Transmission routing
Hepatitis C is mainly transmitted through the following routes:
1, blood transmission
(1) is transmitted through blood transfusion and blood products. Because of the window period of anti -HCV, the quality of anti -HCV detection reagents is unstable, and a few infected people do not produce anti -HCV, so it is impossible to completely screen HCV positive people, and a large number of blood transfusions and hemodialysis may still infect HCV.
(2) Transmission through damaged skin and mucosa. This is the main mode of transmission at present. In some areas, HCV transmission caused by intravenous drugs accounts for 60% ~ 90%. The use of non-disposable syringes and needles, dental instruments without strict disinfection, endoscopy, invasive operation and acupuncture are also important ways of transdermal transmission. Some traditional medical methods that may lead to skin damage and blood exposure are also related to the spread of hepatitis C virus. Sharing razors, toothbrushes, tattoos and pierced earrings is also a potential way for hepatitis C virus to spread through menstruation.
2. Sexual transmission:
3. Mother-to-child transmission: the risk of HCV transmission from anti -HCV positive mothers to newborns is 2%, and if the mother is HCV RNA positive during delivery, the risk of transmission can be as high as 4% ~ 7%; When HIV infection occurs, the risk of transmission increases to 20%. The high load of HCV virus may increase the risk of transmission.
4. Other routes: 15%~30% sporadic hepatitis C, and its transmission route is unknown.
Kissing, hugging, sneezing, coughing, food, drinking water, sharing tableware and water cups, no skin damage and other contact without blood contact generally do not spread HCV.
HCV RNA can be detected in peripheral blood 1 ~ 3 weeks after acute infection with hepatitis c virus. The incubation period is usually 2-26 weeks with an average of 50 days; The incubation period of transfusion infected persons is 7~33 days, with an average of 19 days. When clinical symptoms appear, only 50% ~ 70% patients are anti -HCV positive, and about 90% patients are anti -HCV positive after 3 months.
Disease pathology
The pathological changes of hepatitis C are very similar to those of hepatitis B, mainly manifested as hepatocyte necrosis and lymphocyte infiltration. Chronic hepatitis can appear fibrous tissue hyperplasia in portal area, and in severe cases, it can form false lobules, which is called cirrhosis.
pathogenesis
The pathogenesis of HCV infection mainly includes immune mediation and HCV direct injury, and viral factors include virus genotype, replication ability, immunogenicity of virus polypeptide and so on. Host factors include innate immune response, humoral immune response and cellular immune response. Factors such as drinking alcohol and using immunosuppressants can also affect the progress of HCV infection.
The cause of the disease
Hepatitis C virus infection is the root cause of the disease. Under the influence of external factors, such as drinking, fatigue and long-term use of hepatotoxic drugs, it can promote the development of diseases.
Disease classification
Hepatitis C can be divided into different types clinically:
1, acute hepatitis C.
2, chronic hepatitis C.
3, hepatitis C cirrhosis
clinical picture
1, acute hepatitis C: Adult acute hepatitis C is relatively mild, mostly acute icteric hepatitis, mainly with elevated ALT, and a few acute icteric hepatitis, with slight or moderate jaundice. Nausea, loss of appetite, general weakness, yellow urine and yellow eyes may occur. Hepatitis C virus infection alone rarely leads to liver failure. In the natural state, only 15% patients can spontaneously clear HCV to achieve recovery, and 85% patients develop chronic hepatitis C without antiviral treatment intervention; 50% of children can spontaneously clear HCV after acute infection with HCV.
2, chronic hepatitis C: mild symptoms, manifested as common symptoms of hepatitis, such as fatigue, poor appetite, abdominal distension and so on. You can also have no symptoms of consciousness. ALT fluctuated repeatedly and HCVRNA continued to be positive. Patients with chronic HCV infection with 1/3 have normal liver function, anti -HCV and HCVRNA continue to be positive, and liver biopsy shows chronic hepatitis and even cirrhosis.
