Spectrum of alcoholic liver diseases along with nutritional management. Contains cross references to support the information.

1. ALCOHOLIC LIVER DISEASE
Aetiology ; Pathophysiology &
Nutritional management
MANSI M.SHAH
M.Sc CLINICAL NUTRITION

2. INTRODUCTION
Largest gland - 1500g

3. FUNCTIONS
Ability to regenerate itself ; 10- 20% of functioning liver
CHO , lipid

4. INDIAN JOURNAL OF PUBLIC HEALTH , 2014
Trends of chronic liver disease in a tertiary care referral hospital in Eastern India
Background: There is scarce Indian data on time trends of hepatitis, an impediment to
formulate an effective public health policy on the matter. Objective: The aim was to study
secular trends and burden of hepatitis in a railway population. Materials and Methods:
Outdoor, indoor, endoscopy unit and mortality records of patients attending this hospital from
January 2003 to December 2011 were searched manually and relevant parameters of
hepatitis patients were noted, especially etiology, clinical features, treatment, and mortality.
Cochran-Armitage trend test was used to test significance of any trend in these parameters.
Binary logistic regression analysis of various factors was carried out to study their effect on
the liver related mortality of hepatitis B and C cases and Kaplan-Meyer survival curves were
generated for significant factors. Two-sided P < 0.05 was considered to be significant. Result:
Chronic liver disease (CLD) due to alcohol showed a significant rising trend with early
age (mean 48.4 years) and high percentage of decompensated disease (75%) at
presentation and high early mortality (63%). No trend was observed for hepatitis B and C,
but significant reduction in mortality was observed when definitive therapy was given.
Cryptogenic CLD showed a decreasing trend though overall it still remained the most
important etiology and survival was better compared with alcohol even with conservative
therapy. Only 4% patients had hepatocellular carcinoma. Conclusion: A menace of alcohol
related liver disease affecting young productive work force in this part of India is foreseen,
which might impact the country's economy and mandates immediate containment policy.

5. METABOLISM OF ALCOHOL
First pass metabolism - stomach mucosa
• ADH - alcohol dehydrogenase pathway
• MEOS - microsomal ethanol oxidizing system
Change In Redox Potential In Liver
• Suppression Of Krebs Cycle (Increased Transformation From Pyruvate To Lactate)
• Impaired Gluconeogenesis , Hypoglycemia
• Increased Fatty Acid Synthesis
• Hyperuricemia

6. Pathogenesis
There are a number of hypotheses regarding the pathogenesis
of alcoholic liver injury.
Ethanol metabolism usually takes place in the mitochondria.
Ethanol is oxidised to acetaldehyde by alcohol dehydrogenase,
which in turn is oxidised to acetate by acetaldehyde
dehydrogenase. These oxidation reactions are associated with
the formation of NADH and NAD alter the redox state of
the cell. This has harmful effects on lipid and carbohydrate
metabolism—for example, steatosis. In habitual drinkers, a
microsomal mixed function oxidase, the microsomal ethanol
oxidising system, is increased by enzyme induction and is also
responsible for production of acetaldehyde.

7. The quantity of alcohol consumed is the most important risk factor for
ALD.
ALD - Alcohol consumption of >40g/day
Cirrhosis - Alcohol consumption of >60-80g/day
Women - twice sensitive to hepatotoxicity
Several variables predispose some people to alcoholic liver disease. These
include
• genetic polymorphisms of alcohol
• gender (women more than men),
• simultaneous exposure to other drugs,
• infections with hepato- tropic viruses,
• immunologic factors,
• obesity, and poor nutrition status.
RISK FACTORS

8. CLINICAL PRESENTATION
• Alcohol can cause significant liver damage without
producing any symptoms or signs of liver disease. Many
people are diagnosed when they have routine liver function
tests as part of a medical check-up.
• Patients may present with non-specific features such as
nausea, vomiting, abdominal discomfort, or diarrhoea.
• Patients with fatty liver usually look well and often have
only mild hepatomegaly with no other stigmata of chronic
liver disease.
• Patients with advanced liver disease may present with
jaundice, ascites, encephalopathy, or upper gastrointestinal
bleeding.

