Alcohol Intake and Mortality in Patients with Chronic Viral Hepatitis: A Nationwide Cohort Study

( Dong Hyun Sinn ),( Danbee Kang ),( Eliseo Guallar ),( Yoosoo Chang ),( Seungho Ryu ),( Di Zhao ),( Yun Soo Hong ),( Juhee Cho ),( Geum-youn Gwak ) 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: We evaluated the association between alcohol intake and all-cause and cause-specific mortality in subjects with chronic viral hepatitis, using nationwide population-based cohort study. Methods: A total of 364,361 men and women 40-84 years of age who underwent health screening exam between January 2002 and December 2013 that included assessment of frequency and amount of alcohol consumption were assessed for all-cause and cause-specific mortality. Results: In participants without chronic viral hepatitis, the fully-adjusted hazard ratios (HR) for all-cause mortality comparing light, moderate, and heavy drinkers to non-drinkers were 0.90 (95% CI 0.85-0.96), 1.06 (95% CI 0.99-1.13), and 1.48 (95% CI 1.30-1.68), respectively. In participants with chronic viral hepatitis, the corresponding HRs were 1.15 (95% CI 1.01-1.30), 1.18 (95% CI 1.01-1.37), and 1.66 (95% CI 1.26-2.20), respectively (P-value for alcohol intake by chronic viral hepatitis interaction <0.001). Compared to participants without chronic viral hepatitis, those with chronic viral hepatitis had substantially elevated liver cancer or liver disease (HR 11.76, 95% CI 10.58-13.07) and extrahepatic cancer mortality (HR 1.41, 95% CI 1.30-1.54). In patients with chronic viral hepatitis, the high mortality due to liver cancer or liver disease and the positive association of alcohol intake with liver cancer or liver disease mortality explained the positive association of alcohol intake with all-cause mortality. Conclusions: Even light to moderate alcohol intake was associated with increased all-cause mortality in individuals with chronic viral hepatitis. Clinicians and public health campaigns should advise against any amount of alcohol intake in individuals with chronic viral hepatitis.

만성 B형 간염환자의 간조직에서의 Fas 항원의 발현

차영수,홍성표,최윤정,국진환,최유정,김경철,김배영,박필원,임규성 大韓消化器病學會 1998 大韓消化器病學會誌 Vol.31 No.2

만성 바이러스성 간염의 치료

이민호 한양대학교 의과대학 1998 한양의대 학술지 Vol.18 No.1

Chronic viral hepatitis is the principal cause of chronic liver disease, cirrhosis, and hepatocellular carcinoma. In Korea, of the known hepatits viruses, two can chronic hepatitis: the hepatits B virus(HBV) and the hepatits C virus(HCV). In chronic hepatitis B, a 4-6 month course of interferon alfa is effective in inducing clearlance of HBV DNA and HBeAg from serum and an improvement in serum transaminase concentration. New approaches to theraphy for hepatitis B include lamivudine and famiciclovir. In chronic hepatitis C, characterized by an indolent course, but with the potential for development of serious consequences. At present, the only approved agent is interferon alfa, with a sustained biochemical response rate of 10-22%. New approach to therapy for hepatitis C include combination theraphy with interferon alfa and ribavirin. In this article, strategies for treatment development of chronic B hepatitis and chronic C hepatitis are reviewed.

Comparison of Real-Time Shear Wave Elastography with Various Noninvasive Serum Markers for Assessing Liver Fibrosis in Chronic Viral Hepatitis

( Jae Yoon Jeong ),( Yeon Won Park ),( Joo Hyun Sohn ),( Dae Won Jeon ),( Kyueng Whan Min ),( Yongsoo Kim ) 대한간학회 2017 춘·추계 학술대회 (KASL) Vol.2017 No.1

