China is a large country with hepatitis B (hepatitis B for short), and clinicians and the public are more aware and alert to hepatitis B. Hepatitis C (hepatitis C for short), however, is often overlooked, resulting in a low rate of early detection and diagnosis. In fact, hepatitis C is widely prevalent worldwide and is the leading cause of end-stage liver disease in countries such as Europe, the United States and Japan. In China, the rate of anti-HCV positivity in the general population is 0.43%. The chronicity rate of hepatitis C virus (HCV) infection (50%-85%) is much higher than that of hepatitis B virus (HBV) infection (<10%), and if not intervened, some of these patients will eventually develop cirrhosis or even liver cancer. On the contrary, if HCV-infected patients are given timely standardized antiviral treatment, the treatment effect is far better than that of chronic hepatitis B. More than 70% of chronic hepatitis C patients can be cured after standardized antiviral treatment.
Antiviral treatment indications
As long as HCV RNA is positive, regardless of whether anti-HCV is positive or not, whether liver function is abnormal or not, and there are no contraindications to antiviral therapy (e.g. liver function of child grade C, pregnancy, uncontrolled depressive psychiatric disease, coexisting severe physical disease, uncontrolled autoimmune disease, allergy to antiviral therapy drugs, and white blood cell count, platelet count and hemoglobin level cannot Patients with a high level of antiviral therapy should receive standardized antiviral therapy.
How to detect infected patients early In clinical practice, how to detect HCV RNA-positive chronic hepatitis C patients early?
First, active education is needed to make clinicians and the public aware of hepatitis C.
Second, the following high-risk groups should be screened for HCV infection: anyone with a history of blood transfusion, especially those who received blood transfusion before 1993; those who received long-term hemodialysis and organ transplant recipients; those who use syringes; those with human immunodeficiency virus (HIV) infection and infants born to HCV-infected mothers; those who have been exposed to HCV-positive blood from needle sticks, knife wounds or broken mucous membranes; those who have had sex with HCV-infected people Those who have had sexual intercourse; those who have received interventional diagnostics and treatment (e.g., endoscopic examinations and treatments, dental devices, etc.).
It should be noted that in some immunosuppressed patients (patients with HIV infection, organ transplantation and maintenance hemodialysis), there may be a problem with false negative anti-HCV.
How to proceed with standardized antiviral therapy
Treatment goals and regimens
The primary treatment goal for chronic hepatitis C is to clear HCV, followed by long-term suppression of HCV replication, reduce liver tissue inflammation, and stop the development of cirrhosis and hepatocellular carcinoma.
Our guidelines recommend the combination of pegylated interferon alpha (Peg-IFNα) and ribavirin for the antiviral treatment of patients with chronic HCV infection.
The efficacy of this regimen is influenced by a number of factors, and the following factors favor a sustained virologic response (SVR) in patients: ① HCV genotype 2 or 3; viral levels < 2 × 106 copies/ml; age < 40 years; female; short duration of HCV infection; mild liver fibrosis; good compliance with treatment; no significant obesity; and no co-infection with HBV or HIV.
How to administer anti-HCV therapy Before antiviral therapy, HCV RNA genotyping should be performed to determine the course of antiviral therapy and the dose of ribavirin.
The specific treatment varies for patients with different genotypes of HCV infection.
1.Patients with genotype 1 HCV infection For patients with genotype 1 HCV infection, Peg-IFN α combined with ribavirin is recommended, with the following two regimens.
① Peg-IFNα-2a: 180 μg, once a week, subcutaneously, plus ribavirin orally (1000 mg/d for those weighing ≤75 kg, 1200 mg/d for those >75 kg).
② Peg-IFNα-2b: 1.5 μg/kg once weekly by subcutaneous injection, plus ribavirin orally (800 mg/d for those weighing ≤65 kg, 1000 mg/d for those 66-85 kg, 1200 mg/d for those 86-105 kg, and for those >105 kg, 1400 mg/d).
Three conditions occur in patients receiving the above regimens.
