胰腺炎與脂肪肝的關(guān)系探討

高 帆， 祁興順， 侯 悅， 郭曉鐘

(1 解放軍第二〇二醫(yī)院 醫(yī)務(wù)處， 沈陽 110003； 2 沈陽軍區(qū)總醫(yī)院 消化內(nèi)科， 沈陽 110840)

胰腺炎與脂肪肝的關(guān)系探討

高 帆1， 祁興順2， 侯 悅2， 郭曉鐘2

(1 解放軍第二〇二醫(yī)院 醫(yī)務(wù)處， 沈陽 110003； 2 沈陽軍區(qū)總醫(yī)院 消化內(nèi)科， 沈陽 110840)

胰腺炎系一種常見的、病死率高的消化系統(tǒng)疾病。臨床醫(yī)生常會(huì)遇到胰腺炎合并脂肪肝的患者。從脂肪肝在胰腺炎患者中的患病率、脂肪肝對(duì)胰腺炎預(yù)后的影響、妊娠急性脂肪肝誘發(fā)胰腺炎3個(gè)方面進(jìn)行了闡述，以探討胰腺炎與脂肪肝之間的關(guān)系。

胰腺炎； 脂肪肝； 預(yù)后

胰腺炎為常見的消化系統(tǒng)疾病[1-3]，其中急性胰腺炎的年發(fā)病率為13/10萬～45/10萬[4-5]，而慢性胰腺炎的年發(fā)病率為5/10萬～12/10萬[6-9]。在美國(guó)，急性胰腺炎居院內(nèi)死亡原因的第5位[2]；在英國(guó)，重癥急性胰腺炎的院內(nèi)死亡率可達(dá)15%～20%[10]。至今，國(guó)內(nèi)外專家已針對(duì)胰腺炎管理方面制訂了多部臨床實(shí)踐指南或共識(shí)[11-25]。胰腺炎的主要病因包括膽石癥、高三酰甘油血癥、酗酒等(表1)。目前，尚無指南或共識(shí)將脂肪肝列為胰腺炎的危險(xiǎn)因素或病因。然而，在臨床工作中，經(jīng)常會(huì)遇到胰腺炎合并脂肪肝的患者[26](圖1)。筆者通過PubMed及CNKI數(shù)據(jù)庫以“pancreatitis”及“fatty liver”或“胰腺炎”及“脂肪肝”作為檢索詞鑒定相關(guān)文獻(xiàn)，從脂肪肝在胰腺炎的患病率、脂肪肝對(duì)胰腺炎預(yù)后的影響、妊娠急性脂肪肝誘發(fā)胰腺炎3個(gè)主要方面進(jìn)行闡述，以探討胰腺炎與脂肪肝之間的關(guān)系。

