Etiology of hepatitis C
Characteristics of hepatitis C virus
HCV belongs to flaviviridae, and its genome is single-stranded positive-stranded RNA, which is easy to mutate. At present, it can be divided into 6 genotypes and different subtypes. According to the internationally accepted method, HCV genotypes are represented by Arabic numerals, and gene subtypes are represented by lowercase English letters (such as 1a, 2b, 3c, etc.). ). The gene 1 is distributed all over the world, accounting for more than 70% of all HCV infections. After HCV infects the host, after a certain period of time, a virus group with related mutants of dominant strains is formed in the infected person, which is called quasi-species.
(structural characteristics of HCV genome
HCV genome contains an open reading frame, which encodes 10 multiple structural and nonstructural (ns) proteins. NS3 protein is a multifunctional protein with protease activity at the amino terminal and helicase/nucleosidase triphosphate activity at the carboxyl terminal. NS5B protein is an RNA-dependent RNA polymerase, which is necessary for HCV replication and an important target of antiviral therapy.
(3) Inactivation method of hepatitis C virus
HCV is sensitive to common chemical disinfectants. 100℃ for 5min or 60℃ 60℃ 10h, high pressure steam and formaldehyde fumigation can inactivate the virus.
Epidemiology of hepatitis C
(a) The prevalence of hepatitis C in the world
Hepatitis C is a global epidemic and the main cause of end-stage liver disease in Europe, America, Japan and other countries. According to the statistics of the World Health Organization, the global HCV infection rate is about 3%, and it is estimated that about 654.38+0.7 billion people are infected with HCV, with about 35,000 new cases of hepatitis C every year.
The prevalence of hepatitis C in China.
According to the data of national seroepidemiological survey, the positive rate of anti -HCV in general population in China is 3.2%. The positive rate of anti -HCV varies from place to place, with the Yangtze River as the boundary. The north (3.6%) is higher than the south (2.9%), and the southwest, east China, north China, northwest China, south-central China and northeast China are 2.5%, 2.7%, 3.2%, 3.3%, 3.8% and 4.6% respectively. The positive rate of anti -HCV increased with age, from 2.0% in 1 age group to 3.9% in 50-59 age group. There is no obvious difference between men and women. HCV genotypes 1b and 2a are common in China, among which 1B is the main genotype. In some areas, 1a, 2b and 3b reported it; Type 6 is mainly found in Hong Kong and Macao, and this genotype is also found in the southern border provinces.
Transmission route of hepatitis C
1.HCV is mainly transmitted through blood, mainly including: (1) transmission through blood transfusion and blood products. After anti -HCV screening of 65438-0993 blood donors in China, this approach has been effectively controlled. However, due to the window period of anti -HCV, the unstable quality of anti -HCV detection reagents and the fact that a few infected people do not produce anti -HCV, 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. * * * The use of razors, toothbrushes, tattoos and pierced earrings are also potential modes of transmission of hepatitis C virus through menstruation.
2. Sexual transmission: Sexual intercourse and promiscuity with hepatitis C virus-infected people are at higher risk of contracting hepatitis C virus. At the same time, people with other sexually transmitted diseases, especially those infected with human immunodeficiency virus (HIV), are at higher risk of HCV infection.
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.
The route of transmission of some HCV infected people is unknown. Blood contact such as kissing, hugging, sneezing, coughing, food, drinking water, using tableware and water cups, and skin-friendly contact generally do not spread HCV.
Natural history of hepatitis C
HCV RNA can be detected in peripheral blood 1 ~ 3 weeks after HCV exposure. However, when acute HCV infection showed clinical symptoms, only 50% ~ 70% patients were anti -HCV positive, and about 90% patients were anti -HCV positive after 3 months.
