Nutrition and liver cirrhosis萬芳醫院營養室江詩雯

2005.03.03

Influence of the metabolic complications of liver cirrhosis on dietary intakeNurdan TMed Sci Monit 2000; 6 :1223-1226

Nutritional therapy in cirrhosisGiulio M, Rebecca M, Federica A and Giampaolo BJ Gast Hepa 2004; 19 :S401-405

Post-feeding hyperammonaemia in patients with transjugular intrahepatic portosystemic shunt and liver cirrhosis: role of small intestine ammonia release and route of nutrition administrationPlauth M, Roske AE, Romaniuk P, Roth E, Ziebig R and Lochs HGut 2000; 46 :849-855

www.gutfeelings.com/ CRLIVER.JPG www.gicare.com/ pated/gifs/elv0004.gif

Fatty liver

Normal healthy liver, surface is smooth and uniform

Sever cirrhosis, surface is very nodular

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liver inflammation

liver necrosis

pain

Wt loss

hypoglycemia

ascites

splenomegalyvenous pressure

edema EVerectile dysfunctionmenstrual disorders

nauseavomitinganorexia

constipation

nutrition metabolism

portal pressure

hormone metabolism

bilirubin metabolism

total liver failure

fatigue

anemia

leukopenia

thrombocytopenia bleeding

bilirubinemia

clay-colored stooldark urine

Vit. K absorption

jaundice

intestinal bile

urobilingenHE coma death

Complications of liver cirrhosis

Portal hypertension Esophageal varices (EV) Ascites Hyperammonaemia Hepatic encephalopathy (HE) Hepatorenal syndrome

www.bio.ri.ccf.org/ Henderson/port.html

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Malnutrition is an early and typical aspect of hepatic cirrhosis.

70% of p’t with cirrhosis have signs of PT/Cal malnutrition.

Lautz et al. 1992Crawford et al. 1994

Prijatmoko et al. 1993

Way to lead malnutrition

food intake (anorexia, nausea, drugs) malabsorption energy and PT requirement paracenthesis induced PT loss complications

Malnutrition

mortality (35% v.s. 16% in normal-fed p’t) complications : ascites (44% v.s. 24%)

Lautz et al. 1992

p’t with advanced liver disease should be recommended a diet providing adequate calories, proteins, minerals and vitamines.

Dietary supplementation is much essential in CLD, which can decrease malnutrition, infections and sepsis happened.

Nompleggi and Bonkovsky 1994

p’t with cirrhosis can be observed early postprandial hyperinsulinemia, which results

in early satiety and decrease hunger via cholecystokinin (CCK).

It directly actions on the brain.

Richardson et al. 1994

Nutrition in the complications of liver cirrhosis

Calories (Cal) Fat Protein (PT) Carbohydrate (CHO) Sodium (Na) Fluid Vitamins

Total Cal=REE*1.2 or 30 kcal/kg Fat=30-35% of total Cal PT=1g/kg/d

HE :10-20g/d (3-5d 5-10g)

ESPEN Consensus group : req. 1-1.5g/kg/d

low PT diet may worsen HE

CHO=remainder of the Cal requirement

m.

Plauth et al. 1997

Nurdan 2000

HE

Vegetable PT :1. intraluminal pH

2. ammonia secretion

3. transit time

suggest 30-40g/d

Nurdan 2000

Na : not exceed 2g(88mmol)/d Daily sodium intake :

130 (mmol/kg) * wt change (kg/d) + 24h urinary Na (mmol/d) – 10 (mmol/d)

Tense ascites : 40mmol/d Na free diet : energy, PT, lean body mass Na intake should be restricted before fluid

Way to lead Na depletion

NSAID Vasopression analogues Large volume paracentesis without volume

expansion Diuretic therapy

Fluid : no need to restrict at the beginning Vitamins : supplement water and fat solutab

le vit.(B1, B12, folate, A, D, E, K)

Alb.:

(1)p’t don’t receive alb. had significantly more

distrubances in electrocyte, PRA and

creatinine level than those who received it.

no difference in survival

(2)iv. filtered to ascitic fluid and doesn’t

remain in the intravascular compartment.

Furthermore cause alb. degeneration and

be harmful in PT deficiency states.

iv BCAAs in cirrhosis with acute encephalopathy

7 controlled studies BCAAs group v.s. glucose or non selective AA s

oln. or lipid groups BCAAs was gave for 2-6 d Post treatment observation period : 4-16 d 201(BCAAs) v.s. 179(isocaloric group) No statistically significant in survival

Riggio et al. 1982Wahren et al. 1983Michel et al. 1985Cerra et al. 1985

Fiaccadori et al. 1985Strauss et al. 1986Vilstrup et al. 1990

Certainly BCAAs don’t worsen encephalopathy and may be safely used to maintain an adequate PT intake in subjects at risk of altered mental state.

BCAAs may be easily used as energy sources, thus improving nitrogen balance and have a beneficial on anorexia.

