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肝病的臨床營養 Nutrition in Liver Disorders

肝病的臨床營養 Nutrition in Liver Disorders. 肝病對營養的影響 代謝的改變與營養的需求 肝病的營養治療 肝性腦病變病因 營養的困境 肝性腦病變 治療 BCAA 的利益與臨床上的評估. 龐振宜 藥師. 肝病對營養的影響 消化與吸收. 40%-70% 營養不良 嚴重患者幾乎都營養不良 饑餓的加速 在隔夜的禁食後 熱量的來源 75% 來自身體脂肪 相對的正常人只 35%. 多次間斷性的餵食是有效保留瘦肉組織的方式. 代謝的改變與營養的需求 蛋白質. lean body mass 減少 在腹水情況

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肝病的臨床營養 Nutrition in Liver Disorders

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  1. 肝病的臨床營養Nutrition in Liver Disorders • 肝病對營養的影響 • 代謝的改變與營養的需求 • 肝病的營養治療 • 肝性腦病變病因 • 營養的困境 • 肝性腦病變治療 • BCAA的利益與臨床上的評估 龐振宜 藥師

  2. 肝病對營養的影響消化與吸收 • 40%-70%營養不良 • 嚴重患者幾乎都營養不良 • 饑餓的加速 • 在隔夜的禁食後 • 熱量的來源75%來自身體脂肪 • 相對的正常人只35% 多次間斷性的餵食是有效保留瘦肉組織的方式

  3. 代謝的改變與營養的需求蛋白質 • lean body mass 減少 • 在腹水情況 • 基礎代謝提昇10% • 穩定性的肝硬化 • 0.8~1.0克/公斤/日蛋白質，以維持正氮平衡

  4. 代謝的改變與營養的需求尿素的合成 • glutamic acid的轉換形成glutamine產生ammonia • 肝硬化患者合成尿素速率減緩 • Ammonia的堆積 • 尿素循環酵素活性降低 • 肝內血流量、肝實質量的改變 • 排除ammonia的尿素合成能力下降

  5. 代謝的改變與營養的需求碳水化合物的代謝 • 肝醣儲存量減少，加速脂肪利用 • 葡萄糖不耐症是常見的 • 胰島素的阻礙及肝細胞的葡萄糖攝取量減少 • 胰島素分泌過旺分解減低 • 對肝臟內胰島素感受器造成受體下降 • 上昇的自由脂肪酸、生長激素、昇醣激素也同時造成胰島素的阻抗

  6. Amin Hepa 代謝的改變與營養的需求脂肪的代謝 • 急性肝病血中HDL下降，三酸甘油脂及膽固醇增加，脂化性的膽固醇減少 • 肝硬化患者靜脈注射脂肪乳仍是耐受性良好的熱量來源 • 發揮蛋白質保留效應 • 可能改善肝性腦病變 • 高熱量低容量性的負荷對肝硬化是有益的

  7. 代謝的改變與營養的需求維生素的代謝 葉酸、核黃素、菸草酸、.泛酸及Vit B6，B12，A等儲存量均減低 • 40%脂溶性維生素的缺乏(Vitamin A,E, carotene) • 約17%為葉酸缺乏 • 8至10%有Vit.B12, nicotinic acid, Vit B1, 或 Vit B2的缺乏

  8. 急性非複雜性非酒精性肝炎Acute uncomplicated non-alcoholic hepatitis Amin-Hepa Instant Drink TalAmin-Hepa injection • 營養的治療並無明顯的差異化 • 適當的熱量攝取 • 少量多次的餵食 • 而食物若引起噁心或嘔吐，此時管餵食飲食可能是必須 • 脂肪的受限並不需要，低脂飲食 • 熱量提供性差與口味不良下可能加重食慾不振 • 恢復期 • 可允許給予高脂、高蛋白膳食 • 比低脂餵食能獲得更多熱量以增加體重並縮短恢復期

