酒精性肝硬化患者贫血特征分析
DOI: 10.3969/j.issn.1001-5256.2022.08.017
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摘要:
目的 探讨酒精性肝硬化患者贫血的实验室及临床特征。 方法 对2020年12月—2021年5月于首都医科大学附属北京佑安医院进行网织红细胞及全血细胞分析检测且贫血的住院患者进行研究,筛选出院诊断为酒精性肝硬化且无上消化道出血史及输血史的患者共106例作为研究对象,根据贫血的严重程度、贫血的细胞形态学分类、网织红细胞血红蛋白含量(Ret-He)回顾性分析其临床特征及影响因素。正态分布计量资料两组间比较采用独立样本t检验,多组间比较采用单因素方差分析,进一步两两比较采用SNK-q检验和LSD-t检验。偏态分布计量资料两组间比较采用Mann-Whitney U检验,多组间采用Kruskal-Wallis H检验。计数资料组间比较采用χ2检验。不同贫血分类标准与实验室指标及临床特征相关性采用Spearman相关分析。 结果 (1) 患者中男性103例(97.2%),平均年龄(55.07±10.18)岁,平均血红蛋白(Hb)(87.16±18.55)g/L,轻度贫血49例(46.2%)、中度贫血49例(46.2%)、重度贫血8例(7.5%);Ret-He为33.65(13.3~46.4)pg,≤29 pg者33例(31.1%),>29 pg者73例(68.9%);大细胞性贫血46例(43.4%)、正常细胞性贫血34例(32.1%)、单纯小细胞性贫血2例(1.9%)、小细胞低色素性贫血24例(22.6%)。腹水和/或腹腔感染87例(82.1%)、脾大和/或脾功能亢进82例(77.4%)、食管胃底静脉曲张65例(61.3%)、肝性脑病31例(29.2%)。(2)轻度贫血组Ret-He、平均红细胞体积(MCV)、平均红细胞血红蛋白含量(MCH)、平均红细胞血红蛋白浓度(MCHC)、血清铁(SI)、转铁蛋白饱和度(TS)明显高于对照组(中/重度贫血组)(P值均<0.05);Ret-He>29 pg比例(83.7% vs 56.1%)、正常细胞性贫血比例(44.9% vs 21.1%)均明显高于对照组(P值均<0.05);未饱和铁结合力(UIBC)、小细胞低色素性贫血比例(6.1% vs 36.8%)均明显低于对照组(P值均<0.05)。(3)大细胞性贫血组ALT、Hb、腹水和/或腹腔感染比例(91.3% vs 65.4%)均高于小细胞性贫血组,而重度贫血比例(2.2% vs 19.2%)、食管胃底静脉曲张比例(52.2% vs 84.6%)明显低于小细胞性贫血组(Pc值均<0.05);大细胞性贫血组AST、AST/ALT明显高于小细胞性贫血组及正常细胞性贫血组(Pc值均<0.05);小细胞性贫血组轻度贫血比例明显低于大细胞性贫血组及正常细胞性贫血组,而中度贫血比例明显高于正常细胞性贫血组(Pc值均<0.05)。大细胞性贫血组Ret-He、MCV、MCH、MCHC、SI、TS明显高于其他两组(Pc值均<0.05),而总铁结合力(TIBC)、UIBC明显低于其他两组(Pc值均<0.05)。(4)Ret-He≤29.00 pg患者组Hb、MCV、MCH、MCHC、SI、TS、轻度贫血比例、腹水和/或腹腔感染比例明显低于Ret-He>29 pg组(P值均<0.05),而UIBC、小细胞低色素性贫血比例、食管胃底静脉曲张比例明显高于Ret-He>29 pg组(P值均<0.05)。(5)Hb、Ret-He、MCV、MCH、MCHC、UIBC、SI、TS与贫血的严重程度、贫血的细胞形态学分类及铁缺乏有相关性(P值均<0.05);食管胃底静脉曲张、腹水和/或腹腔感染与贫血的细胞形态学分类及铁缺乏相关(P值均<0.05)。 结论 酒精性肝硬化失代偿期贫血程度以轻度、中度为主,大细胞性贫血和正常细胞性贫血常见。随着贫血程度的加深,铁缺乏的发生率增加;食管胃底静脉曲张、腹水和/或腹腔感染与贫血的细胞形态学分类及铁缺乏相关,临床应加强对此类患者缺铁性贫血的排查。 Abstract:Objective To investigate the laboratory and clinical features of anemia in patients with alcoholic liver cirrhosis. Methods A retrospective analysis was performed for the patients who were hospitalized in Beijing YouAn Hospital, Capital Medical University, from December 2020 to May 2021 and were found to have anemia based on reticulocyte hemoglobin (Hb) content (Ret-He) and whole blood cell analysis, and 106 patients with the discharge diagnosis of alcoholic liver cirrhosis who had no history of upper gastrointestinal bleeding or blood transfusion were screened out as subjects. Clinical features and related influencing factors were retrospectively analyzed based on the severity of anemia, the cytomorphological classification of anemia, and Ret-He. The independent samples