1 脂肪肝在胰腺炎患者中的患病率

胰腺炎患者常伴有脂肪肝。有研究[27-34]報(bào)道了脂肪肝在不同類型胰腺炎患者中的患病率情況(表2)。根據(jù)急性胰腺炎的病因，高脂血癥性急性胰腺炎患者比非高脂血癥性急性胰腺炎患者有著更高的脂肪肝患病率[30-31,34]。相似地，急性胰腺炎伴有脂肪肝患者比無脂肪肝患者的甘油三酯水平更高[34]。這證明了在急性胰腺炎患者中血脂水平與脂肪肝之間的密切關(guān)系。此外，考慮到高脂血癥系急性胰腺炎的確切病因，似乎可以合理地推測(cè)脂肪肝也可能是胰腺炎的誘因。然而，最近的證據(jù)提示，在重度高脂血癥患者(甘油三酯≥1000 mg/dl)中，脂肪肝與急性胰腺炎的發(fā)生也許并無顯著關(guān)系。Tada等[29]回顧性分析了215例重度高脂血癥患者的臨床特征，急性胰腺炎患者中脂肪肝患病率為50%(6/12)，而無急性胰腺炎患者中脂肪肝患病率為55.7%(113/203)，兩組差異無統(tǒng)計(jì)學(xué)意義。然而，由于該研究?jī)H包括12例急性胰腺炎患者，且兩組間基線特征的均衡性不明，因此尚需進(jìn)一步大樣本研究來證實(shí)這一觀點(diǎn)。但該研究卻證實(shí)了血脂水平與急性胰腺炎風(fēng)險(xiǎn)呈正相關(guān)。急性胰腺炎患者較無急性胰腺炎患者有著更高的甘油三酯水平[(1872±1069)mg/dl vs (1440±625) mg/dl]，兩組差異有統(tǒng)計(jì)學(xué)意義(P=0.028)。Xiao等[32]通過分析50例急性胰腺炎患者的MR特征變化也發(fā)現(xiàn)，隨著急性胰腺炎患者的甘油三酯水平下降，MR所示脂肪肝的程度也有所改善。因此，脂肪肝對(duì)急性胰腺炎發(fā)生的影響可能是依賴于甘油三酯水平改變。根據(jù)急性胰腺炎的嚴(yán)重程度，重癥急性胰腺炎患者比非重癥急性胰腺炎患者有著更高的脂肪肝患病率。Xiao等[32]發(fā)現(xiàn)，重癥急性胰腺炎患者中脂肪肝患病率為100%，而輕度急性胰腺炎患者中脂肪肝患病率為59%。Xu等[34]研究發(fā)現(xiàn)，伴有脂肪肝的患者較無脂肪肝的患者更常發(fā)生中重度和重癥急性胰腺炎(30.42% vs 17.89%；15.83% vs 6.66%)；根據(jù)增強(qiáng)CT表現(xiàn)，伴有脂肪肝的患者也更常發(fā)生壞死型急性胰腺炎(38.33% vs 17.62%)。此外，脂肪肝的嚴(yán)重程度與急性胰腺炎的嚴(yán)重程度也密不可分。

圖1 急性胰腺炎合并脂肪肝的患者治療前后的CT比較 a,b: 入院時(shí)CT平掃，胸腔積液，肝周積液，急性胰腺炎，胰周滲出，脂肪肝(肝/脾CT值<1);c，d:治療后CT平掃，胸腔積液消失，肝周積液消失，空腸營(yíng)養(yǎng)管置入，胰周滲液吸收，脂肪肝程度降低(肝/脾CT值>1)

表1 胰腺炎指南或共識(shí)中提及的病因

表2 脂肪肝在胰腺炎患者中的患病率

注：1)胰腺疾病患者

慢性胰腺炎可導(dǎo)致胰頭部組織發(fā)生纖維化，進(jìn)而造成胰管與膽總管共同開口處局部梗阻及膽汁淤積，最終發(fā)生肝纖維化，甚至繼發(fā)性膽汁淤積性肝硬化。此外，酒精性慢性胰腺炎也可同時(shí)發(fā)生酒精性脂肪肝或肝硬化。脂肪肝在慢性胰腺炎患者中的患病率約為36.7%～72.0%。Beer等[27]通過應(yīng)用瞬時(shí)彈性成像技術(shù)評(píng)估54例慢性胰腺炎患者發(fā)現(xiàn)，酒精性慢性胰腺炎患者比特發(fā)性慢性胰腺炎有著更高的脂肪肝患病率，但差異無統(tǒng)計(jì)學(xué)意義。

2 脂肪肝對(duì)胰腺炎預(yù)后的影響

脂肪肝與急性胰腺炎預(yù)后有著密切的關(guān)系。Xu等[34]回顧性分析了2671例急性胰腺炎患者的臨床特征、并發(fā)癥以及病死率。急性胰腺炎伴有脂肪肝的患者較無脂肪肝的患者更常發(fā)生局部并發(fā)癥(22.08% vs 10.81%)、全身并發(fā)癥(40.42% vs 16.07%)、呼吸衰竭(34.38% vs 13.37%)、腎衰竭(11.46% vs 4.43%)、全身炎癥反應(yīng)綜合征(38.13% vs 17.89%)、感染(46.46% vs 37.7%)，差異均有統(tǒng)計(jì)學(xué)意義。更為重要的是，研究者也發(fā)現(xiàn)，脂肪肝與死亡也密切相關(guān)(6.46% vs 1.69%)?；谶@些研究結(jié)果，應(yīng)在急性胰腺炎患者入院時(shí)鑒定是否存在脂肪肝及其嚴(yán)重程度，以初步評(píng)估預(yù)后。未來研究也有必要進(jìn)一步探討脂肪肝作為單一預(yù)后因素或聯(lián)合傳統(tǒng)預(yù)后評(píng)分(Ranson、BISAP、APACHE等)的價(jià)值。