  9. 胺命1號 酒精性肝炎 Alcoholic hepatitis • 足夠的熱量攝取 • 正氮平衡明顯增加其存活率 • 靜脈營養提供胺基酸的補充獲得良好的改善 • 正氮平衡 • 可能使急性期下潛伏性的肝病 的嚴重度，達到良好的改善 Amin Hepa 口服高支鏈胺基酸(BCAA)的營養補充品 在生化檢驗與死亡率均有良好的改善

  10. 猛暴性肝衰竭Fulminant heaptic failure • 蛋白質-熱量營養失調的加速 • 熱量 34至50kcal/kg/日 • 蛋白質 0.8至1.0gm/kg/日 • 肝性腦病變 • 蛋白質 0.4-0.6g/kg/日 靜脈胺基 酸的營養提供較經口途徑較好

  11. 慢性肝病 Chronic Liver Disease • 伴有肝硬化的慢性肝病 • 代謝的改變，身體傾向加速分解作用 • 長期營養護理的目標 • 提供足夠的熱量與蛋白質 • 避免瘦肉組織的減少 胺命1號 營養治療的首要目標 肝性腦病變處置與體液滯留的護理

  12. 肝性腦病變Hepatic Encephalopathy • Neuropsychiatric syndrome • Multifactorial etiology • Secondary to hepatic failure • Synonyms • Portal-systemic encephalopathy • Hepatic coma J.Y. Pang

  13. 肝性腦病變過程Stage of Hepatic Encephalopathy Modified Parsons-Smith Rating Scale J. Y. Pang

  14. Pathogenesis of Hepatic Encephalopathy Theories • Amino acid imbalances • BCAA/AAA False neurotransmitters • Methionine • Tryptophan • Ammonia • Unified theory - BCAA/AAA + NH3 • Mercaptans • Short Chain Fatty Acids (SCFA) • Increased cerebral sensitivity J. Y. Pang

  15. Abnormal plasma amino acids:chronic liver disease 400 Glu 350 Phe Asp Meth 300 250 Tyr % of Normal 200 Try 150 Gly 100 Orn Thr Ser Lys Tau His Val 50 Leu Arg Pro Ala Ileu Essential Non-Essential Cerra, et al; JPEN, 1985 J. Y. Pang

  16. Protein Intolerance/Hepatic Encephalopathy Cycle Hepatic Encephalopathy Liver Failure Protein Intolerance Malnutrition Catabolism Protein Restriction J. Y. Pang

  17. Amino acid imbalancesTheory Blood Brain Barrier Brain Liver AAA MET NH3 BCAA Protein intake Muscle James, et al; Lancet, 1979 J. Y. Pang

  18. Reasons for malnutrition • Outpatient • Anorexia, nausea, vomiting • Poor diet • Malabsorption • Hypermetabolism/hypercatabolic state • Inpatient • Abnormal metabolic state, anorexia, malabsorption • Unpalatable diet (low Na, low protein) • Fasting for tests • G-I bleeding, PSE J. Y. Pang

  19. 肝性腦病變的營養治療 • 蛋白質每日40公克以下 • 通便，清除腸內蛋白質 • 植物性蛋白質具有高纖維 • 可較迅速提昇大腸的蠕動性 • 對於已經無食慾的肝病患者 • 龐大的植物性蛋白質膳食經常是無法忍受 • 熱量的獲得也較低 胺命1號 營養的介入是重要的 攝入的蛋白質品質比數量要來的重要

  20. BCAA於代謝上的利益 • 有效的能量來源 • 正常人 只須6-7% 的BCAA為能量 • 但肝硬化者超過30%能量來源為BCAA • 因為 • Glucose resistance • Hypermetabolism • Decreased ketogenesis • 2 減少其他氨基酸的流量 • 減少AAAs 的循環 Nutrition and Metabolism in the Surgical Patient 2nd p644. 1996

