Feline Hepatic Lipidosis  貓脂肪肝症

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Keywords  關鍵字

Feline
Hepatic lipidosis
Cats
Liver
Triglyceride
Obesity
VLDL
TG

貓肝脂質沉積症貓咪肝臟三酸甘油脂肥胖極低密度脂蛋白三酸甘油脂

Key points  重點摘要

  • •
    The primary metabolic abnormalities leading to triglyceride (TG) accumulation in the hepatocytes are not yet completely understood.
  • •
    The presumptive diagnosis of feline hepatic lipidosis (FHL) is based on patient history, clinical presentation, clinicopathologic findings, and ultrasonographic appearance of the liver; however, history and clinical and clinicopathologic presentation are not specific for lipidosis and any underlying disease process can confound them.
  • •
    Nutrition should be initiated on the day of admission to reverse the negative energy balance and catabolic state typical of FHL; early nutrition is the cornerstone of treatment in FHL.

Introduction  引言

Feline hepatic lipidosis (FHL), the most common hepatobiliary disease in cats,1, 2, 3, 4, 5 is characterized by the accumulation of excessive triglycerides (TGs) in more than 80% of the hepatocytes, resulting in a greater than 50% increase in liver weight,2, 6, 7 secondary impairment of liver function, and intrahepatic cholestasis.2, 6, 8, 9 A specific geographic distribution of the disease has been suggested based on the available reports of FHL from different areas, including North America, Great Britain, Japan, and Western Europe. The higher prevalence of FHL in these areas might be secondary to feeding habits of cat owners and a high incidence of obesity in the feline population.1
貓咪肝臟脂肪沉積症（FHL）是貓最常見的肝膽疾病 1,2,3,4,5，其特徵為超過 80%的肝細胞內堆積過多三酸甘油酯（TGs），導致肝臟重量增加超過 50%2,6,7，繼發肝功能損害及肝內膽汁淤積 2,6,8,9。根據北美、英國、日本和西歐等地區的 FHL 報告顯示，本病可能具有特定地理分布特徵。這些地區 FHL 較高的盛行率，可能與飼主的餵養習慣及貓群體中肥胖發生率較高有關。 1
The pathophysiology of FHL is complex. The primary metabolic abnormalities leading to TG accumulation in the hepatocytes are not yet completely understood, but they could consist of alterations of the pathways of uptake, synthesis, degradation, and secretion of fatty acids (FAs).
FHL 的病理生理學機制相當複雜。導致肝細胞內 TG 堆積的主要代謝異常尚未完全明瞭，但可能涉及脂肪酸（FAs）的攝取、合成、降解和分泌途徑的改變。
Nonetheless, the variability in reported historical, physical, and clinicopathologic findings in cats with naturally occurring hepatic lipidosis (HL) suggests that this is a syndrome with many causative factors.
然而，自然發生肝臟脂肪沉積症（HL）的貓隻在病史、體徵和臨床病理學表現上的差異性顯示，這是一種由多種致病因素引起的症候群。
A negative energy balance, usually caused by anorexia, is considered the primary cause for initiating FHL. In an experimental model of FHL, lipidosis occurs within 2 weeks of the development of anorexia.8, 10 In a clinical setting, FHL has been seen to develop after a period of anorexia that ranges from 2 to 14 days.1, 6 FHL is classified as primary or secondary. In primary FHL, anorexia occurs in a healthy animal secondary to decreased food availability, administration of nonpalatable food,7, 8 or decreased food intake secondary to a stressful event. Secondary lipidosis occurs in animals that develop anorexia as a consequence of underlying disease. Secondary lipidosis is the most common form of lipidosis described, occurring in approximately 95% of cases. The diseases associated with the development of lipidosis are numerous and include diabetes mellitus, pancreatitis, inflammatory hepatobiliary disease, gastrointestinal disease, renal failure, and neoplasia.1, 2
負能量平衡（通常由厭食症引起）被認為是引發貓肝脂質沉積症（FHL）的主要原因。在 FHL 的實驗模型中，厭食症發展後 2 週內就會出現脂質沉積現象[8,10]。臨床觀察顯示，FHL 通常在厭食持續 2 至 14 天後發生[1,6]。FHL 可分為原發性和繼發性兩類：原發性 FHL 發生於原本健康的動物，起因於食物獲取減少、餵食不適口食物[7,8]或壓力事件導致的進食量下降；繼發性脂質沉積則發生於因潛在疾病而產生厭食症狀的動物。臨床上約 95%病例屬於繼發性脂質沉積，這是最常見的形式。可能引發脂質沉積的相關疾病眾多，包括糖尿病、胰臟炎、炎症性肝膽疾病、胃腸道疾病、腎衰竭及腫瘤性疾病等[1,2]。
Because the cat is a pure a carnivore, its lipid and protein metabolism11, 12, 13, 14 make it dependent on obligatory essential FAs (EFAs), amino acids, and vitamins, which become deficient after a period of prolonged anorexia. These deficiencies are considered important cofounding factors for the development of FHL.2, 12
由於貓是純肉食性動物，其脂質與蛋白質代謝 11,12,13,14 使其必須依賴必需脂肪酸(EFAs)、胺基酸及維生素，這些營養素在長期厭食後會出現缺乏。這些缺乏被認為是發展成貓肝性脂肪沉積症(FHL)的重要混雜因素。2,12
The development of HL after a period of anorexia has also been described in other strict carnivores, such as the European polecat (Mustela putorius) and the American mink (Neovison vison).15, 16 The in-depth study of the pathophysiologic mechanisms behind the development of HL in these other obligated carnivores could help better understand the pathophysiology of FHL in cats.
在嚴格肉食性動物如歐洲艾鼬(Mustela putorius)與美洲水貂(Neovison vison)中，也觀察到厭食後發展出肝性脂肪沉積症(HL)的情況。15,16 深入研究這些強制性肉食動物發生 HL 的病理生理機制，將有助於更深入了解貓 FHL 的病理生理學。

Pathophysiology  病理生理學

Due to evolutionary pressure, cats have developed unique adaptations of lipid and protein metabolism reflecting a strict carnivorous state,12, 13, 14, 17, 18, 19 which has an impact on cats’ requirements for EFA and essential amino acids.2, 13, 20 Like other mammals, cats are unable to synthesize EFAs, like linoleic acid (18:2n-6) and α-linoleic acid (18:3n-3). In addition, unlike other mammals, cats have a limited capacity to synthesize the long-chain polyunsaturated FA (LCPUFA), arachidonic acid (AA) (20:4n-6) from linoleic acid, and eicosapentaenoic acid (20:3n-3) and docosahexaenoic acid (22:6n-3) from α-linoleic acid (18:3n-3). The explanation for this peculiarity is that cats have a severely decreased activity of the enzymes Δ5-desaturase and Δ6-desaturase, enzymes involved in the formation of LCPUFA from EFA.21, 22, 23, 24 Recently, Trevizan and colleagues11 revealed that cats have an active Δ5-desaturase and that they are able to synthetize AA from γ-linolenic acid via bypassing the Δ6-desaturase step but not in an amount allows them to store this LCPUFA in condition of anorexia.
由於演化壓力，貓科動物發展出獨特的脂質與蛋白質代謝適應機制，反映出其嚴格的肉食性特質[12,13,14,17,18,19]，這也影響了貓對必需脂肪酸(EFA)及必需胺基酸的需求[2,13,20]。與其他哺乳動物相同，貓無法自行合成必需脂肪酸，如亞油酸(18:2n-6)和α-亞麻酸(18:3n-3)。此外，與其他哺乳動物不同的是，貓從亞油酸合成長鏈多元不飽和脂肪酸(LCPUFA)、花生四烯酸(AA)(20:4n-6)的能力有限，也難以從α-亞麻酸(18:3n-3)合成二十碳五烯酸(20:3n-3)和二十二碳六烯酸(22:6n-3)。這種特殊性是因為貓體內參與從 EFA 形成 LCPUFA 的Δ5-去飽和酶與Δ6-去飽和酶活性嚴重降低[21,22,23,24]。近期 Trevizan 與研究團隊 11 發現，貓雖具有活躍的Δ5-去飽和酶，能透過繞過Δ6-去飽和酶步驟從γ-亞麻酸合成花生四烯酸，但在厭食狀態下仍無法合成足夠量來儲存這類 LCPUFA。
LCPUFAs are involved in numerous processes. Increased levels of LCPUFAs are well known to protect against the development of HL via the so-called fuel partitioning action of LCPUFA.25, 26 LCPUFAs, n-3 LCPUFA species (ie, docosahexaenoic acid) rather than the n-6 LCPUFA (ie, AA), favor FA oxidation over TG storage and they direct glucose away from FA synthesis by facilitating glycogen synthesis.27, 28 LCPUFAs down-regulate sterol regulatory element binding protein-1 expression and impair its processing, resulting in an inhibition of the transcription of lipogenic and glycolytic genes.28, 29, 30 Furthermore, n-3 LCPUFA species act as ligand activators of the peroxisome proliferator-activated receptor-α (PPAR-α) present in liver and adipose tissue, up-regulating the expression of genes encoding enzymes involved in FA oxidation.28, 31
長鏈多元不飽和脂肪酸（LCPUFAs）參與多種生理過程。已知增加 LCPUFAs 水平可通過所謂的「燃料分配作用」有效預防肝脂質沉積症（HL）的發生[25,26]。其中，n-3 系列 LCPUFAs（如二十二碳六烯酸）相較於 n-6 系列（如花生四烯酸），更能促進脂肪酸氧化而非三酸甘油酯儲存，並通過促進肝醣合成使葡萄糖遠離脂肪酸合成途徑[27,28]。LCPUFAs 會下調固醇調節元件結合蛋白-1 的表現量並干擾其加工過程，從而抑制脂肪生成與糖解相關基因的轉錄[28,29,30]。此外，n-3 系列 LCPUFAs 可作為過氧化物酶體增殖物激活受體-α（PPAR-α）的配體激活劑，該受體存在於肝臟與脂肪組織中，能上調參與脂肪酸氧化的酶類編碼基因表現[28,31]。
Cats possess limited ability to adapt their protein metabolic pathways for conserving nitrogen and they rapidly develop essential amino acid deficiency and protein malnutrition after a period of prolonged anorexia. In both experimentally induced and spontaneous FHL, plasma concentrations of alanine, arginine, citrulline, taurine, and methionine become markedly reduced (>50% reduction from baseline).2, 12, 32
貓咪調節蛋白質代謝途徑以保存氮的能力有限，在經歷長期厭食後會迅速出現必需胺基酸缺乏和蛋白質營養不良。無論是實驗誘發或自發性貓肝脂質沉積症(FHL)中，血漿中的丙胺酸、精胺酸、瓜胺酸、牛磺酸和甲硫胺酸濃度都會顯著降低(較基準值下降>50%)。2, 12, 32
Cats with FHL show changes in carbohydrate metabolism that resemble those seen in critically ill cats. Cats with HL, compared with healthy subjects, have higher circulating concentrations of glucose, lactate, glucagon, and nonesterified FAs (NEFAs) and have lower circulating concentrations of insulin.33, 34
患有 FHL 的貓咪會出現類似重症貓咪的碳水化合物代謝變化。與健康貓相比，FHL 病貓的血液中葡萄糖、乳酸、升糖素和非酯化脂肪酸(NEFAs)濃度較高，而胰島素濃度較低。33, 34
Although the exact pathophysiologic mechanism of FHL remains elusive, there is an imbalance between the influx of NEFAs derived from peripheral fat stores, de novo synthesis of FAs, the rate of hepatic FA oxidation for energy, and the dispersal of hepatic TGs via excretion of very low-density lipoproteins (VLDLs).
雖然 FHL 確切的病理生理機制仍不明確，但已知周邊脂肪組織釋放的非酯化脂肪酸(NEFAs)流入、脂肪酸的從頭合成、肝臟脂肪酸氧化供能的速率，以及透過極低密度脂蛋白(VLDLs)排泄肝臟三酸甘油酯(TGs)的過程之間存在失衡現象。