11. • obtaining a reliable history of prolonged alcohol abuse
• Increased γ-Glutamyltransferase
• Increased mean corpuscular volume
• Carbohydrate deficient transferrin - follow up patients
• Bilirubin (markedly raised in acute alcoholic hepatitis)
• Serum transaminases
• Prothrombin time
• Hypoalbuminemia
• Electrolyte abnormalities - hyponatraemia and hypokalaemia
and less commonly hypocalcaemia and hypomagnesaemia
• Serum fibrosis markers: procollagen III propeptide, laminin,
type IV collagen
• Liver ultrasound: detect splenomegaly and ascites
• Liver biopsy
BIOCHEMICAL MARKERS

12. MALNUTRITION IN THE ALCOHOLIC
• Primary: displacing other nutrients in diet;high energy
content
• Secondary: maldigestion / malabsorption
NUTRITIONAL EFFECTS OF ALCOHOLISM
• Imbalanced diet or anorexia
• Intestinal maldigestion & malabsorption
• Increased catabolism of visceral proteins & skeletal
muscle
• Increased excretion of vitamins

14. The pathogenesis of alcoholic liver disease progresses in three stages:
Hepatic steatosis (Fatty liver) - 80%
Alcoholic hepatitis - 10 - 35 %
Cirrhosis - 10%
SPECTRUM OF LIVER DISEASE

15. HEPATIC STEATOSIS
• 90% chronic alcohol abuser ; asymptomatic
• Clinical sign - hepatomegaly
• Elevated SGOT & SGPT levels
• Benign & Reversible condition (abstinence from alcohol)
• Accumulation of lipid exceeds 5% of liver weight
• fatty liver - steatosis
• fatty liver with inflammation - steatohepatitis
• CAUSES: Increased availability of fatty acids in the
liver
• From Adipose tissue
• Lipids synthesised by liver
• Dietary lipids
• Increased synthesis & decreased degradation

16. • The most common and difficult to handle myth about liver
disease is that there should be almost complete restriction of
dietary fat and protein intake in diet, which is in contrast to
the actual scientific dietary advices for such patients.
• Protein should be 1.5 g/kg/day and restricted only in the
presence of encephalopathy. Protein should be from vegetable
source and inclusion of Medium chain triglycerides in the
diet should be done as they are easily digested in the absence
of bile.
• Supplementation of vitamins and minerals should be taken.
• Always take consultation of registered Dietitian which
provides a right diet for right treatment.

17. ALCOHOLIC HEPATITIS
• Toxic liver injury - inflammation of liver
• Chronic ethanol consumption
• Increased susceptibility to infection ( pneumonia ; septicaemia)
• Antibiotics & Corticosteroids - complexity of nutritional
management
• Symptoms: fatigue; anorexia; weakness; fever, hepatomegaly.
• High mortality rates are seen (30%–60%).

18. MNT
• Spare liver & provide nutrients needed for regeneration
1. Abstention from alcohol
2. Small frequent meals
3. Energy: 30-35kcal /kg (conc. liquid formulas)
severe vomiting or diarrhoea- 5-10% glucose
4. CHO - 60 - 65% of calories
5. Protein : 1 - 1.2 g/kg
6. Fat : 20 - 30% of calories
bile obstruction- reduce fat
7. Vitamin -K supplementation (less prothrombin time)
8. Na & K (vomiting or diarrhoea)
9. Correction of nutritional deficiencies:
multivitamin(B12;folate ;thiamine ;pyridoxine ;vit-a ;vit-d)
mineral supplement (Zn; Mg; Ca;Ph)

19. CIRRHOSIS
• Chronic liver disease - healthy tissue replaced by scar
tissue, blocking the flow of blood through the organ - loss
of liver function
• Causes- chronic alcohol consumption; HCV; alcohol
toxicity, genetic predisposition & malnutrition
• Therapeutic interventions & Nutritional treatment -
prevent complications
• Laennec’s cirrhosis - scar tissue fat accumulation
portal hypertension esophageal varices
• Clinical manifestations - hepatomegaly; necrosis of liver
cells; serum protein is low; SGOT is elevated; decreased Hb
levels. Jaundice; ascites ; edema ; fever ; anorexia;
diarrhoea; delirium