3. Hepatitis C cirrhosis: 10%~20% patients infected with HCV can develop cirrhosis within 20-30 years, and 1%~5% patients will develop hepatocellular carcinoma (HCC) and die. Once decompensated liver cirrhosis occurs, such as jaundice, ascites, varicose bleeding, hepatic encephalopathy and so on. Its survival rate dropped sharply.
complication
Chronic hepatitis C may be complicated with some extrahepatic manifestations, including rheumatoid arthritis, conjunctivitis sicca, lichen planus, glomerulonephritis, mixed cryoglobulinemia, B-cell lymphoma and delayed cutaneous porphyria, which may be caused by abnormal immune response. Various complications may occur in the decompensated period of hepatitis C cirrhosis: ascites, abdominal infection, upper gastrointestinal bleeding, hepatic encephalopathy, hepatorenal syndrome, liver failure and so on.
Diagnostic and differential auxiliary examination
The diagnosis of hepatitis C requires the following appropriate tests:
⑴ Liver function: including serum ALT, AST, total bilirubin, direct bilirubin, indirect bilirubin, albumin, globulin, cholinesterase, alkaline phosphatase, transpeptidase, etc.
⑵ Hepatitis C virus antibody: anti-HCV. ⑶ HCV quantification: Serum HCVRNA can understand the active degree of HCV replication.
⑷ Imaging: including color Doppler ultrasound of abdomen, liver, gallbladder and spleen to find out whether there is chronic liver injury. If necessary, abdominal enhanced CT or MRI can be performed to understand the degree of injury. ⑸ Transient elastic wave scanning of liver (Fibroscan): It is a non-invasive examination, which can be used to evaluate the degree of liver fibrosis in patients with chronic hepatitis C, and it is very important to evaluate the degree of liver fibrosis in patients with hepatitis C. [6] Liver biopsy: It is still the gold standard for evaluating liver inflammation grading and fibrosis staging.
differential diagnosis
It can be identified by HCV virological examination. [ 1-2]
Disease treatment
Before treatment, it should be clear whether the patient's liver disease is caused by HCV infection, and only patients with HCV RNA positive serum need antiviral treatment. At present, the most effective antiviral treatment is the combination of long-acting interferon PEG-IFNα and ribavirin, which is also the nursing standard (SOC) approved by EASL for the treatment of chronic hepatitis C, followed by common IFNα or the combination of IFNα and ribavirin, all of which are better than IFNα alone. PEG interferon α(PEG-IFNα) is an inactive and nontoxic PEG molecule crosslinked with IFNα, which can delay the absorption and elimination of IFNα after injection. It has a long half-life, and can maintain effective blood concentration after weekly 1 dose.
The triple therapy of direct-acting antiviral drug (DAA) protease inhibitor, Boceprevir(BOC) or Telaprevir(TVR) and interferon combined with ribavirin was approved for clinical use in the United States in May of 20 1 1 and recommended for HCV infection with genotype 1. Boceprevir(BOC) 800mg after meals, three times a day (once every 7-9 hours), or Telaprevir(TVR)750mg after meals (non-low-fat diet), three times a day (once every 7-9 hours). During this period, HCV RNA should be closely monitored, and if there is a virological breakthrough (the serum HCV RNA rises after the lowest value >; 1 log), protease inhibitors should be stopped.
Indications of antiviral therapy
(A) the general treatment of patients with hepatitis C.
1. acute hepatitis c: there is definite evidence that interferon treatment can reduce the chronic rate of acute hepatitis c, which can be carried out 8- 12 weeks after the onset of acute hepatitis infected with HCV, and the course of treatment is 12-24 weeks. The best treatment scheme has not been finalized, but early treatment is very important, and it is more effective for the high viral load of gene1(>: 800,000 log iu/ml).
2. Chronic hepatitis C: The severity of patients' liver diseases should be evaluated before treatment. Patients with recurrent abnormal liver function, obvious inflammatory necrosis (G≥2) or moderate fibrosis (S≥2) in liver biopsy are prone to liver cirrhosis and should be given antiviral treatment.
3. Hepatitis C cirrhosis: (1) Although the tolerance and therapeutic effect of patients with compensatory cirrhosis (Child-Pugh A grade) have declined, it is recommended to give antiviral treatment under close observation. ⑵ Patients with decompensated cirrhosis: The adverse reaction of IFNα therapy is unbearable, and liver transplantation should be performed if possible.
(2) Treatment of patients with special hepatitis C.
