Malnutrition and Nutrition Support in Alcoholic Liver Disease ALD

1
Malnutrition and Nutrition Support in Alcoholic
Liver Disease (ALD)
2007 Fellows' Nutrition Course (FNC)
Craig J. McClain, M.D., Professor Division of
Gastroenterology/Hepatology Departments of
Medicine, Pharmacology and Toxicology Associate
Vice President for Research Louisville VA Medical
Center University of Louisville Jewish Hospital
Louisville
2
Objectives

• Overview of ALD
• Mechanisms of ALD
• Prevalence of malnutrition in ALD
• Causes of malnutrition in ALD
• Nutrition Support in ALD

3
Overview of ALD

• Alcohol abuse costs U.S. 185 billion annually
• gt 2 million in U.S. with some form of ALD
• Likely underestimated due to social stigma

Harwood, et al., NIAAA, 2000
4
Stages of ALD

• Fatty liver
• 100 of heavy drinkers
• Alcoholic hepatitis
• 10-25 of heavy drinkers
• Cirrhosis 10-20 of heavy drinkers
• Usually gt 10 years

5
Prognosis

• Fatty liver normal
• survival
• AH at 48 months 58 alive
• Cirrhosis 49 alive
• AH Cirrhosis 35 alive
• Prognosis worse than major cancers such as
  breast, colon, prostate

Chedid, et al. Am J Gastroenterol 86210, 1991
6
Mechanisms of Liver Injury
Oxidative stress
Cytokines
Altered Immunity
Genetics
Proteasome dysfunction
Acetaldehyde
Nutritional Abnormalities
Altered methionine metabolism
Mitochondrial dysfunction
7
Prevalence of malnutrition
8
Prevalence of Malnutrition

• Alcoholic hepatitis
• Stable alcoholic cirrhosis with ascites
• Viral liver disease

9
Malnutrition in Alcoholic Hepatitis
10
Nutritional Status in Alcoholic Hepatitis

• Severity of Liver Disease
• Initial Laboratory Mild Moderate
  Severe
• Lymphocytes 2,067 148 1,598 90
  1,366 83
• (1000-4000/mm3)
• Albumin 3.7 0.1 2.7 0.1
  2.3 0.1
• (3.5-5.1 g/dl)
• Creatinine-Height Index 75.7 2.84 62.9
  3.3 64.0 4.65
• ( of standard)

Mendenhall, et al. Am J Med 1984
11
Malnutrition in Alcoholic Cirrhosis with Ascites
12
Nutritional Status in 25 Outpatient Alcoholic
Cirrhotics

• Cirrhotics Normals
• Albumin (g/dl) 3.1 0.1 4.1 0.2
• Prealbumin (mg/dl) 10.8 0.9 26.0 0.3
• Creatinine/height Index 71 8 100

Antonow, et al. Alcohol and the Brain, 1985
13
Malnutrition in Viral-induced Cirrhosis
14
Alcohol vs. viral related cirrhosis

• 120 patients, 77 EtOH, 43 viral
• Alcohol Virus
• albumin (mg/dl) 3.2 3.3
• TSF 93 81
• Cr-height index 74 72

Caregaro, et al. AJCN 1996
15

• Causes of malnutrition

16
Daves Top 10Causes of Malnutrition

• Anorexia
• Altered taste/smell
• Nausea/vomiting
• Diarrhea/malabsorption
• Poor food availability/quality
• Metabolic disturbances (e.g., hypermetabolism/cata
  bolism)
• Cytokine effects
• Complications of liver disease (PSE, ascites, GI
  bleeding)
• Unpalatible diets (Na, protein)
• Fasting for procedures

17
CytokineNutrient interactions
18
Cytokines inALD
serum proinflammatory cytokines (TNF)
monocyte cytokine production liver
immunohistochemical staining
19
Metabolic/Nutritional Effects of TNF

• Anorexia
• Fever
• Neutrophilia
• Synthesis of acute phase reactants
• Hypoalbuminemia
• Hypermetabolism
• Catabolism/muscle wasting