Influx of Free Fatty Acid from Peripheral Fat Stores
周邊脂肪組織釋放的游離脂肪酸流入

FHL is considered a negative energy balance state and it is characterized by increased circulating concentrations of the counter-regulatory hormones (glucagon, growth hormone, cortisol, and catecholamines) that lead to an increased activity of hormone-sensitive lipase, promoting lipolysis and mobilization of NEFAs from the visceral adipose tissue (VAT). Increased levels of counter-regulatory hormones and decreased circulating concentrations of insulin lead to increased hormone-sensitive lipase activity, resulting in decreased lipogenesis, increased peripheral insulin resistance by decreased activity of the glucose transport protein-4, and impaired glucose tolerance.35 High concentrations of circulating free FAs (FFAs) also contribute to peripheral insulin resistance.1, 2, 36, 37
貓咪肝臟脂肪沉積症（FHL）被視為一種負能量平衡狀態，其特徵在於對抗調節激素（升糖素、生長激素、皮質醇和兒茶酚胺）的循環濃度增加，這些激素會導致激素敏感性脂肪酶活性增強，促進內臟脂肪組織（VAT）中非酯化脂肪酸（NEFAs）的分解與動員。對抗調節激素水平升高與胰島素循環濃度降低共同導致激素敏感性脂肪酶活性增加，進而造成脂肪生成減少、周邊胰島素阻抗增加（因葡萄糖轉運蛋白-4 活性降低）以及葡萄糖耐受不良。 35 高濃度的循環游離脂肪酸（FFAs）也會加劇周邊胰島素阻抗。1, 2, 36, 37
NEFAs are released from the adipose tissue and transported to the liver via the portal circulation. The predominant lipid that accumulates within the hepatocyte is TG.4 A higher concentration of palmitate (16:0) was found in liver tissue from cats with FHL compared with control subjects that mirrored the increased concentrations of palmitate in the adipose tissue of the same animals.4 This finding confirmed the hypothesis that FFAs in livers of cats with FHL are derived from VAT.2, 4, 12, 33 Besides adipose tissue being the major site for storage of excess energy as TGs during a positive energy balance state, it has also an important endocrine function by secreting multiple adipokines, including adiponectin, leptin, chemokines, and cytokines.38, 39 These adipokines are involved in energy homeostasis and inflammation and might be responsible for the development of peripheral insulin resistance.38, 39, 40 Common inflammatory cytokines reported to be elevated in obese cats compared with lean individuals are tumor necrosis factor α and interleukin.41, 42 Adiponectin exerts a profound insulin-sensitizing effect as well as anti-inflammatory and antiatherosclerotic effects. Leptin is a regulator of adipose tissue mass and regulates insulin sensitivity.39 The adipose tissue of FHL cats had markedly increased tumor necrosis factor α concentrations compared with that of healthy subjects.43 In cats with FHL, both the serum concentrations of adiponectin and leptin were found increased compared with healthy subjects, but only leptin was significantly increased in cats with FHL compared with cats with other liver diseases.39 Obesity predisposes cats to FHL during a period of anorexia, because of the quantity of FAs that can be rapidly released from peripheral fat stores and VAT, release of inflammatory adipokines from the adipose tissue, and the insulin resistance associated with obesity.1, 2, 37, 42, 44
非酯化脂肪酸（NEFAs）從脂肪組織釋放後，通過門脈循環運輸至肝臟。肝細胞內積累的主要脂質為三酸甘油脂（TG）。 4 與對照組相比，罹患貓肝脂質沉積症（FHL）的貓隻肝臟組織中棕櫚酸（16:0）濃度較高，此現象與相同動物脂肪組織中棕櫚酸濃度增加的情況相符。 4 此發現證實了假說：FHL 貓隻肝臟中的游離脂肪酸（FFAs）源自內臟脂肪組織（VAT）2,4,12,33。除了作為正向能量平衡狀態下以三酸甘油脂形式儲存過剩能量的主要場所外，脂肪組織還具有重要的內分泌功能，能分泌多種脂肪激素，包括脂聯素、瘦素、趨化因子和細胞因子 38,39。這些脂肪激素參與能量穩態和炎症反應，並可能是周邊胰島素阻抗發展的原因 38,39,40。與瘦貓相比，肥胖貓常見升高的炎症細胞因子包括腫瘤壞死因子α和白細胞介素 41,42。脂聯素具有顯著的胰島素增敏作用，以及抗炎和抗動脈粥樣硬化效應。 瘦素是脂肪組織質量的調節因子，並能調節胰島素敏感性。 39 與健康貓相比，FHL 貓的脂肪組織中腫瘤壞死因子α濃度顯著增加。 43 研究發現，與健康貓相比，FHL 貓的血清脂聯素和瘦素濃度均有所上升，但與其他肝病貓相比，僅有瘦素在 FHL 貓中顯著增加。 39 肥胖會使貓在厭食期間更容易發生 FHL，這是由於周邊脂肪儲存和內臟脂肪組織能快速釋放大量游離脂肪酸、脂肪組織釋放促炎性脂肪因子，以及肥胖相關的胰島素阻抗所導致。1, 2, 37, 42, 44

De Novo Lipogenesis  新生脂肪生成

De novo lipid (DNL) synthesis in cats occurs mainly in the adipose tissue, followed by the liver, mammary glands, and muscle. This differs from human and rodents where the liver is the primary site for DNL synthesis.45, 46, 47 Although glucose is the precursor for DNL in humans, in cats acetate resulting from incomplete FA oxidation (ie, ketogenesis), typically increased in FHL, is the substrate for the formation of the FFA palmitate (16:0).2, 36, 46, 48 Palmitate is found both in the adipose tissue and liver of cats with FHL, whereas it is not in healthy cats.4 It cannot be ruled out that palmitate accumulation is the result of the de novo lipogenesis contributing to HL. Similarly in the mink, an animal that has metabolic similarities with the domestic cat,19, 46 DNL from acetate in HL may be accompanied by the adipogenic transformation of hepatocytes, as is seen in human nonalcoholic fatty liver disease (NAFLD), where the liver begins to express gene profiles characteristic of healthy adipose tissue.46, 49, 50 To date, the concept of adipogenic transformation of hepatocytes has not been evaluated in cats.
貓科動物的從頭合成脂質(DNL)主要發生在脂肪組織，其次才是肝臟、乳腺和肌肉。這與人類和囓齒類動物以肝臟為主要 DNL 合成部位的情況不同[45,46,47]。雖然葡萄糖是人類 DNL 的前驅物，但在貓體內，由脂肪酸不完全氧化(即酮體生成)產生的乙酸鹽(在 FHL 中通常會增加)才是形成游離脂肪酸棕櫚酸酯(16:0)的基質[2,36,46,48]。在患有 FHL 的貓隻中，棕櫚酸酯同時存在於脂肪組織和肝臟，而健康貓隻則未見此現象。 4 不能排除棕櫚酸酯的堆積是導致脂肪肝的從頭脂肪生成之結果。類似情況也出現在與家貓具有代謝相似性的貂類動物中[19,46]，在脂肪肝狀態下由乙酸鹽進行的 DNL 可能伴隨肝細胞的脂肪化轉變，這與人類非酒精性脂肪肝疾病(NAFLD)中所觀察到的現象相似，即肝臟開始表現出健康脂肪組織特有的基因譜[46,49,50]。截至目前，關於貓科動物肝細胞脂肪化轉變的概念尚未被評估。
Once having reached the liver, FFAs can enter 2 pathways: either they undergo β-oxidation in the mitochondria or they can be esterified to TG and secreted via the VLDL pathway.
一旦進入肝臟，游離脂肪酸(FFAs)可進入兩條代謝途徑：一是在粒線體中進行β-氧化，或是被酯化為三酸甘油脂(TG)並透過極低密度脂蛋白(VLDL)途徑分泌。