t-test was used for comparison of normally distributed continuous data between two groups; a one-way analysis of variance was used for comparison between multiple groups, and the SNK-q test and the least significant difference t-test were used for further comparison between two groups. The Mann-Whitney U test was used for comparison of continuous data with skewed distribution between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups. The chi-square test was used for comparison of categorical data between groups. A Spearman correlation analysis was performed to investigate the correlation of different classification criteria for anemia with laboratory markers and clinical features. Results Among the 106 patients, there were 103 male patients (97.2%), with a mean age of 55.07±10.18 years and a mean Hb level of 87.16±18.55 g/L; there were 49 patients (46.2%) with mild anemia, 49 (46.2%) with moderate anemia, and 8(7.5%) with severe anemia; mean Ret-He was 33.65(13.3-46.4) pg, and there were 33 patients (31.1%) with ≤29 pg and 73 patients (68.9%) with Ret-He > 29 pg; among these patients, 46(43.4%) had macrocytic anemia, 34(32.1%) had normocytic anemia, 2(1.9%) had simple microcytic anemia, and 24 (22.6%) had microcytic hypochromic anemia; among these patients, 87(82.1%) had ascites and/or intra-abdominal infection, 82(77.4%) had splenomegaly and/or hypersplenism, 65(61.3%) had esophageal and gastric varices, and 31(29.2%) had hepatic encephalopathy. Compared with the control group (moderate/severe anemia), the mild anemia group had significantly higher Ret-He, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular-hemoglobin concentration (MCHC), serum iron (SI), and transferrin saturation (TS) (all P < 0.05), a significantly higher proportion of patients with Ret-He > 29 pg (83.7% vs 56.1%, P=0.002) or normocytic anemia (44.9% vs 21.1%, P=0.009), a significantly lower unsaturated iron-binding capacity (UIBC) (P < 0.05), and a significantly lower proportion of patients with microcytic hypochromic anemia (6.1% vs 36.8%, P < 0.05). Compared with the microcytic anemia group, the macrocytic anemia group had significantly higher alanine aminotransferase (ALT), Hb, and proportion of patients with ascites and/or intra-abdominal infection (91.3% vs 65.4%, Pc < 0.05) and a significantly lower proportion of patients with severe anemia (2.2% vs 19.2 %, Pc < 0.05) or esophageal and gastric varices (52.2% vs 84.6%, Pc < 0.05); the macrocytic anemia group had significantly higher aspartate aminotransferase (AST) and AST/ALT ratio than the microcytic anemia group and the normocytic anemia group (all Pc < 0.05); the microcytic anemia group had a significantly lower proportion of patients with mild anemia than the macrocytic anemia group and the normocytic anemia group, as well as a significantly higher proportion of patients with moderate anemia than the normocytic anemia group (all Pc < 0.05); compared with the other two groups, the macrocytic anemia group had significantly higher Ret-He, MCV, MCH, MCHC, SI, and TS (all Pc < 0.05) and significantly lower total iron-binding capacity (TIBC) and UIBC (all Pc < 0.05). Compared with the Ret-He > 29 pg group, the Ret-He ≤29 pg group had significantly lower Hb, MCV, MCH, MCHC, SI, TS, and proportion of patients with mild anemia or ascites and/or intra-abdominal infection (all P < 0.05), a significantly higher UIBC (P < 0.05), and a significantly higher proportion of patients with microcytic hypochromic anemia or esophageal and gastric varices (P < 0.05). Hb, Ret-He, MCV, MCH, MCHC, UIBC, SI, and TS were correlated with the severity of anemia, the cytomorphological classification of anemia, and iron deficiency (all P < 0.05), and esophageal and gastric varices and ascites and/or abdominal infection were correlated with the cytomorphological classification of anemia and iron deficiency (all P < 0.05). Conclusion The degree of anemia is mostly mild and moderate in the decompensated stage of alcoholic liver cirrhosis, and macrocytic anemia and normocytic anemia are more common. The incidence rate of iron deficiency increases with the severity of anemia, and esophageal and gastric varices and ascites and/or intra-abdominal infection are correlated with the cytomorphological classification of anemia and iron deficiency; therefore, it is necessary to enhance the monitoring of iron deficiency anemia in such patients in clinical practice. -
Key words:
- Liver Cirrhosis, Alcoholic /
- Anemia, Iron-Deficiency /
- Disease Attributes
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表 1 酒精性肝硬化贫血患者一般情况、实验室指标及临床特征
Table 1. Demographic, laboratory data, and clinical features of patients with alcoholic liver cirrhosis and anemia