After HCV infection, those who have not cleared viremia for 6 months are chronic infection, and the chronic rate of hepatitis C is 50% ~ 85%. Twenty years after infection, the incidence of cirrhosis in children and young women is 2% ~ 94%; Middle-aged people infected by blood transfusion account for 20% ~ 30%; The general population is 10% ~ 15%. The spontaneous clearance rate of HCV infection is higher in people under 40 years old and women. People over 40 years old when they are infected with HCV, men and people with low immune function caused by HIV infection can promote the progress of the disease. Hepatitis B virus (HBV) infection, alcoholism (above 50g/d), nonalcoholic fatty liver (NASH), high iron load in the liver, schistosomiasis infection, hepatotoxic drugs and toxic substances caused by environmental pollution can also promote the progress of the disease.
The incidence of HCV-related HCC after 30 years of infection is 1% ~ 3%, which mainly occurs in patients with cirrhosis and progressive liver fibrosis. Once cirrhosis develops, the annual incidence of HCC is 65438 0% ~ 7%. The above factors that promote the progress of hepatitis C and diabetes can promote the occurrence of HCC. The incidence of HCC in patients with hepatitis C after blood transfusion is relatively high. The quality of life of patients with liver cirrhosis and HCC decreased.
Cirrhosis and HCC are the main causes of death in patients with chronic hepatitis C, among which decompensated cirrhosis is the most important. It has been reported that once cirrhosis occurs, the annual survival rate of 10 is about 80%, and in the case of decompensation, the annual survival rate of 10 is only 25%. HCC； Patients with complete remission after interferon (IFNα) treatment (including those who relapse after complete remission); The incidence rate is low, but the incidence rate of HCC is high in nonresponders.
Prevention of hepatitis C virus transmission
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 use razors and dental instruments. 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.
Clinical diagnosis of hepatitis C.
(A) the diagnosis of acute hepatitis C
1. Epidemiological history: history of blood transfusion, history of using blood products or clear history of HCV exposure. The incubation period of acute hepatitis C after blood transfusion is 2 ~ 16 weeks (average 7 weeks), and the incubation period of sporadic acute hepatitis C needs to be studied.
2. Clinical manifestations: general weakness, loss of appetite, nausea, right costal pain, etc. A few patients are accompanied by low fever and mild hepatomegaly, some patients may have splenomegaly, and a few patients may have jaundice. Some patients have no obvious symptoms and show recessive infection.
3. Laboratory examination: ALT increased slightly and moderately, and anti -HCV HCV RNA was positive. HCV RNA often turns negative before ALT returns to normal, but there are also cases where ALT returns to normal and HCV RNA continues to be positive.
The above 1+2+3 or 2+3 can be diagnosed.
(2) Diagnosis of chronic hepatitis C.
1. Diagnostic basis: HCV infection is more than 6 months, or the onset date is unknown, and there is no history of hepatitis, but the liver histopathology conforms to chronic hepatitis, or the diagnosis can be made according to the comprehensive analysis of symptoms, signs, laboratory and imaging results.
2. Diagnosis of pathological changes: The diagnosis of pathological changes refers to the grading and staging diagnostic criteria of liver inflammation and fibrosis in the Prevention and Treatment Plan for Viral Hepatitis (Xi 'an, 2000) jointly revised by the Branch of Infection and Parasitology of Chinese Medical Association and the Branch of Hepatology. HCV infection alone rarely causes severe hepatitis. When HCV overlaps with HIV, HBV and other viruses, drinks too much or uses hepatotoxic drugs, it can develop into severe hepatitis. The clinical manifestations of severe hepatitis caused by HCV infection are basically the same as those caused by other hepatotropic viruses, which can be manifested as acute, subacute and chronic course.
3. Extrahepatic manifestations of chronic hepatitis C: Extrahepatic clinical manifestations or syndromes may be caused by abnormal immune response, including rheumatoid arthritis, conjunctivitis sicca, lichen planus, glomerulonephritis, mixed cryoglobulinemia, B-cell lymphoma and delayed cutaneous porphyria.
4. Cirrhosis and HCC: The most serious results of chronic HCV infection are cirrhosis and HCC caused by progressive liver fibrosis.
5. Mixed infection: The overlapping and mixed infection of HCV and other viruses are collectively referred to as mixed infection. Mixed infection of HCV with HBV or HIV is more common in China.