Hepatic β-Oxidation  肝臟β-氧化作用

Mitochondrial β-oxidation is the main oxidative pathway for the disposal of FA under normal physiologic conditions.51 Short-chain NEFAs and medium-chain NEFAs freely enter the mitochondria, whereas the activity of the enzyme carnitine palmitoyl transferase-1 regulates the entry of the long-chain FAs. Oxidation of FA produces acetyl coenzyme A, which can be used to provide energy via the tricarboxylic acid (Krebs) cycle to provide energy and/or to form ketone bodies. l-Carnitine is part of the 2 enzymes that regulate transport of FA from the circulation into the mitochondria and from the hepatic cytosol back into plasma.
在正常生理條件下，粒線體β-氧化是脂肪酸(FA)分解代謝的主要途徑。 51 短鏈非酯化脂肪酸(NEFAs)和中鏈非酯化脂肪酸可自由進入粒線體，而長鏈脂肪酸的進入則受到肉鹼棕櫚醯轉移酶-1 活性的調控。脂肪酸氧化會產生乙醯輔酶 A，可透過三羧酸循環(克氏循環)提供能量，或形成酮體。L-肉鹼是調節脂肪酸從循環系統進入粒線體，以及從肝細胞質返回血漿的兩種酶組成部分。
Ketone body formation is increased in cats with FHL, suggesting an enhanced rate of β-oxidation of FA.1, 2, 32, 36, 37 It is unknown, however, if the rate of β-oxidation is adapted to compensate for the greatly increased FA accumulation in the hepatocytes.
患有貓肝脂質沉積症(FHL)的貓隻體內酮體生成增加，顯示脂肪酸β-氧化的速率提升。1, 2, 32, 36, 37 然而，目前尚不清楚β-氧化速率是否已適應性增加，以補償肝細胞中大幅增加的脂肪酸累積。
The increase of ketone bodies in cases of lipidosis is most likely the result of the more complex catabolic state, increased insulin resistance, and decreased tolerance to glucose that develops in these patients than being the result of an increased rate of β-oxidation.12, 34, 36
在脂肪肝病例中酮體的增加，更可能是由於這些患者發展出更複雜的分解代謝狀態、胰島素阻抗增加以及葡萄糖耐受性降低所導致，而非β-氧化速率增加的結果。12, 34, 36
In human medicine, abnormal β-oxidation from mitochondrial dysfunction has been suggested and reported as a potential cause for lipid accumulation in hepatocytes during NAFLD.51 Center and colleagues52 reported that in FHL hepatocyte mitochondria were reduced in number and markedly abnormal, suggesting that mitochondrial dysfunction could also occur in FHL.
在人體醫學中，已有研究提出並報告線粒體功能障礙導致的異常β-氧化，可能是非酒精性脂肪肝(NAFLD)期間肝細胞中脂肪堆積的潛在原因。 51 Center 及其同事 52 報告指出，貓脂肪肝(FHL)的肝細胞線粒體數量減少且明顯異常，這表明線粒體功能障礙也可能發生於貓脂肪肝中。
There is a lot of discussion about the role of carnitine in FHL. Because l-carnitine is essential for the transportation of FA into the mitochondria, l-carnitine deficiency has been proposed as one of the main pathophysiologic mechanisms for the accumulation of FAs in the liver.2, 32, 53, 54 Measurement of l-carnitine concentrations in different tissues (liver, kidney, and blood) from cats affected with FHL, however, failed to support this hypothesis.53, 55, 56 On the other hand, there is also evidence that supplementation of l-carnitine in experimental lipidosis dramatically reduces hepatic lipid accumulation57 and increases the rate of β-oxidation in obese cats.53, 54, 58 Furthermore, a protective effect of l-carnitine was demonstrated in fasting cats and in cats with HL where supplementation of l-carnitine reduced the increase of plasma FA concentrations compared with control cats.53 Therefore, it is possible that in a situation of anorexia and an increased catabolic state tissue concentrations of l-carnitine are insufficient to meet demand and supplementation might be beneficial.
關於肉鹼在貓肝脂質沉積症(FHL)中所扮演的角色有許多討論。由於左旋肉鹼對於脂肪酸(FA)進入粒線體的運輸過程至關重要，因此左旋肉鹼缺乏被認為是導致肝臟中脂肪酸累積的主要病理生理機制之一[2,32,53,54]。然而，對患有 FHL 的貓隻不同組織(肝臟、腎臟和血液)中左旋肉鹼濃度的測量結果並未支持這一假說[53,55,56]。另一方面，也有證據表明，在實驗性脂質沉積症中補充左旋肉鹼能顯著減少肝臟脂質累積[0]，並提高肥胖貓隻的β-氧化速率[53,54,58]。此外，研究證實左旋肉鹼對禁食貓隻和患有肝脂質沉積症的貓具有保護作用，補充左旋肉鹼能減少血漿脂肪酸濃度的上升，與對照組貓隻相比有顯著差異[1]。因此，在厭食和分解代謝狀態加劇的情況下，組織中的左旋肉鹼濃度可能不足以滿足需求，此時補充左旋肉鹼可能具有益處。
Methionine is an essential amino acid fundamental for numerous methylation reactions and an important thiol donor involved in the synthesis of glutathione. Glutathione is an important oxygen free radical scavenger and is involved in the hepatocellular protection against oxidative injury and its hepatic concentrations are reduced in cats with liver disease.59 Because methionine and its coenzyme S-adenosylmethionine together are precursors of carnitine, methionine deficiency might contribute to inefficient levels of l-carnitine.2, 12, 32, 55
甲硫胺酸是一種必需胺基酸，對於眾多甲基化反應至關重要，同時也是合成穀胱甘肽的重要硫醇供體。穀胱甘肽作為重要的氧自由基清除劑，能保護肝細胞免受氧化損傷，而在患有肝病的貓隻體內，其肝臟中的穀胱甘肽濃度會降低。由於甲硫胺酸及其輔酶 S-腺苷甲硫胺酸共同構成肉鹼的前體物質，甲硫胺酸缺乏可能導致左旋肉鹼水平不足。

Dispersal of Hepatic Triglycerides via Very Low-Density Lipoprotein Excretion
透過極低密度脂蛋白排泄來分散肝臟三酸甘油酯

Once in the hepatocyte, NEFAs can be esterified to TG. TGs usually accumulate in vacuoles within hepatocytes or can be incorporated into VLDLs to be excreted into the peripheral circulation.
非酯化脂肪酸進入肝細胞後，可被酯化為三酸甘油酯。三酸甘油酯通常會積聚在肝細胞內的液泡中，或可被整合入極低密度脂蛋白後分泌至外周循環系統。
Rapid onset of protein malnutrition and deficiency of essential amino acids are thought to be important pathophysiologic mechanisms for the development of FHL. A lack of apolipoprotein B100, a major component of the VLDL, was proposed as a reason for the diminished ability to excrete TGs from the liver.3, 6 Cats with HL, however, are known to have increased levels of TG in plasma, with greatest distribution in the VLDL fraction (approximately 62% vs 25% in healthy, lean cats),60 and increased serum concentrations of VLDL, with the VLDL fraction representing approximately 19% of the total lipoprotein mass compared with 2% in healthy lean cats. This suggests that VLDL secretion seems enhanced and not deficient in FHL.20, 60, 61, 62 Despite hepatic VLDL secretion increased in cats with FHL, this increase might not be sufficient to prevent the lipid overload of hepatocytes, in face of a dramatic increase of NEFA transport to the liver.
快速發生的蛋白質營養不良與必需胺基酸缺乏被認為是發展出貓肝性脂肪沉積症(FHL)的重要病理生理機制。曾有研究提出缺乏極低密度脂蛋白(VLDL)的主要成分載脂蛋白 B100，是肝臟排出三酸甘油酯(TG)能力下降的原因[3,6]。然而已知患有肝性脂肪沉積症的貓隻，其血漿中 TG 水平會升高，且主要分布在 VLDL 部分(約 62%，健康瘦貓為 25%)，血清 VLDL 濃度也會增加，VLDL 部分約佔總脂蛋白質量的 19%(健康瘦貓僅 2%)。這顯示在 FHL 中 VLDL 的分泌似乎是增強而非缺乏[20,60-62]。儘管患有 FHL 的貓隻肝臟 VLDL 分泌增加，但在非酯化脂肪酸(NEFA)向肝臟運輸量急劇增加的情況下，這種增加可能仍不足以防止肝細胞的脂質超載。
Arginine and taurine deficiency in cats with FHL could also compromise lipid metabolism and excretion of TG via the VLDL excretion pathway. Arginine is an important urea cycle substrate, and arginine deficiency has been associated with the development of hyperammonemia and hepatic encephalopathy (HE) in cats with FHL.63, 64 Taurine deficiency has been shown to increase lipolysis in peripheral tissues and has been linked to secondary accumulation of NEFAs in the liver.12, 65 Supplementation of taurine in experimental cats during initial weight gain followed by weight loss was associated with decreased hepatic lipid accumulation.12, 62
貓隻罹患貓肝脂質沉積症(FHL)時，精胺酸與牛磺酸的缺乏可能進一步損害脂質代謝，並影響透過極低密度脂蛋白(VLDL)途徑的三酸甘油酯(TG)排泄。精胺酸是尿素循環的重要基質，研究顯示 63,64，FHL 病貓若缺乏精胺酸，可能導致高氨血症與肝性腦病變(HE)的發生。此外，牛磺酸缺乏會促進周邊組織的脂解作用，文獻 12,65 指出這與肝臟中非酯化脂肪酸(NEFAs)的二次堆積有關。實驗研究 12,62 發現，在貓隻體重初始增加後又減輕的過程中補充牛磺酸，可減少肝臟脂質的累積。
As discussed previously, HL in the American mink and the European polecat, other obligatory carnivores, shares numerous clinical, clinicopathologic, and pathophysiologic characteristics with FHL in domestic cats.16, 46, 48, 66, 67 Both the American mink and the European polecat have been used as animal models to investigate the pathophysiology of NAFLD in people.16 In the American mink and European polecat, FA data of various adipose tissue depots and liver tissue showed a decrease in the n-3 LCPUFAs.16, 48, 67, 68, 69 The depletion of n-3 PUFAs during food deprivation could be partly due to the mechanisms of selective FA mobilization: the location of the first double bond from the methyl end affects the fractional mobilization of LCPUFAs and n-3 substrates are often preferred over n-6 ones in FA desaturation reactions and β-oxidation.70 The decrease in n-3 LCPUFAs causes an increase in the n-6/n-3 PUFA ratio. NAFLD in human seems to be the result of an unfavorable n-6/n-3 PUFA ratio, with an increase in the n-6 LCPUFAs.26, 27 n-3 LCPUFAs are more potent activators of the PPAR-α receptors than n-6 LCPUFAs, and a depletion of n-3 PUFA has been proposed to favor FA and TG synthesis over hydrolysis and FA oxidation and may impair lipid export from the liver by suppressing VLDL secretion.28, 48 An increase in the n-6 LCPUFA concentration in response to food deprivation has been associated with increased inflammation and oxygen free radical formation and n-6 LCPUFAs are considered a key contributor to the pathophysiology and progression of liver steatosis in NAFLD, in the American mink and in the European polecat.16, 27, 28, 48 A lower concentration of both total n-6 and total n-3 PUFAs was noted in adipose tissue of cats with FHL compared with controls. The n-6/n-3 PUFA ratio was not statistically assessed, but a study from Hall and colleagues4 suggest that a derangement in the n-6/n-3 PUFA ratio might occur in FHL compared with healthy control cats.
如先前所述，美洲水貂與歐洲艾鼬（同為專性肉食動物）所患的肝脂質沉積症（HL），與家貓的貓肝脂質沉積症（FHL）在臨床表現、臨床病理學及病理生理學特徵上具有高度相似性。16, 46, 48, 66, 67 這兩種動物已被用作研究人類非酒精性脂肪肝病（NAFLD）病理機制的動物模型。 16 研究顯示，美洲水貂與歐洲艾鼬的脂肪組織儲存庫及肝臟組織中，n-3 長鏈多元不飽和脂肪酸（LCPUFAs）含量均呈現下降趨勢。16, 48, 67, 68, 69 禁食期間 n-3 多元不飽和脂肪酸（PUFAs）的耗損，可能部分源自脂肪酸選擇性動員機制：甲基末端首個雙鍵的位置會影響 LCPUFAs 的分餾動員效率，且在脂肪酸去飽和反應與β-氧化過程中，n-3 底物通常較 n-6 底物更易被優先利用。 70 此 n-3 LCPUFAs 的減少將導致 n-6/n-3 PUFA 比例上升。 人類的非酒精性脂肪肝疾病(NAFLD)似乎是由不利的 n-6/n-3 多元不飽和脂肪酸(PUFA)比例所導致，其中 n-6 長鏈多元不飽和脂肪酸(LCPUFAs)增加。26,27 n-3 LCPUFAs 比 n-6 LCPUFAs 更能有效激活 PPAR-α受體，而 n-3 PUFA 的耗竭被認為會促進脂肪酸(FA)和三酸甘油酯(TG)的合成而非水解與脂肪酸氧化，並可能通過抑制極低密度脂蛋白(VLDL)分泌來損害肝臟的脂質輸出。28,48 食物匱乏導致的 n-6 LCPUFA 濃度增加與炎症反應加劇和氧自由基形成有關，且 n-6 LCPUFAs 被認為是 NAFLD、美洲水貂和歐洲艾虎肝臟脂肪變性病理生理學和進展的關鍵因素。16,27,28,48 與對照組相比，FHL 貓咪的脂肪組織中總 n-6 和總 n-3 PUFAs 濃度均較低。雖然未對 n-6/n-3 PUFA 比例進行統計學評估，但 Hall 及其同事的研究 4 表明，與健康對照貓相比，FHL 貓可能出現 n-6/n-3 PUFA 比例失調的情況。
Due to the limiting nature of the Δ5-desaturase and especially Δ6-desaturase activities, the LCPUFA status, especially the n-3 LCPUFA status, of domestic cats may be severely compromised during food deprivation and/or rapid weight loss contributing to the pathogenesis of FHL.
由於Δ5-去飽和酶（尤其是Δ6-去飽和酶）活性的限制特性，家貓在禁食和/或快速減重期間的長鏈多元不飽和脂肪酸（LCPUFA）狀態（特別是 n-3 LCPUFA 狀態）可能會嚴重受損，這促進了貓肝脂質沉積症（FHL）的發病機制。
Recently, research has been performed in experimental animals and in humans on the immunomodulatory role of circulating bile acids and on their role in suppressing the hypothalamic-pituitary-adrenal (HPA) axis. In humans, the link between critical illness–related corticosteroid insufficiency (CIRCI) and high circulating bile acid concentrations has been established.71, 72 High levels of circulating conjugated or unconjugated bile acids in critical illness has been shown to inhibit glucocorticoids metabolizing enzyme and to inhibit the release of corticotropin-releasing hormone and corticotropin from the HPA axis.71, 72, 73 The hallmark of CIRCI is hemodynamic instability that manifests itself as refractory hypotension despite fluid resuscitation and levels of corticosteroids that are insufficient for the severity of the underlying illness.74, 75 To evaluate if CIRCI also is present in cats with cholestasis, a pilot study was performed.76 Basal serum cortisol and delta cortisol (the difference between basal and postcorticotropin cortisol) concentrations were evaluated in 20 cats with cholestasis. Cats with refractory hypotension had a lower mean delta cortisol than cats with normal blood pressure, but this was not statistically significant.76 From human medicine, however, it is known that delta cortisol is not a specific indicator of the HPA axis and adrenal function because it does not take into consideration cortisol breakdown and its availability at the cellular level.72 Therefore, CIRCI should be suspected in a subpopulation of cats with FHL and refractory hypotension.
近期研究已在實驗動物和人體中探討循環膽酸的免疫調節作用及其對下視丘-腦下垂體-腎上腺軸(HPA 軸)的抑制作用。在人體研究中，已證實危重症相關皮質類固醇不足(CIRCI)與高循環膽酸濃度之間的關聯性[71,72]。研究顯示，危重症時高濃度的結合型或非結合型循環膽酸會抑制糖皮質激素代謝酶，並阻礙 HPA 軸釋放促腎上腺皮質激素釋放激素和促腎上腺皮質激素[71,72,73]。CIRCI 的典型特徵是血流動力學不穩定，表現為即使進行液體復甦仍持續頑固性低血壓，且皮質類固醇水平不足以應對潛在疾病的嚴重程度[74,75]。為評估膽汁淤積貓咪是否也存在 CIRCI，我們進行了一項先導研究。 76 研究測量了 20 隻膽汁淤積貓的基礎血清皮質醇濃度及Δ皮質醇濃度(基礎與促腎上腺皮質激素刺激後皮質醇的差值)。 患有頑固性低血壓的貓隻，其平均皮質醇變化值(delta cortisol)低於血壓正常的貓隻，但此差異未達統計學顯著意義。 76 然而根據人類醫學研究已知，皮質醇變化值並非下視丘-腦下垂體-腎上腺軸(HPA axis)與腎上腺功能的特異性指標，因其未考量皮質醇代謝分解及細胞層級的可用性。 72 因此，對於部分罹患貓肝脂質沉積症(FHL)且合併頑固性低血壓的貓群，應懷疑可能併發腎上腺皮質功能不全相關之危象(CIRCI)。

