Tenofovir versus Entecavir in Treatment of Chronic Hepatitis B Virus with Severe Acute Exacerbation

Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) are effective antivirals recommended as first-line monotherapies for treatment of chronic hepatitis B (CHB) infection. This study aimed to compare the short-term efficacies of TDF and ETV in the treatment of CHB with severe acute exacerbation. From 2008 to 2013, 189 consecutive treatment-naive CHB patients receiving TDF (n = 41) or ETV (n = 148) for severe acute exacerbation were enrolled. The primary endpoint was overall mortality or receipt of liver transplantation by week 24. The baseline characteristics were comparable between these two groups. By week 24, 8 (19% [95% confidence interval {CI}, 7% to 32%]) patients in the TDF group and 26 (18% [95% CI, 11 to 24%]) patients in the ETV group died (n = 30) or received liver transplantation (n = 4) (P = 0.749). The two groups of patients developed similar rates of liver-related complications and achieved comparable biochemical and virological responses at week 24. Cox regression analysis showed that baseline viral DNA level (P = 0.002), hypertension (P = 0.002), model for end-stage liver disease (MELD) score (P = 0.01), platelet count (P = 0.005), early presence (within 4 weeks) of ascites (P = 0.005), hepatic encephalopathy (P = 0.002), and hepatorenal syndrome (P < 0.001) were independent factors for mortality or liver transplantation. Among the patients who survived by week 24, there was no difference between the two groups in the percentage of patients who had a serum creatinine increase of ≥0.5 mg/dl from baseline (6.7% [95% CI, 0% to 16%] versus 2.0% [95% CI, 0% to 4.8%] in the TDF and ETV groups, respectively; P = 0.231), whereas a significant reduction in the estimated glomerular filtration rate (eGFR) was found in the two groups (P = 0.001 for both). In conclusion, TDF and ETV produce a similar treatment response and clinical outcome in patients with severe acute exacerbation of CHB.     

恩替卡韦治疗乙型肝炎肝硬化疗效观察

目的:观察恩替卡韦治疗乙肝肝硬化患者48周疗效。方法:60例乙肝肝硬化患者,给予恩替卡韦0·5mg,每天1次口服,持续治疗48周。观察治疗后12周、24周、36周、48周病毒学、生化指标、凝血酶原活动度及Child-Pugh积分等变化情况。结果:患者血清HBV DNA对数值在治疗前平均为6·76±1·80log拷贝/mL,在接受恩替卡韦治疗后12周、24周、36周、48周时分别下降至3·00±0·66log拷贝/mL(P<0·01)、3·00±0·24log拷贝/mL(P<0·01)3·00±0·11log拷贝/mL(P<0·01)、3·00±0·05log拷贝/mL(P<0·01)。(治疗后HBV DNA检测不到的患者被定为<103拷贝/mL)。在12周、24周36周和48周时分别为75%(45/60),95%(57/60),96·67%(58/60)和98·33%(59/60)。在治疗48周时,44·44%(12/27)的患者出现了HBeAg阴转,22·22%(6/27)的患者出现了HBeAg血清学转换。与治疗前相比在治疗48周时ALT、AST明显下降,Alb、TBil、前白蛋白(PAlb)、胆碱酯酶(CHE)、凝血酶原活动度(PTA)及Child-Pugh积分等指标均有所改善(P<0·05)。结论:恩替卡韦对于乙肝肝硬化的患者在48周内即能有效抑制病毒复制,使HBV DNA水平下降,同时可以改善肝功能、凝血酶原活动度及Child-Pugh积分等指标。     

Sequential Combination Therapy with Pegylated Interferon Leads to Loss of Hepatitis B Surface Antigen and Hepatitis B e Antigen (HBeAg) Seroconversion in HBeAg-Positive Chronic Hepatitis B Patients Receiving Long-Term Entecavir Treatment

