Interferon (IFN)α is widely used in the antiviral treatment of chronic hepatitis B (CHB) and chronic hepatitis C (CHC), but there are more adverse reactions. Common adverse reactions include flu-like symptoms, decreased peripheral blood cell and platelet counts, endocrine and metabolic disorders, gastrointestinal symptoms and neuropsychiatric abnormalities, etc. The incidence is shown in Table 1. A small number of patients can cause serious adverse reactions, such as interstitial pneumonia, body immune hemolysis or severe psychiatric disorders. Proper management of adverse reactions in IFNα treatment can improve patient compliance and thus effectively improve the efficacy of IFNα. Serious adverse reactions often require discontinuation of treatment to ensure patient safety. In order to further standardize and optimize the management and treatment of IFNα adverse reactions in patients with chronic viral hepatitis, the editorial departments of the Chinese Journal of Experimental and Clinical Infectious Diseases (Electronic Edition), the Chinese Journal of Liver Diseases (Electronic Edition) and InfectionInternational (ElectronicEdition) organized some domestic experts to The Consensus on Clinical Management of Adverse Reactions to Interferon Alpha in Patients with Chronic Viral Hepatitis (hereinafter referred to as the Consensus) was formed by organizing and analyzing relevant information by some domestic experts. This Consensus is based on the latest achievements in this field and is prepared in accordance with the principles of evidence-based medicine, and can be used as a guide for the clinical management of IFNα adverse reactions in patients with chronic viral hepatitis. The content of the Consensus will be updated continuously as relevant clinical evidence continues to accumulate. The corresponding evidence and recommendation levels are shown in Table 2. 1. Influenza-like symptoms: IFNα can cause the release of a series of cytokines including interleukin (IL)1, IL-6 and tumor necrosis factor (TNF)α, thus causing influenza-like symptoms. Clinical manifestations: Influenza-like symptoms include fever, muscle and joint pain, and malaise, which can occur in the majority of patients, but the severity varies from patient to patient. Influenza-like symptoms often occur in the first injection, and fever usually appears 2-4 h after the initial IFNα injection, and it usually subsides after 2-4 h. The fever and muscle and joint pain gradually decrease during subsequent treatment, but patients may still feel weak, especially in CHC patients treated with combined ribavirin, and the weakness is often more obvious due to the anemia caused by ribavirin. Clinical management: Those with insignificant symptoms may be left untreated. Those with significant symptoms are advised to rest and drink plenty of fluids; those with significant and intolerable high body temperature and muscle and joint pain can be treated with oral antipyretic and analgesic drugs such as acetaminophen (Al). In the course of long-term use of IFNα appears longer fever, and with IFNα injection has a certain regularity of fever, muscle aches and pains, etc., the patient should be checked for blood sedimentation and autoantibodies to exclude autoimmune-related fever (Bl). 2, peripheral blood cell decline: Overview and mechanism: In the peripheral blood cell decline due to IFNα treatment, the most obvious decline is in neutrophils and platelets, and the mechanism of its occurrence is not completely clear, which may be related to the direct inhibition of bone marrow progenitor cell proliferation by IFNa, or may be related to the decrease in granulocyte colony-stimulating factor (G-CSF) or macrophage granulocyte colony-stimulating factor (GM-CSF) secretion. In addition, the decrease in neutrophil count due to IFNα may be related to the single nucleotide polymorphism (SNP) of the IFNα signaling pathway gene in patients, and therefore shows individual differences. Clinical manifestations: Significant decreases in neutrophils often occur between 2 and 314 d of treatment (mean 47 d) and may be more pronounced in patients with low body mass. If patients have a 100% neutrophil decline, the decline is approximately 20% at week 1, 40%-60% at week 2, and reaches a minimum at week 12. Neutrophil decline is dose-dependent and is often the most important reason for IFNα dose adjustment, with approximately 22% of patients requiring dose adjustment due to neutrophil decline. However, there is no evidence to suggest