Historical and clinical findings
病史與臨床發現

Although FHL is mainly reported in middle-aged cats (median age 7 years), cats of any age can be affected.1, 2, 6 There seems to be no clear breed or gender predilection, although in some studies female cats seem to be overrepresented.6, 33 Actual (body condition 4/5) or historical obesity has been mentioned by several investigators as a predisposing factor for the development of FHL.1, 2, 4, 6, 12 Cats affected with HL present with a history of anorexia and weight loss. Other reported clinical signs include icterus, dehydration, vomiting, nausea and ptyalism, constipation or diarrhea, and a poor hair coat (Figs. 1 and 2).2, 6 The mentation of cats with FHL can be severely altered if hypokalemia HE are present. In cats with FHL, HE is associated with arginine deficiency and can be worsened by hypokalemia and decreased liver function, which further impairs the urea cycle.63, 64, 77 Cats with HE can present with severe mental depression, ptyalism, and severe nausea.2, 6, 78 The plasma ammonia concentration should be measured in patients with severely altered mental states. Ammonia tolerance testing is not recommended in cats with FHL.2 Ventroflexion of the neck, often seen in cats with FHL, and severe muscle weakness can be secondary to the concurrent presence of severe hypokalemia.
雖然貓咪肝性脂肪沉積症(FHL)主要發生於中年貓(中位年齡 7 歲)，但任何年齡的貓都可能患病。1,2,6 目前似乎沒有明確的品種或性別偏好，不過某些研究中雌性貓的比例似乎較高。6,33 多位研究者指出，實際肥胖(體況評分 4/5)或曾有肥胖病史是發展 FHL 的誘發因素。1,2,4,6,12 罹患 FHL 的貓會出現厭食和體重減輕的病史。其他報告的臨床症狀包括黃疸、脫水、嘔吐、噁心和流涎、便秘或腹瀉，以及被毛狀況不良(圖 1 和圖 2)。2,6 若同時存在低鉀血症和肝性腦病(HE)，FHL 病貓的精神狀態可能嚴重改變。在 FHL 病貓中，HE 與精胺酸缺乏有關，並可能因低鉀血症和肝功能下降而惡化，這會進一步損害尿素循環。63,64,77 患有 HE 的貓可能表現出嚴重精神抑鬱、流涎和劇烈噁心。2,6,78 對於精神狀態嚴重改變的病患應測量血漿氨濃度。不建議對 FHL 病貓進行氨耐受性測試。 2 頸部腹側屈曲（常見於患有 FHL 的貓隻）以及嚴重的肌肉無力，可能是由於同時存在嚴重低鉀血症所導致的繼發性症狀。
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Fig. 1. Cat with FHL. Note the visible icterus of (A) skin and (B) sclera and (C) poor kept hair coat.
圖 1. 患有 FHL 的貓隻。請注意(A)皮膚和(B)鞏膜可見的黃疸，以及(C)被毛狀態不佳。

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Fig. 2. Ptyalism secondary to nausea in a cat with FHL.
圖 2. 一隻患有 FHL 的貓因噁心導致的繼發性流涎症狀。

Serum biochemistry  血清生化檢查

FHL is characterized by an increased bilirubin concentration and increased serum activities of alkaline phosphatase and alanine aminotransferase compared with healthy cats and cats with other liver disease (ie, cholangitis).2, 6, 79 Hyperglycemia is often present and is due to insulin resistance and an increase in the counter-regulatory hormones.2, 34, 37 Hypoglycemia, when present, indicates severely decreased or even end-stage liver function.
與健康貓隻和其他肝臟疾病（如膽管炎）的貓相比，FHL 的特徵是膽紅素濃度升高以及鹼性磷酸酶和丙氨酸氨基轉移酶的血清活性增加[2,6,79]。高血糖經常出現，這是由於胰島素抗性和反調節激素增加所致[2,34,37]。當出現低血糖時，則表示肝功能嚴重下降甚至已進入終末期。
Mild hypoalbuminemia is often reported in FHL secondary to anorexia and decreased hepatic function. Blood urea nitrogen was found decreased in 51% of cats as consequence of chronic anorexia and/or insufficient urea-cycle function.1, 2, 6 Commonly reported electrolyte alterations include hypokalemia (30% of cats with FHL), hypomagnesemia (28%), and hypophosphatemia (17%) that can be present at admission or can develop after administration of fluid therapy to correct dehydration.6 Hypokalemia and hypophosphemia have been associated with an increased morbidity and mortality in FHL.6 Hypokalemia can increase the encephalopathic effects of ammonia and cause muscle weakness, paralytic ileus, and anorexia; hypophosphatemia can cause severe hemolysis resulting in the need for a blood transfusion.1, 2, 6 Cats with HL often have higher serum concentrations of β-hydroxybutyric acid (BHBA) compared with normal cats as reflection of their negative energy balance.10, 36, 60 High serum BHBA concentrations are the result of stimulation of the increased lipolysis with mobilization of NEFA, leading to increased hepatic β-oxidation and production of ketone bodies. Clinical signs associated with increased serum BHBA concentrations are usually vague and include anorexia, lethargy, cachexia, and weight loss. Serum BHBA has been suggested as a marker for FHL.36
輕微的低白蛋白血症常見於因厭食症和肝功能下降所繼發的貓肝脂質沉積症(FHL)。研究顯示 51%的貓咪因長期厭食和/或尿素循環功能不足而出現血尿素氮降低現象[1,2,6]。常見的電解質異常包括低鉀血症(30% FHL 病貓)、低鎂血症(28%)及低磷血症(17%)，這些症狀可能在入院時即存在，也可能在進行輸液治療糾正脫水後出現[0]。低鉀血症和低磷血症與 FHL 的發病率和死亡率增加有關[1]。低鉀血症會加劇氨的腦病效應，導致肌肉無力、麻痺性腸梗阻和厭食；低磷血症可能引發嚴重溶血而需輸血治療[1,2,6]。與健康貓相比，FHL 病貓血清中β-羥基丁酸(BHBA)濃度通常較高，反映其負能量平衡狀態[10,36,60]。高血清 BHBA 濃度是脂解作用增強、非酯化脂肪酸(NEFA)動員的結果，進而導致肝臟β-氧化作用增強及酮體生成增加。 與血清 BHBA 濃度升高相關的臨床症狀通常不明顯，包括厭食、嗜睡、惡病質和體重減輕。血清 BHBA 已被建議作為貓肝脂質沉積症(FHL)的標記物。 36