3 妊娠期急性脂肪肝與胰腺炎

妊娠期并發(fā)急性胰腺炎已被廣泛報(bào)道，其發(fā)病率為1/1000～1/3000，其主要誘因與非妊娠期急性胰腺炎相似。相比之下，妊娠期急性脂肪肝與急性胰腺炎的關(guān)系少有報(bào)道。

妊娠期急性脂肪肝常發(fā)生在妊娠晚期，發(fā)病率為1/7000～1/16 000，孕婦病死率為7%～18%，胎兒病死率為9%～23%[35-37]。長(zhǎng)鏈-3-羥酰基輔酶A脫氫酶及其相關(guān)編碼基因突變可導(dǎo)致胎兒線粒體脂肪酸β氧化缺陷，進(jìn)而增加妊娠期急性脂肪肝發(fā)病風(fēng)險(xiǎn)。此病常在并發(fā)癥出現(xiàn)時(shí)才得以診斷。主要的并發(fā)癥包括肝性腦病、低血糖、腎衰竭、彌漫性血管內(nèi)凝血、先兆子癇等。目前，也有學(xué)者[38-45]報(bào)道了妊娠期急性脂肪肝誘發(fā)急性胰腺炎的個(gè)案(表3)。其可能的發(fā)病機(jī)制包括：(1)妊娠期雌激素增加，繼而導(dǎo)致高脂血癥；(2)孕激素增加，繼而導(dǎo)致脂肪酶及胰蛋白酶分泌增加，同時(shí)可導(dǎo)致Oddi氏括約肌痙攣和胰管壓力過低；(3)免疫因素[42]。Moldenhauer等[46]對(duì)15例妊娠期急性脂肪肝誘發(fā)急性胰腺炎患者進(jìn)行分析顯示，平均孕婦年齡為26.3歲(21～37歲)；以持續(xù)性惡心、嘔吐為主要臨床表現(xiàn)；11例患者伴有淀粉酶升高，另外1例患者伴有脂肪酶升高；8例行影像學(xué)檢查的患者中，7例患者存在胰腺炎的影像學(xué)表現(xiàn)；主要合并疾病包括腦病、急性呼吸窘迫綜合征、腎衰竭；孕婦病死率為17%(2/15)。

表3 妊娠期急性脂肪肝誘發(fā)胰腺炎的個(gè)案匯總

4 結(jié)語

脂肪肝在胰腺炎患者中較常見，且可增加胰腺炎相關(guān)并發(fā)癥的發(fā)生風(fēng)險(xiǎn)及病死率。另外，雖然妊娠期急性脂肪肝誘發(fā)的胰腺炎罕見，但一旦發(fā)生，患者預(yù)后極差。因此，臨床醫(yī)生應(yīng)加強(qiáng)對(duì)脂肪肝與胰腺炎之間關(guān)系的認(rèn)識(shí)，積極防治脂肪肝也許有助于降低胰腺炎的發(fā)病風(fēng)險(xiǎn)并改善預(yù)后。

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(本文編輯：葛 俊)

Association between pancreatitis and fatty liver disease

GAOFan,QIXingshun,HOUYue,etal.

(MedicalDepartment, 202HospitalofPLA,Shenyang110003,China)

Pancreatitis is a common digestive disease with a high mortality rate. Clinical physicians often encounter patients with pancreatitis and fatty liver disease. This article investigates the association between pancreatitis and fatty liver disease from the aspects of the prevalence of fatty liver disease in patients with pancreatitis, the influence of fatty liver disease on the prognosis of pancreatitis, and pancreatitis induced by acute fatty liver disease during pregnancy.

pancreatitis； fatty liver； prognosis

10.3969/j.issn.1001-5256.2017.01.008

2016-10-11；

2016-11-19。作者簡(jiǎn)介：高帆(1982-)，女，主要從事內(nèi)科診療研究。

祁興順，電子信箱：xingshunqi@126.com；郭曉鐘，電子信箱：guoxiaozhong1962@126.com。

R576； R575.5

A

1001-5256(2017)01-0040-06