China is a large country with high awareness and alertness of hepatitis B (hepatitis B) among clinicians and the public, while hepatitis C (hepatitis C) is often neglected, 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 standardized antiviral therapy is provided to HCV-infected patients in a timely manner, 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 therapy.
Antiviral treatment indications
Patients who are positive for HCV RNA, regardless of whether they are positive for anti-HCV or not, have abnormal liver function, and have no contraindications to antiviral therapy (e.g., child C liver function, pregnancy, uncontrolled depressive mental illness, coexisting serious physical illness, uncontrolled autoimmune disease, allergy to antiviral therapy, and white blood cell count, platelet count, and hemoglobin level that cannot Patients with a high level of antiviral therapy should receive standardized antiviral therapy.
How to detect infected patients early in the clinical setting, how to detect HCV RNA positive chronic hepatitis C patients early?
I. Active education is needed to make clinicians and the public aware of hepatitis C.
II. The following high-risk groups should be screened for HCV infection.
1. Anyone with a history of blood transfusion, especially those who received blood transfusion before 1993.
2. Those receiving long-term hemodialysis and organ transplant recipients.
3. those who share syringes.
4, human immunodeficiency virus (HIV) infected persons and infants born to HCV-infected mothers.
5.People who have been exposed to HCV-positive blood from needle sticks, knife wounds or broken mucous membranes
6.Persons who have had sexual intercourse with HCV-infected persons
7.Persons who have received interventional diagnosis and treatment (such as those who have received various endoscopic examinations and treatments and 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 of false negative anti-HCV.
How to proceed with standardized antiviral therapy
The primary treatment goal for chronic hepatitis C is to clear HCV, followed by long-term suppression of HCV replication, reduction of liver tissue inflammation, and stopping 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, with the following factors favoring a sustained virologic response (SVR) in patients with.
1. HCV genotypes 2 and 3.
2. viral levels < 2 × 106 copies/ml.
3, age < 40 years.
4, female.
5, short duration of HCV infection.
6.Low degree of liver fibrosis.
7, good compliance with treatment.
8.No significant obesity.
9.No co-infection with HBV and 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 therapy is recommended in 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, subcutaneously, 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-responder, 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 as for type 1 HCV-infected patients) combined with ribavirin (800 mg/d) is also administered for a total duration of 24 weeks. If the HCV RNA is negative at the end of treatment, and if the 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 patients infected with this genotype is Peg-IFN α (same usage as for type 1 HCV-infected patients) combined with ribavirin (same usage as for type 1 HCV-infected patients) for 12 weeks of treatment. If the HCV RNA is tested negative, continue the regimen for 36 to 48 weeks, and if the HCV RNA is still measurable but decreases >2 logs from the pre-treatment period, continue the regimen for 48 weeks of treatment.
4.Antiretroviral treatment failure
Retreatment for those who failed 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 exchange of different species of Peg-IFN α.
How to monitor the treatment
Because both interferon and ribavirin may cause a number of adverse events, and there are individual differences in patient response and tolerance 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 These two drugs are HCV-specific protease inhibitors, and their use has given humans a new and powerful weapon in the fight against HCV.
Therefore, both clinicians and patients 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.