20. MANAGEMENT
• Abstinence: support groups, alcohol withdrawal syndrome.
1. Small frequent meals
2. Energy: 40 - 50 kcal /kg dry body weight (minimise
endogenous protein catabolism)
3. CHO - 300 - 400g to spare protein
4. Protein : 1 - 1.5 g/kg dry weight
5. Fat : 30 - 40% of non protein calories
restrict fat in case of jaundice
• Vitamins & minerals - thiamine, folic acid, and other
B vitamins carotenoids, selenium, vitamin E, folate and
zinc.
• Nutrition supplements: nasogastric feeding in malnourished

21. Journal of nutrition and food science , 2013
Effect of a Late Evening Snack of Amazake in Patients with Liver Cirrhosis:
A Pilot Study
Yumiko Nagao1 and Michio Sata
Background: Liver Cirrhosis (LC) is a state of accelerated starvation. A late evening
snack improves protein energy malnutrition, caused by overnight starvation and the
catabolic state of patients with LC. This study was designed to evaluate the effects of
amazake, a traditional sweet Japanese beverage, as a late evening snack for cirrhotic
patients.
Methods: Serum biochemical parameters and the visual analogue scale (VAS) were
examined at 0, 4, 8, and 12 weeks. Each patient drank 200 kcal of amazake at bedtime
every night for 12 weeks.
Results: Four patients (mean age 67.3 ± 5.7 years) with viral LC were recruited and their
VAS score determined, along with a biochemical examination of the blood. White blood
cell counts (WBC), especially neutrophil counts, were elevated following a period of
amazake intake. Each VAS score was reduced following amazake intake. Amazake intake
improved the Quality of Life (QOL) in all terms of sense of abdomen distension, edema,
fatigue, muscle cramps, loss of appetite, taste disorder, constipation, diarrhea, vomiting,
and sleep disorder. Any sense of abdominal distension, constipation and vomiting had
disappeared after 8 weeks of amazake intake and taste disorder and sleep disorder
had disappeared after 12 weeks of amazake intake. No major clinical events or
virological rebounds occurred in the subjects.
Conclusions: Amazake, which is rich in vitamins and amino acids, could be effective
in reducing the subjective symptoms and improving the QOL of patients with LC.

22. Probiotics for patients with compensated liver cirrhosis: a double-blind
placebo-controlled study.
Pereg D1, Kotliroff A, Gadoth N, Hadary R, Lishner M, Kitay-Cohen Y., February , 2011
BACKGROUND:
Gut flora is related to the major complications of liver cirrhosis including hepatic
encephalopathy, spontaneous bacterial peritonitis, and variceal bleeding. Prior studies have
reported a beneficial effect of gut flora modification with probiotic bacteria in patients with
minimal hepatic encephalopathy. We aimed to study the effect of probiotics on clinical and
laboratory parameters of patients with compensated cirrhosis.
METHODS:
A double-blind placebo-controlled study that included patients with liver cirrhosis and at
least one major complication of cirrhosis in the past, clinical evidence of portal
hypertension, or decreased hepatic synthetic function. Participants were randomly assigned to
receive probiotic capsules containing Lactobacillus acidophilus, Lactobacillus bulgaricus,
Bifidobacterium lactis, and Streptococcus thermophiles or placebo for a period of 6
months.
RESULTS:
A total of 36 patients were available for final analysis (distributed equally between the
probiotic and placebo groups). The administration of probiotics was not associated with
significant differences in either clinical or laboratory parameters between the two groups.
Because the lack of a beneficial effect may be related to the compensated liver disease of
patients, we conducted a subanalysis of patients with baseline ammonia levels > 50 mmol/L. In
this subgroup, the administration of probiotics appeared to significantly reduce the
ammonia levels starting after 1 month of treatment. However, this effect diminished and
lost its significance following comparison to the placebo group.

23. The effect of a late-evening protein-containing snack on nitrogen balance in cirrhotic
patients , 2014
tanta medical journal
Purpose
The aim of the study was to evaluate the effect of a late-evening protein-containing snack
on nitrogen balance in cirrhotic patients.
Patients and methods
Thirty cirrhotic patients were divided into the following groups: group I, comprising 15
patients who received a late-evening 300-cal, 15-g protein-containing snack daily for 15
days; and group II, comprising 15 patients who received a late-evening supplement of
amino acids (branched and essential) containing 22-g protein daily for 15 days. All
patients were subjected to full history taking, clinical examination, and pelvic abdominal
ultrasound. Liver function tests, complete blood picture analysis, and estimation of blood
urea and serum creatinine, urinary nitrogen loss, urea concentration in both serum and
urine, and nitrogen balance were performed for all patients.
Results
There was a significant increase in the mean level of serum albumin and red blood
cell counts. The mean nitrogen balance significantly increased in both groups but
more in patients who received branched chain amino acid (BCAA) supplementation.
The mean serum ammonia significantly decreased in group II patients who received
a late-evening BCAA supplementation, but not in patients of group I who received a
late-evening protein-containing snack. There was no statistically significant difference in
the levels of serum bilirubin or fasting blood glucose in either group.

