Ashfaq Ahmed, Abdul Haleem Khan, Shahab Abid, Zaigam Abbas, Abdullah Assiri.
Profound Hearing Impairment in Patients with Chronic Hepatitis C treated with Interferon Alpha-2b.
J Coll Physicians Surg Pak Jan ;11(12):773-82.

Alpha interferon is the approved agent for treatment of hepatitis C. Its use is becoming common and with this increase in its use new side effects are being observed. These side effects should be identified early and one should be familiar with their course and outcome. The knowledge of the incidence, severity and reversibility of these side effects would impact on the treatment strategy. We are reporting three cases of recombinant alpha interferon related hearing impairment.The severity of deafness varied from moderate to severe, and with discontinuation of therapy the improvement was unpredictable. In some patients there was marked improvement while in others there was little or no improvement.

Case I :A 42 years old Pakistani female physician was seen in the Gastroenterology Clinic in May 1993 with fatigue and abnormal liver function tests (ALT was 96 i.u. normal up-to 33 i.u., albumin was 3.8 gm/dl). Antibody to hepatitis C was positive. She was positive for HCV RNA by PCR. Her serum ceruloplasmin level, serum ferritin and total iron binding capacity was within normal limits. She was negative for ANA, ASMA and AMA antibodies. Past medical history was significant for labile hypertension. In 1983, she had undergone a cesarean section and received 4 units of packed red blood cells during the surgery. Her family history was positive for liver cirrhosis. Her aunt and cousin had chronic hepatitis. Physical examination of the patient revealed hepatomegaly and palpable spleen tip without any other stigmata of chronic liver disease. Liver biopsy showed distorted architecture with nodules surrounded by trabeculae of fibrous tissue. Balloon degeneration of hepatocytes was noted with widened portal tracts with piece-meal necrosis and chronic inflammatory cell infiltration consistent with chronic hepatitis C with moderately active cirrhosis. Histological activity score of Knodell was 8. Therapy with interferon alpha 2b was initiated at a dose of 3 million units three times a week. During follow-up she complained of myalgia and mild depression. Total and differential leucocytes count and platelet counts were normal. Eleven weeks after starting interferon treatment the dose was increase to 5 million units three times a week because of increased in transaminases after an initial decline. When the patient received this increased dose of interferon for 6 weeks she presented with spontaneous bruising and platelet count of 25,000/mm3. Interferon therapy was discontinued and the patient was briefly hospitalized until her platelet counts started increasing. Interferon therapy was restarted. 14 weeks later, she was re-admitted for treatment of cellulitis of left foot caused by Staphylococcus aureus treated with intravenous cloxacillin. Interferon therapy was continued at 5 million units in three times weekly dosages. Six weeks later she developed recurrent episodes of dysequilibrium associated with loss of hearing. The patient denied any history of auricular trauma, pain or drainage. The right and left tympanic membranes were both intact and normal. WBC count was 6.2 x 103 mm3, hemoglobin was 12 gm/dl and platelet count was 35,000/mm3. Sedimentation rate was 40 mm in first hour. Prothrombin time was 14 sec. (control 12 sec.). LFT revealed total bilirubin of 2.2 mg/dl, ALT 34 i.u. and alkaline phosphatase of 54 u/1. The patient was hospitalized and started empirically on cefotaxime because of history of fever. Blood and urine cultures and chest x-ray were negative so the antibiotic was stopped. An abdominal ultrasound revealed coarse liver texture but was otherwise unremarkable without ascites. An otolaryngologist evaluated her. Her audiogram revealed bilateral sensory neural hearing loss with more than 40% impairment in hearing. Interferon was stopped and 6 weeks later, her hearing returned to normal and platelet count increased to 103,000/mm3. On last follow-up in November 1998, transaminases were normal and repeat hepatitis C RNA by PCR was positive. She did not receive any further therapy with interferon.

Case II: A 58 years old Pakistani businessman, with a 20 years history of alcohol abuse was followed at the Gastroenterology clinics since 1987 with anorexia and abnormal liver function test, ALT 24-63 i.u. (Normal value less than 33 i.u.). Viral serology was negative for hepatitis BsAg. Autoimmune profile was negative. Synthetic liver functions were preserved (Albumin 4.4 gm/dl, prothrombin time 13 sec/control 13 sec). Liver biopsy showed fatty changes with chronic inflammatory cells in the periportal area. Knodell score was 9. In 1993-94, he was found to be positive for Anti HCV antibody. His ALT level remained around 93 i.u. (normal value < 33 i.u.). Serum hepatitis C RNA was positive by polymerase chain reaction. Hb level was 13.4 gm/dl and platelet count was 145,000/mm3. Therapy with alpha interferon 2b was started in the dose of 3 million units given subcutaneously three times a week. Initially the patient developed marked myalgia and low-grade fever, which settled after two weeks of therapy. The platelet count gradually decreased to 70,000 /mm3 after two more weeks of therapy and remained the same afterwards. After fifteen more injections of interferon the patient complained of decreased hearing. Ear examination was normal. Audiometry showed sensineural deafness with more than 50% loss of hearing. Subsequently, the hearing was worsening with further injections. Alpha interferon 2b was stopped at that point. Within a few weeks his hearing started improving subjectively. Repeated audiometry showed marked improvement in the deafness. Interferon was not given after that. Later the patient developed hepatoma in 1999.

Case III: A 63 years old male physician from Quetta was assessed in Gastroenterology clinic with history of jaundice and blood transfusion. He was already a known patient of HCV antibody positive chronic active hepatitis. He was referred from Quetta for interferon therapy. His liver functions were abnormal (ALT 123 i.u.. Albumin 3.2 gm/dl, prothrombin time 16/13 seconds. Platelets 120,000/mm3). HCV RNA was positive by PCR. Liver biopsy showed distorted architecture with nodules surrounded by trabeculae, fatty change in hepatocytes with piecemeal necrosis and grade III fibrosis. Knodell score was 13. Alpha interferon 2b was given to him in a dose of 3 million units subcutaneous three times a week. He tolerated the injection very well and his ALT level gradually started decreasing. At the end of one month, the patient started noticing some hearing impairment and after another two weeks his hearing was profoundly reduced. Audiometry did show sensineural deafness (hearing loss of more than 75%). Interferon was stopped. His hearing did not improve. The patient went back to Quetta where after few months he had progressive deterioration in his condition. He later developed hepatic encephalopathy and ascites. He died after 8 months.

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