that IFNα-induced neutrophil decline increases the rate of bacterial infections. Platelet count declines were more commonly seen in CHC patients treated with IFNα in combination with ribavirin, with platelet counts decreasing by 42% from baseline, similar to neutrophil declines, to a minimum level at 12 weeks of treatment, with 9.3% of patients declining to <50,000/ul and 2.8% to <25,000/ul; 9.3% had platelet counts of 25,000/ul- 50,000/ul and 33.3% of patients with platelet counts <25,000/ul experienced bleeding, but severe bleeding was rare. Clinical management: (1) The product insert for pegylated interferon (PEG-IFNα) α-2a states that IFNα dose adjustment is required for peripheral blood neutrophil counts <0.75×109/L, and IFNα therapy must be discontinued for <0.5×109/L. Soza et al. showed that although bacterial infections occurred in 18% of long-term IFNα patients, they were not significantly associated with a decrease in neutrophil Soza et al. showed that although bacterial infections occurred in 18% of those on long-term IFNα therapy, there was no significant correlation with a decrease in neutrophil count, so it was concluded that neutropenic patients could be treated with leukocyte-raising drugs without discontinuation. However, the Puoti et al. cohort study found that decreased neutrophils were associated with respiratory infections and that patients with CHC with decreased neutrophils were more effective with leukostatic drugs than with lower IFN doses. Therefore, recombinant human granulocyte colony-stimulating factor (rhG-CSF) injection or oral leukocyte-raising drugs are recommended for those with significantly decreased neutrophils, and the use of G-CSF may be more important, especially for those with immunocompromised or suppressed immune function. (2) The PEG-IFNα product specification states:The dose of PEG-IFNα must be reduced for platelet counts of 25,000 to 50,000/ul during PEG-IFNα treatment, while PEG-IFNα treatment must be discontinued for those <25,000/ul. In contrast, induction chemotherapy for acute granulocytic leukemia, platelet transfusion is required only for those with platelet counts below 10,000/ul and significant bleeding, and IFNα treatment for CHC has a very low incidence of severe bleeding even in patients with platelet counts <50,000/ul or even <25,000/ul. Therefore, in the absence of other antiviral options and with full informed consent of the patient, even if the patient's platelet count is <25,000/ul, IFNα dose can be reduced for treatment under close monitoring instead of blindly discontinuing the drug. If the platelet count is <20,000/ul, even if it is only accompanied by skin and mucosal bleeding, it is recommended to be cautious and consider discontinuing IFNα if necessary. In particular, it should be noted that the decline in neutrophil and platelet counts due to IFNα itself is often progressive, and rapid or dramatic decline in neutrophil and platelet counts, including hemoglobin, in clinical practice should be considered as an IFNα-induced auto In the event of a rapid decline in white blood cells, platelet count and hemoglobin during IFNα treatment, IFNα treatment should be stopped immediately and a hematologist should be consulted. IFNα may induce or aggravate depression and other psychoneurological adverse effects in patients by altering the secretion of central adrenaline, 5-hydroxytryptamine, opioid-like substances and neuroendocrine factors. psychiatric abnormalities occur more commonly in CHC patients and are associated with HCV-induced IL-1β and IFNα expression. Clinical manifestations: Psychoneurological adverse effects due to IFNα treatment include acute psychiatric disturbances, depression, trance, anxiety, irritability, and occasionally euphoria. Neurological complications include epileptiform seizures, cerebral leukomalacia, actinic nerve palsy, and trigeminal sensory neuropathy. Acute psychiatric disorders are commonly seen in high-dose IFNα therapy. Depression is mostly seen in CHC patients, with an incidence of about 21% to 58%, often occurring after 2 months of IFNα therapy and peaking after 3 months, while anxiety peaks in the 3rd-4th months. Clinical management: (1) The incidence of psychiatric disorders is related to pretreatment risk factors, IFNα dose and treatment duration. patients should be carefully asked about their history of psychiatric disorders and family history before IFNα treatment, and patients with such a history should be scored on the Montgomery I. Eisenberg