① Early virologic response, i.e., undetectable HCV RNA after 12 weeks of treatment. such patients with a total duration of Peg-IFN α combined with ribavirin therapy of 48 weeks and who test negative for HCV RNA at this time will be tested again for HCV RNA 24 weeks after stopping treatment, and if still negative, they will have developed SVR and can be considered virologically cured.
② Non-response, i.e. HCV RNA decreased <2 logs after 12 weeks of treatment compared to pre-treatment. such patients were discontinued after 12 weeks of treatment for observation.
(iii) Partial response, i.e. HCV RNA decreased >2 logs after 12 weeks of treatment compared to pre-treatment, but still detectable. For such patients, HCV RNA testing is repeated after 24 weeks of treatment and if still positive, the drug is discontinued, and if it turns negative, the antiviral therapy is continued and the total course of treatment must be extended to 72 weeks. This standard therapy can induce SVR in 40% to 50% of HCV type 1 infected patients.
2.Patients with genotype 2 and 3 HCV infection
For genotype 2 and 3 HCV-infected patients, Peg-IFN α (same usage as for type 1 HCV-infected patients) combined with ribavirin (800 mg/d) is also administered for a total duration of 24 weeks. If HCV RNA is negative at the end of treatment, and if HCV RNA is still negative when retested 24 weeks after the end of treatment, it is considered virologically cured. This therapy can induce SVR in 80% or more of patients with genotype 2 or 3 HCV infection.
3.Patients with genotype 4 HCV infection
The treatment regimen for those infected with this genotype is Peg-IFN α (used as in type 1 HCV-infected patients) combined with ribavirin (used as in type 1 HCV-infected patients) for 12 weeks of treatment, test for HCV RNA, and if negative, continue the regimen for 36 to 48 weeks, and if HCV RNA is still measurable but decreases >2 logs from pre-treatment, continue the regimen for 48 weeks of treatment.
4. Retreatment for those who fail antiviral therapy After the course of combined Peg-IFN α and ribavirin therapy, if the patient does not develop SVR, retreatment is not recommended, including the switch to different species of Peg-IFN α.
How to monitor treatment Because both interferon and ribavirin may cause a number of adverse events, and there are individual differences in patient response and tolerability to the drugs. Therefore, clinicians should monitor closely during the course of antiviral therapy and take the right measures when appropriate.
Specific monitoring methods are as follows.
1.Monitoring items needed before treatment
In addition to the virological examination items required for HCV infection itself, the tests required before treatment include liver and kidney function, blood routine, thyroid function, blood glucose and urine routine, etc.
2.Biochemical tests during treatment
After starting treatment, blood tests should be performed once a week for the first month, then once a month until 6 months, and then once every 3 months. During the treatment period, liver function should be checked every month, and every 2 months for 6 months after the end of treatment.
3. Virological examination during and after treatment
HCV RNA must be detected at 3 months of treatment, at the end of treatment and after treatment.
4.Monitoring of adverse reactions
Thyroid function tests should be performed every 6 months during treatment and every 3 to 6 months after the end of treatment. If thyroid function abnormalities exist before treatment, thyroid function should be checked every month. In elderly patients, electrocardiogram and cardiac function assessment should be performed prior to treatment. Mental status should also be evaluated periodically.
New hope for antiviral therapy
Currently, nearly 30% of patients with chronic hepatitis C are still not cured after standardized antiviral therapy due to poor response to drug therapy or intolerance of drug side effects. Therefore, new drugs or treatments are needed to provide new treatment opportunities for these patients.
In 2011, the American Association for the Study of Liver Diseases (AASLD) added two oral antivirals, telaprevir and baceprevir, which are specific protease inhibitors of HCV, to the first-line drugs for the treatment of hepatitis C in an update of the guidelines for the treatment of chronic type 1 HCV infection, and their use has given humans The use of these two drugs, which are HCV-specific protease inhibitors, has given humans a new and powerful weapon in the fight against HCV.
Therefore, both clinicians and patients themselves should have a positive and optimistic attitude when facing chronic HCV infection, and most patients can be cured after receiving regular treatment; for some refractory patients, the cure rate and prognosis are improving with the development of medical technology.