Hematology  血液學檢查

The complete blood cell count (CBC) is often normal in cats with FHL, but, in some cases, a mild nonregenerative anemia and mild leukocytosis might be present. Underlying inflammatory, infectious, or neoplastic disease could result in an inflammatory leukogram. Heinz bodies can be detected on blood smear evaluation both on admission and during recovery.1, 2, 6 Thrombocytopenia does not occur frequently in cats with HL, unless they are suffering from disseminated intravascular coagulation.6, 33, 80, 81, 82, 83, 84
患有貓肝脂質沉積症(FHL)的貓隻，其全血細胞計數(CBC)通常正常，但在某些情況下可能出現輕度非再生性貧血和輕度白血球增多。潛在的炎症、感染或腫瘤疾病可能導致炎症性白血球像。在入院時和恢復期間的血塗片評估中均可檢測到海因茨小體。1, 2, 6 除非貓隻患有瀰漫性血管內凝血，否則血小板減少症在 HL 貓中並不常見。6, 33, 80, 81, 82, 83, 84

Tests of coagulation  凝血功能檢測

Coagulation abnormalities and clinical bleeding tendencies are reported to be common (45%–73%) in cats with FHL, especially during venipuncture or catheter placement or if invasive procedures, such as esophageal feeding tube placement or liver biopsy, are performed.2, 81, 82, 83 Lisciandro and colleagues83 reported that prolongation of prothrombin time was the most common abnormality (found in 77% of cats with FHL), whereas factor VII activity was reduced in 68% and activated partial thromboplastin time was prolonged in 55% in a population of cats affected with liver disease. In a study by Center and colleagues82 in cats with HL, 75% had increased proteins invoked by vitamin K absence clotting times, whereas only a minimal percentage had prolonged prothrombin time or activated partial thromboplastin time (4% and 25%, respectively). More recently, Dircks and colleagues81 found that 40% of cats affected with liver disease had a significant prolongation of the activated partial thromboplastin time compared with healthy cats. Protein C was also decreased in 44% of cats with liver disease, whereas fibrinogen was increased compared with health controls. No significant difference was found for vitamin K–dependent clotting factors (II, VII, IX, and X) between healthy controls and cats with liver disease.
據報導，凝血功能異常和臨床出血傾向在患有貓肝脂質沉積症(FHL)的貓咪中相當常見(45%-73%)，特別是在靜脈穿刺、導管放置或進行侵入性程序(如食道餵食管放置或肝臟活檢)時。Lisciandro 及其同事 83 的研究指出，凝血酶原時間延長是最常見的異常(在 77%的 FHL 貓咪中發現)，而在患有肝病的貓群體中，68%出現第七凝血因子活性降低，55%出現活化部分凝血活酶時間延長。Center 及其同事 82 在針對 HL 貓咪的研究中發現，75%的貓咪維生素 K 缺乏誘導蛋白凝固時間增加，而僅有極少比例出現凝血酶原時間或活化部分凝血活酶時間延長(分別為 4%和 25%)。最近 Dircks 及其同事 81 的研究顯示，40%患有肝病的貓咪與健康貓咪相比，其活化部分凝血活酶時間顯著延長。此外，44%的肝病貓咪出現蛋白 C 降低，而纖維蛋白原則較健康對照組升高。 健康對照組與患有肝病的貓隻之間，在維生素 K 依賴性凝血因子（II、VII、IX 和 X）方面未發現顯著差異。
The most consistent abnormalities in cats with FHL were an increased factor V activity and D-dimer concentrations, with 54% of cats having values above the reference range for both parameters. Furthermore, 31% of cats with FHL had a severely decreased factor XIII (fibrin stabilizing factor) activity.81 Not only decreased production but also activation of hemostasis with secondary increased consumption of coagulation factors could be responsible for the bleeding tendencies of patients with FHL.
FHL 貓隻最一致的異常是因子 V 活性增加和 D-二聚體濃度升高，54%的貓隻這兩項參數值均高於參考範圍。此外，31%的 FHL 貓隻出現因子 XIII（纖維蛋白穩定因子）活性嚴重降低。 81 不僅是凝血因子生成減少，止血系統的活化伴隨繼發性凝血因子消耗增加，都可能是導致 FHL 患者出血傾向的原因。

Diagnosis of feline hepatic lipidosis
貓肝脂質沉積症的診斷

The presumptive diagnosis of FHL is based on patient history, clinical presentation, clinicopathologic findings, and ultrasonographic appearance of the liver. History and clinical and clinicopathologic presentation, however, are not specific for lipidosis and any underlying disease process can confound them.
FHL 的推定診斷基於患者病史、臨床表現、臨床病理學檢查結果及肝臟超音波影像特徵。然而，病史與臨床及臨床病理學表現對脂肪肝並不具特異性，任何潛在疾病過程都可能使這些表現複雜化。
On ultrasound examination, the liver in cats with FHL appears enlarged and diffusely hyperechoic liver compared with the falciform fat.78 Using these criteria, abdominal ultrasound performed by 3 board-certified radiologists had an accuracy of 70% for diagnosing lipidosis in cats.85 Comparable ultrasonographic findings of a diffusely hyperechoic liver can be found in healthy obese cats.86
超音波檢查中，罹患貓脂肪肝症候群(FHL)的貓隻肝臟會呈現腫大，且與鐮狀脂肪相比呈現瀰漫性高回音性。 78 根據這些標準，由 3 位委員會認證放射科醫師執行的腹部超音波檢查，對貓脂肪肝診斷準確率達 70%。 85 類似的瀰漫性高回音肝臟超音波表現也可見於健康的肥胖貓隻。 86
The definitive diagnosis is usually made by cytologic evaluation of a fine-needle aspirate and in some cases by histologic evaluation of a liver biopsy.1, 2, 87, 88, 89 Cytology of the liver has been advocated because it is considered a safer procedure. It often does not require general anesthesia and it is associated with few minor complications compared with liver biopsy.1, 2, 88, 90 The hallmark of lipidosis on cytology is the presence of steatosis, which can be macrovesicular or microvesicular.1, 2, 52 Although vacuolar hepatopathy was the category with the highest percentage of agreement between liver cytology and liver histology, only 51% of feline cases had overall agreement between cytologic and histologic diagnosis of FHL.87 Furthermore, Willard and colleagues89 reported 4 cases of cats diagnosed with FHL based on cytology where the underlying liver disease (cholangitis or lymphoma) was missed. Cats that are sick tend to accumulate lipid in their liver, often mimicking FHL, and for this reason a definitive diagnosis of FHL can only be made when greater than 80% of the hepatocytes are affected.2, 6
確診通常需透過細針抽吸的細胞學檢查，部分病例則需進行肝臟活檢的組織學評估。1,2,87,88,89 由於被認為是較安全的程序，肝臟細胞學檢查常被推薦採用。該檢查通常無需全身麻醉，且與肝臟活檢相比僅伴隨極少輕微併發症。1,2,88,90 細胞學上診斷脂肪肝的關鍵特徵是肝細胞脂肪變性（steatosis），可分為大泡型（macrovesicular）或小泡型（microvesicular）。1,2,52 雖然空泡性肝病變（vacuolar hepatopathy）在肝臟細胞學與組織學診斷一致性最高，但僅 51%的貓病例在細胞學與組織學對 FHL 的診斷結果完全一致。 87 此外，Willard 及其研究團隊 89 曾報告 4 例經細胞學診斷為 FHL 的貓病例，其潛在肝臟疾病（膽管炎或淋巴瘤）卻被漏診。病貓肝臟常會出現脂肪堆積現象而易與 FHL 混淆，因此唯有當超過 80%的肝細胞受影響時，才能確診為 FHL。2,6
Liver biopsy requires general anesthesia and assessment of a patient’s hemostatic system (see Jonathan A. Lidbury’s article, “Getting the Most Out of Liver Biopsy,” in this issue). Thrombocytopenia (<80,000 platelets/μL) and elevated activated partial thromboplastin time (>1.5 times the upper limit of the reference range) were the 2 reported abnormalities that had the strongest association with severe bleeding.91 Furthermore, liver biopsy collection using Tru-Cut rapid-firing automatic biopsy needles has been associated with the development of vagotonic shock in cats, characterized by bradycardia and cardiovascular collapse up to 30 minutes after the biopsy was performed.90 These are the reasons why a majority of investigators do not recommend liver biopsies as the initial tool to diagnose FHL. Cats with FHL present a series of cardiovascular, metabolic, and coagulation derangements that make them unsuitable for undergoing general anesthesia and liver biopsy.
肝臟活檢需要全身麻醉並評估患者的止血系統（請參閱本期 Jonathan A. Lidbury 的文章《如何充分利用肝臟活檢》）。血小板減少症（<80,000 血小板/μL）和活化部分凝血活酶時間延長（>參考值上限 1.5 倍）是報告中與嚴重出血最具相關性的兩項異常指標。 91 此外，使用 Tru-Cut 快速自動活檢針採集肝臟活檢樣本，可能導致貓咪發生迷走神經性休克，其特徵為心搏過緩和心血管衰竭，最長可在活檢後 30 分鐘內發生。 90 這些是多數研究者不建議將肝臟活檢作為診斷貓肝脂質沉積症(FHL)首選工具的原因。患有 FHL 的貓會出現一系列心血管、代謝和凝血功能異常，使牠們不適合接受全身麻醉和肝臟活檢。
Liver biopsy should be considered in subjects that despite appropriate treatment fail to improve or if they have a history, clinical finding, or clinicopathologic findings suggestive of a possible underlying hepatic disease other than HL.1, 2
對於儘管接受適當治療仍未改善，或具有病史、臨床發現或臨床病理學檢查結果提示可能存在除肝脂質沉積症(HL)外其他潛在肝臟疾病的病患，應考慮進行肝臟活檢。1, 2
The use of non–contrast-enhanced CT has been advocated in human medicine as a more reliable and repeatable method for the detection fatty hepatic infiltration in patients with NAFLD compared with cytologic and histologic assessment of the liver.92, 93 Fatty infiltration of organs is associated with x-ray attenuation on CT94 and level of attenuation of adipose tissue in human medicine is inversely correlated with hepatic fat content.92, 95, 96 CT has been used to detect VAT deposition in cats and CT evaluation of total body fat seems to correlate well with the body condition score.97 Two recent studies evaluated the use of CT to detect liver fatty deposition in FHL but yielded contrasting results. The first experimental study by Nakamura and colleagues98 evaluated a colony of adult healthy cats where the mean hepatic fat attenuation was 54 Hounsfield units (HU) (range: 43.5–65.9 HU). HL was then experimentally induced and, when CT images of the liver were evaluated, decreased hepatic x-ray attenuation was observed (<35 HU). In a more recent study, Lamb and colleagues99 evaluated x-ray attenuation in the liver and kidneys of a population of client-owned cats with suspected FHL. Cats were divided into 3 different groups based on the risk of suffering from mild lipidosis, moderate lipidosis, or severe lipidosis.
在人類醫學中，非對比增強 CT 被認為是比肝臟細胞學和組織學評估更可靠且可重複的方法，用於檢測非酒精性脂肪肝病(NAFLD)患者的肝臟脂肪浸潤。92,93 器官脂肪浸潤與 CT 上的 X 射線衰減有關 94 ，而在人類醫學中，脂肪組織的衰減程度與肝臟脂肪含量呈負相關。92,95,96 CT 已被用於檢測貓的內臟脂肪組織(VAT)沉積，且 CT 評估的全身脂肪量似乎與體況評分有良好相關性。 97 近期有兩項研究評估了使用 CT 檢測貓肝脂質沉積症(FHL)中的肝臟脂肪沉積，但結果相互矛盾。Nakamura 及其同事的第一項實驗研究 98 評估了一群成年健康貓，其平均肝臟脂肪衰減值為 54 Hounsfield 單位(HU)(範圍：43.5–65.9 HU)。實驗誘發肝脂質沉積症後，當評估肝臟 CT 影像時，觀察到肝臟 X 射線衰減降低(<35 HU)。 在最近的一項研究中，Lamb 及其同事 99 評估了一群飼主家貓疑似患有貓肝脂質沉積症(FHL)時的肝臟與腎臟 X 光衰減值。研究根據罹患輕度、中度或重度脂質沉積症的風險將貓隻分為三個不同組別。
The study however, failed to highlight any differences between groups and the values obtained for x-ray attenuation of the liver were different from the previously published ones. The conclusion of Lam and colleagues99 was that hepatic CT attenuation of the liver might be of limited value in detecting FHL in patients at risk for lipidosis and that values obtained for hepatic x-ray attenuation could vary between CT scanners.
然而該研究未能凸顯各組別間的差異，且所獲得的肝臟 X 光衰減值與先前發表的數據有所不同。Lam 及其同事 99 的結論是，肝臟 CT 衰減值對於檢測有脂質沉積症風險患者的 FHL 可能價值有限，且不同 CT 掃描儀器所獲得的肝臟 X 光衰減值可能存在差異。
Based on the results of these 2 studies and the need for sedation or anesthesia in a clinically compromised patient, the routine use of CT to diagnose lipidosis cannot yet be recommended and further studies are necessary.
根據這兩項研究結果，以及臨床狀況不佳患者需要鎮靜或麻醉的考量，目前尚不建議常規使用 CT 診斷脂質沉積症，仍需進一步研究。

