Since the application of interferon in the antiviral treatment of chronic hepatitis C, especially the development of pegylated interferon and the application of ribavirin, with the further development of clinical experimental research, pegylated interferon combined with ribavirin has become the “gold standard” of antiviral treatment for chronic hepatitis C, bringing great hope for the cure of chronic hepatitis C. This has brought great hope for the cure of chronic hepatitis C. However, the antiviral treatment of chronic hepatitis C is influenced by many factors, especially the viral genotype, viral load, the patient’s age and the degree of liver fibrosis, the type and dose of therapeutic drugs, the combination therapy and the course of treatment, and the clinical practice still requires individualized treatment according to the patient’s situation. I. Who needs treatment Chronic hepatitis C Because most patients have only mildly elevated ALT or even completely normal, most patients often do not feel discomfort in the chronic hepatitis stage, and some patients have progressed to cirrhosis once they have obvious discomfort, so treatment cannot be decided by whether they have clinical discomfort. Clinical studies have shown that chronic hepatitis C is still associated with the development of fatty liver and diabetes mellitus, and is even considered a metabolic disease by some scholars. There is increasing evidence that even in patients with minimal liver histological damage, so-called “asymptomatic carriers”, quality of life is affected in a significant number of patients and that the degree of quality of life is not correlated with ALT levels. The above results suggest that in those with ALT one should not simply assume that the inflammation of liver tissue is mild, and it is best to perform liver histological examination to clarify the necessity of treatment. The chronicity of chronic hepatitis C virus infection is as high as 50%-80%, so once patients are found to be infected, they are often chronically infected. Since chronic hepatitis C virus infection which whether ALT is normal or not does not correlate with interferon antiviral efficacy, antiviral therapy should be performed once patients are found to be chronically infected with HCV. Second, the efficacy evaluation and treatment goals The long-term presence of the virus is the main reason for the progression of chronic hepatitis C. To stop the development of the disease, the removal of the virus through antiviral therapy is the fundamental means, therefore, the goal of antiviral therapy for chronic hepatitis C is to remove the virus to achieve a cure. Therefore, the goal of antiviral therapy for chronic hepatitis C is to clear the virus to achieve a cure. A large number of studies have shown that if there is no relapse (sustained viral response) 6 months after stopping treatment, the virus can remain negative for a long time. Third, the choice of therapeutic drugs The currently listed drug with anti-hepatitis C virus activity is interferon, either common interferon or pegylated interferon, the effect of treatment alone is not ideal, and requires combination therapy with ribavirin. All current studies have shown that the efficacy of pegylated interferon in combination with ribavirin is significantly higher than that of regular interferon, and therefore, where possible, pegylated interferon in combination with ribavirin is the gold standard of antiviral therapy for chronic hepatitis C. The pegylated interferons are Roche’s 40
KD (Peroxyn) from Roche and 12 KD (Pellegrin) from Schering-Polymer.
KD (Pellegrin) from Schering-Polymer. The dose of Pyroxine does not need to be adjusted according to body weight, i.e., a fixed dose can be used, while Pellegrin requires subcutaneous injections once a week according to 1.5 μg/kg. There is no difference in the efficacy of these two pegylated interferons in primary care patients. The contribution of ribavirin to antiviral efficacy is similar to that of interferon, who mainly affects sustained viral response, and those who do not use ribavirin are prone to relapse. The dose of ribavirin is significantly correlated with efficacy, and the higher the dose within a certain range, the higher the efficacy should be, if possible, 10.5
The duration of treatment should be determined by the genotype of the virus, as a longer period of treatment is required to achieve a sustained viral response. The duration of treatment is 48 weeks for genotypes 1, 4, 5 and 6 and 24 weeks for genotypes 2 and 3, but this is the minimum duration of treatment. Because of differences in patient response patterns to treatment, the course of treatment should be determined clinically based on the specific response of the patient. For patients with rapid viral response (RVR at 4 weeks of treatment) or complete early responders (EVR at 12 weeks of treatment), the basic course of treatment should be completed according to the viral genotype. The course of treatment should be extended to 72 weeks in order to achieve viral clearance. The key to the course of antiviral therapy for chronic hepatitis C is to keep the virus continuously negative for a certain period of time during the treatment. V. Treatment of side effects and adjustment of drug dose Since the occurrence of side effects can reduce the patient’s quality of life, reduce the patient’s compliance to treatment, and therefore reduce the patient’s response to treatment, about 10% to 15% of patients stop treatment due to side effects of drugs. The common adverse effects of IFN+RBV antiviral therapy include fever, flu-like syndrome, decreased peripheral blood neutrophils, decreased platelet count, anemia, weight loss, and hair loss. These adverse reactions are not permanent and will recover after the completion of the treatment course and discontinuation of the drug. Fever can be prevented and reduced by taking one tablet orally before IFN injection, which is usually administered during the first few injections and then gradually disappears. IFN has an inhibitory effect on the bone marrow, so peripheral blood neutropenia can occur during IFN treatment, and the degree and incidence of decline increases with increasing drug dose. Absolute neutrophil counts above 1.0×109/L are still tolerated by most patients and do not require treatment. When below 1.0×109/L and above 0.75×109/L, some drugs with leukocyte-raising function can be used, below 0.75×109/L, the drug dose needs to be reduced, while below 0.5×109/L, the drug needs to be discontinued. Since the efficacy of antiviral therapy is related to the dose and course of IFN, there is no doubt that premature dose reduction and discontinuation of therapy will prevent these patients from obtaining SVR. Therefore, patients are required to closely observe the changes in neutrophils, and when their neutrophil count decreases to a certain level, prompt clinical management is required to ensure that they are on an effective IFN dose and complete the entire course of therapy. Reduced platelets are less likely to occur than neutrophils, with thrombocytopenia occurring in less than 5% of cases. Evaluation of the clinical significance of thrombocytopenia should start from the clinical reality, firstly whether thrombocytopenia has clinical manifestations, those with clinical manifestations such as petechiae of skin and mucous membrane, gingival bleeding, etc. should be treated even if the platelet count is >5.0×109/L. Counts in the range of 2.5×109/L to 3.0×109/L without clinical symptoms can also be treated under close observation, but Those with counts <2.5×109/L should be treated, requiring a reduction in IFN dose or even discontinuation of the drug. About 1/3 of patients on IFN+RBV antiviral therapy have varying degrees of anemia, and 15% of patients have a decrease in hemoglobin below 10 g/dL, mainly due to the increased destruction of red blood cells caused by RBV. The development of anemia often requires a 20% to 25% reduction in the dose of RBV. When hemoglobin falls to 10 g/dL to 8.5 g/dL, the dose of RBV needs to be reduced, and when it falls below 8.5 g/dL, RBV needs to be discontinued. in order to complete the whole course of treatment, the reduction of hemoglobin can also be treated with erythropoietin, especially for those who have been treated and have failed due to discontinuation of RBV. Since the combination of RBV can significantly improve the efficacy of anti-HCV therapy with regular IFN or PEG-IFN, the combination of RBV and IFN should be emphasized for both economic and efficacy reasons, and should be handled rationally according to the clinical situation.