Aims: To investigate the diagnostic accuracy of liver fibrosis using liver stiffness measurement (LSM) by real-time shear wave elastography (SWE) in patients with chronic viral hepatitis and to compare the diagnostic performance of SWE with serum liver fibrosis markers. Methods: We consecutively analyzed 92 patients with chronic viral hepatitis (45 with hepatitis B, 46 with hepatitis C and 1 with hepatitis B+C). Liver fibrosis was staged from F0 to F4 according to the Batts and Ludwig scoring system. The accuracy of prediction for liver fibrosis for SWE, hyaluronic acid (HA), type 4 collagen, AST to Platelet Ratio Index (APRI), FIB-4, Forns index and red cell volume distribution width-to-platelet ratio (RPR) was analyzed using receiver operator curve (ROC) analysis. Results: There were 10, 30, 20, and 32 patients at stages F0-1, F2, F3, and F4, respectively. The overall diagnostic accuracies of LSM and serum markers, as determined by the area under ROC, were LSM=0.909, APRI=0.810, FIB-4=0.768, type IV collagen=0.763, Forns index=0.750, RPR 0.717 and HA=0.712 and for predicting significant fibrosis (≥F2); LSM=0.861, type IV collagen=0.804, HA=0.801, RPR=0.770, Forns index=0.768, FIB-4=0.767, and APRI=0.728 for predicting advanced fibrosis (≥F3); and LSM=0.860, Forns index= 0.822, HA=0.817, FIB-4=0.816, RPR=0.799, type IV collagen= 0.783, and APRI=0.723 for predicting cirrhosis (=F4). LSM was superior to HA (P=0.029) and Forns index (P=0.049) for predicting significant fibrosis, and to APRI for predicting advanced fibrosis (P=0.011) and cirrhosis (P=0.011). Conclusions: SWE was the most accurate method to predict the degree of liver fibrosis in patients with chronic viral hepatitis. Also, the majority of six liver fibrosis markers were comparable to SWE to assess liver fibrosis.

How Many Valid Measurements Are Necessary to Assess Liver Fibrosis Using FibroScan® in Patients with Chronic Viral Hepatitis? An Analysis of Subjects with at Least 10 Valid Measurements

장희원,김도영,김승업,박준용,안상훈,한광협,전재윤,박영년,최은희 연세대학교의과대학 2012 Yonsei medical journal Vol.53 No.2

Purpose: Using FibroScan® to obtain a reliable liver stiffness measurement (LSM) may require more than 10 valid measurements (VMs), according to the manufacturer’s recommendations. However, this requirement lacks scientific evidence in support thereof. We investigated the minimal number of VMs required to assess liver fibrosis without significant loss of accuracy in patients with chronic hepatitis B (CHB) and C (CHC) and predictors of discordance between LSM and liver biopsy (LB). Materials and Methods: Between January 2005 and December 2009, we prospectively enrolled 182 patients with CHB and 68 patients with CHC who were to undergo LB and LSM before starting antiviral treatment. Only LSMs with at least 10 VMs were considered reliable. The Batts and Ludwig scoring system was used for histologic assessment. Results: The mean age and body mass index were 46.0 years and 23.4 kg/m2 in patients with CHB and 49.7 years and 23.1 kg/m2 in those with CHC, respectively. The median elasticity scores from the first 3, first 5, and all VMs taken significantly predicted fibrosis stages ≥F2 and F4 (all p<0.05) without significant differences (all p>0.05 by DeLong’s method). Alanine aminotransferase (ALT) was the only predictor of discordance in fibrosis stage as estimated by the median elasticity score from the first 3 VMs and by LB in patients with CHB, whereas no significant predictor was identified in those with CHC. Conclusion: After comparison of patients who had more than 10 valid measurements for LSM, three VMs may be enough to assess liver fibrosis using LSM without significant loss of accuracy in patients with CHC and patients with CHB. However, ALT should be considered when interpreting LSM for patients with CHB.

Interferon과 Ribavirin 병용요법 시행중인 만성 C형간염 환자에서 발생한 부작용에 대한 침구치료 증례

김성환,홍상훈,박동일,Kim, Sung-hwan,Hong, Sang-hoon,Park, Dong-il 대한침구의학회 2003 대한침구의학회지 Vol.20 No.1

Objective : Interferon-alpha and Rivabirin are much used at the same time to treat Chronical C viral hepatitis. But interferon caused lots of unexpected side effects, Acupuncture Treatment for them will be an alternative plan. Methods : We first posed questions to a 4 year-old man who ha skin flare, fatigue, itching, insomnia, pronounced a diagnosis based on overall of symptoms and signs and then treated Acupuncture, Moxibustion and Electroacupuncture. We acupunctured a BL17, BL18, BL20 and removed it at once. We electroacupunctured at GV20, Yin tang(Ex-HN3) form 20 minutes, acupunctured at Bi yi(鼻翼, Extra-point), S36, P6. Pizhengge(脾定格) was acupunctured for 10 minutes. Results : The symptoms of fatigue, insomnia, itching are reduced after acupuncture treatments and they made a person keep interferon treatment on. Conclusions : We confirmed that acupuncture treatments make a patient of chronic C viral hepatitis reduce and improve side effects of interferon treatment. We should keep on studying the various and efficient method of acupuncture treatment to improve living quality and treatment efficiency of patients.

