European Guidelines for the Management of Hepatitis C I. Preventing the Spread of Hepatitis C People exposed to HCV-contaminated needles need to be tested for HCV RNA within 4 weeks, and anti-HCV and alanine aminotransferase (ALT) after 12 and 24 weeks. HCV-infected people should not share potentially contaminated items, such as razors, scissors, toothbrushes, and thimbles, with other people. Cesarean section is not recommended to prevent vertical transmission of HCV in pregnant women with HCV infection at the time of delivery. For mothers with chronic hepatitis C, breastfeeding is allowed as long as they are anti-Human Immunodeficiency Virus (HIV) negative and have not engaged in intravenous drug use. II. Goals and endpoints of HCV treatment The goal of treatment for HCV infection is to clear the virus. The endpoint of treatment is to achieve a sustained virologic response (SVR). Once SVR is achieved, more than 99% of patients are equivalent to cure.Once HCV is cleared, inflammatory necrosis will cease and liver fibrosis will stop progressing in non-cirrhotic patients. In cirrhotic patients, HCV clearance reduces the incidence of decompensation but does not reduce the risk of hepatocellular carcinoma (HCC). Third, efficacy and predictive factors For patients with HCV genotype 1, 48 weeks of treatment with standard-dose pegylated interferon-α (Peg-IFN-α) combined with ribavirin (RBV) results in SVR in 40% to 54% of patients. For patients with HCV genotype 2 or 3, 24 weeks of treatment results in SVR in 65% to 82% of patients. the rate of SVR in genotype 2 patients is is slightly higher than for type 3. The most important factors for baseline prediction of SVR include HCV genotype, genetic polymorphism of IL28B (the gene encoding interferon λ-3), and the stage of liver fibrosis. Fourth, first-line treatment of chronic hepatitis C The accepted standard treatment regimen is Peg-IFN-α in combination with RBV. Both Peg-IFN-α-2a and Peg-IFN-α-2b can be used in combination with RBV at doses of 180 μg/w and 1.5 μg/(kg・w), respectively. The dose of RBV is 15 mg/(kg/d) for genotype 1 and 4-6 patients, and 800 mg/d for genotypes 2 and 3. For patients with genotypes 2 and 3 whose baseline characteristics are unfavorable for response, the dose of RBV should be 15 mg/(kg/d). Efficacy as well as adverse effects should be assessed at Weeks 4 and 12 of treatment, and then every 12 weeks until the end of treatment. SVR should be assessed at week 24 after the end of treatment.The cut-off for differentiating between high and low HCV RNA levels is 400,000 IU/ml and 800,000 IU/ml. v. Viral Response-Guided Treatment For patients of any genotype, if HCV RNA decreases <2 log10 IU/ml at 12 weeks, or if HCV RNA (≥50 IU/ml) is still detectable at 24 weeks, then treatment should be discontinue treatment. For those who achieve a rapid virologic response (RVR) and have a low baseline viral load (<400,000 to 80,000 IU/ml), consider treatment for 24 weeks (genotype 1 or 4) or 12 to 16 weeks (genotype 2 or 3). If there are poor predictors of response, there is insufficient evidence of equivalence of short versus long courses of treatment. If only an early virologic response (EVR) occurs, treatment should be for 48 weeks. If only a delayed virologic response (DVR) is achieved and the virus is undetectable at 24 weeks, treatment should be given for 72 weeks. For patients without cirrhosis, ALT and HCV RNA should be tested at 48 and 96 weeks after the end of treatment.For patients with cirrhosis, in addition to the above tests, esophageal varices should be monitored every 1 to 2 years, and HCC should be monitored by ultrasound and alpha-fetoprotein (AFP) every 6 months. VI. Follow-up of patients with SVR For patients without cirrhosis, ALT and HCV RNA should be tested at 48 and 96 weeks after the end of treatment. 96 weeks after the end of treatment, ALT and HCV RNA (C2) must be tested. For patients with cirrhosis, in addition to the above tests, esophageal varices should be monitored every 1 to 2 years, and HCC should be monitored by ultrasound and alpha-fetoprotein (AFP) every 6 months. Re-treatment of patients who do not obtain SVR For patients with genotype 1 who fail to clear the virus after treatment with Peg-IFN-alpha in combination with RBV, re-treatment with the same drug is usually not indicated (A2). Subsequent retreatment with a combination of three drugs, Peg-IFN-α, RBV, and a protease inhibitor, may be considered. However, when there is an urgent need for treatment, or when the dose of Peg-IFN-α and RBV is insufficient at the time of initial treatment, Peg-IFN-α in combination with RBV may be given again. For patients with non-genotype 1 who fail to achieve SVR, Peg-IFN-α in combination with RBV may be given again. Low-dose Peg-IFN-α maintenance