Nucleos(t)ide analogues rarely result in a durable off-treatment response in chronic hepatitis B infection, whereas pegylated interferon (Peg-IFN) induces a long-lasting response only in a subset of patients. We assessed the effect of sequential combination therapy with Peg-IFN-α2a and entecavir in hepatitis B e antigen (HBeAg)-positive patients with prior long-term entecavir therapy and investigated the predictors of response to treatment. HBeAg-positive individuals who did not achieve HBeAg seroconversion during previous long-term entecavir therapy, receiving Peg-IFN-α2a added to ongoing entecavir therapy (sequential combination [S-C] therapy; n = 81) for 48 weeks or remaining on entecavir monotherapy (n = 116), were retrospectively included. A matched pair was created at a 1:1 ratio from each treatment group. The primary endpoint was HBeAg seroconversion at week 48. Subgroup analysis of response prediction was conducted for 81 patients with S-C therapy. More patients in the S-C therapy group achieved HBeAg seroconversion than those in the entecavir group (44% versus 6%; P < 0.0001). An HBeAg level of <200 signal-to-cutoff ratio (S/CO) at baseline was a strong predictor for higher HBeAg seroconversion than that achieved when HBeAg was ≥200 S/CO (64.2% versus 17.9%; P < 0.0001). Hepatitis B surface antigen (HBsAg) levels at baseline and the decrease in HBsAg levels predicted HBsAg loss in the S-C therapy group. The combination of baseline HBeAg of <200 S/CO and HBsAg of <1,000 IU/ml and an HBsAg decline at week 12 of ≥0.5 log₁₀ IU/ml provided the highest rate of HBeAg seroconversion (92.31%) and HBsAg loss (83.3%) at week 48. Patients receiving sequential combination therapy have a higher rate of HBeAg seroconversion and are more likely to experience HBsAg clearance than do those continuing entecavir monotherapy. Sequential combination therapy can be guided by baseline HBsAg/HBeAg levels and on-treatment HBsAg dynamics.     

恩替卡韦治疗慢性重型乙型肝炎48例临床观察

[目的] 探讨恩替卡韦治疗慢性重型乙型肝炎的近期疗效和安全性.[方法]48例HBV DNA阳性的慢性重型乙型肝炎在综合治疗的基础上,使用恩替卡韦0.5 mg,每晚口服1次,对照组42例为常规综合治疗.[结果]恩替卡韦治疗组HBV DNA阴转率81.25%,临床有效率75%;对照组HBV DNA阴转率21.43%,临床有效率50%.治疗组好转率明显高于对照组,差异有非常显著性（P＜0.05）.[结论]在综合治疗的基础上,应用恩替卡韦治疗慢性重型乙型肝炎可改善患者临床症状,提高生存率,降低病死率.     

Tenofovir Monotherapy versus Tenofovir plus Lamivudine or Telbivudine Combination Therapy in Treatment of Lamivudine-Resistant Chronic Hepatitis B

Tenofovir disoproxil fumarate (TDF) monotherapy is a therapeutic option for chronic hepatitis B (CHB) patients infected with hepatitis B virus (HBV) variants resistant to lamivudine (LAM). We evaluated the antiviral efficacy and safety of TDF alone compared to those of TDF plus LAM or telbivudine (LdT) combination in patients harboring HBV variants with genotypic resistance to LAM. This multicenter retrospective study included consecutive patients who had LAM-resistant HBV variants and were treated with TDF alone (monotherapy group) or TDF combined with LAM or LdT (combination therapy group) for at least 6 months. Inverse probability of treatment weighting (IPTW) for the entire cohort was applied to control for treatment selection bias. Overall, 153 patients (33 in the monotherapy group and 120 in the combination therapy group) were analyzed. The overall probability of achieving complete virologic suppression at month 12 was 91.6%: 88.6% in the monotherapy group and 92.6% in the combination therapy group. Combination therapy was not superior to monotherapy in viral suppression before and after IPTW (P = 0.562 and P = 0.194, respectively). Hepatitis B e antigen (HBeAg) loss, biochemical response, and virologic breakthrough did not differ between treatment groups. The probabilities of complete virologic suppression were comparable between treatment groups in the subsets according to HBeAg status and HBV DNA levels at baseline. No patient experienced any significant renal dysfunction during the treatment period. In conclusion, TDF monotherapy has antiviral efficacy comparable to that of TDF plus LAM or LdT combination therapy, with a favorable safety profile in CHB patients with LAM-resistant HBV variants.     