만성(慢性) B형(型) 간염환자(肝炎患者) 삶의 질(質)

김헌수,이민규,Kim, Hun-Soo,Lee, Min-Kyu 한국정신신체의학회 1998 정신신체의학 Vol.6 No.1

Objectives : The purpose of this study was to determine correlation between coping strategies to disease and quality of life in chrome viral B hepatitis patients ; to investigate difference of coping strategies to disease and quality in life between chronic viral B hepatitis patients and normal persons ; and to identify major variables related to quality in life of chronic viral B hepatitis patients. Methods: The authors used Weisman coping strategy scale for measuring coping ability and efficacies, and the questionnaire for measuring quality of life including physical, psychological, social and economical aspects and satisfaction of sexual life was made by authors based on related literatures. Data were collected through questionnaire survey over a period from Sep 15, 1994 to Nov 11, 1994. Subjects served for this study consisted of 94 chronic viral B hepatitis patients visited to department of internal medicine at one general hospital and 100 normal persons visited to one general hospital for routine check up of health. The collected data were analyzed by SAS and the statistical methods for analysis were Chisquare, t-test and multiple regression analysis. Results : 1) It was revealed that coping strategies to disease significantly correlated to individual's quality of life. 2) There was no significant difference in coping strategies to disease between chronic viral B hepatitis patients and normal persons. However, chronic viral B hepatitis patients showed the lower scroes of quality of life in physical, psychological and economical aspects. 3) The most important variables which were influenced upon quality of life were coping strategies to disease and satisfaction of sexual life. That is, the more active coping strategies to diseases and the higher satisfaction of sexual life, consequently the higher quality of life was. Especially male patient group or normal persons showed each other the higher scores of quality of life in physical and psychological area than female group or patient group. 4) No statistically significant difference in coping strategies to disease and quality of life was found between HBeAg positive group and HBeAg negative group. Conclusions : The authors suggest that chronic viral B hepatitis patients may show the lower score of quality of life than normal person. Therefore, quality of life assessment should become an integral part of all clinical area that seek to assess the effectiveness of treatment. Also, through the interdisciplinary approach, a comprehensive paradigm that can better account for the effects of chronic disease on the individual' s quality of life should be developed.

HbeAg 음성인 만성 B형 간염 환자에서 라미부딘 투여중 Viral Breakthrough의 발생 빈도

장윤정,임정윤,조남영,최창원,백수정,안수현,최도원,권용대,김선숙,권오상,김주현,연종은,송진원,변관수,이창홍 대한간학회 2002 Clinical and Molecular Hepatology(대한간학회지) Vol.8 No.4