Treatment  治療

Fluid and Electrolyte Therapy
液體與電解質療法

Cats presented with FHL can suffer from differing degrees of hypoperfusion secondary to vomiting, anorexia, and adipsia. Hypoperfusion in cats is characterized by tachycardia (heart rate >220 bpm) or inappropriate bradycardia (heart rate <140 bpm), pale mucous membranes, prolonged capillary refill time, often hypothermia, and mild hypotension. Dehydration is a common abnormality seen in cats with FHL. Initial fluid therapy should be directed to correct hypoperfusion if it is present. A balanced isotonic crystalloid infusion (0.9% NaCl, lactated Ringer solution, or Ringer acetate solution) is the fluid type of choice.
患有貓肝脂質沉積症(FHL)的貓可能因嘔吐、厭食和飲水減少而出現不同程度的低灌注。貓的低灌注特徵包括心動過速（心率>220 次/分）或不適當的心動過緩（心率<140 次/分）、黏膜蒼白、毛細血管再充盈時間延長、常伴隨低體溫以及輕度低血壓。脫水是 FHL 患貓常見的異常現象。初始輸液治療應針對糾正存在的低灌注情況。首選的輸液類型為平衡等張晶體溶液（0.9%生理鹽水、乳酸林格氏液或醋酸林格氏液）。
Small volume resuscitation, with a 5 mL/kg to 10 mL/kg intravenous (IV) bolus given over 30 minutes should be instituted in hypovolemic cats while slow rewarming is implemented. Repeated examination of the cardiovascular system helps decide if further fluid administration is necessary to achieve euvolemia.
對於低血容量的貓，應實施小容量復甦治療，以 5-10 mL/kg 的劑量靜脈推注，在 30 分鐘內完成，同時進行緩慢復溫。通過反覆檢查心血管系統狀況，可判斷是否需要進一步輸液以達到正常血容量狀態。
Fluid therapy to provide for maintenance requirements and correct deficits according to the estimated percentage of dehydration should then be started (Tables 1 and 2) and the total volume is usually administered over 24 hours. There is a lot of debate on what is the best fluid to administer in patients with FHL. Due to poor hepatic function, lactate clearance might not be appropriate in cats with FHL. Therefore, the administration of lactate-based solutions might worsen hyperlactatemia in these patients.1, 2 This seems to only be a theoretic concern, however, because lactated Ringer solution has been used without major complication in cats with FHL.1 Fluids containing glucose should be avoided in cats with FHL to avoid worsening glucose intolerance and concurrent hyperglycemia.37 The fluid therapy plan should be re-evaluated and adjusted at least once a day based on the cat’s new requirements and clinical condition. The newly formulated plan should take into consideration the fluid balance and the body weight of the patient, percentage of dehydration, and if ongoing losses (vomiting and diarrhea) are still occurring. If enteral or parenteral feeding is implemented, the amount of fluid administered with the nutritional plan should be deducted from the calculated rate of fluid infusion to avoid fluid overload.
接著應開始進行液體治療，以滿足基本需求並根據估算的脫水百分比來矯正體液缺失（表 1 和表 2），通常會在 24 小時內輸注完總液體量。關於貓脂肪肝（FHL）患者最適合使用何種輸液，目前存在許多爭議。由於肝功能不佳，FHL 病貓可能無法有效代謝乳酸，因此使用含乳酸的溶液可能會加劇高乳酸血症。1,2 然而，這似乎僅是理論上的顧慮，因為乳酸林格氏液在 FHL 病貓中使用並未出現重大併發症。 1 應避免對 FHL 病貓使用含葡萄糖的輸液，以免加劇葡萄糖耐受不良和伴隨的高血糖症。 37 液體治療計畫應每天至少重新評估和調整一次，根據病貓的新需求和臨床狀況。新制定的治療計畫需考量患者的體液平衡、體重、脫水百分比，以及是否仍有持續性體液流失（嘔吐和腹瀉）的情況。 若實施腸道或腸外營養，應從計算的輸液速率中扣除營養計畫所含的液體量，以避免體液過量。

Table 1. Clinical estimation of dehydration
表 1. 脫水程度的臨床評估

Estimated Dehydration (% of Body Weight)
估計脫水程度（佔體重百分比）		Physical Examination Findings
理學檢查發現
<5Normal (history consistent with excessive fluid loss compared with intake)
正常（病史顯示體液流失量明顯多於攝入量）
5–6Skin turgor is mildly reduced; mucous membranes are dry.
皮膚彈性輕度降低；黏膜乾燥
7–8Skin turgor is moderately reduced; mucous membranes are dry.
皮膚彈性中度降低；黏膜乾燥
8–10Skin turgor is severely reduced; mucous membranes are dry; eyes sunken in the orbit.
皮膚彈性嚴重降低；黏膜乾燥；眼球凹陷
10–12Skin turgor is severely reduced; mucous membranes are dry; eyes sunken in the orbit; initial signs of shock (mild tachycardia, pale/pink mucous membranes, slightly prolonged CRT, weak peripheral pulse)
皮膚彈性嚴重降低；黏膜乾燥；眼睛凹陷於眼窩中；休克初期徵兆（輕度心搏過速、蒼白/粉紅黏膜、微延長的毛細血管再充盈時間、周邊脈搏微弱）
12–15Clinical signs consistent with shock (tachycardia, pale mucous membranes, weak peripheral pulse, prolonged capillary refill time)
與休克相符的臨床徵兆（心搏過速、黏膜蒼白、周邊脈搏微弱、毛細血管再充盈時間延長）
Percentage of dehydration is evaluated based on physical evaluation of the turgor, mucous membranes, and position of the eyes in the orbit. The estimated percentage is used to calculate the amount of fluid necessary for the correction of dehydration in the fluid therapy plan (Table 2).
脫水百分比是根據對皮膚彈性、黏膜狀態及眼睛在眼窩中位置的理學評估來判定。估算的百分比用於計算液體治療計劃中矯正脫水所需補充的液體量（表 2）。