6. Recurrence of hepatitis C infection after liver transplantation: Hepatitis C often recurs after liver transplantation, and its course of disease progresses significantly faster than that of patients with normal immune function. Once the transplanted liver has cirrhosis, the risk of complications will be higher than that of patients with cirrhosis with normal immune function. The recurrence of hepatitis C after liver transplantation is related to HCV RNA level and the degree of immunosuppression after transplantation.
Laboratory diagnosis of hepatitis C
Biochemical detection of (1) serum
ALT and AST levels can reflect the degree of hepatocyte injury, but they are not necessarily parallel to the degree of liver inflammation and disease severity caused by HCV infection. The levels of ALT and AST in patients with acute hepatitis C are generally low, but some of them are high. Serum albumin, prothrombin activity and cholinesterase activity decreased less in patients with acute hepatitis C, but decreased significantly in patients with chronic hepatitis, cirrhosis or severe hepatitis, and the degree of decline was directly proportional to the severity of the disease.
In patients with chronic hepatitis C, about 30% of the ALT level is normal, and about 40% of the ALT level is lower than the upper limit of twice the normal level. Although most of these patients have only mild liver injury, some patients can develop cirrhosis. The decrease of ALT level is one of the important indexes of antiviral treatment response. Prothrombin time can be used as a monitoring index for the progress of patients with chronic hepatitis C, but up to now, no serological marker or group can accurately stage liver fibrosis.
(2) Anti -HCV detection
Anti -HCV enzyme immunoassay is suitable for the screening of high-risk population, and can also be used for the primary screening of HCV infected people. However, whether anti -HCV turns negative or not can not be used as an indicator of antiviral efficacy. The sensitivity and specificity of the third-generation EIA method for detecting hepatitis C patients can reach 99%, and RIBA is not needed for verification. However, some patients with dialysis, immunodeficiency and autoimmune diseases may have false positive anti -HCV, so HCV RNA detection is helpful to confirm whether these patients are infected with HCV.
(3) Detection of HCV RNA
In acute HCV infection, the viral genome level in plasma or serum can reach 105 ~ 107 copy /ml. In patients with chronic HCV infection, the level of HCVRNA varies greatly among different individuals, ranging from 5×104 to 5×106 copy /ml, but the level of HCV RNA in the blood of the same patient is relatively stable.
1.HCV RNA qualitative detection: Anti -HCV positive HCV persistent infection needs to be diagnosed by HCV RNA qualitative detection. The specificity of qualitative detection of HCV RNA is above 98%. As long as the virus is positive once, HCV infection can be diagnosed, but HCV infection can not be completely ruled out once, so it should be checked repeatedly.
2. Quantitative detection of HCV RNA: Quantitative polymerase chain reaction (qPCR), branched DNA(bDNA) and real-time fluorescence quantitative PCR can all detect HCV RNA viral load. Foreign HCV RNA quantitative detection kits include PCR amplification Cobas V2.0, SuperQuant, LCx HCV RNA quantitative analysis, etc. , but the quantitative analysis of Versant HCVRNA 2.0 and 3.0 of bDNA is widely used. The domestic real-time fluorescence quantitative PCR method has been officially approved by the US Food and Drug Administration (SFDA). Different quantitative detection methods of HCV RNA can be expressed in two ways: copy /ml and IU/ml. The conversion formulas of different detection methods should be adopted in the conversion. For example, the conversion formula between the IU/ml of Cobas V2.0 of Roche Company and the copy number /ml of SuperQuant of National Genetic Institute of the United States is: IU/ml=0.854× copy number /ml+0.538.
There is no absolute correlation between HCV viral load and the severity and progress of the disease, but it can be used as an observation index to evaluate the antiviral efficacy. In the detection of HCV RNA, we should pay attention to the possible false positive and false negative results.
(4) HCV genotyping
There are many genotyping methods for HCV RNA, and Symonds et al. 1 ~ 6 genotyping method is the most widely used method in the evaluation of antiviral efficacy at home and abroad. The results of HCV RNA genotyping are helpful to judge the difficulty of treatment and make individualized plans for antiviral treatment.