목적: 라미부딘 치료는 HBeAg 양성 만성 B형 간 염환자에서 효과적인 것으로 알려져 있지만 HBeAg 음성 만성 B형 간염 환자에서 장기간의 치료효과와 BT의 발생률은 아직 확실치 않다. 이에 HBeAg 존재유무에 따른 BT의 발생률을 비교하고 BT의 발생과 YMDD 변이종의 출현과의 관계를 확인하고자 하였다. 대상과 방법: 최소한 9개월이상 라미부딘을 투여받은 만성 B형 간염 환자를 대상으로 하였으며 HBeAg 양성군은 205명, HBeAg 음성군은 49명이었다. 라미부딘 치료기간은 HBeAg 양성군 176개월, HBeAg 음성군은 155개월으로 양군 간에 차이가 없었다. YMDD 변이종은 RFLP 분석과 직접 염기서열 분석으로 확인하였다. 결과: 대상 군의 임상적 특성은 HBeAg 음성군이 양성군에 비해 나이는 더 많았고(43±9세 vs. 39±10세; p<0.05) 치료전 HBV DNA 역가가 낮았다(670±1499 vs. 1877±5168 pg/ mL; p<0.01). 치료 12개월, 24개월 의 누적 BT 발생률은 HBeAg 양성군에서는 12%, 39%였으며 음성군에서는 0%, 7%로서 음성군에서의 발생율이 양성군에 비하여 낮았다(p<0.01). 다변량 분석으로 확인한 BT와 관계있는 유일한 인자는 HBeAg의 존재 유무였다(p<0.05). YMDD 변이종은 HBeAg 유무에 관계없이 BT가 발생한 모든 예에서 확인할 수 있었으나 BT가 발생하지 않은 경우에서 YMDD 변이종의 발생률은 HBeAg 양성군보다 HBeAg 음성군에서 유의하게 더 높았다(14.3% vs. 50.0%; p<0.01). 결론: HBeAg 음성 만성 B형 간염 환자에서의 라미부딘 치료는 YMDD 변이종이 발생 하여도 BT 발생 빈도가 낮아서 라미부딘의 지속적인 치료효과를 기대해 볼 수 있으리라 생각된다. Background/Aims: Long-term efficacy and the rate of viral breakthrough in patients with HBeAg- negative chronic hepatitis B receiving lamivudine therapy is uncertain. This study was conducted to determine the rate of viral breakthrough according to the HBeAg status and the relation of viral breakthrough with YMDD mutants. Methods: Two hundred and five patients with HBeAg-positive and 49 patients with HBeAg-negative chronic hepatitis B, who had received lamivudine for at least 9 months, were included. The mean durations of the lamivudine treatment were 176 months and 155 months in HBeAg-positive and negative patients, respectively. Analysis of HBV genome for YMDD mutations was performed by restriction-fragment-length polymorphism assay and direct sequencing. Results: While the cumulative rates of viral breakthrough at 12th and 24th months of the lamivudine therapy were 0% and 7% in the HBeAg-negative group, they were 12% and 39% in the HBeAg-positive group. The cumulative rate of viral breakthrough in the HBeAg-negative group was significantly lower than in the HBeAg-positive group (p<0.01). In multivariate analysis, the only significant factor related to viral breakthrough was the HBeAg status (p<0.05). The YMDD mutants were detected in all patients with viral breakthrough irrespective of HBeAg status. However, in patients without viral breakthrough, the rate of YMDD mutants was significantly higher in the HBeAg-negative group than in the HBeAg-positive group (13.3% vs 5.1%; p<0.01). Conclusions: Lamivudine is expected to be more persistently effective in HBeAg-negative chronic hepatitis B because of a lower viral breakthrough rate than in HBeAg-positive chronic hepatitis B in spite of the emergence of YMDD mutants.(Korean J Hepatol 2002;8:397-404)

만성 B형 간염에서 라미부딘 치료중 발생한 Viral Breakthrough 예의 임상 결과

안수현,장윤정,오성남,최도원,백수정,정원석,최창원,김경오,임형준,조남영,박종재,김재선,박영태,이명석,연종은,변관수,이창홍 대한간학회 2002 Clinical and Molecular Hepatology(대한간학회지) Vol.8 No.4