项目 总体(n=106) 参考范围 男性[例(%)] 103(97.2) 年龄(岁) 55.07±10.18 ALT(U/L) 20(4~797) 9~50(男); 7~40(女) AST(U/L) 39(10~323) 15~40(男); 13~35(女) AST/ALT 2.06(0.41~7.75) Hb(g/L) 87.16±18.55 130~175(男);115~150(女) 贫血程度[例(%)] 轻度贫血 49(46.2) 中度贫血 49(46.2) 重度贫血 8(7.5) Ret-He(pg) 33.7(13.3~46.4) 30.3~36.0 Ret-He水平[例(%)] ≤29 pg 33(31.1) >29 pg 73(68.9) MCV(fL) 96.7(60.0~123.2) 82~100 MCH(pg) 33.3(16.7~43.1) 27~34 MCHC(g/L) 337(269~371) 316~354 TIBC(μmol/L) 38(13~67) 50~77(男); 54~77(女) UIBC(μmol/L) 24(1~62) 31~51 SI(μmol/L) 13(2~43) 10.6~36.7(男);7.8~32.2(女) TS(%) 34.78(4.26~97.62) 20~55 贫血的细胞形态学分类[例(%)] 大细胞性贫血 46(43.4) 正常细胞性贫血 34(32.1) 单纯小细胞性贫血 2(1.9) 小细胞低色素性贫血 24(22.6) 肝硬化并发症[例(%)] 脾大和/或脾功能亢进 82(77.4) 食管胃底静脉曲张 65(61.3) 腹水和/或腹腔感染 87(82.1) 肝性脑病 31(29.2) 表 2 酒精性肝硬化贫血患者不同贫血分类标准实验室及临床特征比较
Table 2. Comparison of laboratory and clinical characteristics of different anemia classification standards in patients with alcoholic liver cirrhosis and anemia
项目 贫血程度 贫血细胞形态 铁缺乏 轻度贫血(n=49) 中/重度贫血(n=57) 统计值 P值 大细胞性贫血(n=46) 正常细胞性贫血(n=34) 小细胞性贫血(n=26) 统计值 P值 Ret-He≤29 pg(n=33) Ret-He > 29pg(n=73) 统计值 P值 男性[例(%)] 47(95.9) 56(98.2) χ2=0.52 0.595 43(93.5) 34(100.0) 26(100.00) χ2=4.03 0.134 33(100.0) 70(95.9) χ2=1.40 0.550 年龄(岁) 56.35±11.20 53.96±9.18 t=1.20 0.232 54.07 ±11.25 57.50 ±8.91 57.50 + 9.82 F=0.81 0.498 58(35~68) 55(32~80) Z=-1.12 0.263 ALT(U/L) 22(6~797) 19(4~158) Z=-1.54 0.125 24(7~158) 19(4~797) 16(8~41)1) χ2=10.53 0.005 17(8~41) 22(4~797) Z=-1.54 0.125 AST(U/L) 46(20~323) 37(10~251) Z=-1.67 0.094 51(18~260) 36(10~323)1) 28(17~92)1) χ2=23.34 < 0.001 31(17~92) 43(10~323) Z=-1.67 0.094 AST/ALT 2.02(0.41~5.33) 2.07(1.00~7.75) Z=-0.00 0.997 2.40(1.02~4.85) 1.74(0.41~5.33)1) 1.77(1.00~7.75)1) χ2=9.07 0.011 1.80(1.07~7.75 2.18(0.41-5.33) Z=-0.00 0.997 Hb(g/L) 104(91~118) 73(48~90) Z=-8.85 < 0.001 92(48~118) 98(57~118) 68(56~97)1) χ2=27.19 < 0.001 75.64±16.64 92.37±17.04 t=-4.72 < 0.001 贫血程度[例(%)] 轻度贫血 / / 24(52.2) 22(64.7) 3(11.5)1)2) χ2= 17.91 < 0.001 8(24.2) 41(56.2) χ2=9.32 0.003 中度贫血 / / 21(45.7) 10(29.4) 18(69.2)2) χ2=9.41 < 0.001 20(60.6) 29(39.7) χ2=3.99 0.059 重度贫血 / / 1(2.2) 2(5.9) 5(19.2)1) χ2=7.13 0.028 5(15.2) 3(4.1) χ2=3.97 0.104 Ret-He(pg) 34.8(21.0~40.7) 31.1(13.3~46.4) Z=-2.55 0.011 37.6(29.6~46.4) 33.0(21.6~38.6) 20.9(13.3~32.1) χ2=65.85 0.009 21.8(13.3~28.9 36.1(29.3~46.4) Z=-2.55 0.011 Ret-He水平[例(%)] χ2=9.32 0.002 χ2=60.70 < 0.001 ≤29 pg 8(16.3) 25(43.9) 0 10(29.4) 23(88.5) / / > 29 pg 41(83.7) 32(56.1) 46(100.0) 24(70.6) 3(11.5) / / MCV(fL) 98.7(72.3~118.3) 90.5(60.0~123.2) Z=-2.29 0.022 104.9(97.6-123.2) 92.5(85.4~100.4) 75.4(60.0~87.3) χ2=89.99 < 0.001 80.3(60.0~100.4) 101.2(78.0~123.2) Z=-2.29 0.022 MCH(pg) 34.3(22.9~42.3) 29.4(16.7~43.1) Z=-2.47 0.014 37.0(33.7~43.1) 31.9(27.2-34.9) 22.5(16.7~26.7) χ2=89.26 < 0.001 24.5(16.7~33.4) 34.9(24.7~43.1) Z=-2.47 0.014 MCHC(g/L) 343(308~367) 332(269~371) Z=-3.28 0.001 346(324~371) 337(303~358) 295(269~332) χ2=60.69 < 0.001 