therapy is not recommended. VIII. Treatment of patients with indication for liver transplantation For patients with liver function Child-Pugh A, antiviral therapy should be given. For cirrhotic patients with Child-Pugh B, prioritize treatment of those with good predictive factors. For cirrhotic patients with Child-Pugh C, they should not be treated with current antiviral agents. Treatment can be started with small doses of Peg-IFN-α and RBV, followed by gradual dosage increases; it can also be initially treated at full dosage (but more than 50% of patients need to be reduced or even terminated). Nine, the treatment of recurrence after liver transplantation For patients with recurrence of hepatitis C after liver transplantation, once the diagnosis of chronic hepatitis is established and there is evidence of liver histology, treatment should be started. If significant hepatic fibrosis or portal hypertension occurs 1 year after liver transplantation, it predicts rapid disease progression and graft loss and requires immediate antiviral therapy. If liver function impairment occurs during antiviral therapy, liver tissue biopsy should be performed to guide treatment. X. Treatment of special populations For patients with co-infection of HIV, the dose of Peg-IFN-α is the same as that for HCV alone, but the dose of RBV should be 15 mg/(kg・d). The course of treatment is 72 weeks for genotype 1 patients and 48 weeks for genotype 2 or 3 patients. For patients with co-infection with hepatitis B virus (HBV), Peg-IFN-α may be given in combination with RBV, following the same principles as those for HCV alone. If HBV replication levels are high, nucleoside (acid) analogs should be combined. For patients on hemodialysis, Peg-IFN-α therapy alone is safer but less effective. For some patients, combination therapy with individualized doses of RBV may be given. Antiviral therapy with Peg-IFN-α should be given before renal transplantation. In patients with hemoglobinopathies, combination antiviral therapy may be given, but close monitoring for hematologic adverse effects is required. For patients with acute hepatitis C, Peg-IFN-α monotherapy can be used, the dose of Peg-IFN-α-2a and Peg-IFN-α-2b is 180 μg/w or 1.5 μg/(kg・w) respectively, and the course of treatment is 24 weeks, and the treatment can lead to the clearance of the virus in more than 90% of the patients. For those who failed treatment, the standard antiviral regimen could be given again. Compared to the American Association for the Study of Liver Diseases (AASLD) 2009 Guidelines for the Management of Hepatitis C, the EASL guidelines give some new recommendations based on the results of the last 2 years of research. The EASL guidelines do not recommend delivery by cesarean section to prevent vertical transmission of HCV; they recommend breastfeeding for mothers with chronic hepatitis C, as long as they are anti-HIV-negative and do not use drugs intravenously. Regarding predictors of efficacy, the EASL guidelines add the important predictor of host genotype, IL28B, which is significantly associated with treatment response. The European population expresses this "good gene" in significantly higher proportions than the African population, which partly explains the nearly half-year difference in outcomes between patients of European and African descent. The first line of treatment for chronic hepatitis C remains Peg-IFN-alpha in combination with RBV, but the dose and duration of RBV is dependent on baseline characteristics such as HCV genotype and virologic response during treatment, which is the first time that the EASL guideline has introduced the concept of first-line treatment, demonstrating both the complexity and standardization of treatment. The EASL guidelines recommend that patients who obtain an RVR and have a low viral load at baseline (<400,000 to 80,000 IU/ml) be considered for treatment for 24 weeks (genotype 1 or 4) or 12 to 16 weeks (genotype 2 or 3). However, the course should not be shortened if poor predictors of response (progressive liver fibrosis/cirrhosis, metabolic syndrome, insulin resistance, hepatic steatosis, etc.) are present. Recommendations for shorter regimens can largely reduce the economic burden on patients and minimize adverse drug reactions. The EASL guideline looks forward to the three-drug combination of standard therapy with protease inhibitors, and may consider giving the above three-drug combination for re-treatment in genotype 1 patients who are usually not re-treated with the same drugs after standard therapy if the virus fails to clear. The guidelines take a cautious welcome to specific protease inhibitors that have been in phase III trials, mainly because clinical studies of protease inhibitors bring new hope but also leave more room to be studied.