목적: 만성 B형 간염의 치료 중 발생하는 약제 내성 변이종은 임상적으로는 치료 중 음전되었던 혈청 HBV DNA가 다시 양전되는 viral breakthrough 로 진단할 수 있다. 현재 약제 내성 변이종이 발생했을 경우라도 라미부딘 치료를 계속 유지하는 것을 권장하고 있으나, viral breakthrough 발생 예들의 장기적 임상경과가 아직도 불명확하여 이것을 일반화하기는 어려운 상황이다. 이에 라미부딘 사용 중 viral breakthrough 가 발생한 예들을 대상으로 그 임상경과를 알아보고자 하였다. 대상과 방법: 9개월 이상 라미부딘을 투약한 만성 B형 간염 환자로 viral breakthrough가 발생한 74명을 대상으로 하였다(남/여 54/20, 평균연령 42세). Viral breakthrough 후 혈청 ALT치, 총 빌리루빈치, HBV DNA 역가, HBeAg, anti-HBe를 정기적으로 검사하면서 임상경과를 관찰하였다. Viral breakthrough 후 라미부딘의 투약기간은 평균 13개 월(1-41개월)이었다. 결과: Viral breakthrough 발생후 혈청 ALT치가 정상으로 유지되었던 환자는 8예(11%)에 불과했고 나머지 66예(89%)에서는 ALT치가 증가하였으며, 이중 30예(41%)에서 급성 악화(ALT 정상 상한치의 5배 이상 상승)를 보였다. 급성악화는 viral breakthrough 후 3개월 내에 19예 (63%)에서 발생하여 3개월 내에 발생한 예가 많았으나 12개월 이상 지나서 나타나는 예도 약 20%에서 있었다. 비대상성 악화는 6예에서 관찰되었다. Viral breakthrough 후 급성악화가 일어난 예와 없었던 예의 비교에서 급성악화를 예측할 수 있는 인자는 발견할 수 없었다. Viral breakthrough 후 발견할 수 없었다. Viral breakthrough 후 HBeAg이 음전된 예는 8예(11%)였으나 그 임상경과는 양호하지 않았다. 결론: 만성 B형 간염 환자 에서 라미부딘 투여 중 발생한 viral breakthrough 예 중 상당수에서 급성악화가 발생하였으며, HBeAg 이 소실되더라도 그 임상경과는 양호하지만은 않았다. Viral breakthrough 발생 후 주의 깊은 임상경과 의 관찰이 요구되며, 앞으로 viral breakthrough 후 급성악화 예에 대한 대규모 연구와 적절한 치료방향의 제시가 이루어져야 할 것으로 생각된다. Background/Aims: Long-term lamivudine therapy can induce the emergence of lamivudine resistant hepatitis B virus (HBV) mutants. Clinically emergence of the mutant is expressed by the reappearance of disappeared HBV DNA in serum. Continued lamivudine treatment has been usually recommended in cases of viral breakthrough. However, the clinical outcome in patients with viral breakthrough is not clear. The aim of this study was to investigate the clinical course of chronic hepatitis B patients after viral breakthrough during lamivudine therapy. Methods: A total of 74 patients with chronic hepatitis B who showed viral breakthrough after at least 6 months of lamivudine treatment were included in this study. They had positive HBeAg and HBV DNA before treatment. The median follow-up duration after breakthrough was 13 months. Results: After viral breakthrough, only 8 patients (11%) maintained normal ALT levels and 66 patients (89%) showed elevation of ALT. 30 patients (41%) showed acute exacerbation of hepatitis (ALT increase over five-times upper normal limit). These acute exacerbations occurred within three months after breakthrough in 19 patients (63%). In the cases of acute exacerbation, 6 patients showed decompensated progression such as elevation of serum total bilirubin. One of them died of hepatic failure. A predictive factor for acute exacerbation was not found. HBeAg seroconversion occurred in 8 patients after viral breakthrough but their clinical course was highly variable. Conclusions: Chronic hepatitis B patients who had viral breakthrough during lamivudine therapy should be followed carefully and regularly in mind of potential clinical deterioration. New strategies are needed to manage the cases of acute exacerbation after viral breakthrough.(Korean J Hepatol 2002;8:389-396)

만성 B형 간질환에서 라미부딘 내성의 임상경과 및 예측인자

박능화,신정우,박종호,방성조,김대현,주광로,김도하 대한간학회 2003 Clinical and Molecular Hepatology(대한간학회지) Vol.9 No.4

