Alcoholic-assocaiated Liver Disease

metabolism of alcohol

-disulfiram inhibits acetaldehyde dehydrogenase

-80% of alcohol passes through the liver to be detoxified

-TNF alpha

-IL 6

-IL 8

-Oxidative stress

-Lipid peroxidation

-acetaldehyde

What are the pro inflammatory cytokines that are secreted with chronic consumption of alcohol?

acetaldehyde

What pro inflammatory cytokine causes the "hangover"?

risk factors for alcoholic liver disease

-quantity of alcohol taken

-pattern of drinking

-gender

-hep C

-genetic factors

-iron overload

-diet

quantity of alcohol taken as a risk factor for ALD

•Women: 20g/day for 20 years or more

•Men: 60-80g/day for 20 years are more

•Increases risk of hepatitis and fibrosis by 7 to 47%

pattern of drinking that is a risk factor for ALD

drinking outside of meal time increases risk of ALD 3 times

gender risk factor for ALD

women are twice as susceptible to alcohol-related liver disease

Hep C risk factor for ALD

concomitant hep C infection significantly accelerates the process of liver injury

genetic factors that are risk factors for ALD

-predispose both alcoholism and ALD

-polymorphisms

iron overload risk factor for ALD

hemochromatosis

diet risk factor for ALD

-malnutrition

-vitamin A and E can worsen alcohol-induced liver damage by preventing regeneration of heptocytes

skin symptoms of ALD

-jaundice

-small, red spider like veins on the skin

-very dark or pale skin

-redness on the feet or hands itching

jaundice

yellow color of skin, mucus membranes, or eyes

brain and nervous system symptoms of ALD

-probs with thinking, memory, and mood

-fainting and light headedness

-numbness in legs and feet

vitamin deficiencies

Alcohol used as nutrition can create _____________

yes

Is MAFLD reversible?

yes

Is MASH reversible?

no

Is Cirrhosis reversible?

no

Is hepatocellular carcinoma reversible?

MAFL

presence of hepatic steatosis with no evidence of hepatocellular injury

MASH

presence of hepatic steatosis plus inflammation and scarring

fatty change (steatosis)

is the accumulation of fatty acids in liver cells

macro vesicular steatosis

large fatty globules that develop throughout the liver and can begin to occur after a few days of heavy drinking

alcohol

is metabolized by alcohol dehydrogenase (ADH) into acetaldehyde

higher

A ___________ NADH concentration induces fatty acid synthesis while a decreased NAD level results in decreased fatty acid oxidation.

-weakness

-N

-abdominal pain

-loss of appetite

-malaise (generally feeling unwell)

What are the alcoholic fatty liver disease symptoms?

alcoholic hepatitis

is characterized by the inflammation of hepatocytes.

Between 10% and 35% of heavy drinkers develop alcoholic hepatitis

no

Is the development of hepatitis directly related to the dose of alcohol?

alcoholic steato necrosis

inflammation appears to predispose to liver fibrosis

inflammatory cytokines (TNF-alpha, IL6 and IL8)

are essential in the initiation and perpetuation liver injury by inducing apoptosis and necrosis

-pain in the abdomen

-jaundice

-spider like veins on the skin

-malaise

-fever

-N

-loss of appetite

alcoholic hepatitis s/s:

-hair loss

-dark urine

-black or pale stools

-dizziness

-fatigue

-loss of libido

-bleeding gums or nose

-edema

-V

-muscle cramps

-weight loss

end stage alcoholic hepatitis s/s:

cirrhosis

is a late stage of serious liver disease marked by inflammation (swelling), fibrosis (cellular hardening) and damaged membranes preventing detoxification of chemicals in the body, ending in scarring and necrosis

10-20%

What % of heavy drinkers will develop cirrhosis of the liver?

acetaldehyde

may be responsible for alcohol-induced fibrosis by stimulating collagen deposition by hepatic stellate cells

-jaundice (yellowing)

-hepatomegaly

-pain and tenderness from structural changes in damaged liver architecture

What are the symptoms of cirrhosis?

liver function tests

These are simple, inexpensive and easy to perform but cannot be used in alone to make diagnosis which include

-serum albumin levels

-prothrombin time

-bilirubin

-alk phos

-transaminase levels

serum albumin levels and prothrombin time

indicates hepatic protein synthesis

bilirubin

is a marker of whole liver function

transaminase levels

indicate hepatocellular injury and death

alkaline phosphatase levels

estimate the impedance of bile flow

imaging tests

▪An ultrasound scan, CT scan, or a MRI scan be performed

▪Imaging studies do not confirm the presence of alcoholic liver disease

▪Can be used to assess for hepatic parenchymal changes

▪Ultrasound, CT scan, and MRI can be used to diagnose fatty change, cirrhosis, or neoplastic diseases of the live

liver biopsy

a fine needle is inserted into body and a small sample of liver cell is taken under local anesthesia and is examined under microscope