Table 2. Fluid requirements for a hospitalized cat
表 2. 住院貓咪的液體需求

Maintenance fluid therapy
維持性輸液治療		40–60 mL/kg/d  40–60 毫升/公斤/天
Correction of dehydration
脫水矯正		Deficit in mL (to be administered in 12–24 h) = % dehydration × 10 × body weight (kg)
脫水補充量（需於 12-24 小時內給予）= 脫水百分比 × 10 × 體重（公斤）
Ongoing fluid losses  持續性體液流失
  • Based observed fluid loss
    根據觀察到的體液流失量
    • •
      Minimal fluid loss: 2 mL/kg/h
      輕微體液流失：2 毫升/公斤/小時
    • •
      Moderate fluid loss: 4 mL/kg/h
      中度體液流失：4 毫升/公斤/小時
    • •
      Severe fluid loss: 6 mL/kg/h
      嚴重體液流失：6 毫升/公斤/小時
Based on the cat fluid balance, the fluid therapy plan takes into consideration maintenance fluid therapy plus the correction of dehydration (based on the estimated percentage of dehydration) and the ongoing fluid losses (via vomiting, diarrhea, or polyuria).
根據貓咪的體液平衡狀況，輸液治療方案需考慮維持性輸液治療，加上脫水矯正（根據估計的脫水百分比）以及持續性體液流失（透過嘔吐、腹瀉或多尿）。
Correction of electrolytes abnormalities should take place in the initial phase of hospitalization and before nutrition is started, because insulin release can cause a further decrease in serum/plasma potassium and phosphate concentrations. Abnormalities of potassium and phosphate should be adequately corrected (Tables 3 and 4) and these electrolytes should be checked at least twice daily in the beginning of hospitalization. The rate of potassium administration must not exceed 0.5 mEq/kg/h. If hypokalemia is difficult to correct, the serum/plasma magnesium concentration should be also measured and if needed this electrolyte should be supplemented (Table 5), as hypomagnesemia can worsen renal wasting of potassium.
電解質異常的矯正應在住院初期且開始營養支持前進行，因為胰島素分泌可能導致血清/血漿中鉀和磷酸鹽濃度進一步下降。鉀和磷酸鹽的異常應充分矯正（表 3 和表 4），且在住院初期這些電解質應至少每日檢測兩次。鉀的補充速率不得超過 0.5 mEq/kg/h。若低鉀血症難以矯正，應同時測量血清/血漿鎂濃度，必要時需補充此電解質（表 5），因為低鎂血症可能加劇腎臟對鉀的流失。

Table 3. Guide to potassium supplementation
表 3. 鉀補充指南

Serum Potassium Concentration (mEq/L)
血清鉀離子濃度 (mEq/L)		Milliequivalent of Potassium Added to 1 Liter of Fluid
每公升輸液添加的鉀毫當量數		Maximum Fluid Infusion Rate (mL/kg/h)a
最大輸液速率 (毫升/公斤/小時) a
<2.0806
2.1–2.5608
2.6–3.04012
3.1–3.52818
3.6–5.02025
a
So as not exceed a potassium supplementation of 0.5 mEq/kg/h.
為避免超過每小時每公斤 0.5 毫當量的鉀補充量

Adapted from Greene RW, Scott RC. Lower urinary tract disease. In: Ettinger SJ, editor. Textbook of veterinary internal medicine. Philadelphia: WB Saunders; 1975.
改編自 Greene RW, Scott RC. 下泌尿道疾病。見：Ettinger SJ 主編。獸醫內科學教科書。費城：WB Saunders；1975 年。

Table 4. Guide to phosphate supplementation
表 4. 磷酸鹽補充指南

Supplement  補充劑Dose/Route  劑量/途徑Comments  評論
Potassium phosphate  磷酸鉀0.01–0.03 mEq/kg/h IV as a CRI for 6 h or
以 0.01-0.03 毫當量/公斤/小時的速率靜脈連續輸注(CRI)6 小時
0.12 mEq/kg/h for severe deficits IV as a CRI
0.12 mEq/kg/h 靜脈輸注作為持續性輸液，用於嚴重缺乏時		Use a dedicated line and syringe pump. Ensure that this line is not flushed.
使用專用管路和注射泵，確保該管路不被沖洗
It is important to consider the amount of potassium administered via phosphate correction and subtract it from the potassium correction.
必須考慮經由磷酸鹽校正所給予的鉀量，並從鉀校正量中扣除
Potassium phosphate (alternative method)
磷酸鉀（替代方案）		Calculate the amount of potassium (in milliequivalents) that should be added to 1 L of fluid using Table 3; provide half this as potassium chloride and half with potassium phosphate.
使用表 3 計算應添加至 1 公升液體中的鉀量(以毫當量計)；其中一半以氯化鉀形式給予，另一半以磷酸鉀形式給予		This method is simple but it does not allow phosphate supplementation to be adjusted independently of total potassium supplementation.
這種方法雖然簡單，但無法在調整磷酸鹽補充量時獨立於總鉀補充量之外進行調整。
Do not administer potassium phosphate with calcium-containing fluids, for example, lactated Ringer solution.
請勿將磷酸鉀與含鈣輸液（例如乳酸林格氏液）共同給藥。

Table 5. Guide to magnesium supplementation
表 5. 鎂補充指南

Supplement  補充劑Dose/Route  劑量/途徑Comments  評論
Magnesium sulfate or  硫酸鎂或
Magnesium chloride  氯化鎂		Rapid replacement: 0.75–1 mEq/kg/d IV as a CRI for first 24 h
快速補充：前 24 小時以 0.75–1 mEq/kg/天的劑量靜脈持續輸注(CRI)
Slow replacement: 0.3–0.5 mEq/kg/d IV as a CRI for 2–3 d
緩慢補充：0.3–0.5 mEq/kg/d 靜脈注射，以持續輸注方式給藥 2-3 天		Administered as 20% solution diluted in 5% dextrose
以 20%溶液稀釋於 5%葡萄糖溶液中給藥

Nutritional Management of Feline Hepatic Lipidosis
貓肝性脂肪沉積症的營養管理

The cornerstone of treatment in FHL is early nutrition. Nutrition should be initiated on the day of admission to reverse the negative energy balance and catabolic state typical of FHL. The only reason to delay nutrition is the presence of cardiovascular instability (hypoperfusion or hypotension) and severe electrolyte abnormalities.
貓肝脂質沉積症(FHL)治療的關鍵在於早期營養支持。應於住院當日即開始營養治療，以逆轉 FHL 典型的負能量平衡與分解代謝狀態。唯一需要延遲營養治療的情況是出現心血管不穩定（低灌注或低血壓）及嚴重電解質異常。
Nutrition can be provided via the enteral or parenteral routes. Wherever possible, enteral feeding is preferred over parenteral nutrition because it helps maintaining intestinal structure and function.100 In cases of intractable vomiting or because of minimal tolerance to enteral feeding, however, the parenteral route should be taken into consideration.100 Partial parenteral nutrition could be easily administered via a peripheral catheter and does not require a central venous access, which might initially not be advisable due to coagulation abnormalities.
營養可通過腸道或腸外途徑提供。在可能的情況下，應優先選擇腸道餵養而非腸外營養，因其有助於維持腸道結構與功能。 100 然而，對於頑固性嘔吐或對腸道餵養耐受性極低的病例，則應考慮採用腸外途徑。 100 部分腸外營養可輕易通過周邊靜脈導管給藥，無需中央靜脈通路，這在初期可能因凝血功能異常而不建議使用。
The ideal diet for FHL should be high in protein (30%–40% of the metabolizable energy), moderate in lipids (approximately 50% of the metabolizable energy), and poor in carbohydrate (approximately 20% of the metabolizable energy).1, 2 Glucose should be used as carbohydrate source because it does not require digestion and can be used by enterocytes as an energy source.1 In critically ill cats, 6 g of protein/100 kcal (or 25%–35% of their total energy requirements) is considered enough to support their unique metabolism.100 In FHL, a diet with a protein content of 25% of the metabolizable energy was shown to attenuate but not to ameliorate HL, whereas a diet with a higher protein content (35%–45% of the metabolizable energy) was shown to reverse the catabolic state and improve clinical signs associated with FHL.7, 32 A majority of the veterinary commercial diets formulated for recovery in cats meet these requirements.
貓咪脂肪肝（FHL）的理想飲食應為高蛋白（佔可代謝能量的 30%–40%）、適量脂肪（約佔可代謝能量的 50%）及低醣類（約佔可代謝能量的 20%）。1, 2 葡萄糖應作為醣類來源，因其不需消化即可被腸道細胞直接利用作為能量來源。 1 對於重症病貓，每 100 大卡攝取 6 克蛋白質（或佔總能量需求的 25%–35%）即足以支持其特殊代謝需求。 100 研究顯示，在 FHL 治療中，蛋白質含量佔可代謝能量 25%的飲食可緩解但無法改善脂肪肝；而蛋白質含量較高（35%–45%）的飲食則能逆轉分解代謝狀態，並改善與 FHL 相關的臨床症狀。7, 32 目前多數市售貓用康復配方飼料均符合這些營養要求。
The calorie requirements of these patients can be estimated using the formula:
這類病患的熱量需求可透過以下公式估算：RER = 70 × (body weight in kg)0.75
The use of an illness factor, typically ranging from 1.0 to 2.0, by which the resting energy requirement (RER) is multiplied to meet the increased caloric needs of critically ill patients is no longer recommended.101 The use of illness factor leads to overfeeding and has been associated with hyperglycemia and gastrointestinal dysfunction as well as hepatic dysfunction. The development of hyperglycemia is especially concerning (particularly during parenteral nutrition) because it is associated with an increased rate of complications and a worse outcome.102
使用疾病係數（通常範圍為 1.0 至 2.0）乘以靜態能量需求（RER）以滿足重症病患增加的熱量需求之做法已不再被建議。 101 使用疾病係數會導致過度餵食，並與高血糖、胃腸功能障礙以及肝功能障礙有關。高血糖的發生尤其令人擔憂（特別是在腸外營養期間），因為它與併發症發生率增加和預後較差有關。 102
Forced enteral feeding should never be considered in a sick cat with FHL because of the risk of the development of food aversion2 and because it is usually difficult to administer cats enough food to meet their energy requirements. Feeding tubes (nasoesophageal, esophageal, and gastric) allow clinicians to provide enteral nutrition without excessive stress to the patient (Table 6). The preferred initial feeding tube choice of the authors and others1, 2 for cats with FHL is the nasoesophageal feeding tube. The introduction of a nasoesophageal feeding tube does not require general anesthesia or heavy sedation and is noninvasive (Fig. 3). Cats with FHL are often unstable on admission to undergo general anesthesia and are often coagulopathic.
對於患有貓肝性脂肪沉積症（FHL）的病貓，絕不應考慮強制灌食，因為這可能導致食物厭惡症 2 的風險，且通常難以讓貓咪攝取足夠食物以滿足其能量需求。餵食管（鼻食道管、食道造口管和胃造口管）能讓臨床醫師在不造成病患過度壓力的情況下提供腸道營養（表 6）。作者與其他學者 1,2 針對 FHL 貓咪首選的初始餵食管類型為鼻食道管。鼻食道管的置入無需全身麻醉或深度鎮靜，屬於非侵入性處置（圖 3）。FHL 貓咪入院時通常狀況不穩定，不適合接受全身麻醉，且常伴有凝血功能障礙。
For these reasons, the insertion of esophagostomy and gastrostomy tubes should be considered potentially unsafe in these patients and should be delayed until fluid and coagulation abnormalities have been addressed and the cat is considered stable enough to undergo anesthesia (Fig. 3).
基於這些原因，食道造口管與胃造口管的置入應被視為對這些病患具有潛在危險性，應延遲至液體與凝血異常問題獲得處理，且確認貓咪狀況穩定足以承受麻醉後再進行（圖 3）。