  21. BCAA於代謝上的利益 • Leucine • 減少肌肉蛋白質分解增加蛋白質合成 • 增加肝臟蛋白質合成 • Leucine - the most potent in this regard • 血漿氨基酸值的正常 • Decrease muscle protein breakdown • Increase protein synthesis • Utilizition the AAAs Nutrition and Metabolism in the Surgical Patient 2nd p644. 1996

  22. BCAA於代謝上的利益 • 增加穿透BBB 的競爭性 • BCAA provide the bulk of competition • 增加 腦內減少的norepinephrine in hepatectomized animals • 周邊catecholamine 合成的正常化 • more normal precursor pool • 增加ammonia 的代謝 • donate the amino group for glutamine synthesis Nutrition and Metabolism in the Surgical Patient 2nd p644. 1996

  23. Hapatic failure - Hypercatabolism 氨基酸 0.55-1.1g/kg/day ,熱量30-35kcal/kg/day BCAA Enriched Solution • 蛋白質耐受性不 良 • 耐受至125 g BCAA-enriched solutions • 心智實質上的改善 • 針對慢性肝衰竭急性期設計 • fulminant hepatitis - massive hyperaminoacidemia, reflecting a dying liver

  24. 臨床上BCAA的利益評估 • Wake-Up Time • Nutritional effects • Outcome and Survival

  25. 甦醒時間 Wake-Up Time • 甦醒至grade 1 : BCAA 77% , lactulose/neomycine 26% JPEN 9:288,1985 • 肝性腦病變改善:BCAA 較glucose 快至少2倍 Scand J Gastreoenterol 18S:19,1983 • 甦醒度(48hr後):BCAA + dextrose 77% lactulose 47% Dig Dis Sci 27:929,1982 • 甦醒度:BCAA單獨或併用 lactulose 94% and 100% 單獨 lactulose 56% Hepaatic Encephalopathy in Chronic liver failure N.Y. Plenum..p.333, 1984 • 甦醒時間: BCAA 33小時, Neomycin 71小時 Hepatology3:862,1983 • 治療總評估: BCAA+Dextrose 有效Gastroenterology 97:1033,1989

  26. Nutrition Effects • 營養支持療法肯定減少疾病產生的分解代謝 Hepatic Failure 為 Hypercatabolism 須要 1.1g protein/kg/24 hr. • BCAA營養液 接近正氮平衡JPEN 9:288, 1985 不提供營養支持的療法 10g/24hr 的負氮平衡 Hepatic Encephalopathy in Chronic Liver Failure. N.Y. Plenum. 1984 P 301.

  27. Outcome and Survival Mortality (%) * Figures in parentheses represent overall in-hospital mortality • Hepatic Encephalopathy 為 critical ill • 營養的介入 只能增加10-15%的差異

  28. Resection of hepatocellular carcinoma N=124人 * 7 days preoperation and 7 days postoperation nutrition Fan S-T et al , N Engl J Med 331:1547, 1994

  29. 肝臟疾病氨基酸配方TalAmine Hepa 8% inj. • 高枝鏈氨基酸 High BCAA (36%) • 低芳香環氨基酸 Low Aromatics • BCAA:AAA = 37:1 • Low Methionine • Iso:Leu:Val ratio =1:1:1 • 完整蛋白質配製 (for liver disease) • 48小時改善肝昏迷 • 療效優於傳統治療 • 改善體內氨基酸不平衡 • 良好正氮平衡 龐振宜

  30. Hepatic Amino Acids Supplement AMIN-HEPA • BCAA (42%) • AAA • MET • BCAA/AAA ratio ( 15:1) J. Y. Pang

  31. Hepatic Amino Acids Supplement AMIN-HEPA Per Serving % Calories Serving Size 55g Calories 250 Kcal Carbohydrate 35g 56 Fat 8g 28 Protein 10g 16 Lactalbumin Hydrolysate 7.25g L-leucine 1.10g L-isoleucine 0.88g L-Valine 0.77g

