委縮性慢性心不全Ⅱ～Ⅳ機能分類患者における肝線維化指数の臨床的および検査室的関連性

[Clinical and laboratory associations of liver fibrosis indexes in patients with decompensated Chronic Heart Failure II-IV Functional Classes].

• S K Stolbova
• N A Dragomiretskaya
• I G Beliaev
• V I Podzolkov

抄録

研究の目的 NYHA 機能クラス II-IV 慢性心不全（CHF）患者における肝線維化指標の臨床的および検査室的関連性を研究する。全患者に肝疾患の徴候（身体検査での肝肥大±超音波データによる肝組織のびまん性変化）を認めた。平均年齢は70.59±10.71歳であった．一般臨床検査に加えて、肝線維症の重症度をFIB-4、APRI、MELD-XI、BARDという計算指標で評価した。すべての計算は、除圧性CHFの入院後2日以内に得られた検査データに基づいており、積極的な利尿剤の静脈内投与が開始された時点で行われた。結果 NYHA FC II-IV CHF患者では，NYHA FCの増加に伴ってFIB-4指数が有意に上昇した( р<0.05)．また、ほとんどの線維化指標で肝臓密度が高いことは、LV EFが<40"Zs_200A"%まで低下する確率と相関していた（FIB-4: RR, 1.32 at 95"Zs_200A"% CI 0.53～3.28, р=0.079; MELD-XI.RR, 1.62 at 95"Zs_200A"% CI 1.19～2.20, р=0.004; BARD: LVEF中央値, 42.5"Zs_200A"% vs. 56"Zs_200A"%, р=0.019)と心拍障害傾向が認められた(FIB-4: RR, 1．92 at 95"Zs_200A"% CI 0.75〜4.90、 р=0.218; BARD：RR, 1.09 at 95"Zs_200A"% CI 0.97〜1.22、 р=0.174; MELD-XI.RR, 1.34 at 95"Zs_200A"% CI 0.94～1.90, р=0.101)。肝線維化指標の増加は、血小板数の減少（FIB-4: р<0.01、APRI: р=0.045）やヘモグロビンの減少傾向（FIB-4: 127g/l vs. 137g/l、p=0.249、APRI: 127g/l vs. 136g/l、p=0.749）として明らかなように、CHF患者の他の多臓器障害と相関していました。肝密度の高い患者では、CKD-EPIで推定される糸球体濾過率（GFR）が60ml/min"Zs_200A"/"Zs_200A"1.73m2以下に低下することで心筋症候群と診断される頻度が高かった（FIB-4: р<0.03、MELD-XI: p=0.0001、BARD: р=0.005）。左室駆出率（LVEF）が温存・低下したCHF患者のサブグループにおける肝線維化指標を比較したところ、有意差が認められたのはMELD-XIのみであった（12.08 vs. 9.32, р=0.001）。BARD、FIB-4、MELD-XIでは、予後不良や重症度の他の予測因子（LV EF、NYHA FC、2型糖尿病の存在、慢性腎臓病、低GFR）の存在と高い計算結果が相関していた。肝線維症指標は、CHF患者の予後を評価するための新しい有望な指標であるが、十分に研究されていないため、最も適切な予後予測式を決定するためにさらなる研究が必要である。

Aim To study clinical and laboratory associations of hepatic fibrosis indexes in patients with decompensated NYHA functional class II-IV chronic heart failure (CHF).Material and methods The study included 128 patients admitted to the cardiological or therapeutic department of the University Clinical Hospital #4 at the I. M. Sechenov First Moscow State Medical University (Sechenov University) with symptoms of CHF associated with ischemic heart disease (IHD) and/or arterial hypertension (AH). All patients had signs of liver disease (liver enlargement on physical examination ± diffuse changes in hepatic tissue according to ultrasound data). Mean age was 70.59±10.71 years. Along with general clinical examination, severity of hepatic fibrosis was evaluated by calculated indexes, FIB-4, APRI, MELD-XI, and BARD. All calculations were based on laboratory data obtained within the first two days of hospitalization for decompensated CHF, at the onset of active therapy with intravenous diuretics. Statistical analyses were performed with the R programming language (3.6.1).Results In patients with NYHA FC II-IV CHF, the FIB-4 index significantly increased with the increase in NYHA FC (р&lt;0.05). Also, the high liver density by most fibrosis indexes correlated with the probability of LV EF decrease to &lt;40 % (FIB-4: RR, 1.32 at 95 % CI from 0.53 to 3.28, р=0.079; MELD-XI: RR, 1.62 at 95 % CI from 1.19 to 2.20, р=0.004; BARD: median LV EF, 42.5 % vs. 56 %, р=0.019), and a tendency to heart rhythm disorders was observed (FIB-4: RR, 1.92 at 95 % CI from 0.75 to 4.90, р=0.218; BARD: RR, 1.09 at 95 % CI from 0.97 to 1.22, р=0.174; MELD-XI: RR, 1.34 at 95 % CI from 0.94 to 1.90, р=0.101). Increases in liver fibrosis indexes correlated with other multiorgan disorders in CHF patients evident as a decrease in platelet count (FIB-4: р&lt;0.01; APRI: р=0.045) and a tendency to a decrease in hemoglobin (FIB-4: 127 g/l vs. 137 g/l, p=0.249; APRI: 127 g/l vs. 136 g/l, p=0.749). Patients with a high liver density more frequently had cardiorenal syndrome diagnosed by reduced glomerular filtration rate (GFR) estimated by CKD-EPI to less than 60 ml/min / 1.73 m2 (FIB-4: р&lt;0.03; MELD-XI: p=0.0001; BARD: р=0.005). In comparing liver fibrosis indexes in subgroups of CHF patients with preserved and reduced left ventricular ejection fraction (LV EF), significant differences were found only for MELD-XI (12.08 vs. 9.32, р=0.001).Conclusions For all studied indexes, correlations were observed with LV EF, decreases in hemoglobin, and incidence of heart rhythm disorders. For the BARD, FIB-4, and MELD-XI indexes, high results of calculations correlated with the presence of other predictors for unfavorable prognosis and disease severity (LV EF, NYHA FC, presence of type 2 diabetes mellitus, chronic kidney disease, and lower GFR). Liver fibrosis indexes are a new and promising but understudied instrument for evaluation of prognosis in CHF patients, which requires further study to determine most appropriate prognostic formulas.