Pathological diagnosis of hepatitis C
Pathological examination is very important for the diagnosis of hepatitis C, measuring the degree of inflammation and fibrosis, evaluating the curative effect of drugs and judging the prognosis. Acute hepatitis C can present interlobular inflammation and various lesions in portal area similar to hepatitis A and B, but other histological features can also be observed, such as: (1) mononucleosis-like lesions. That is, monocytes infiltrate into hepatic sinuses to form beads; ⑵ Fatty degeneration of hepatic vesicles; (3) Bile duct injury is accompanied by a large number of lymphocyte infiltration in portal area, even the formation of lymphatic follicles. Bile duct cells are destroyed and the number of interlobar bile ducts is reduced, which is similar to autoimmune hepatitis. ⑷ Common interface inflammation.
In the liver tissue of chronic hepatitis C, the formation of lymph follicles in portal area, bile duct injury, fatty degeneration of lobular hepatocytes, kupffer cells or lymphocyte aggregation in lobules are often seen. These characteristic histological manifestations have certain reference value for the diagnosis of chronic hepatitis C. ..
The grading of inflammation degree of liver tissue and the staging diagnosis of fibrosis degree can refer to the pathological diagnosis standard in the Prevention and Treatment Plan of Viral Hepatitis. For scientific research or evaluation of the efficacy of therapeutic drugs, various semi-quantitative scoring methods at home and abroad can be selected according to different needs.
The purpose and drugs of antiviral therapy
The purpose of antiviral therapy
The purpose of antiviral therapy is to eliminate or continuously inhibit HCV in the body, so as to improve or alleviate liver injury, prevent progression to cirrhosis, liver failure or HCC, and improve the quality of life of patients.
(2) Effective drugs for antiviral treatment
Interferon (IFN)α is an effective anti-HCV drug, including common IFNα, compound IFN α and PEG-IFN α. The latter is an inactive and non-toxic PEG molecule cross-linked to IFNα, which delays the absorption and clearance of IFNα in vivo after injection, has a long half-life, and can still maintain the effective blood concentration after weekly 1 dose. Compound IFN 9μg is equivalent to common IFNα 3MU. PEG-IFNα combined with ribavirin is the most effective antiviral therapy at present, followed by common IFNα or IFNα combined with ribavirin, all of which are better than IFN α alone. The latest clinical trials abroad show that subcutaneous injection of PEG-IFN α-2A (1.80μ g) or PEG-IFNα-2b (1.5μg/kg) combined with ribavirin for 48 weeks has similar curative effects, and the rate of sustained virological response (SVR) can reach 54% ~ 56%. The SVR rate of IFNα (3MU) intramuscular injection combined with ribavirin for 48 weeks was slightly lower, ranging from 44% to 47%. After 48 weeks of treatment with PEG-IFNα-2a or common IFNα, the SVR rates were only 25% ~ 39% and 12% ~ 19%, respectively. The results of domestic clinical trials show that the total SVR rate of PEG-IFN α-2A (180μ g) in the treatment of chronic hepatitis C for 24 weeks is 4 1.5%, of which 35.4% are patients with gene 1 and 66.7% are patients without gene 1. Therefore, if there is no contraindication to ribavirin, combined therapy should be adopted.
Indications of antiviral therapy
Only patients with HCV RNA positive serum need antiviral treatment.
(A) the general treatment of patients with hepatitis C.
1. Acute hepatitis C: IFNα treatment can significantly reduce the chronic rate of acute hepatitis C. Therefore, if HCV RNA is positive, antiviral treatment should be started. At present, there is no unified plan for the treatment of acute hepatitis C. It is suggested to give ordinary IFNα 3MU, 1 intramuscular or subcutaneous injection every other day for 24 weeks, and take ribavirin 800 ~ 10 at the same time.
