1.Anti-viral treatment plan
Before treatment, it should be clarified whether the patient’s liver disease is caused by HCV infection. Only patients with confirmed serum HCV RNA-positive viral hepatitis C need antiviral therapy. Antiviral therapy is currently recognized as the most effective regimen: long-acting interferon PEG-IFNα in combination with ribavirin, and is now the EASL-approved standard of care (SOC) for the treatment of chronic viral hepatitis C, followed by plain IFNα or combination IFN and ribavirin therapy, both of which are superior to IFNα alone. pegylated glycol (PEG) interferon α (PEG- IFNα) is an inactive, non-toxic PEG molecule cross-linked to the IFNα molecule, which delays the absorption and in vivo clearance process of IFNα after injection, and its half-life is long enough to maintain effective blood concentrations with one dose per week.
The direct-acting antiviral (DAA) protease inhibitors boceprevir (BOC) or telaprevir (TVR), a triple combination therapy with interferon combined with ribavirin, became clinically approved in the United States in May 2011 and is recommended for HCV-infected patients with genotype 1 to improve cure rates. Boceprevir (BOC) with meals, three times daily (every 7-9 hours), or telaprevir (TVR) with meals (non-low-fat diet), three times daily (every 7-9 hours). HCV RNA should be closely monitored during this period and protease inhibitors should be discontinued if virological breakthrough (rise in serum HCV RNA >1log after nadir) occurs.
2.Treatment of patients with general viral hepatitis C
(1) Acute viral hepatitis C has definite evidence suggesting that interferon therapy can reduce the chronicity rate of acute viral hepatitis C. It can be administered 8-12 weeks after an acute hepatitis episode of HCV infection with a course of 12-24 weeks. The optimal treatment regimen has not been finalized, but early treatment is more effective in patients with high viral load (>800,000 logIU/ml) of genotype 1.
(2) The severity of liver disease in patients with chronic viral hepatitis C should be assessed prior to treatment. Those with recurrent abnormal liver function or those with significant inflammatory necrosis (G ≥ 2) or moderate or greater fibrosis (S ≥ 2) on liver puncture histology are prone to progression to cirrhosis and should be given antiviral therapy.
(3) Cirrhosis of viral hepatitis C
(1) Patients with compensated cirrhosis (Child-Pugh grade A) are recommended to be given antiviral therapy under close observation in order to stabilize the disease and delay or stop the occurrence of complications such as liver failure and HCC, despite the reduced tolerance and effect of treatment.
②Patients with decompensated cirrhosis: it is mostly difficult to tolerate the adverse effects of IFNα treatment, and liver transplantation should be performed if available.
3.Treatment of patients with special viral hepatitis C
(1) Children and the elderly have insufficient experience regarding the treatment of chronic viral hepatitis C in children. The results of preliminary clinical studies show that the SVR rate of IFNα monotherapy seems to be higher than that of adults, and the tolerance of the drug is also better. 65 or 70 years old or older patients should also be treated with antiviral therapy in principle, but the tolerance of the treatment is generally poor. Therefore, the decision to give antiviral therapy should be made based on a comprehensive assessment of the patient’s age, tolerance to drugs, comorbidities (e.g., hypertension, coronary artery disease, etc.) and the patient’s wishes.
(2) Chronic alcoholism and drug addiction may promote HCV replication and exacerbate liver damage, thus accelerating the progression to cirrhosis or even HCC. Because of the low compliance, tolerance and SVR rate of antiviral therapy in alcohol and drug addicts, treatment of hepatitis C must be accompanied by alcohol and drug abstinence.
(3) Co-infection with HBV or HIV accelerates the progression of chronic viral hepatitis C to cirrhosis or HCC. For those who are HCV RNA positive/HBVDNA negative, anti-HCV therapy should be given first; for those who have active replication of both viruses, IFNα plus ribavirin is recommended to clear HCV first, and then anti-HBV therapy can be given to those who are still HBVDNA positive after treatment. The treatment of such patients needs to be studied in depth to determine the best treatment option.
Co-infection with HIV can also accelerate the progression of chronic viral hepatitis C. Anti-HCV therapy depends primarily on the patient’s CD4+ cell count and the stage of fibrosis in the liver tissue. Patients with normal immune function and no immediate indication for highly active antiretroviral therapy (HAART) should be treated first for HCV infection; patients on HAART with S2 or S3 liver fibrosis must be given concurrent anti-HCV therapy; however, special attention should be paid to the possibility of interaction between ribavirin and anti-HIV nucleoside analogs, including lactic acidosis. For those who are severely immunosuppressed (CD4+ positive lymphocytes <2×108/L), anti-HIV therapy should be given first, and anti-HCV therapy should be considered after the immune function is reestablished.
(4) Chronic renal failure For chronic viral hepatitis C with renal failure and not on dialysis, anti-HCV therapy should not be administered. Patients already on dialysis and not yet histopathologically cirrhotic (especially those preparing for renal transplantation) may be treated with IFNα alone (care should be taken to administer the drug after dialysis). Since severe hemolysis can occur in patients with renal insufficiency, ribavirin combination therapy is generally not indicated.
(5) Recurrence of viral hepatitis C after liver transplantation Patients with HCV-related cirrhosis or HCC have a high rate of recurrence of HCV infection after liver transplantation. IFNα therapy is effective in such patients, but has the potential to promote rejection of the transplanted liver, and antiviral therapy can be administered under the guidance and close observation of an experienced specialist.
Anti-viral therapy for viral hepatitis C has a long course and large side effects, and requires safe use under the guidance of an experienced specialist assessment; the efficacy needs to be evaluated in a timely manner during treatment, and treatment should be guided according to the response, and the adverse effects of the drugs should be monitored closely at the same time to avoid serious adverse effects as much as possible.
4. Contraindications to antiviral therapy
(1) Absolute contraindication to interferon
(1) Pregnancy.
(ii) history of psychiatric disorders such as major depression.
(3) uncontrolled epilepsy.
④ unabstained alcohol or drug abusers.
⑤ uncontrolled autoimmune disease.
⑥decompensated cirrhosis of the liver.
(vii) Symptomatic heart disease.
⑧ Granulocytes <1.0×109/L prior to treatment.
⑨ platelets <50×109/L before treatment.
(⑩Organ transplant recipients in acute stage (except liver transplant).
(2) Relative contraindications to interferon thyroid disease, retinopathy, psoriasis, previous history of depression, uncontrolled diabetes mellitus, uncontrolled hypertension.
(3) Absolute contraindications to ribavirin are pregnancy, severe heart disease, renal insufficiency, hemoglobinopathy, HB<80g/L.
(4) Relative contraindications to ribavirin: uncontrolled hypertension, uncontrolled coronary artery disease, HB<100g/L.