AMIN-HEPA INSTANT DRINK Nutrition in Liver Disorders HE EtiologyHE Etiology HE PathologenesisHE Pathologenesis Treatments of HETreatments of HE Nutritional

AMIN-HEPAAMIN-HEPA INSTANT DRINKINSTANT DRINKNutrition in Liver DisordersNutrition in Liver Disorders

• HE EtiologyHE Etiology

• HE PathologenesisHE Pathologenesis

• Treatments of HETreatments of HE

• Nutritional DilemmaNutritional Dilemma

• Unique Amino Acid formulationUnique Amino Acid formulation

• Clinic EvidenceClinic Evidence

龐振宜藥師

Hepatic EncephalopathyHepatic Encephalopathy

• Neuropsychiatric syndromeNeuropsychiatric syndrome• Multifactorial etiologyMultifactorial etiology• Secondary to hepatic failureSecondary to hepatic failure• SynonymsSynonyms

Portal-systemic encephalopathyPortal-systemic encephalopathyHepatic comaHepatic coma

J.Y. Pang

Stage of Hepatic EncephalopathyStage of Hepatic Encephalopathy

Grade Description

0 Normal mental state

1 M ild confusion, T rivial lack ofawareness

2 L ethargy; Disorientation;Personalitychange; Asterixis

3 Stuporous, M arkedconfusion; B izarre behaviour

4 Coma

Modified Parsons-Smith Rating ScaleModified Parsons-Smith Rating Scale J. Y. Pang

Pathogenesis of Hepatic Pathogenesis of Hepatic Encephalopathy TheoriesEncephalopathy Theories

1 Amino acid imbalancesAmino acid imbalances BCAA/AAA False neurotransmittersBCAA/AAA False neurotransmitters MethionineMethionine TryptophanTryptophan

2 AmmoniaAmmonia3 Unified theory - BCAA/AAA + NHUnified theory - BCAA/AAA + NH33

4 MercaptansMercaptans5 Short Chain Fatty Acids (SCFA)Short Chain Fatty Acids (SCFA)6 Increased cerebral sensitivityIncreased cerebral sensitivity

J. Y. Pang

Amino acid imbalancesAmino acid imbalancesTheoryTheory

James, et al; Lancet, 1979

Liver

BloodBloodBrainBrainBarrierBarrier

Brain

MuscleProteinProteinintakeintake

AAAAAAMETMETNH3NH3

BCAABCAA

J. Y. Pang

ValVal

Abnormal plasma amino acids:Abnormal plasma amino acids:chronic liver diseasechronic liver disease

400400

350350

300300

250250

150150

200200

100100

5050ThrThr

LeuLeu

IleuIleu

LysLys

TryTry

MethMeth

PhePhe

TauTau

AspAsp

GluGlu

SerSer

ProPro

GlyGly

AlaAla

TyrTyr

OrnOrnHisHis

ArgArg

EssentialEssential Non-EssentialNon-Essential

% o

f N

orm

al%

of

Nor

mal

Cerra, et al; JPEN, 1985 J. Y. PangJ. Y. Pang

Protein Intolerance/Hepatic Protein Intolerance/Hepatic Encephalopathy CycleEncephalopathy Cycle

HepaticHepaticEncephalopathyEncephalopathy

LiverLiverFailureFailure

MalnutritionMalnutritionCatabolismCatabolism

ProteinProteinRestrictionRestriction

ProteinProteinIntoleranceIntolerance

J. Y. Pang

Reasons for malnutritionReasons for malnutrition

OutpatientOutpatient• Anorexia, nausea, vomitingAnorexia, nausea, vomiting• Poor dietPoor diet• MalabsorptionMalabsorption• Hypermetabolism/hypercatabolic stateHypermetabolism/hypercatabolic state

InpatientInpatient• Abnormal metabolic state, anorexia, malabsoAbnormal metabolic state, anorexia, malabso

rptionrption• Unpalatable diet (low Na, low protein)Unpalatable diet (low Na, low protein)• Fasting for testsFasting for tests• G-I bleeding, PSEG-I bleeding, PSE

J. Y. Pang

肝臟疾病氨基酸配方肝臟疾病氨基酸配方 TalAmine Hepa 8% inj.TalAmine Hepa 8% inj.