▪ Any patient with serum aminotransferases elevations that persist for >6 months, even if the patient is asymptomatic

▪ Patients who have evidence of liver failure (e.g., abnormal prothrombin time,

hypoalbuminemia) in addition to elevated aminotransferases. If a coagulopathy is present, transjugular biopsy is usually safer than percutaneous biopsy

▪ Patients in whom the diagnosis of alcoholic hepatitis is uncertain based upon clinical and laboratory findings

▪ Patients who may have more than one type of liver disease (such as alcohol and hepatitis C) in whom a liver biopsy may help determine the relative contribution of these factors

Who may be indicated for a liver biopsy?

endoscope

is a thin long flexible tube with a light and video camera at one end this tube is passed into esophagus and stomach and examine for varices

complications of cirrhosis

-portal hypertension is a common complication

-these new blood vessels are known as varices

-this can cause long term bleeding which can lead to anemia

▪ Ascites

▪ Hepatic encephalopathy

▪ Pancytopenia

▪ Splenomegaly

▪ Bloody vomiting

▪ melena

What are symptoms of portal hypertension?

▪Black stools

▪Bloody stools

▪Light headedness

▪Paleness

▪vomiting

What are the symptoms of varices?

beta blockers to prevent a bleeding episode

What is the tx for varices?

propranolol for varices tx

-40 mg initially increasing every 3-7days

-Maintenance 80-240 mg Q8-12H

-Not exceed 60 mg/day

nadolol for varices tx

10-30 mg Q12h

Timolol for varices tx

-10-30 mg Q21H

-maintenance 20-40 mg/day

Isosorbide mononitrate for varices tx

30-60 mg once a day in the morning

-propranolol

-nadolol

-timolol

-isosorbide mononitrate

What are the beta blockers used for varices?

ascites

-accumulation of fluid in the peritoneal vacity

-a low salt diet may be enough to facilitate the elimination of ascites and delay re-accumulation of fluid (60-90 mEq/day)

-abdominal distension with fullness in the flanks

-abdominal and back pain

-gastroesophageal reflux

What are the symptoms of ascites?

-bed rest

-sodium restriction (60-90 mEq/day to 1500-2000 mg of salt/day)

-Spironolactone: 100-400 mg/day

-Furosemide: 40-160 mg/day

-HCTZ: 50 mg/day

How do you treat cirrhotic ascites?

hepatic encephalopathy

a high level of toxins in the blood due to liver damage is known as hepatic encephalopathy

s/s of hepatic encephalopathy

▪ Agitation

▪ Confusion

▪ Disorientation

▪ Muscle stiffness

▪ Muscle tremors

▪ Difficulty speaking

▪ Coma

-Lactulose: 15-30 ml orally 2-4 times daily

-antibiotics

How do you manage hepatic encephalopathy?

-Metronidazole: 250 mg orally 3 times daily

-Neomycin: 0.5-1 g orally every 6-12 hrs for 7 days

-Rifaximin: 400 mg orally 3 times daily

-LOLA: L-ornithine L-aspartate 9 g orally 3 times daily

What are the antibiotics used for hepatic encephalopathy?

ALD tx

-Abstinence

-Nutrition

-Drug therapy:

▪ Prednisolone

▪ Folic acid

▪ Thiamin

▪ Vitamin D

▪ Vitamin E

▪ Vitamin A

▪ Slymarin

-Liver transplantation

abstinence

-is the most important therapeutic intervention for pts with ALD

-has shown to improve the outcome and histological features of hepatic injury, to reduce portal pressure and decrease progression to cirrhosis, and to improve survival at all stages in pts with ALD

20%

Less than _____% of pts with demonstrate progression of liver disease after abstinence.

60%

5 yr survival improves from 34% to ____% for those with decompensated liver disease.

alcoholism

is associated with nutritional deficiencies

presence of significant protein calorie malnutrition

is a common finding in alcoholics, as are deficiencies in a number of vitamins and trace minerals, including vitamins A, D, thiamine, folate, pyridoxine, and zinc

prednisolone

-used as tx for ALD

-40 mg orally daily for 4 weeks

-taper the dose

folic acid

used in folic acid deficiency 1 mg orally in conjugation with improved dietary intake until repletion occurs

thiamine

-used for thiamine deficiency

-100 mg orally or subq daily for 2 weeks

ergocalciferol

-used for vit D deficiency

-12,000 to 50,000 international units (IU) orally daily

-reassess vit D serum levels in 2-3 months

vitamin E

-used for vit E deficiency

-400 IU orally daily

Vitamin A

-used in vit A deficiency

-25,000 to 50,000 IU orally 3 times weekly

Silymarin

-anti-oxidative and anti-fibrotic properties

-believed to enhance liver regeneration and protect hepatocytes from toxicity

-recommended dose is 140 mg Q8-12H daily

liver transplantation

remains the only definitive therapy for ALD

no

Can someone with alcoholic hepatitis be considered for a liver transplant?