2. Peripheral blood cell decline 2.1 Overview and mechanism Among 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. 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. 2.2 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% decline in neutrophils, the decline is approximately 20% at week 1, 40%-60% at week 2, and the lowest level 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. 2.3 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, while IFNα therapy must be discontinued for <0.5 × 109/L. Soza et al. showed that although bacterial infections occurred in 18% of those on long-term IFNα therapy, they were not significantly associated with a decrease in neutrophil count. Soza et al. showed that although bacterial infections occurred in 18% of those on long-term IFNα therapy, there was no significant correlation with decreased neutrophil counts, so it was concluded that those with decreased neutrophils could be treated with leukocyte-raising drugs without discontinuation. However, a cohort study by Puoti et al. 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 therapy, and PEG-IFNα therapy 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. 3. Neuropsychiatric system 3.1 Overview and mechanism IFNα can 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. 3.2 Clinical manifestations Psychoneurological adverse reactions 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%-58%, often occurring after 2 months of IFNα therapy and peaking after 3 months, while anxiety peaks in the 3rd-4th months. 3.3 Clinical management (1) The incidence of psychiatric disorders is related to pre-treatment 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 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 (2) Patients with depressed mood, anxiety and irritability during IFNα treatment should be promptly evaluated and treated by a psychiatrist, and IFNα should be discontinued in a timely manner if the symptoms are severe or accompanied by suicidal or harming tendencies; (3) Patients with depression or mania that cannot be controlled by medication should discontinue IFNα in a timely manner; (4) High-risk patients should be evaluated by a psychiatrist before treatment, and IFNα should be used cautiously with fully informed consent and closely monitored by psychologists and psychiatrists and family members. closely monitored, and there is no evidence of benefit from preventive dosing 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. Cutaneous mucosal lesions 4.1 Overview and mechanism Cutaneous mucosal lesions during IFNα treatment may be related to IFNα-induced cutaneous metaplasia and autoimmune reactions, especially in patients with chronic HCV infection and allergic diseases. 4.2 Clinical manifestations Skin mucosal lesions caused by IFNα are most common in the form of rash, which is often non-specific with pruritus, and other manifestations include injection site erythema, skin ulceration, oral mucosal ulceration and orofacial lipitis. 4.3 Treatment (1) rash with pruritus: avoid seafood or spicy foods that are allergic or aggravate the disease, avoid using powerful skin decontaminants, apply glycopyrrolate 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 if there is no contraindication to hormone therapy; ( 3) skin mucosal lesions that cannot be controlled by drugs and seriously affect the patient's quality of life should also stop IFNα treatment and ask for the assistance of a dermatologist for consultation and treatment. Generally the rash can gradually disappear 4-7 weeks after discontinuation.