297(269~335) 344(301~371) Z=-3.28 0.001 TIBC(μmol/L) 36(17~65) 40(13~67) Z=-0.48 0.633 30(13~52) 41.5(19~65) 47(31~67) χ2=36.47 < 0.001 47(22~67) 31(13~65) Z=-0.48 0.633 UIBC(μmol/L) 15(1~56) 34(2~62) Z=-2.62 0.009 4(1~31) 26(1~52) 43(24~62) χ2=55.73 < 0.001 42(2~62) 11(1~47) Z=-2.62 0.009 SI(μmol/L) 15(3~41) 7(2~43) Z=-4.43 < 0.001 19(4~43) 13(3~41) 3.5(2~11) χ2=48.38 < 0.001 5(2~20) 17(3~43) Z=-4.43 < 0.001 TS 56.52(5.08~97.62) 17.63(4.26~95.56) Z=-3.81 0.001 82.61(16.67~96.67) 35.45(5.45~97.62) 8.03(4.26~25.00) χ2=58.29 < 0.001 10.20(4.26~90.91) 60.36(6.98~97.62) Z=-3.81 < 0.001 贫血的细胞形态学分类[例(%)] 大细胞性贫血 24(49.0) 22(38.6) χ2= 1.16 0.282 / / / 0 46(63.0) χ2=36.74 < 0.001 正常细胞性贫血 22(44.9) 12(21.1) χ2=6.88 0.009 / / / 10(30.3) 24(32.9) χ2=0.07 0.826 单纯小细胞性贫血 0 2(3.5) χ2= 1.75 0.498 / / / 1(3.0) 1(1.4) χ2=0.34 0.528 小细胞低色素性贫血 3(6.1) 21(36.8) χ2= 14.20 < 0.001 / / / 22(66.7) 2(2.7) χ2=53.03 < 0.001 肝硬化并发症[例(%)] 脾大和/或脾功能亢进 34(69.4) 48(84.2) χ2=3.31 0.102 32(69.6) 28(82.4) 22(84.6) χ2=2.86 0.239 28(84.8) 54(74.0) χ2= 1.54 0.316 食管胃底静脉曲张 30(61.2) 35(61.4) χ2=0.00 1.000 24(52.2) 19(55.9) 22(84.6)1) χ2=8.00 0.018 26(78.8) 39(53.4) χ2=6.16 0.017 腹水和/或腹腔感染 39(79.6) 48(84.2) χ2=0.39 0.615 42(91.3) 28(82.4) 17(65.4)1) χ2=7.59 0.023 22(66.7) 65(89.0) χ2=7.73 0.012 肝性脑病 10(20.4) 21(36.8) χ2=3.44 0.087 17(37.0) 8(23.5) 6(23.1) χ2=2.34 0.311 8(24.2) 23(31.5) χ2=0.58 0.497 注:与大细胞性贫血组比较,1) Pc<0.05;与正常细胞性贫血组比较,2) Pc<0.05。 表 3 不同贫血分类标准与酒精性肝硬化贫血患者实验室指标及临床特征相关性
Table 3. Correlation of different classification criteria for anemia with laboratory parameters and clinical features in alcoholic liver cirrhosis patients with anemia
变量 贫血程度 贫血细胞形态学分类 铁缺乏(Ret-He≤29 pg) r值 P值 r值 P值 r值 P值 男性 0.070 0.476 0.179 0.066 -0.115 0.241 年龄 -0.109 0.265 0.050 0.614 -0.053 0.587 ALT -0.150 0.125 -0.316 0.001 0.239 0.014 AST -0.163 0.094 -0.471 <0.001 0.342 <0.001 AST/ALT <0.001 0.997 -0.282 0.003 0.186 0.057 Hb -0.864 <0.001 -0.345 <0.001 0.420 <0.001 Ret-He -0.249 0.010 -0.783 <0.001 0.802 <0.001 MCV -0.224 0.021 -0.926 <0.001 0.727 <0.001 MCH -0.241 0.013 -0.922 <0.001 0.754 <0.001 MCHC -0.320 0.001 -0.721 <0.001 0.752 <0.001 TIBC 0.049 0.635 0.616 <0.001 -0.542 <0.001 UIBC 0.267 0.008 0.760 <0.001 -0.699 <0.001 SI -0.453 <0.001 -0.684 <0.001 0.694 <0.001 TS -0.389 <0.001 -0.767 <0.001 0.730 <0.001 肝硬化并发症 脾大和/或脾功能亢进 0.177 0.070 0.158 0.106 -0.120 0.219 食管胃底静脉曲张 0.002 0.985 0.237 0.014 0.241 0.013 腹水和/或腹腔感染 0.060 0.541 -0.258 0.007 0.270 0.005 肝性脑病 0.180 0.065 -0.138 0.158 0.074 0.451 -
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