만성 B형 간염 환자에서 자발성 급성 악화의 원인 및 임상 경과
Etiology and Clinical Consequence of Spontaneous Acute Exacerbation of Chronic Hepatitis B
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목적: 저자 등은 만성 B형 간염 경과 중 급성 악화가 심하게 발생한 환자에서 그 원인을 조사하고, 자발적 악화시 HBeAg 혈청전환 및 임상 경과에 대하여 알아보고자 하였다. 대상과 방법: 1992년 1월부터 2001년 12월까지 만성 B형 간염의 급성 악화로 입원하였던 환자를 대상으로 하였다. 중증 급성 악화의 정의는 AST/ALT가 정상 상한치의 10배 이상 증가한 경우로 하였다. 후향적으로 의무기록을 조사하여 성별, 연령, 원인, 간기능검사, 혈청학적 검사 및 생존 등에 대하여 성별 및 연령이 유사한 대조 환자군과 비교 분석하였다. 결과: 중증 급성 악화 환자는 남자 29명, 여자 15명 등 44명으로 평균 38.6±0.1세였다. 급성 악화 원인으로는 자발적 악화가 34예(77%), 약물 복용 7예(16%), 음주 2예(5%), HCV 중복감염 1예(2%)였다. 혈액검사에서 총 빌리루빈은 8.3±8.3 mg/dL, 알부민 3.6±0.7 g/dL, ALT 924±597 IU/L, 프로트롬빈 시간 1.58±1.29 (INR), α-PF 108±163 ng/mL이었다. 자발적 급성 악화 34예 중 HBeAg 양성인 경우는 27예(79%)였으며, 추적 기간(579±459일) 동안 51.9%에서 HBeAg 혈청전환이 일어났으나, 3개월째 혈청전환율은 15%에 불과하였으며, 12개월 및 24개월째는 각각 18.5%, 48.1%였다. 한편 ALT가 199 IU/L 이하인 대조 환자의 경우는 같은 기간의 혈청전환율이 각각 4.3%, 10.9%로 낮았으며, 기저 ALT치에 따른 누적 혈청전환율도 200 IU/L을 중심으로 유의한 차이가 있었다(P<0.05). 간경변으로의 진행은 대조 환자군에 비하여 높은 경향을 보였으며(17.6% vs. 5.5%, P<0.08), 사망한 경우는 급성 악화군에서만 1예(2%) 있었다. 결론: 만성 B형 간염 환자 중 중증의 급성 악화는 자발적 악화가 가장 흔하였으며, 약 반수에서 2년내 HBeAg 혈청전환되었고 18% 정도에서 간경변으로 진행되었다. 그러나 3개월 이내의 조기 혈청전환은 15%로 낮았으며, 전반적인 혈청전환율도 외국의 보고에 비하여 다소 낮았다.
Abstract
Background/Aims: Acute exacerbation (AE) of chronic hepatitis B (CHB) can occur spontaneously, and may be followed by HBeAg clearance. HBeAg seroconversion often coincides with the normalization of liver biochemical tests and clinical remission. The purpose of this study was to identify the etiology and the clinical consequence of severe AE in Korean patients with CHB. Methods: The medical records of CHB patients with severe AE (defined by the sudden increase of ALT above 400 IU/L) who were admitted to Kyung Hee University Hospital between January 1992 and December 2001, were reviewed retrospectively. Forty-four patients were included in the severe AE group. Results: The most common etiology of severe AE was spontaneous exacerbation (77%). Drugs (16%), alcohol (5%), and HCV coinfection (2%) were suspected of causing AE in the remaining patients. HBeAg seroconversion at 12, 18, and 24 months following severe spontaneous AE was 18.5%, 40.7%, and 48.1%, respectively. These were significantly higher compared to CHB patients without AE (4.3%, 4.3%, and 10.9%, respectively). Seroconversion within 3 months, however, occurred in only 15% of CHB patients with AE. There was a tendency to progress to liver cirrhosis more frequently in the patients with AE as compared to the patients without AE (17.6% vs. 5.5%, P<0.08). Conclusions: Severe AE in patients with CHB is mainly caused by spontaneous exacerbation. Although HBeAg seroconversion occurs frequently in these patients, the rates are relatively low compared to those reported in other countries and early seroconversion is expected only in a small proportion. Further studies will be warranted to determine the efficacy of the early use of antiviral agents at the time of AE.
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