1. Children and the elderly: Insufficient experience in treating chronic hepatitis C in children. The preliminary clinical research results show that the SVR rate of IFNα monotherapy seems to be higher than that of adults, and the drug tolerance is better. In principle, elderly patients aged 65 or over should also receive antiviral treatment, but their tolerance to treatment is generally poor. Therefore, patients' age, drug tolerance and complications (such as hypertension and coronary heart disease) should be comprehensively measured. ) and the patient's wishes to decide whether to give antiviral treatment.
2. Alcoholism and drug addiction: Chronic alcoholism and drug addiction may promote HCV replication and aggravate liver damage, thus accelerating the development of cirrhosis and even HCC. Because of the low compliance, tolerance and SVR rate of alcohol and drug addicts in antiviral treatment, it is necessary to abstain from alcohol and drug at the same time in the treatment of hepatitis C.
3.HBV or HIV infection: HBV infection will accelerate the progress of chronic hepatitis C to cirrhosis or HCC. Patients with HCV RNA positive /HBV DNA negative should be treated with anti-HCV. For patients with active replication of both viruses, it is suggested that IFNα plus ribavirin should be used to clear HCV first, and those who continue to be positive for HBV DNA after treatment can be given anti-HBV treatment. The treatment of such patients needs further research to determine the best treatment plan.
HIV infection can also accelerate the progress of chronic hepatitis C, and anti-HCV treatment mainly depends on CD4+ cell count and liver fibrosis stage. If the immune function is normal, and there is no indication for immediate highly active antiretroviral therapy (HAART), HCV infection should be treated first. Patients who are receiving HAART and have S2 or S3 hepatic fibrosis should also receive anti-HCV therapy. However, special attention should be paid to the possibility of interaction between ribavirin and anti-HIV nucleoside analogues, including lactic acidosis. For patients with severe immunosuppression (CD4+ positive lymphocytes
4. Chronic renal failure: For patients with chronic hepatitis C and renal failure who have not received dialysis, antiviral treatment is not appropriate. Patients who have received dialysis and have no liver cirrhosis (especially those who are preparing for kidney transplantation) can be treated with IFNα alone (pay attention to the administration after dialysis). Because severe hemolysis can occur in patients with renal insufficiency, ribavirin combination therapy is generally not used.
5. Hepatitis C recurrence after liver transplantation: HCV-related cirrhosis or HCC patients have a high recurrence rate of HCV infection after liver transplantation. IFNα therapy is effective for this kind of patients, but it may promote the rejection of transplanted liver. Antiviral therapy can be carried out under the guidance and close observation of experienced specialists.
Contraindications of antiviral therapy
Interferon has 10 absolute contraindications:
1. Pregnant
History of mental illness such as severe depression.
3. uncontrollable epilepsy,
4. An alcoholic or drug addict who asks for nothing in return.
5. Uncontrollable autoimmune diseases.
6. decompensation
7. Symptomatic heart disease.
8. Before treatment, granulocytes
9 platelets before treatment
10. Acute organ transplantation (except liver transplantation)
Interferon has six relative contraindications: thyroid disease, retinopathy, psoriasis, past history of depression, uncontrolled diabetes and uncontrolled hypertension.
Ribavirin has five absolute contraindications: pregnancy, severe heart disease, renal insufficiency, hemoglobinopathy and HB.
There are many adverse drug reactions during antiviral treatment, which need close observation and timely treatment.
(A) the main adverse reactions of interferon α
It is influenza-like syndrome, myelosuppression, mental disorder, thyroid disease, anorexia, weight loss, diarrhea, rash, alopecia and aseptic inflammation at the injection site.
1. Influenza-like syndrome: characterized by fever, chills, headache, muscle aches, fatigue, etc. IFNα can be injected before going to bed, or non-steroidal anti-inflammatory and analgesic drugs can be taken at the same time with IFNα to relieve flu-like symptoms. With the progress of the course of treatment, such symptoms gradually abate or disappear.
2. Bone marrow suppression: Transient bone marrow suppression is mainly manifested as leukopenia and thrombocytopenia in peripheral blood. If the absolute number of neutrophils is ≤≤≤0.75× 109/L/L and platelets are < 50× 109/L, the dose of IFNα should be reduced; 1 ~ 2 weeks later. If it is restored, it will gradually increase to the original amount. If the absolute number of granulocytes is less than or equal to 0.50×109/L/L and platelets are less than 30× 109/L, the drug should be stopped. Patients with significantly decreased neutrophils can be treated with granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage colony stimulating factor (GM-CSF).
