Intracerebral hemorrhage in a patient receiving combination therapy of pegylated interferon alpha-2b and ribavirin for chronic hepatitis C.

The combination therapy of pegylated interferon alpha-2b (Peg-IFNα-2b) and ribavirin is quickly becoming standard treatment for patients with a high serum viral load of hepatitis C virus (HCV) genotype Ib (1-3). Herein, we present a case of intracerebral hemorrhage (ICH) that developed in a patient receiving combination treatment for chronic hepatitis C. The patient was a 55-year-old male, height 170 cm, weight 72 kg, with no notable past history, including hypertension or diabetes. He had consumed the equivalent of 55 g of ethanol and 15 cigarettes per day for 30 years, however, had completely stopped both habits for 4 months prior to the initiation of treatment. He was serologically diagnosed as infected with HCV in 1994, and had been treated with glycyrrhizin and ursodeoxycholic acid since 1996. However, transaminase had not become normalized. A combination therapy of standard type IFNα-2b (10 MIU/day) and ribavirin (800 mg/day) was initiated on December 8, 2004. Laboratory data prior to the commencement of combination therapy were as follows: WBC 5140/μl, RBC 436×10/μl, Hb 14.8 g/dl, platelets 11.2×10/μl, AST 47 IU/l, ALT 67 IU/l, γGTP 76 IU/l, albumin 4.3 g/dl, glucose 96 mg/dl, total cholesterol 177 mg/dl, HCV-RNA 130 KIU/ml, and HCV genotype 1b. Following a daily administration of IFNα-2b for 2 weeks, the regimen was changed to 3 times per week until January 19, 2005, when Peg-IFNα-2b became available at our hospital and weekly administration of that drug (100 μg) was commenced in place of the 3 times per week administration of standard IFNα-2b. No particular adverse reaction, apart from an elevation in temperature, was evident. However, mild blood pressure (BP) elevation was occasionally observed. The clinical course during the combination therapy is shown in Fig. 1A. On February 8, the day before receiving the fourth administration of Peg-IFNα-2b, the patient developed left hemiparesis. At that time a physical examination showed him to be consciousness alert and orientated, with a temperature of 36.0°C, BP at 136/84 mmHg, heart rate at 86 beats/minute and regular, eyes deviated to the right, and Babinski reflex positive on the left side. A plain CT scan disclosed a putamenal hemorrhage in the right hemisphere of the brain (Fig. 1B). Laboratory data showed WBC 3240/μl, RBC 390×10/μl, Hb 12.7 g/dl, platelets 10.2×10/μl, albumin 4.2 g/dl, AST 53 IU/l, ALT 65 IU/ l, glucose 133 mg/dl, total cholesterol 193 mg/dl, hepaplastin 79%, thrombotest 75%, and serum HCV-RNA undetectable by a RT-PCR assay. Cerebral angiography revealed no abnormalities such as aneurysm or arteriovenous malformation. Risk factors leading to ICH were not evident during the period of combination therapy, except for an occasional mild elevation in BP. The patient underwent an open evacuation of the hematoma and, following a period of rehabilitation, was discharged on March 29 with slight residual left hemiparesis. The Ministry of Health, Labour and Welfare announced to the public that medical professionals must be aware of the occurrence of ICH during treatment with standard IFNα-2b plus ribavirin therapy (http://www.mhlw.go.jp/houdou/2002/ 10/h1015-2.html), while the first post-marketing surveillance of the combination therapy of Peg-IFNα-2b and ribavirin also identified 4 cases of ICH, including the present case (4). According to that information, hypertension or diabetes was found to be an underlying condition in most of the patients with ICH. Although the exact total number of patients who have received the combination therapy remains speculative, the incidence of ICH during therapy seems to be not high when compared with the rate of ICH in the general Japanese population (5). However, since ICH is a rare and life threatening condition it should be well publicized as a complication of such combination therapy, regardless of the type of IFNα-2b used, not only in cases with hypertension or diabetes, but also in non-hypertensive and non-diabetic patients with chronic hepatitis C, as seen in the present case.