Table 6. Type and characteristics of available feeding tubes for enteral nutrition in cats
表 6. 貓咪腸道營養可用餵食管類型與特性

Feeding Tube for Enteral Nutrition
腸道營養餵食管		Size  尺寸Advantages  優點Disadvantages  缺點
Nasoesophageal  鼻食道7–8 French  7-8 法式尺寸No anesthesia required; easy to place; inexpensive
無需麻醉；易於放置；價格低廉		Short-term solution; only allows administration of a liquid diet
短期解決方案；僅允許給予流質飲食
Esophageal  食道14 French  14 法式尺寸Easy to place, inexpensive; most diets can be administered; suitable for longer duration feeding
易於放置，價格低廉；大多數飲食均可使用；適合長期餵食		Anesthesia is required; hemorrhage is a potential risk; cellulitis is a potential complication.
需要麻醉；可能發生出血；蜂窩性組織炎是潛在併發症
Gastric  胃管14–18 FrenchSuitable for longer duration feeding; most diets can be administered.
適合長期餵食；大多數飲食均可使用		Anesthesia is required; tube displacement can result in peritonitis.
需要進行麻醉；餵管位移可能導致腹膜炎。
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Fig. 3. Cats with (A) nasoesophageal and (B) esophageal feeding tubes.
圖 3. 使用(A)鼻食道和(B)食道餵管的貓隻。

Typically, sufficient amounts of a commercial high protein recovery food to provide one-third of the calculated RER is fed on the first day followed by a slow incremental increase in the amount over the next 2 to 3 days until the total RER is provided. The slow increase of the caloric load should decrease the risk of refeeding syndrome.
通常第一天會餵食足夠量的商業高蛋白恢復食品，提供計算所得靜息能量需求(RER)的三分之一，隨後在接下來 2 至 3 天內緩慢增量，直到提供完整的 RER。這種緩慢增加熱量負荷的方式應能降低再餵食症候群的風險。
Refeeding syndrome is characterized by severe hypophosphatemia, hypokalemia, and hyperglycemia, with clinical signs of vomiting, diarrhea, and/or shock.103, 104 It is the consequence of a rapid caloric administration to a starved patient in a chronic negative catabolic state, causing rapid insulin release.103, 104, 105
再餵食症候群的特徵是嚴重的低磷血症、低鉀血症和高血糖，臨床症狀包括嘔吐、腹瀉和/或休克。103, 104 這是因快速給予處於長期負分解代謝狀態的飢餓患者熱量，導致胰島素快速釋放所產生的後果。103, 104, 105
Cats with FHL are considered feeding volume sensitive and the amount of food they can tolerate per meal might be drastically reduced.1 The total volume of food required each day should be initially divided into 6 to 8 portions, or administered as a constant rate infusion (CRI). The authors prefer to administer food as a CRI because it seems to reduce nausea, gastric discomfort, and vomiting associated with gastric distension after intermittent food administration.
患有貓肝脂質沉積症（FHL）的貓咪對餵食量相當敏感，單次進食所能耐受的食物量可能大幅減少。 1 每日所需的總食物量最初應分成 6 至 8 份餵食，或採用恆速輸注（CRI）方式給予。本文作者傾向採用 CRI 方式餵食，因為這種方式似乎能減少因間歇性餵食後胃部擴張所伴隨的噁心、胃部不適及嘔吐症狀。
The food should always be administered lukewarm and, if the intermittent administration is chosen, it should be administered over 10 to 15 minutes. If any signs of discomfort, retching, or vomiting is present, the administration of food should be interrupted.
食物應始終保持微溫狀態餵食，若選擇間歇性餵食方式，每次餵食時間應控制在 10 至 15 分鐘內。若出現任何不適、乾嘔或嘔吐跡象，應立即停止餵食。
Antiemetics and gastroprotectants should be considered in cats that are nauseated and/or vomit. Metoclopramide (0.2 mg/kg IV 4 times a day or 1 mg/kg/d IV as a CRI), ondansetron (0.1–0.5 mg/kg IV 2–3 times per day), and maropitant106 (1 mg/kg subcutaneously [SQ] once a day) can be used alone or in combination to decrease vomiting and nausea. Metoclopramide is not a potent antiemetic in cats but has some prokinetic effect and can facilitate gastric emptying.107 Omeprazole (1 mg/kg orally twice a day) or ranitidine (2.5 mg/kg IV twice a day) can be used to prevent reflux esophagitis in animals with frequent emesis.107 The use of appetite stimulants has been discouraged in cats with FHL.1, 2, 100, 108
對於出現噁心和/或嘔吐的貓咪，應考慮使用止吐劑和胃腸保護劑。可單獨或合併使用 metoclopramide（靜脈注射 0.2 mg/kg 每日 4 次，或 1 mg/kg/日靜脈持續輸注）、ondansetron（靜脈注射 0.1-0.5 mg/kg 每日 2-3 次）及 maropitant（皮下注射 1 mg/kg 每日一次）以減輕嘔吐與噁心症狀。Metoclopramide 對貓咪的止吐效果不強，但具有促動力作用，可促進胃排空。Omeprazole（口服 1 mg/kg 每日兩次）或 ranitidine（靜脈注射 2.5 mg/kg 每日兩次）可用於預防頻繁嘔吐動物發生逆流性食道炎。對於罹患貓肝性脂肪沉積症(FHL)的貓咪，不建議使用食慾刺激劑。
Vitamin K1 should be administered in cats with impaired coagulation and some clinicians routinely administer it to all cats with FHL. Because the absorption of vitamin K1 from the gastrointestinal tract might be compromised by cholestasis, 0.5 mg/kg to 1.5 mg/kg SQ at 12-hour intervals for 3 to 4 doses has been recommended.2
凝血功能異常的貓咪應補充維生素 K，部分臨床醫師會常規性給予所有 FHL 病貓使用。由於膽汁淤積可能影響胃腸道對維生素 K 的吸收，建議以 0.5-1.5 mg/kg 劑量皮下注射，每 12 小時一次，共給予 3-4 次。
Other medications and supplements are often suggested for the treatment of FHL (Table 7) but their efficacy has not been adequately demonstrated to make definitive recommendations regarding their use.54, 58, 59, 109, 110 l-carnitine supplementation has received more interest than any other food supplements and there are experimental and clinical studies that highlight its benefits. In an experimental study in overweight cats undergoing rapid weight loss, dietary l-carnitine supplementation increased the rate of FFA β-oxidation and decreased TG accumulation in the liver.53, 54, 58, 62 Furthermore, clinical observation of improvement of the clinical signs and probability of survival in cats with FHL when supplemented with l-carnitine suggests that carnitine should be considered an important addition to nutrition support.2 A dose of 250 mg/cat/d to 500 mg/cat/d orally has been suggested.1, 2
其他藥物和營養補充劑常被建議用於治療貓肝脂質沉積症（表 7），但其療效尚未得到充分證實，因此無法對其使用做出明確建議。54, 58, 59, 109, 110 左旋肉鹼補充劑比其他營養補充劑受到更多關注，實驗和臨床研究都強調了其益處。在一項針對快速減重的過重貓咪的實驗研究中，飲食中添加左旋肉鹼補充劑提高了游離脂肪酸β-氧化速率，並減少了肝臟中三酸甘油脂的堆積。53, 54, 58, 62 此外，臨床觀察發現補充左旋肉鹼的 FHL 患貓其臨床症狀改善和存活機率提高，這表明肉鹼應被視為營養支持的重要補充。 2 建議口服劑量為每日每貓 250 毫克至 500 毫克。1, 2

Table 7. Medications and nutraceuticals suggested by the treatment of feline hepatic lipidosis
表 7. 建議用於治療貓肝脂質沉積症的藥物與營養製劑

Medications or Nutraceuticals
藥物或營養製劑		Route of Administration  給藥途徑Dosage  劑量
l-carnitine  左旋肉鹼PO250–500 mg total daily dose
每日總劑量 250–500 毫克
Vitamin B12  維生素 B 群SQ250 μg/injection once weekly for 6 wk, once every 2 wk for 6 wk, and then monthly
每週注射 250 微克，持續 6 週；之後每 2 週注射一次，持續 6 週；然後改為每月注射一次
Taurine  牛磺酸PO250 mg total daily dose during the first 7–10 d
最初 7–10 天期間每日總劑量 250 毫克
N-acetylcysteine  N-乙醯半胱胺酸IV, PO  靜脈注射, 口服Initial first dose 140 mg/kg (20% solution diluted 1:4 or greater with saline) over 30 min, followed by 70 mg/kg every 8–12 h
首次初始劑量為 140 毫克/公斤（20%溶液以生理鹽水稀釋 1:4 或更高比例），30 分鐘內輸注完畢，之後每 8–12 小時給予 70 毫克/公斤
S-adenosylmethionine  S-腺苷甲硫胺酸PO20 mg/kg/d  每日 20 毫克/公斤
Give at least 1 h before meals
至少於餐前 1 小時給予

Prognosis  預後

If appropriately and rapidly treated with nutritional support and in the absence of a serious underlying disease, cats with FHL have a reported recovery rate of 80% to 85%.2, 10 Reported positive prognostic factors were a younger age and a higher median serum potassium concentration and hematocrit.2, 6 A low albumin concentration on admission was associated with a worse prognosis in a population of cats affected with FHL (C. Valtolina and R.P. Favier, unpublished data, 2016).
若適當且迅速地以營養支持治療且無嚴重潛在疾病，貓脂肪肝(FHL)的報告康復率為 80%至 85%。2,10 報告顯示較年輕的年齡、較高的血清鉀離子中位數濃度及血容比為正向預後因子。2,6 入院時的低白蛋白濃度與貓脂肪肝患者較差的預後相關(C. Valtolina 與 R.P. Favier 未發表數據，2016 年)。

References

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