2. Chronic hepatitis C: (If ALT or AST rises continuously or repeatedly, or if there is obvious inflammatory necrosis (G≥2) or moderate fibrosis (S≥2) in liver histology, it is easy to develop into cirrhosis and should be actively treated. Most patients with normal ALT have mild liver lesions, and whether to treat them should be decided according to the pathological results of liver biopsy. Those with obvious fibrosis (S2, S3) should be given antiviral treatment regardless of the degree of inflammation and necrosis. For patients with mild inflammatory necrosis and no obvious fibrosis (S0, S 1), no treatment can be given for the time being, but liver function should be tested every 3 ~ 6 months. ⑶ ALT level is not an important index to predict patients' response to IFNα. In the past, it was reported that the treatment effect of hepatitis C patients with normal ALT with common IFNα was not obvious, so IFNα was not recommended. However, recent studies have found that the virological response rate of patients with normal ALT treated with PEG-IFNα-2a combined with ribavirin is similar to that of patients with elevated ALT. Therefore, as long as HCV RNA is positive, patients with normal or slightly elevated ALT can be treated, but more cases need to be accumulated for further clinical research.
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 It is difficult for patients with decompensated cirrhosis to tolerate the adverse reaction of IFNα therapy, and those who can tolerate it should undergo liver transplantation.
4. 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.
(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. Anti-HCV therapy 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.
Types and influencing factors of antiviral treatment response
Types of response to antiviral therapy
According to the observed indexes, it can be divided into biochemical reaction, virological reaction and histological reaction.
1. Biochemical reaction: ALT and AST returned to normal.
2. Virological response: (1) Early virological response (EVR): After treatment 12 weeks, the qualitative detection of serum HCV RNA was negative (or the quantitative detection was lower than the minimum detection limit), or the quantitative detection decreased by more than 2 log levels. It is easy for early EVR patients to obtain SVR, but it is difficult for non-EVR patients to obtain SVR, so EVR can be used as an index to predict SVR. (2) Virological response (ETVR) at the end of treatment: that is, the qualitative detection of HCV RNA is negative at the end of treatment (or the quantitative detection is lower than the minimum detection limit); (3) SVR: at least 24 weeks after treatment, the qualitative detection of HCV RNA was negative (or the quantitative detection was lower than the minimum detection limit); (4) No response (NR): refers to people who have never obtained EVR, ETVR and SVR. (5) Recurrence: it means that the qualitative detection of HCV RNA is negative (or the quantitative detection is lower than the minimum detection limit) at the end of treatment, but HCV RNA turns positive again after drug withdrawal; (6) Breakthrough during treatment: HCV RNA load decreased or turned negative during treatment, but increased or turned positive before drug withdrawal.
3. Histological reaction: refers to the improvement of inflammatory necrosis and fibrosis in liver histopathology, which can be evaluated by liver tissue grading (degree of inflammatory necrosis), staging (degree of fibrosis) or semi-quantitative scoring system commonly used at home and abroad.
(B) Influencing factors of antiviral treatment response
The response to antiviral efficacy of chronic hepatitis C is influenced by many factors, and the following factors are favorable for obtaining SVR: (1) HCV genotypes 2 and 3; (2) Virus level
Treatment of chronic hepatitis C
Before treatment, HCV RNA genotyping (1 and non-1) and HCV RNA quantification in blood should be carried out to determine the course of antiviral treatment and the dose of ribavirin.
(a) hepatitis C virus RNA gene is 1 type, or (and) hepatitis C virus RNA quantitative ≥2× 106 copies/ml, you can choose one of the following schemes:
1.PEG-IFN α combined with ribavirin treatment scheme: PEG-IFNα-2a 180μg, subcutaneous injection/kloc-0 times per week, combined with oral ribavirin 1 000 mg/d, 12 weeks to detect HCV RNA: (. (2) If the qualitative detection of HCV RNA is negative or below the minimum detection limit of quantitative method, continue treatment for 48 weeks; (3) If HCV RNA did not turn negative, but decreased by ≥2 logarithmic steps, the treatment was continued for 24 weeks. If HCVRNA turns negative in 24 weeks, treatment can continue until 48 weeks; If it doesn't turn negative after 24 weeks, stop taking the medicine and observe.