Depression Scale; (2) patients with depressed mood, anxiety and irritability during IFNα treatment should be promptly referred to a psychologist for (2) Patients with depressed mood, anxiety and irritability during IFNα treatment should be evaluated and treated by a psychiatrist in a timely manner, and IFNα should be discontinued in a timely manner if the symptoms are severe or if there is a tendency to commit suicide or harm others. monitoring, and there is no evidence of benefit from prophylactic use in high-risk groups (Bl). The prognosis for IFNα-related neuropsychiatric symptoms is good, with most patients achieving relatively rapid remission with antidepressant therapy. The corresponding psychiatric symptoms may resolve within weeks to 3 months after discontinuation. Because IFNα-related neuropsychiatric symptoms may occur again, it is not recommended to use it again for those who discontinue it due to serious psychoneurological adverse effects. 4. Skin and mucosal lesions: Overview and mechanism: The appearance of skin and mucosal lesions during IFNα treatment may be related to IFNα-induced skin metaplasia and autoimmune reactions, especially in patients with chronic HCV infection and metaplastic diseases. Clinical manifestations: Skin mucosal lesions caused by IFNα are most commonly seen as rash, which is often non-specific with pruritus, and other manifestations include injection site erythema, skin ulceration, oral mucosal ulceration and stomatitis. Treatment: (1) rash with pruritus: avoid seafood or spicy foods that are allergic or aggravate the disease, avoid using powerful skin decontaminants, apply glycolic lotion, creams containing glucocorticoids, or take oral antihistamines (Bl); (2) for skin mucosal lesions that cannot be controlled by conventional drugs, oral low-dose hormone therapy can be given without contraindications to hormone therapy; (3) Skin mucosal lesions that cannot be controlled by drugs and seriously affect the patient's quality of life should also be discontinued from IFNα treatment and consult a dermatologist for assistance. Generally the rash can gradually disappear 4-7 weeks after discontinuation. 5. Endocrine and metabolic diseases: 1. Abnormal thyroid function: Overview and mechanism: IFNα treatment can cause abnormal thyroid function through autoimmune and non-autoimmune mechanisms. In the autoimmune mechanism, IFNα increases the expression of major histocompatibility complex (MHC)1 on the cell surface and induces autoantibody formation, and patients are often positive for anti-thyroid peroxidase antibody (TPoAb) and anti-thyroglobulin antibody (TGAb); the non-autoimmune mechanism may be related to the direct effect of IFNα on the thyroid gland, manifested by destructive thyroiditis and non-self Immune hypothyroidism was negative for both TPoAb and TGAb. Thyroid function abnormalities were most commonly seen in hypothyroidism. About 40% of CHC patients treated with IFNα develop anti-thyroid antibodies and 15% develop clinical thyroid disease. 60% of patients with positive TPoAb or TGAb develop thyroid disease on IFNα treatment, compared to less than 15% of patients with negative anti-thyroid antibodies, and those with positive TPoAb or TGAb prior to treatment are more likely to develop persistent thyroid disease. Clinical manifestations: Patients with abnormal thyroid function indicators [total triiodothyronine (TT3), total thyroxine (TT4), free triiodothyronine (FT3), free thyroxine (FT4), thyrotropin (TSH)] and clinical manifestations of corresponding hyper- or hypothyroidism can be diagnosed as corresponding thyroid function abnormalities. Patients may present with the following thyroid disorders: (1) Graves' disease: systemic hypermetabolic manifestations with diffuse, symmetric, painless goiter, simple or infiltrative proptosis; (2) Hashimoto's thyroiditis: thyroid autoantibodies and hypothyroidism with or without goiter; (3) some patients may present with positive TPoAb or TGAb and abnormal thyroid function indicators, but do not present with clinical symptoms; (3) some patients may present with positive TPoAb or TGAb and abnormal thyroid function indicators. (4) non-autoimmune thyroid disease, manifested as destructive thyroiditis and hypothyroidism. It is important to note that patients with destructive thyroiditis may change from hyperthyroidism to hypothyroidism. Clinical management: (1) All patients treated with IFNα, especially those with CHC, should have thyroid function tests TPoAb and TGAb before IFNα