  32. Hepatic Amino Acids Supplement AMIN-HEPA ** No US RDA as been established J. Y. Pang

  33. AMIN - HEPA INSTANTA nutritionally complete diet for liver disease 配製 口服 210ml water with one pack of Amin-Hepa 管餵 4 packs of Amin-Hepa into 840ml water as 1 liter solution 用量 完全以Amin-Hepa 為營養來源, 每日6-8 包 治療劑量每日4包 J. Y. Pang

  34. AMIN - HEPA INSTANTA nutritionally complete diet for liver disease • INDICATION • Hepatic encephalopathy / protein intolerance • Malnourished liver disease patients • Cirrhosis • Hepatitis • Liver transplant J. Y. Pang

  35. Hepatic Amino Acids SupplementMulticenter Study • Inclusion Criteria • Stable hepatic disease • Protein intolerant (20-40 Gm/day) • Exclusion Criteria • > Grade 1 encephalopathy • Acute illness Horst, et. al; Hepatology, 1984. J. Y. Pang

  36. Hepatic Amino Acids Supplement Multi center Study Protein Group BCAA Group 80 80 Dietary protein g/day Dietary protein g/day 80 60 60 60 40 40 40 20 20 20 1 4 2 3 4 0 0 1 2 3 Weeks Weeks Horst, et. al; Hepatology, 1984

  37. Tolerance to Hepatic AA Supplementvs.. Dietary Protein 88% 10% Percent of Patients Developing Encephalopathy J. Y. Pang Horst, et. al; Hepatology, 1984

  38. 營養補充對肝性腦病變等待換肝移植病患 利益評估 肝病營養配方不論在營養的補充及對於入院時的照顧 及肝性腦病變的改善均有利益 JPEN Vol.21,No.1 Jan-Feb. 1997. S16

  39. Increased the blood Fischer's ratio compared to the hepatopathy diet alone (on a molar basis) 2.0 p<0.01 Group first receiving the control treatment Fischer's ratio 1.0 Group first receiving Hepatic AA Suppl. 0.5 Control period 0 Before treatment Week 4 Week 1 Week 2 Week 3 Period of the Hepatic AA Suppl. Hayashi, S., et al: JJPEN 9(3):425-435, 1987 J.Y. Pang

  40. Time course of blood ammonia level (%) 150 Group first receiving Hepatic AA Suppl. 100 Percentage relative to the pretreatment value Group first receiving the control treatment 50 Control period 0 Week 1 Week 2 Week 3 Week 4 Before treatment Period of the Hepatic AA Suppl. Hayashi, S., et al: JJPEN 9(3):425-435, 1987 J.Y. Pang

  41. Improved the impaired nitrogen balance in a severe hepatopathy model (mg N) Aminals that underwent hepatic resection Nitrogen balance value day 1 Day 2 Day 3 Group treatd with marketed preparation for enteral nutrition Group treated with Hepatic AA Suppl. Ohashi, H.,et al:The Clinical Reports, 21(6):2533-2541,1987

  42. AMIN - HEPA INSTANTA nutritionally complete diet for liver disease Log rank test p<0.05 Wilcoxon rank test p<0.05 Gehan-Wilcoxon test p<0.05 Hepatic AA Suppl. (n=31) 纍積生存率 Historical Data (n=31) (月) 16th Asia Pacific Hepatologic Congress Feb. 1988 J. Y. Pang

  43. AMIN - HEPA INSTANTA nutritionally complete diet for liver disease BENETITS • Significantly lessens risk of protein-induced HE • Promotes positive nitrogen balance • Modified AA pattern is better tolerated than dietary protein • Flexibility as oral drink or tube feeding can improve patient compliance J. Y. Pang

  44. 體液的滯留Fluid Retention • 限制鈉鹽攝取有效處理體液的滯留 • 在膳食上可減少鈉鹽每日至200mg或更低 • 也同時造成飲食口味的不佳，減少蛋白質的攝取量 • 水份的限制 • 只在低鈉症而無能力排泄水的負荷的病患上 明智的使用利尿劑 通常可使過度限制膳食內的鈉鹽成為不必要

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