• 高枝鏈氨基酸高枝鏈氨基酸 High BCAA (36%)High BCAA (36%)• 低芳香環氨基酸低芳香環氨基酸 Low AromaticsLow Aromatics• BCAA:AAA = 37:1BCAA:AAA = 37:1• Low MethionineLow Methionine• Iso:Leu:Val ratio =1:1:1Iso:Leu:Val ratio =1:1:1• 完整蛋白質配製完整蛋白質配製 (for liver disease)(for liver disease)

龐振宜

• 4848 小時改善肝昏迷小時改善肝昏迷• 療效優於傳統治療療效優於傳統治療• 改善體內氨基酸不平衡改善體內氨基酸不平衡• 良好正氮平衡良好正氮平衡

Hepatic Amino Acids SupplementAMIN-HEPA

LeucineLeucine• Increase protein synthesisIncrease protein synthesis• Decrease protein breakdownDecrease protein breakdown

BCAABCAA• Energy sourceEnergy source• Regulation amino acidsRegulation amino acids• Hepatic protein synthesisHepatic protein synthesis• Metabolism of ammoniaMetabolism of ammonia• Decrease plasma AAADecrease plasma AAA• Decrease proteolysisDecrease proteolysis• Competition of BCAA with AAA for BBBCompetition of BCAA with AAA for BBB

increase norepinephrine synthesisincrease norepinephrine synthesisJ. Y. PangJ. Y. Pang

Hepatic Amino Acids SupplementHepatic Amino Acids Supplement

AMIN-HEPA AMIN-HEPA

BCAA (42%)BCAA (42%) AAAAAA METMET BCAA/AAA ratio ( 15:1)BCAA/AAA ratio ( 15:1)

J. Y. Pang

Per Serving % CaloriesServing Size 55gCalories 250 KcalCarbohydrate 35g 56 Fat 8g 28Protein 10g 16 Lactalbumin Hydrolysate 7.25g L-leucine 1.10g L-isoleucine 0.88g L-Valine 0.77g

Hepatic Amino Acids SupplementHepatic Amino Acids Supplement

AMIN-HEPA AMIN-HEPA

Vitamins PerServing

% US RDA

Minerals Per serving % US RDA

Vitamin A 625 IU 12.5 Choline 75mg **Vitamin D 100 IU 25.0 Sodium 125mg **Vitamin E 8 IU 25.0 Potassium 312mg **Vitamin K 10 ug ** Chloride 250mg **Vitamin C 37.5mg 62.5 Calcium 125mg 12.5Folic Acid 100ug 25.0 Phosphorus 125mg 12.5Thiamine 0.37mg 25.0 Magnesium 50mg 12.5Riboflavin 0.43mg 25.0 Iodine 18.8ug 12.5Vitamin B6 0.5mg 25.0 Manganese 0.62mg **Vitamin B12 1.5ug 25.0 Copper 0.25mg 12.5Niacin 5mg 25.0 Zine 1.88mg 12.5Biotin 75ug 25.0 Iron 2.25mg 12.5Pantothenic Acid 2.5mg 25.0 Selenium 25ug **

Chromium 18.8ug **Molybdenum 18.8ug **

Hepatic Amino Acids SupplementHepatic Amino Acids Supplement AMIN-HEPA AMIN-HEPA

** No US RDA as been established** No US RDA as been established J. Y. Pang

Hepatic Amino Acids SupplementHepatic Amino Acids SupplementMulticenter StudyMulticenter Study

Inclusion CriteriaInclusion Criteria• Stable hepatic diseaseStable hepatic disease

• Protein intolerant (20-40 Gm/day)Protein intolerant (20-40 Gm/day)

Exclusion CriteriaExclusion Criteria• > Grade 1 encephalopathy> Grade 1 encephalopathy

• Acute illnessAcute illness

Horst, et. al; Hepatology, 1984.Horst, et. al; Hepatology, 1984. J. Y. Pang

Tolerance to Hepatic AA SupplementTolerance to Hepatic AA Supplementvs.. Dietary Proteinvs.. Dietary Protein

0

50

100

Hepatic AA Suppl. Dietary protein

Percent of Patients Developing EncephalopathyPercent of Patients Developing Encephalopathy

Horst, et. al; Hepatology, 1984Horst, et. al; Hepatology, 1984 J. Y. Pang

10%10%

88%88%

Increased the blood Fischer's ratio compared to tIncreased the blood Fischer's ratio compared to the hepatopathy diet alonehe hepatopathy diet alone

Before treatmentBefore treatment Week 1Week 1 Week 2Week 2 Week 3Week 3 Week 4Week 4

00

0.50.5

1.01.0

2.02.0(on a molar basis)(on a molar basis)

Group first receivingGroup first receivingHepatic AA Suppl.Hepatic AA Suppl.