treatment, and thyroid disease should be diagnosed in combination with thyroid ultrasound; (2) Those with abnormal thyroid function before IFNα treatment should be treated accordingly before IFNα treatment under the guidance of an endocrinologist, and thyroid (3) Thyroid function should be closely monitored during the treatment period, and TPoAb and TGAb should be monitored as well. (5) Controllable abnormal thyroid function can be treated with IFNα, while uncontrollable hyperthyroidism, such as Graves' disease with thyrotoxicosis, should be terminated immediately, especially if thyroid crisis occurs. (7) Subclinical hypothyroidism or hyperthyroidism with TSH abnormalities without FT3, FT4, TT3, TT4 abnormalities may be left untreated and continue to be observed; (8) Persistent positive TPoAb and TGAb after discontinuation of IFNα therapy indicates possible development of thyroid insufficiency. 2 Diabetes mellitus: Overview and mechanism: IFNα can induce autoimmune damage to pancreatic β-cells and induce diabetes mellitus. PEG-IFNα treatment induces diabetes in 0.1-0.7% of CHC patients. It should be noted that since the liver is an important glucose metabolizing organ, some patients, especially those with CMC, already have diabetes before IFNα treatment. IFNα treatment may aggravate diabetes or may help control diabetes by improving liver function during antiviral therapy. Clinical manifestations: The diagnosis of diabetes mellitus during IFNα treatment is based on the diagnostic criteria for the general population, but patients often lack the typical symptoms of diabetes mellitus, and endocrinologists can be consulted to assist in the diagnosis if necessary. Treatment: (1) Fasting and postprandial glucose testing should be performed before IFNα treatment; (2) Regular monitoring during IFNα treatment. For those with family history of diabetes and obesity, even if fasting glucose is normal, fasting glucose and glycosylated hemoglobin levels should be rechecked every 2 months during IFNα treatment; (3) Patients who develop diabetes before treatment should treat diabetes before IFNα treatment and wait for (4) Patients with diagnosed diabetes mellitus should choose oral hypoglycemic drugs with less liver damage based on dietary control and moderate exercise, while those whose blood glucose cannot be effectively controlled by oral drugs should use insulin, and those with severe elevation of blood glucose should prefer insulin injection therapy; (5) Elevated blood glucose that cannot be controlled by drug therapy or acute complications such as diabetes mellitus IFNα must be discontinued for ketoacidosis or hypertonic non-ketotic diabetic coma. 6, other rare adverse reactions 1, interstitial lung disease: Overview and mechanism: The pathogenesis of IFNα-induced interstitial lung disease is still unclear and may be related to autoimmune and metabolic reactions. pulmonary complications associated with IFNα treatment are rare, but are one of the serious adverse reactions and should be given high priority; (2) clinical manifestations : Respiratory symptoms such as dry cough and shortness of breath are frequently seen in IFNα therapy, with incidence rates of 24% and 26%, respectively. The incidence of interstitial pneumonia induced by IFNα treatment for CHC is common within the first 12 weeks of IFNα treatment, mostly in elderly patients; (3) Clinical management: ① Perform double lung imaging before IFNα treatment to exclude potential or pre-existing lung lesions; ② Occurrence of persistent cough, fever and respiratory symptoms during IFNα treatment ②Patients with persistent cough, fever and dyspnea should progress to chest x-ray or CT examination; ③Patients with persistent and progressively worsening cough, sputum and even dyspnea should be examined by imaging, and once diagnosed as interstitial pneumonia, IFNα therapy must be stopped and a respiratory specialist should be consulted; ④For those with obvious dry cough without thoracic imaging changes, antihistamines can be used for treatment, and for Those who cannot control the symptoms can use low-dose hormones without contraindication to hormone use. Retinopathy: (1) Overview and mechanism: IFNα-induced retinopathy is rare. Most retinopathies do not represent vision loss. The resulting retinal hemorrhage may be related to IFNα-induced vasospasm, deposition of immune complexes in the retinal vascular system, and is often secondary to systemic diseases such as retinal ischemia, diabetes mellitus, and