목적: 라미부딘의 투여기간이 길수록 약제내성 변이형 바이러스의 발생률이 증가하게 된다. 변이형의 장기적인 임상적 의의는 논란이 많다. 본 연구는 B형 간염 바이러스에 의한 만성 간질환자에서 변이형이 생긴 뒤의 임상적 경과와 변이형의 발생을 예측할 수 있는 인자를 알아보고자 하였다. 대상과 방법: 만성 B형 간 질환자로 진단 받은 환자 중 라미부딘 치료도중에 viral breakthrough가 생긴 124명을 대상으로 하였다. 평균 연령은 40세였고 남녀 비는 105:19였다. 치료 전 혈청 평균 ALT치는 223 IU/L, 혈청 평균 AST치는 127 IU/L, 혈청 평균 HBV DNA치 1216 pg/mL, 치료 전 정량적 평균 HBeAg치 259이였다. 라미부딘은 1일 100 ㎎씩 breakthrough가 발생한 124명에게 계속 투여하였으며 1, 2개월 간격으로 간기능 검사, HBeAg, anti HBe, HBV DNA 검사를 시행하였다. 라미부딘 총 평균투여 기간은 30.5개월(범위: 10-59개월)이었으며 breakthrough 후 라미부딘 평균 투여기간은 12.5개월(범위: 1-42개월)이였다. 결과: 라미부딘 투여 환자 519명 중 124명에서 viral breakthrough가 5-41개월 사이에 발생하였으며 누적발생률은 12개월 후 8%, 18개월 후 24%, 24개월 후 36%, 36개월 후 52%였다. Viral breakthrough가 생긴 6개월 이내에 120명에서 혈청 ALT치가 상승하였으나 4명에서는 계속 정상으로 유지되었다. 혈청 ALT치는 대부분 상승한 뒤 5개월 내에 최고치에 도달하였으나 6명에서는 12개월 이후에 최고치에 도달하기도 하였다. ALT치는 72명(65%)에서 치료 전 값 이상으로 상승하였으며, 67명(56%)에서 정상치의 5배 이상, 29예(24%)에서 10배 이상 상승하였다. Breakthrough후에 라미부딘 계속투여로 혈청 ALT치가 정상으로 유지된 경우는 22예(18%)에 불과하였으며 98예는 치료전보다 높게 유지되었고 16예에서는 지속적으로 상승하였다. Breakthrough후의 혈청 ALT치 및 AST치가 치료 전보다 의미 있게 상승하였으나 혈청 HBV DNA치는 차이가 없었다. Breakthrough후에 10명에서 HBeAg의 음전이 있었으나 5예에서는 음전 후에 HBV DNA가 재양전되고 혈청 ALT치가 상승되는 HBeAg 음성 만성 간염형태로 나타났다. Breakthrough와 관련된 예측자로 치료 중 정량적 HBeAg의 변화양상만이 유일하게 의미가 있어 감소 후 증가군 82.5%에서,. 지속적 유지군 23.7%에서 Breakthrough가 발생하였으나 지속적 감소군에서는 단지 3.5%만이 발생하였다. 또한 감소 후 증가군에서 정량적 HBeAg치의 감소 후 재상승시점은 약물투여후 평균 9개월로 HBV DNA가 재양전되는 평균시점인 16개월보다 의미 있게 짧았다. Breakthrough후에 투약을 중지한 예는 40예(33%)였다. 이 중 11예에서 중단전보다 혈청 ALT치가 상승되었으며 8개월 내에 전예에서 발생하였다. 중단시 혈청 ALT치가 치료 전 수치보다 높은 경우에서 중단한 26예 중 25명은 중단 후에 혈청 ALT치가 중단 시보다 낮았지만 치료 전 수치보다 낮은 경우에서 중단한 14명 중 10예에서 중단 후에 중단 시보다 더 높아졌다. 결론: 만성 B형 간염환자에서 라미부딘 투여 중에 발생한 HBeAg후의 임상양상은 상당수에서 급성악화를 보였다. Breakthrough를 예측할 수 있는 인자로는 치료 중 정량적 HBeAg치의 변화양상만이 유일한 인자였으며 HBeAg치가 지속적 감소 후에 다시 증가하는 양상을 보인 경우에는 HBV DNA의 재양전보다 더 빨리 Breakthrough을 예측할 수 있었다. Background/Aims: Long-term treatment with lamivudine causes breakthrough, but the clinical course after lamivudine breakthrough is not well known. The aims of this study were to evaluate the clinical course in lamivudine after breakthrough, and to identify predictive factors of breakthrough. Methods: 124 patients with chronic hepatitis B infection, who represented viral breakthrough during lamivudine therapy, were included. The mean duration of lamivudine therapy and additional lamivudine therapy after breakthrough was 30.5 months and 12.5 months, respectively. Results: The cumulative breakthrough rates at 12, 18, 24 and 36 months were 8, 24, 36 and 52%, respectively. After viral breakthrough, only 4 patients maintained normal ALT levels. 120 patients showed ALT elevation. The number of patients with ALT levels greater than 5 times, and greater than 10 times, the upper normal limit were 67(56%) and 29 (24%), respectively. While still on lamivudine therapy after breakthrough, 98 patients presented ALT elevation. Only 22 had normalized ALT levels. Hepatic decompensation developed in 2 patients. HBeAg seroconversion after breakthrough occurred in 10 patients. The changing pattern of quantitative HBeAg levels during lamivudine therapy was the only predictive factor associated with viral breakthrough. The mean time of turning points in decrescendo-crescendo patterns of HBeAg levels during lamivudine therapy was earlier than viral breakthrough (9 months vs. 17 months). Conclusions: These results suggested that deterioration of hepatic function can usually be observed after breakthrough. The serial monitoring of serum quantitative HBeAg levels may allow an early recognition of viral breakthrough.(Korean J Hepatol 2003;9:293-303)