24. COMPLICATIONS

25. MNT
• High protein to replenish serum albumin & raise oncotic
pressure
• salt restriction - 2g / day
• fluid restriction- 1500ml/day if Na is below 120 mEq/l
• Acute bleeding episodes - PN
• Adequate energy
• Diuretic therapy
• Paracentesis
• TIPS (Transjugular intrahepatic portosystemic shunt )

26. HEPATIC ENCEPHALOPATHY
• Syndrome of impaired mental status & abnormal
neuromuscular function resulting in failure of liver
function
• Contributing factors:
• degree of hepatocellular failure
• portosystemic shunting
• exogeneous( sepsis& variceal bleeding)
• Clinical manifestations:
• changes in mental status & personality
• neuromuscular changes
• Asterixis

28. Child - Pugh score

29. Nitrogen metabolism plays a major role in the development of hepatic
encephalopathy (HE) in patients with cirrhosis.
1. Energy and nitrogen requirements in patients with HE are unlikely to
differ substantially from those recommended in patients with cirrhosis per
se viz. 35-45 kcal/g and 1.2-1.5g/kg protein daily.
2. Small meals evenly distributed throughout the day and a late-night
snack will help minimize protein utilization.
3. Diets rich in vegetables and dairy protein may be beneficial and are
therefore recommended.
4. Branched chain amino acid (BCAA)supplements ; Increasing dietary fiber
& probiotics may be of value.
5. Short-term multivitamin & mineral supplementation should be
considered in patients admitted with decompensated cirrhosis.
6. Hyponatremia may worsen HE; it should be prevented as far as possible
and should always be corrected slowly.
7. Effective management of these patients requires an integrated
multidimensional approach.
American association for the study of liver disease AASLD , 2013

30. Probiotic VSL#3 Reduces Liver Disease Severity and Hospitalization in Patients
With Cirrhosis: A Randomized, Controlled Trial , 2014
Background & Aims
Little is known about whether probiotics can affect outcomes of patients with cirrhosis and
hepatic encephalopathy (HE). We assessed the efficacy of a probiotic preparation in preventing
the recurrence of HE (primary outcome) and reducing the number of hospitalizations and severity
of liver disease in patients with cirrhosis.
Methods
We performed a double-blind trial at a tertiary care hospital in India. Patients with cirrhosis
who had recovered from an episode of HE during the previous month were assigned
randomly (using computer-generated allocation) to groups given a probiotic preparation (VSL#3,
9 × 1011 bacteria; CD Pharma India Private Limited, New Delhi, India) (n = 66) or placebo (n =
64) daily for 6 months.
Results
There was a trend toward a reduction in the development of breakthrough HE among patients
receiving the probiotic (34.8% in the probiotic group vs 51.6% in the placebo group; hazard ratio
[HR], 0.65; 95% confidence interval [CI], 0.38–1.11; P = .12). Fewer patients in the probiotic
group were hospitalized for HE (19.7% vs 42.2%, respectively; HR, 0.45; 95% CI, 0.23–0.87; P =
.02) or for complications of cirrhosis (24.2%) than in the placebo group (45.3%) (HR, 0.52; 95%
CI, 0.28–0.95; P = .034). Child–Turcotte–Pugh and model for end-stage liver disease scores
improved significantly from baseline to 6 months in the probiotic group, but not in the placebo
group. There were no adverse events related to VSL#3.
Conclusions
Over a 6-month period, daily intake of VSL#3 significantly reduced the risk of hospitalization
for HE, as well as Child–Turcotte–Pugh and model for end-stage liver disease scores, in patients
with cirrhosis.

31. LIVER TRANSPLANT
• Atleast 6 months of alcohol abstinence
• Psychosocial & nutritional status
MNT - individualised
• Goal - lessen the effects of malnutrition &
complications (ascites)
• Before transplant: 35 - 45 kcal/kg;
• 1.0 - 1.5g protein/kg
• After transplant: 30 - 35kcal/kg;
• 1.0 - 1.2g protein/kg
• Immunosuppressant drugs- hyperglycaemia.