恩替卡韦治疗HBeAg阳性慢性乙型肝炎疗效观察

目的研究恩替卡韦治疗HBeAg阳性慢性乙型肝炎的疗效。方法 66例慢性乙型肝炎患者随机分为两组：观察组予恩替卡韦治疗48周;对照组予拉米夫定治疗48周。观察两药对HBV-DNA、ALT、血清学应答及耐药的影响。结果治疗48周后,两组HBV-DNA阴转率和耐药率差异有统计学意义;而ALT复常率和血清学应答率差异无统计学意义。结论恩替卡韦在HBV-DNA阴转率和控制HBV耐药方面优于拉米夫定。     

恩替卡韦与阿德福韦酯治疗慢性乙型肝炎的早期病毒学反应观察

目的:观察恩替卡韦(ETV)与阿德福韦酯(ADV)治疗慢性乙型肝炎的早期血清生化指标与病毒学反应。方法:试验组口服恩替卡韦,每日0·5mg;对照组口服阿德福韦酯,每日10mg。定期检测肝功能和血清HBV DNA定量,以服药前数据作为基线值,服药后第4、12、24周分别作为快速病毒学反应(RVR)、初始病毒学反应(IVR)、早期病毒学反应(EVR)。结果:两组服药前HBV DNA基线水平无显著差异(P>0·05)。ETV组RVR、IVR、EVR期的HBV DNA降幅(logcp/ml)分别为2·60±0·85、3·22±1·24、3·06±1·29,显著高于同期ADV组的1·69±0·82、2·03±1·10、2·00±1·25(P<0·05);ETV组早期病毒学应答率和HBV DNA下降至检测水平以下者比例分别达到82%、51%,高于ADV对照组的69%、36%;ETV原发无应答比例(18%)低于ADV组(31%)。两组ALT完全复常的比例均为64%。ETV组有2例治疗后1月ALT显著升高,而在治疗3月后ALT完全恢复正常,血清HBV DNA下降至检测水平以下。结论:ETV组抗HBV作用相对较强,但与ADV的生化学应答相近。少数恩替卡韦治疗者出现短暂ALT显著升高,似乎其病毒学早期反应更好。     

Comparison of the Efficacy of Lamivudine Plus Adefovir Versus Entecavir in the Treatment of Lamivudine-Resistant Chronic Hepatitis B: A Systematic Review and Meta-Analysis

Background

Hepatitis B virus infection remains 1 of the major health threats worldwide. Currently, lamivudine plus adefovir combination therapy or entecavir monotherapy is usually used for the treatment of patients with lamivudine-resistant chronic hepatitis B (CHB). However, there are few systematic comparisons between the efficacy of lamivudine plus adefovir and the efficacy of entecavir in the treatment of these patients.

Objective

The goal of this systematic study and meta-analysis was to assess the efficacy of lamivudine plus adefovir compared with entecavir for the treatment of patients with lamivudine-resistant CHB.

Methods

A comprehensive literature search of PUBMED, Web of Science, WANFANG database, the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Review, were screened to obtain citations from January 1990 to January 2012 in this study. Data analysis was done by using the Review Manager Software 5.1.

Results

Eight studies were suitable for analysis. A total of 696 patients with lamivudine-resistant CHB were studied and grouped according to treatment: 341 patients in the entecavir group and 355 patients in the lamivudine plus adefovir group. The results found that the rates of undetectable hepatitis B virus DNA levels, alanine aminotransferase normalization, hepatitis B e antigen loss, and hepatitis B e antigen seroconversion were not significantly different between the lamivudine plus adefovir group and the entecavir group. Moreover, the rate of adverse reactions was also not significantly different between the 2 groups. However, virologic breakthrough for the patients with lamivudine resistance was higher in the entecavir group than in the lamivudine plus adefovir group.

Conclusions

For these CHB patients with lamivudine resistance, lamivudine plus adefovir was a better treatment option than entecavir alone.     

Effect of Pegylated Interferon Plus Tenofovir Combination on Higher Hepatitis B Surface Antigen Loss in Treatment-naive Patients With Hepatitis B e Antigen -positive Chronic Hepatitis B: A Real-world Experience

