Recently, Wang SS, the First Hospital of Jilin University in our country, reported a rare case of severe autoimmune hemolytic anemia (AIHA) during pegylated interferon combined with ribavirin in the treatment of chronic hepatitis C. The article was published in the journal Clinical Case Reports.
This case is a 57-year-old woman with HCV type 1b who started treatment with pegylated interferon (PEG-IFN) α 2b (80 μg once a week) in combination with ribavirin (900 mg/d) in March 2015. No previous history of allergies or autoimmune diseases. At week 8 of treatment, levothyroxine was initiated due to significant hypothyroidism.
After 12 weeks of antiviral treatment, serum HCV RNA was reduced below the detection limit.
After 28 weeks of treatment, the dose of ribavirin was reduced to 600 mg/d due to anemia (hemoglobin 106 g/L). After 4 weeks of ribavirin reduction, ribavirin was discontinued due to a further decrease in hemoglobin levels and treatment continued with pegylated interferon.
At 34 weeks of treatment, the patient was treated with paracetamol for fever (1 tablet, 3 times a day), and after 1 day of treatment, the hemoglobin was 94 g/L.
At 35 weeks of treatment, PEG-IFN was discontinued and admitted to the author's hospital for treatment. A few days before hospitalization, there was a deepening of urine color and back pain.
| Indicator | Result |
|---|---|
| Hemoglobin | 48 g/L |
| Reticulocyte ratio | 10.24% |
| Total Bilirubin | 71.2 μmol/L |
| Indirect bilirubin | 57.4 μmol/L |
| AST | 62.8 U/L |
| ALT | 36 U/L |
| TSH | 27.960 mIU/mL (Normal: 0.27-4) |
| Free T3 | 2.45 pmol/L (Normal: 3.1-6) |
| Free T4 | 12.91 pmol/L (Normal: 12.0-22) |
| Anti-thyroglobulin antibody (TgAb) | 4000.00 IU/mL (Normal <115.0) |
| Anti-thyroid peroxidase antibody (TPOAb) | 373.50 IU/mL (normal <35.0) |
| No plasma hemoglobin | 50.0 mg/L (normal <40) |
| Urine hemosiderin test | positive |
| Direct and Indirect Coombs Testing | positive |
| Ham test | Negative |
| Bone piercing | Proliferative anemia with an increased proportion of erythroids |
| Abdominal CT scan | Chronic liver injury |
Autoimmune hemolytic anemia
Discontinuation of PEG-IFN did not eliminate hemolytic anemia, nor did intravenous administration of immunoglobulin delay the progression of autoimmune responses.
According to literature reports, patients with chronic hepatitis were treated with glucocorticoids after developing interferon-induced AIHA, and hemoglobin gradually returned to normal. The patient refused to use the hormone due to fear of hepatitis C recurrence. However, after receiving splenectomy, the patient's condition gradually improved and hemoglobin returned to normal levels. AIHA did not recur.
In March 2016, the patient experienced a relapse of hepatitis C and received Laidipaevesofosbuvir treatment with sustained virologic response. During follow-up, thyroid function remained stable with levothyroxine replacement therapy.
Anemia is a very common and important adverse reaction in the treatment of patients with chronic hepatitis C. Ribavirin is the main drug causing anemia. Ribavirin-induced hemolytic anemia is dose-dependent and reversible. In this case, hemolysis continued to progress after ribavirin was discontinued, indicating that ribavirin may not be the cause of hemolysis.
Although the patient has taken paracetamol, it is unlikely to be the cause of hemolysis due to the short duration of the medication and the low dose.
Since this patient developed an immune-mediated disease (hypothyroidism) during treatment, it was considered that hemolysis may be related to an autoimmune response. Combined with his laboratory findings, the diagnosis was autoimmune hemolytic anemia.
Considering the time relationship between antiviral therapy and the onset, the gradual decrease of hemoglobin after ribavirin withdrawal, and other possible causes of AIHA (such as tumors, immunodeficiency, lymphoproliferative diseases, etc.), consider PEG-IFN as the cause of AIHA.
AIHA has previously been reported in patients with multiple sclerosis and blood disorders treated with IFN monotherapy. This case had no history of autoimmune disease or allergies before interferon therapy, suggesting that PEG-IFN not only exacerbates existing diseases, but also induces autoimmune diseases.
In addition, it has been reported in the literature that AIHA and hypothyroidism can occur simultaneously or successively, and this case also showed this feature.