hypertension. (2) Clinical manifestations may include retinal hemorrhage, absorbent cotton spots, loss of color vision, and occasionally blindness. Much less common is retinal artery or vein obstruction. Typical retinal lesions include massive absorbent cotton spots and flame-like hemorrhages around the posterior pole optic papilla, with superficial linear or discoid hemorrhages that do not significantly affect visual acuity and present a separation of symptoms and signs, but can lead to significant vision loss if the lesion affects the macula and optic nerve. IFNα can also be directly toxic to the optic nerve, leading to blurred vision similar to optic neuritis. Ocular complications due to IFNα often occur in the posterior pole of the retina, mostly at 1 or 3 months of IFNα treatment; (3) Clinical management: Patients with diabetes mellitus and hypertension should undergo fundus examination prior to IFNα treatment, and IFNα should be used with caution in patients with severe fundus lesions. Absorbent cotton spots and retinal hemorrhages often resolve spontaneously during or after IFNα treatment. 3. Body mass reduction: (1) Overview and mechanism: 19.7% of patients may experience a decrease in body mass during IFNα treatment (may decrease by 5-10%). It may be associated with a variety of adverse effects such as decreased appetite, nausea, diarrhea, abnormal thyroid function, diabetes mellitus, etc. (2) Clinical manifestations: Those with a rapid decrease in body mass often have a decreased appetite during the 1st week of IFNα treatment. (3) clinical management, patients can eat less and more meals diet should be less but fine, should ensure the necessary protein, fat, carbohydrates and vitamin intake. Regular work and rest, to develop good habits of work and rest. Patients with decreased body mass generally do not affect normal school, life, work, and therefore can continue IFNα treatment (Bl). For those who have too obvious and significant decrease in body mass within a short period of time, hyperthyroidism, malignant tumors and other special diseases should be excluded. 4. Diarrhea: A few patients develop diarrhea during treatment, the specific mechanism has not been clarified, and it is speculated that it may be related to intestinal dysfunction. If diarrhea occurs during IFNα treatment, routine stool, occult blood and even bacteriological examination should be carried out first, and those with a significant decrease in body mass should undergo colonoscopy to exclude organic lesions of the colon, inflammatory bowel disease and infectious diarrhea before continuing IFNα treatment. 5, hair loss: IFNα can cause reversible hair loss in about 30% of patients, mostly manifested as thinning hair, irreversible baldness and autoimmune baldness can occur, but is relatively rare. Alopecia areata occurs mainly after 3 months of IFNα application and is dose dependent. Alopecia areata is transient and can be accompanied by hair regrowth during the hair loss process. There are no effective measures to prevent alopecia. The frequency of shampooing and hair friction can be reduced, and chemical shampoos and perms can be avoided. Hair loss does not affect IFNα treatment, and those with significant hair loss that affects aesthetics can wear a wig. Hair growth can be restored 3-6 months after discontinuation. (Bl) 6. Other: Other rare IFNα adverse reactions such as hearing loss and tinnitus can be seen in K-pass IFNα and PEG-IFNα combined with ribavirin therapy, the exact mechanism of which has not been clarified and may be related to IFNα direct ototoxicity, autoimmune or hematologic alterations. Hearing loss does not fully recover if IFNα treatment is interrupted; continued IFNα treatment can worsen symptoms (B1). oral ulcers can also occur during IFNα application and may be associated with autoimmune reactions. if patients cannot tolerate it, discontinuation of IFNα is recommended in CHB patients, and oral prednisone 5 mg once/d after informed consent in CHC patients without contraindications to hormone use. If acute pancreatitis occurs, it is considered to be related to autoimmune reaction and discontinuation of IFNα is recommended. Patients with only positive autoantibodies without clinical manifestations are most commonly seen clinically, especially CHC patients who are not contraindicated for IFN therapy, and need to be closely monitored for autoimmune diseases during IFNα therapy, and IFNα should be discontinued immediately in case of uncontrollable autoimmune diseases.