PurposeThe loss of serum hepatitis B surface antigen (HBsAg) in patients with chronic hepatitis B (CHB) is considered an ideal clinical outcome but rarely achieved with current standard of care. We evaluated the effectiveness in inducing HBsAg seroclearance in a real-world clinical cohort of Chinese patients with CHB treated with a combination of pegylated interferon (Peg-IFN) with tenofovir disoproxil fumarate (TDF) or monotherapy with each agent.MethodsA total of 330 patients with CHB were assigned to receive Peg-IFN plus TDF for 48 weeks (Peg-IFN plus TDF group), Peg-IFN alone for 48 weeks (Peg-IFN group), or TDF alone for 144 weeks (TDF group). The primary end point was the percentages of patients who achieved HBsAg seroclearance at week 72. Differences from the baseline characteristics and treatment data were compared using the χ² test for categorical variables or 1-way ANOVA for continuous variables. A Kaplan–Meier test was performed to compare the HBsAg loss among the 3 groups. Discrimination of responders versus nonresponders was quantified using AUC curves. Optimal cut-offs were selected based on Youden's J statistic defined as J = sensitivity + specificity-1.FindingsAt week 72, the Kaplan–Meier cumulative HBsAg loss was 11.5% in the Peg-IFN plus TDF group, 5.7% in the Peg-IFN group, and 0% in the TDF group. The percentage of patients with HBsAg loss was comparable in the Peg-IFN plus TDF and Peg-IFN groups (P = 0.143), but both were significantly higher than that in the TDF group (P = 0.000 and P = 0.010). In addition, a significantly higher percentage of patients in the combination group and Peg-IFN group had serum HBsAg of <100 IU/mL compared with the TDF group (32.7% vs 23.6% vs 9.2%; P < 0.001) but no significant differences in the percentages of patients with HBsAg <1000 IU/mL, the undetectable serum HBV DNA and hepatitis B e antigen seroconversion. Our model predicted serum HBsAg loss at week 72 (AUC = 0.846) if the HBsAg level was reduced by > 1.5 log₁₀ IU/mL from baseline at treatment week 24, an optimal timepoint for prediction of HBsAg loss in this cohort.ImplicationsA 48-week course of Peg-IFN and TDF combination therapy led to profound reduction in serum HBsAg level, resulting in a significantly higher rate of HBsAg loss compared with TDF monotherapy. Patients with steep HBsAg decline >1.5 log₁₀ IU/mL at week 24 well signaled a higher probability of achieving HBsAg loss at week 72.     

进口与国产恩替卡韦治疗慢性乙型肝炎的效果评定

目的比较进口恩替卡韦片与国产恩替卡韦分散片治疗慢性乙型肝炎的疗效。方法选取我院慢性乙型肝炎患者98例,选取时间为2012年5月~2014年7月,将其随机分组,分别为对照组和观察组各49例,其中对照组患者采取进口恩替卡韦片治疗,观察组患者采取国产恩替卡韦分散片治疗,比较两组患者的平均血清HBV DNA下降水平、HBV DNA转阴率、ALT复常率以及治疗费用。结果两组慢性乙型肝炎患者治疗期间不同时期的HBV DNA下降水平无明显差异,且HBV DNA转阴率和ALT复常率与对照组患者对比,差异不明显(P0.05),但是,两组患者的治疗成本对比,观察组患者明显低于对照组患者(P0.05)。结论在对慢性乙型肝炎患者的治疗中,采用国产恩替卡韦分散片治疗疗效与采用进口恩替卡韦片治疗疗效相当,但国产恩替卡韦治疗成本低于进口恩替卡韦。     

恩替卡韦合水飞蓟宾治疗慢性乙型肝炎合并脂肪肝疗效观察

目的:探讨恩替卡韦联合水飞蓟宾治疗慢性乙型肝炎合并脂肪肝的临床疗效。方法:选取我院2017年4月～2018年6月收治的慢性乙型肝炎合并脂肪肝128例患者,以EXCEL随机函数法分为参照组和联合组各64例。参照组采取恩替卡韦治疗,联合组在此基础上增加水飞蓟宾治疗。观察两组患者临床疗效。结果:联合组治疗总有效率显著高于参照组(P0.05);治疗前,两组肝功能、血脂及肝纤维化各指标比较无显著性差异(P0.05);治疗后,两组肝功能、血脂及肝纤维化各指标均较治疗前改善,且联合组改善程度大于参照组(P0.05)。结论:恩替卡韦联合水飞蓟宾可有效改善慢性乙型肝炎合并脂肪肝患者临床症状及肝功能,并可稳定血脂水平,遏制肝纤维化进展,值得临床应用。     

恩替卡韦治疗对乙型肝炎肝硬化患者血清前白蛋白的影响研究

目的检测70例恩替卡韦治疗的乙型肝炎肝硬化患者血清前白蛋白(PA)水平,以探讨抗病毒治疗对PA水平的影响。方法采用免疫比浊法检测血清PA水平。结果肝硬化Child-Pugh A、B、C级基线PA水平呈递减趋势,均低于对照组血清PA水平(P0.01)。治疗24周58例HBV DNA阴性患者血清PA水平上升,治疗前后差异有统计学意义(P0.01)。结论血清PA含量可作为判断肝脏合成功能的有效指标,对评价肝硬化患者病情变化及预后判断具有重要的临床参考意义。恩替卡韦治疗可改善肝硬化患者血清PA水平。     