32. Bacterial sepsis after living donor liver transplantation: the impact of early
enteral nutrition. , 2012
Ikegami T1Shirabe K, Yoshiya S, Yoshizumi T, Ninomiya M, Uchiyama H, Soejima Y,
Maehara Y.
BACKGROUND:
Bacterial sepsis is a significant problem that must be addressed after living donor liver
transplantation (LDLT).
STUDY DESIGN:
A retrospective analysis of 346 adult-to-adult LDLT patients was performed.
RESULTS:
Forty-six patients (13.3%) experienced bacterial sepsis, with primary and secondary origins in
23.9% and 76.1%, respectively. Gram-negative bacteria accounted for 71.7% of the bacteria
isolated. The 2-year cumulative graft survival rate in patients with bacterial sepsis was 45.7%.
Patients with bacterial sepsis secondary to pneumonia (n = 12) had poorer 2-year graft
survival rates (16.7%) than did those with primary or other types of secondary sepsis (p =
0.004). Multivariate analysis showed that intraoperative massive blood loss >10L (p <
0.001) and no enteral feeding started within 48 hours after transplantation (p = 0.005)
were significant risk factors for bacterial sepsis. Among patients who received enteral
nutrition, the incidences of bacterial sepsis in patients who received enteral nutrition within 48
hours (n = 135) or later than 48 hours (n = 57) were 5.9% and 21.0%, respectively (p = 0.002).
The incidence of early graft loss was 8-fold higher in recipients with massive intraoperative
blood loss without early enteral nutrition (p < 0.001).
CONCLUSIONS:
Early enteral nutrition was associated with significantly reduced risk of developing
bacterial sepsis after LDLT.

33. Parenteral Nutrition improves nutritional state and liver
function in malnourished patients . PN is safe and improves
mental state in patients with cirrhosis and severe HE. In
acute liver failure PN reduces the rate of complications & is
a safe second-line option to adequately feed patients in whom
enteral nutrition is insufficient or impossible.

35. POMR: A 40yr old male came with c/o right upper quadrant pain ;
anorexia; nausea ; dysgeusia & frequent loose stools.
PMH: N/K/C/O - DM;HTN;BA;TB
PSH: Nil significant
SH: alcohol abuse x 15yrs
Diagnosis: alcoholic hepatitis; on biopsy - steatosis and fibrosis
A/D
Height : 177cm
Weight : 67kg
IBW : 77kg
UBW : 82kg (5 yrs ago )
73kg( 6 months ago )
B/P
Serum albumin : 2.5 g/dl
Ammonia : 55mmol/l
Transferrin: 150mg/dl
Elevated liver enzymes & total bilirubin
Megaloblastic anemia profile.
CASE STUDY

36. C/E : mild peripheral edema with jaundice
muscle wasting ; stomatitis
PLAN : (Dry weight = 66kg)
Energy: 1980kcal/day @ 30kcal/kg/DW
Protein: 79.2g/day @ 1.2g/kg/DW
CHO : 321g/day @ 65% of T.calories
Fat : 41g/day @ 19% of T.calories
Fluid : 1900ml ~ 2L/day
Fibre : 25g/day
Salt : 5g/day
• Abstention from alcohol
• Small frequent meals with late evening snacks
• Vegetable protein to be included ; MCT to be given
• Multivitamin supplementation

37. THANK YOU !!

38. REFERENCES
Krause’s Food Nutrition & Diet Therapy - 11Th Edition
- Kathleen Mayan Saliva ; Escort Stump (Pg 743 - 755)
Nutrition Therapy & Pathophysiology
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Present Knowledge In Nutrition - 10Th Edition
-John W. Edam (Pg 912-930)
Krause - Food & Nutrition Care Process - 13Th Edition
Kathleen Mayan Saliva ; Escort Stump (Pg 651 - 653)
Modern Nutrition In Health & Disease
-Catharine (Pg 1115-11124)
Modern Nutrition In Health & Disease - 10Th Edition
-Maurice Shills (Pg1246-1256)
Contemporary Nutrition Support Practice - A Clinical Guide
-Laura E Matures ; Michele M Gottschlich (Pg 455)