high body weight (>75 kg), regular IFN 5MU should be applied by intramuscular injection every other day or three times a week, PEG-IFNα-2a 180μg or PEG-IFNα-2b 1.5μg/kg subcutaneously once a week and RBV 1000-1200mg (10.6-13mg/kg/d for weight 75kg) orally for 48 weeks for those with early response; for those with early response and still HCV RNA positive for 24 weeks or no early response, do not simply stop the drug, but change the regimen in time. Replace regular IFN with PEG-IFN, and increase the amount of RBV treatment for those treated with PEG-IFN, especially for those with high body weight, if it is 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 an adequate course of therapy, and the course 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 patients who relapse after initial treatment with IFNα alone be retreated with PEG-IFNα-2a or regular IFNα combined with RBV; for patients who do not respond to initial IFNα alone, 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 combination therapy with regular IFNα and RBV or who relapse. For those who relapsed on IFN monotherapy, 47% of those who were retreated with IFN+RBV achieved SVR, and for those who relapsed on IFN+RBV, the SVR of PEG-IFN+RBV retreatment was 32%-50%. In contrast, only 12%-15% of the non-responders to IFN alone and 16%-28% of the PEG-IFN+RBV retreatment achieved SVR, while only 6%-15% of the non-responders to IFN+RBV and PEG-IFN+RBV retreatment achieved SVR. 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 a 50% relapse rate at 24 weeks for genotypes 2 and 3, so the course of IFN needs to be extended to 1 year for general IFN. 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 was positively correlated with the dosage of RBV, although in the anti-HCV therapy of PEG-IFN + RBV it was pointed out that for genotype 1, those weighing 75 kg, the dosage of RBV was 1200 mg/d. The results of the study of RBV dosage and clinical efficacy showed that a high dose (15.2 mg/kg) of RBV significantly improved genotype 1 SVR. The results suggest that for those patients who relapse and fail with PEG-IFN + RBV treatment, except for treatment failure because the course of treatment is too short, the chances of obtaining SVR can be increased by increasing the dose of RBV for retreatment. although the high dose application of RBV has some side effects, the drug can be applied to reduce its side effects once virological response is obtained, after 20 weeks Decreasing the RBV dosage will not affect the occurrence of SVR. In patients who have relapsed or partially responded to previous treatment, a change in treatment regimen or correction of factors unfavorable to treatment can lead to SVR in 25-40% of patients, 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 the histology of the liver, delay the progression of the disease and reduce the incidence of HCC, which can reduce the occurrence of post-hepatitis C cirrhotic complications significantly prolonging 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.
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