Group first receivingGroup first receivingthe control treatmentthe control treatment

Control periodControl period

Period of the Hepatic AA Suppl.Period of the Hepatic AA Suppl.Hayashi, S., et al: JJPEN 9(3):425-435, 1987Hayashi, S., et al: JJPEN 9(3):425-435, 1987 J.Y. PangJ.Y. Pang

Fis

cher

's r

atio

Fis

cher

's r

atio

p<0.01p<0.01

Time course of blood ammonia levelTime course of blood ammonia level

Before treatmentBefore treatment Week 1Week 1 Week 2Week 2 Week 3Week 3 Week 4Week 4

0

5050

100100

150150(%)(%)

Group first receivingGroup first receivingHepatic AA SupplHepatic AA Suppl..

Group first receivingGroup first receivingthe control treatmentthe control treatment

Control period

Period of the Hepatic AA Suppl.Period of the Hepatic AA Suppl.

J.Y. Pang

Per

cent

age

rela

tive

to

the

pre

trea

tmen

t va

lue

Per

cent

age

rela

tive

to

the

pre

trea

tmen

t va

lue

Hayashi, S., et al: JJPEN 9(3):425-435, 1987Hayashi, S., et al: JJPEN 9(3):425-435, 1987

Improved the impaired nitrogen balance in a sevImproved the impaired nitrogen balance in a severe hepatopathy modelere hepatopathy model

day 1day 1 Day 2Day 2

Group treated with Hepatic AA Suppl.Group treated with Hepatic AA Suppl.

Group treatd with marketed preparation for enteral nutrition

(mg N)(mg N)

Aminals that underwent hepatic resection

Ohashi, H.,et al:The Clinical Reports, 21(6):2533-2541,1987

Nit

roge

n b

alan

ce v

alu

eN

itro

gen

bal

ance

val

ue

Day 3Day 3

AMIN - HEPA AMIN - HEPA INSTANTINSTANTA nutritionally complete diet for liver diseaseA nutritionally complete diet for liver disease

纍積生存

纍積生存

率率

(月 )

Log rank test p<0.05Wilcoxon rank test p<0.05Gehan-Wilcoxon test p<0.05

16th Asia Pacific Hepatologic Congress Feb. 1988

Historical DataHistorical Data(n=31)(n=31)

Hepatic AA Suppl.Hepatic AA Suppl.(n=31)(n=31)

J. Y. Pang


J. Y. PangJ. Y. Pang

配製配製

210ml water with one pack of Amin-Hepa210ml water with one pack of Amin-Hepa 口服口服

管餵管餵4 packs of Amin-Hepa into 840ml water4 packs of Amin-Hepa into 840ml wateras 1 liter solutionas 1 liter solution

用量用量完全以完全以 Amin-Hepa Amin-Hepa 為營養來源為營養來源 , , 每日每日 6-8 6-8 包包治療劑量每日治療劑量每日 44 包包


INDICATIONINDICATION

• Hepatic encephalopathy / protein Hepatic encephalopathy / protein intoleranceintolerance

• Malnourished liver disease patientsMalnourished liver disease patients

• CirrhosisCirrhosis

• HepatitisHepatitis

• Liver transplantLiver transplant

J. Y. Pang


• Well tolerated enteral supplement for protein iWell tolerated enteral supplement for protein intolerant patientsntolerant patients

• Reduces risk of protein - induced hepatic enceReduces risk of protein - induced hepatic encephalopathyphalopathy

• Promotes positive nitrogen balancePromotes positive nitrogen balance

• Improves abnormal plasma amino acid patternImproves abnormal plasma amino acid pattern

• Does not elevate blood ammonia levelsDoes not elevate blood ammonia levels



BENETITSBENETITS• Significantly lessens risk of protein-induced HESignificantly lessens risk of protein-induced HE• Promotes positive nitrogen balancePromotes positive nitrogen balance• Modified AA pattern is better tolerated than dietary Modified AA pattern is better tolerated than dietary

proteinprotein• Flexibility as oral drink or tube feeding can improve Flexibility as oral drink or tube feeding can improve

patient compliancepatient compliance


Documents

AMIN-HEPA INSTANT DRINK Nutrition in Liver Disorders HE EtiologyHE Etiology HE PathologenesisHE Pathologenesis Treatments of HETreatments of HE Nutritional