Increased Risk of New-Onset Fibromyalgia Among Chronic Osteomyelitis Patients: Evidence From a Taiwan Cohort Study

Chronic inflammation, which changes the neurotransmitter metabolism and kindles neuroendocrine system dysfunction in the central nervous system, might cause fibromyalgia (FM) formation. In FM patients without traditional FM risk factors, such as hypertension, hyperlipidemia, diabetes, sleep disorder, depression, and anxiety, the chronic inflammatory process is a possible risk factor for FM. Thus, we investigated whether chronic osteomyelitis (COM), a disease characterized by chronic inflammation, increases FM risk. Including data for 1 million enrollees, the Longitudinal Health Insurance Database was used, and 1,244 COM patients without FM history and 4,976 randomly selected sex- and age-matched control subjects without COM or FM history were extracted. The development of FM over a 13-year follow-up period from 1999 to 2011 was evaluated, and FM risk was estimated using the Cox proportional regression model. The aforementioned FM risk factors were more common in COM patients, who had a significantly greater FM risk than did the control subjects. Compared with those who had no associated risk factors, patients with COM had a greater FM risk than did the control subjects (adjusted hazard ratio [aHR] = 1.32, 95% confidence interval [CI], .99–1.75). Younger people had an even greater risk (age younger than 35 years: aHR = 1.58, 95% CI, 1.03–2.44; age 60 years or older: aHR = 1.03, 95% CI, .78–1.36). To our knowledge, this is the first study to link COM to an enhanced risk of FM development. The results imply that COM is a predictor of FM, suggesting that close follow-up for patients with COM is required to prevent FM, especially in younger populations.

Prior Exposure to Lamivudine Increases Entecavir Resistance Risk in Chronic Hepatitis B Patients without Detectable Lamivudine Resistance

The efficacy of entecavir (ETV) treatment in chronic hepatitis B (CHB) patients who were exposed to lamivudine (LAM) but had no detectable LAM resistance (LAM-R) is not well evaluated. In this study, we aimed to evaluate whether the probability of developing genotypic resistance to ETV in LAM-exposed patients with or without LAM-R is comparable to that in antiviral-naive patients. This retrospective cohort study included 500 consecutive patients with CHB who started ETV monotherapy at a single tertiary hospital in Korea. The patients were divided into three groups: nucleos(t)ide analogue (NA)-naive patients (group 1, n = 142), patients who were previously exposed to LAM and had no currently or previously detected LAM-R (group 2, n = 233), and patients with LAM-R when starting ETV (group 3, n = 125). The overall median ETV treatment duration was 48.7 months. The probabilities of virologic breakthrough were significantly increased not only in group 3 (hazard ratio [HR] = 14.4, P < 0.001) but also in group 2 (HR = 5.0, P < 0.001) compared to group 1. Genotypic ETV resistance (ETV-R) developed more frequently in group 2 (HR = 13.0, P = 0.013) as well as group 3 (HR = 43.9, P < 0.001) than in group 1: the probabilities of developing ETV-R in groups 1, 2, and 3 were <1.0%, 8.0%, and 28.2%, respectively, at month 48. The results of this study indicate that ETV-R occurred more frequently in LAM-exposed patients, even though they had no detectable LAM-R, than in NA-naive patients. Therefore, LAM-exposed CHB patients, regardless of the presence or absence of LAM-R, should be monitored more cautiously for the development of ETV-R during ETV monotherapy.     