2. Treatment scheme of common IFNα combined with ribavirin: IFN α for 3mu ~ 5mu, intramuscular or subcutaneous injection 1 time every other day, combined with oral ribavirin 1000mg/d, it is recommended to treat for 48 weeks.
3. Treatment scheme for those who can't tolerate the adverse reaction of ribavirin: common IFNα, compound IFN or PEG-IFN can be used alone, and the method is the same as above.
(2) HCV RNA gene is non 1 type, or (and) HCV RNA quantification.
1.PEG-IFN α combined with ribavirin: PEG-IFNα-2a 180μg, subcutaneous injection 1 time per week, combined with ribavirin 800mg/d for 24 weeks.
2. Treatment scheme of common IFNα combined with ribavirin: IFN α was injected intramuscularly or subcutaneously for 3 times a week, and ribavirin was combined with 800 ~ 1000mg/d for 24 ~ 48 weeks.
3. Treatment plan for those who can't tolerate the adverse reaction of ribavirin: common IFNα or PEG-IFNα can be used alone.
Note: (1) Foreign literatures reported that PEG-IFN α-2B (1.0 ~1.5 μ g/kg) and PEG-IFN α-2A (180μ g)1time were injected subcutaneously once a week, combined. (2) When using common IFNα therapy, some people use the so-called "induction therapy", that is, intramuscular injection of IFNα3 mu ~ 5 mu every day for15 ~ 30 days, and then three times a week. Foreign studies show that patients' tolerance to the scheme is reduced, and it is uncertain whether the curative effect can be improved. (3) Reference dose value of ribavirin: weight >; 85kg， 1200mg/d； /d； 1000mg/d； /d is 65 ~ 85kg；; < 65 kg, 800 mg/d. It is reported that the effective dose of ribavirin is >: 10.6mg/kg body weight.
(3) Treatment of patients who relapse or have no response after treatment.
For patients who relapse after receiving IFNα monotherapy for the first time, a higher SVR rate (47%, 60%) can be obtained by receiving PEG-IFNα-2a or common IFNα combined with ribavirin again. For patients who failed to take IFNα alone for the first time, the SVR rate was lower when they were treated with common IFNα or PEG-IFNα-2a combined with ribavirin (12% ~ 15% and 34% ~ 40% respectively). For patients who have no response or relapse after the first combination of common IFNα and ribavirin, PEG-IFNα-2a combined with ribavirin can be tried.
Adverse reactions of antiviral therapy and its 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. Mental disorders: can be manifested as depression, paranoia, serious anxiety and mental illness. 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.
4.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 severe cases, the drug should be stopped.
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.
Monitoring and follow-up of patients with hepatitis C.
(1) Follow-up monitoring of patients receiving antiviral therapy
1. monitoring items before treatment: liver and kidney function, blood routine, thyroid function, blood sugar and urine routine should be tested before treatment. In the first month after starting treatment, the blood routine should be checked 1 time every week, then 1 time every month until 6 months, and then 1 time every 3 months.
2. Biochemical detection: ALT was detected every month during treatment, and 1 time every two months within 6 months after treatment. Even if hepatitis C is not cleared, ALT should be checked regularly.
3. Virological examination: HCV RNA was confirmed after 3 months of treatment; HCV RNA should also be detected at the end of treatment and 6 months after treatment.
4. Monitoring of adverse reactions: All patients should have thyroid function tested every 6 months during treatment and every 3-6 months after treatment. If thyroid function is abnormal before treatment, thyroid function should be tested every month. For elderly patients, ECG examination and cardiac function judgment should be done before treatment. Mental state should be assessed regularly, especially for patients with obvious depression and suicidal tendency, drug withdrawal and strict protection should be given.
(2) Follow-up patients who have no indications or contraindications for treatment and are unwilling to receive antiviral treatment.
1. liver biopsy: if there is no or only slight injury, the possibility of liver disease progression is very small, but it should still be every 2