• Collagen deposition
• Bone resorption
• Intestinal permeability
• Stress gastritis
• Endothelial permeability
• Bile flow, cholestasis
• Zinc

20
Cytokine Effects are Complications of Liver
Disease
Anorexia
Encephalopathy
Fever
Energy expenditure
Neutrophilia
Portal vein thrombosis
Muscle wasting
Liver Injury
Altered amino acid metabolism
triglycerides
Collagen formation
Delayed gastric emptying
gut permeability
Altered mineral metabolism ( zinc)
Osteoporosis
Endothelial permeability with edema formation
Hypoalbuminemia
21
Hypothesis

• Cytokines mediate many of the nutritional/metaboli
  c abnormalities of AH
• Cytokines mediate at least in part, the liver
  injury of AH

22
Traditional NutritionSupport
23
Nutrition Support
1
0
0
9
0
8
0
7
0
6
0
5
0
Survival ()
4
0
3
0
G
o
o
d

D
i
e
t
2
0
1
0
P
o
o
r

D
i
e
t
0
0
0
.
5
1
2
3
4
5
Years
Patek, et al. JAMA 1948139543
24
(40)
100
80
60
(30)
MORTALITY ()
40
(54)
(39)
(55)
20
(27)
0
lt1000
gt3000
2500-3000
2000-2499
1500-1999
1000-1500
CALORIC INTAKE (Kcal/d)
Mendenhall, et al. Alc Clin Exp Res 19635, 1995.
25
VA Cooperative Study on AH
Anorexia Mild 46 Moderate 63 Severe 66
26
Daily protein intake for treatment and control
groups peaked at 119 and 61 g of protein,
respectively
140
120
TREATMENT
100
80
g/day
60
CONTROL
40
20
0
0
1
2
3
4
Week
Kearns, et al. Gastro 1992102200
27
Controls Treated
Serum bilirubin
Kearns, et al. Gastroenterol 1992102200
28
Nutrition vs. Steroids
Per protocol
Survival
2000 cal/day via tube (liver specific) vs. 40
mg/day Prednisone
Cabre, et al. Hepatology 20003236
29
Late Evening Meals

• Cirrhosis
• Increases protein turnover
• Decreased hepatic glycogen stores
• Late evening snacks/meals prevent nocturnal amino
  acid breakdown for gluconeogenesis decrease
  amino acid loss and improve nitrogen balance

Swart, et al. BMJ 2991202, 1989 Yamauchi, et al.
Hep Research 21199, 2001 Hirsch, et al. JPEN
17119, 1993
30
PSE How Much Protein?

• gt50-60 g/day for nitrogen balance
• 1-1.2 g protein/kg/day stable
• 1.5 g protein/kg/day in malnourished

31
Enteral vs. Parenteral?OrWill the Varices Burst?

• enteral

32
Serum IGF-1 Concentrations
Why cant my patient gain muscle mass?
Normal serum concentration for age and
sex-matched controls (100-600 ng/ml)
IGF-1 Ng/ml
Months
Mendenhall, et al. Am J Gastroenterol
33
CAM

• S-adenosylmethionine (SAMe)
• Silymarin (Milk Thistle)
• Antioxidants (Vitamin E)
• Polyenylphosphatidylcholine (Lecithin)

X
X
Lieber, et al. Alcohol Clin Exp Res 271765,
2003 Hanje, et al. Nutr Clin Pract 21255,
2006 McClain, et al. Alcohol 27185, 2002 Mezey,
et al. J Hepatol 4040, 2004 Phillips, et al. J
Hepatol 44784, 2006
34
(SAMe)
(SAH)
Methyl acceptor
35
SAMe Improved survival ? transplantation in
Childs A,B Alcoholic Cirrhosis
Cochrane Evaluation Cannot Support or Refute Use
Mato, et al. J Hepatol, 1999, 301081-9. Rambaldi,
et al. Cochrane Reviews 2006
36
CONCLUSIONS

• Patients with advanced liver disease are
  regularly malnourished
• Traditional nutrition support improves nutrition
  and may improve outcome
• CAM provides unique opportunities for nutritional
  modulation of liver disease (further research is
  required!)