乙肝肝硬化合并脾功能亢进患者行脾部分栓塞术后恩替卡韦治疗的效果分析

目的探讨行部分栓塞术后采用恩替卡韦治疗对乙型肝硬化合并脾亢进患者肝功能的影响。方法选取52例乙型肝炎肝硬化合并脾功能亢进患者为研究对象,随机分为对照组和观察组,每组26例。部分栓塞术后,对照组给予常规治疗,观察组在对照组治疗基础上联合恩替卡韦治疗,连续治疗72周。比较两组丙氨酸转氨酶(ALT)、天门冬氨酸氨基转移酶(AST)、总胆红素(TBil)、血清白蛋白(ALB)、HBV DNA转阴情况、HBe Ag/抗-HBe转阴情况、血清透明质酸(HA)、III型前胶原(PC-III)、IV型胶原(IV-C)。结果治疗后,观察组ALT、AST、TBi L、HA、PC-III及IV-C显著降低,ALB显著增高,与对照组比较具有统计学差异(P0.05)。观察组对照组患者HBe Ag/抗-HBe血清发生转换者分别为13例和2例,组间比较差异显著(P0.05)。观察组和对照组HBV-DNA转阴者分别为15、2例,组间比较差异显著(P0.05)。结论乙型肝炎肝硬化合并脾功能亢进患者行部分脾栓塞术后采用恩替卡韦治疗,可起到长期抗病毒作用,改善肝功能。     

慢性乙型肝炎患者应用拉米夫定治疗发生HBV YMDD变异的研究

目的 探讨慢性乙型肝炎（CHB）患者应用拉米夫定治疗发生HBV YMDD变异后与患者血清HBVDNA载量关系的临床意义.方法 选择46例应用拉米夫定治疗并发生HBV YMDD变异的CHB患者,另选择未发生HBV YMDD变异的CHB患者作对照组.探讨血清HBVDNA载量与HBV YMDD变异类型、变异发生时间的关系.结果 CHB患者接受拉米夫定治疗前,HBV YMDD变异组HBVDNA载量明显高于HBV YMDD未变异组（P〈0.01）.HBV YMDD变异类型（YVDD、YIDD、YVDD/YIDD）的分布与血清HBVDNA载量无相关性.HBVDNA载量与发生HBV YMDD变异的时间有相关性.随着HBVDNA载量的升高,发生HBV YMDD变异的时间越来越早.结论 应用荧光定量PCR方法检测血清HBVDNA载量和HBV YMDD变异,可动态观察CHB患者拉米夫定治疗后发生HBV YMDD变异的情况,对临床治疗和观察预后具有重要的临床意义.     

慢性乙型肝炎患者依从性现状的调查分析

目的了解慢性乙型肝炎（chronic hepatitis B，CHB）患者依从性现况，分析目前存在的主要问题，为今后护理工作提供科学依据。方法采用自行设计的一般资料调查问卷及依从性问卷对104例住院CHB患者的依从性进行调查。结果CHB患者抗病毒治疗、复查的依从率最低，分别为39．3％和42．3％；家人检查、提供病史、避免医嘱外用药的依从率分别为53．8％、61．5％和66．3％。结论CHB患者的依从性不佳，抗病毒治疗、复查的依从性应引起更多关注。     

High Risk of Gastrointestinal Hemorrhage in Patients With Epilepsy: A Nationwide Cohort Study

ObjectiveTo examine the association between epilepsy and gastrointestinal hemorrhage.Patients and MethodsWe conducted a nationwide retrospective cohort study by using data from Taiwan’s National Health Insurance Research Database. Patients 20 years and older newly diagnosed as having epilepsy and nonepileptic adults were identified between January 1, 2000, and December 31, 2003, and were observed through December 31, 2008. Cox proportional hazards models were performed to calculate adjusted hazard ratios (HRs) and 95% CIs of gastrointestinal hemorrhage associated with epilepsy.ResultsCompared with the nonepileptic group (n=449,541), epileptic patients (n=1412) had a higher incidence of gastrointestinal hemorrhage (13.4 vs 2.9 per 1000 person-years), with an HR of 2.97 (95% CI, 2.49-3.53). The HRs of gastrointestinal hemorrhage for patients with generalized epilepsy, inpatient care, emergency care, and frequent outpatient visits for epilepsy were 3.50 (95% CI, 2.59-4.72), 3.96 (95% CI, 2.85-5.50), 4.35 (95% CI, 3.15-6.01), and 4.96 (95% CI, 3.97-6.21), respectively. Risks were significantly higher in epileptic patients with mental disorders (HR, 3.20; 95% CI, 2.55-4.01), aged 70 years and older (HR, 4.08; 95% CI, 2.89-5.77), and in the first year after epilepsy (HR, 4.81; 95%, CI, 3.14-7.34).ConclusionEpilepsy is an independent determinant for gastrointestinal hemorrhage in a chronological and severity-dependent pattern. We urge the development of an adequate surveillance policy and strategy for the early prevention of gastrointestinal hemorrhage in epileptic patients.