3.IFN α can induce the production of autoantibodies, including antithyroid antibodies, antinuclear antibodies and anti-insulin antibodies. In most cases, there is no obvious clinical manifestation. Some patients may suffer from thyroid diseases (hypothyroidism or hyperthyroidism), diabetes, thrombocytopenia, hemolytic anemia, psoriasis, leukoplakia, rheumatoid arthritis and systemic lupus erythematosus-like syndrome. In serious cases, they should stop taking medicine.
4. Mental system performance: it can be manifested as depression, paranoia, serious anxiety and psychosis. Among them, depression is a common adverse reaction during IFNα treatment, and the symptoms can range from irritability to severe depression. Therefore, the mental state of patients should be evaluated before using IFNα, and patients should be closely observed during treatment. Antidepressants can alleviate this adverse reaction. For those with severe symptoms, IFNα should be stopped in time.
5. Other rare adverse reactions: including renal damage (interstitial nephritis, nephrotic syndrome and acute renal failure, etc. ), cardiovascular complications (arrhythmia, ischemic heart disease and cardiomyopathy, etc. ), retinopathy, hearing loss and interstitial pneumonia. When the above reaction occurs, the treatment should be stopped.
(II) The main adverse reactions of ribavirin
The main adverse reactions of ribavirin are hemolysis and teratogenesis.
1. Timely detection of hemolytic anemia: hematological examination should be done regularly, including hemoglobin, red blood cell count and reticulocyte count. Renal insufficiency can cause severe hemolysis, so ribavirin should be banned. When Hb drops to ≤ 100g/L, it should be reduced; When Hb≤80g/L, the drug should be stopped.
2. Teratogenic effect: Both male and female patients should take contraceptive measures during treatment and within 6 months after drug withdrawal.
3. Other adverse reactions: Ribavirin can also cause nausea, dry skin, itching, cough and hyperuricemia.
(3) The outstanding adverse reactions of 3)Boceprevir(BOC) are anemia and taste disorder.
(4) The outstanding adverse reactions of telaprevir (TVR) include rash, itching, anemia and anorectal reaction. [3-4]
Disease prognosis
Interferon has a good antiviral effect in acute hepatitis C, and 90% patients can get a complete response and recover completely. The condition of chronic hepatitis C is relatively milder than that of hepatitis B. After standardized antiviral treatment, it is possible to get rid of the virus and be cured. Some patients may develop cirrhosis or liver cancer after 20-30 years of infection.
pay attention to the diet
There is no special requirement for the diet of hepatitis C, only the diet in acute phase, and a balanced diet for chronic hepatitis. Pay attention to avoid taking a lot of nourishing foods such as turtle soup and ginseng tonic.
disease prevention
Hepatitis C vaccine prevention
At present, there is no effective vaccine to prevent hepatitis C.
(2) Strictly screen blood donors.
Strictly implement the "People's Republic of China (PRC) Blood Donation Law" and promote voluntary blood donation. Blood donors were strictly screened by detecting serum anti -HCV and alanine aminotransferase (ALT). The detection method of HCV antigen should be developed to improve the detection rate of window infection.
(3) Prevention of transcutaneous and mucosal transmission
Advocate safe injection. Dental instruments, endoscopes and other medical instruments should be strictly disinfected. Medical personnel should wear gloves when they come into contact with patients' blood and body fluids. Provide psychological counseling and safety education to intravenous drug users to persuade them to give up drugs. Don't share razors and dental appliances. Barber tools, piercings and tattoos should be strictly disinfected.
Preventive transmission
Those with a history of sexual promiscuity should have regular check-ups and strengthen management. It is suggested that HCV infected people use condoms during sexual intercourse. Teenagers should receive correct sex education.
(5) Prevention of mother-to-child transmission
For pregnant women with HCV RNA positive, amniocentesis should be avoided, the delivery time should be shortened as much as possible, the integrity of placenta should be ensured, and the chances of newborns contacting maternal blood should be reduced.
expert opinion/advice
Hepatitis C antiviral therapy has a long course of treatment and great side effects, so it needs to be used safely under the guidance of experienced experts. In the course of treatment, we should evaluate the curative effect in time, guide the treatment according to the response, and closely monitor the adverse reactions of drugs to avoid serious adverse reactions as much as possible.