Plauth et al. 1997

Panella et al. 1987Tessair et al. 1996Laviano et al. 1997

Davidson et al. 1999

Oral BCAAs in cirrhosis with or without chronic encephalopathy

Oral BCAAs are generally used in athletes 9 controlled studies BCAAs (7-30g), alcoholic cirrhosis (29-90%), lat

ent encephalopathy (0-79%), lactulose (8-100%)

BCAAs supplementation can only be recommended in p’t at high risk of encephalopathy

Eriksson et al. 1982Sieg et al. 1983

Simko et al. 1983McGhee et al. 1983

Horst et al. 1984Guarnieri et al. 1984Christie et al. 1985

Fiaccadori et al. 1988Marchesini et al. 1990

A multicenter, randomized study, > 1 yr,

174 p’t (a) BCAA supplementation group (b) maltodextrins group (equicaloric)

(c) lactoalbumin group (equicaloric/nitrogenous)Non-BCAA group

Long term BCAA supplementationincreases survival time and prevents to decrease hospital admission rates.

BCAA-enriched formulations can be useful in p’t who are intolerant to PT and malnourished, which can improve PT synthesis and reduce post injury catabolism.

Nompleggi and Bonkovsky 1994

BCAA-enriched soln. increased serum alb. also reduced morbidity and improved the quality of life.

BCAAs strongly activate mTOR signaling in liver, which is the cellular nutrition sensor for PT translation initiation.

Poon et al, 2004

Nishitani et al, 2004

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Transjugular Intrahepatic Portosystemic Shunt (TIPS)

Expandable stent

Portal vein

Hepatic vein

Liver cirrhosis, ascites, hepatorenal syndrome

Small intestine mucosa extracts glutamine

from arterial blood for metabolism of enterocytes

and releases ammonia into portal vein

hyperammonaemia

Hepatic encephalopathy

TIPS

Methods

Enteral AA infusion (TIPS : 5/8) Parenteral AA infusion (TIPS : 3/8) ND tube (2mL/kg/h) Drugs: tobramycin 80mg, colistin 100mg, a

mphotericin B 500mg qid to reduce ammonia production from intestinal bacterial

Ammoniagenic AA :Glycine & Gln.

Gln. : 274 μmol/kg/h

CHO:182g/LFat:56g/L

NaCl:170mmol/L

Provide Cal substrates and maintain hormonal response, mucosal perfusion comparable

Blood was sampled in triplicant and then centrifugated and deproteinisated/

Analysis for ammonia and Gln.

-10 -5 15 30 60 90 180 240min

120

Infusion over

0

Enteral or parenteral AA infusion

Methods

Arterial blood Superior mesenteric venous (SMV) blood Data are given as mean (SEM) Values were calculated as area under the curve

of venous-arterial differences Two tailed t test SPSS and Excel P <0.05

EN ammonia Gln.

60

157

74

PN ammonia Gln.

115

ammonia Gln.

ammonia Gln.SMV-artery SMV-artery

50 6285

65107

166

ammonia Gln.

EN ENPN PN

ammonia Gln.

Small intestine is a source of post-feeding hyperammonaemia in liver cirrhosis.

EN is associated with higher degree of systemic hyperammonaemia than isonitrogenous PN in cirrhosis and TIPS p’t.

Results

Discussion

TIPS can be used to control variceal haemorrhage or ascites, but aslo associated with an increased risk of HE.

Ochs et al, 1995Nolte et al,1998

Somberg et al, 1994Jalan et al, 1997

None of p’t had worsening of their mental state when feeding a substantial nitrogen load of 40.5g of AA/ 75kg BW within 120 min.

PT test meals in cirrhosisStaedt et al, 1993

Gln. 5.9g (14.5% of total AA) as more ammoniagenic than other AA and capable of inducing HE.

Gln. as a potentially essential PN in malnourished cirrhotic p’t deserves further clarification.

Conclusion

Gln. metabolism of small intestine is a source of increased portal ammonia concentrations and that post-feeding hyperammonaemia is caused.

PN feeding should be regarded as superior to EN in cirrhotic p’t.

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Child-Pugh score

score 1 2 3

Alb. >3.5 3.5-2.8 <2.8

Bilrubin <2 2-3 >3

Ascites Absent Mild-Moderate

Severe/

Refractory

HE Absent Mild (I-II) Severe (III-IV)

PT prolongation

<4 sec.

(<1.7)

4-6 sec. (1.7-2.3)

>6 sec.

(>2.3)Interpretation:Class A: 5-6 Class B: 7-9 Class C: 10-15

BCAAs and amyotrophic lateral sclerosis active glutamate dehydrogenase (deficient in AL

S, also called Lou Gehrig’s disease double-blind trial 26g/d of BCAA supplements help ALS p’t maint

ain muscle strength a larger study was ended early when people usi

ng BCAAs not only failed to improve, but experienced higher death rates than the placebo group

Plaitakis et al, 1988

The Italian ALS Study Group 1993

Thanks for your attention!!