Alcoholic Liver disease: an introduction part 2

Pratap Sagar Tiwari, Lecturer, NGMC

Our Journey

Hepatic encephalopathy

Management

Portal Hypertension

Complications

Making a diagnosis

Clinical Features

Alcohol & Liver

Alcoholic liver disease

liver dysfunction because of Alcohol

Liver Dysfunction AlcoholBecause of

What then ? How ?

Functions that are affected..• Detoxification• Bilirubin

metabolism• Clotting factors

Synthesis of • Thrombopoietin• Albumin• AngiotensinogenCHO /protein/ lipid metabolismStorage of Vitamins

Manifestations…

Encephalopathy

Coagulopathy

Jaundice

• Bilirubin metabolism

• Clotting factors

• Detoxification

Definition

• Any pathological conditions of liver as a result of chronic and excessive alcohol consumption leading to a spectrum of conditions from ranging from asymptomatic fatty liver to alcoholic hepatitis to end-stage liver failure with jaundice, coagulopathy, and encephalopathy.

Metabolism of Alcohol

Ethanol

Acetic acid

Acetaldehyde

acetyl-CoA

Citric Acid cycle

Oxidizedalcohol dehydrogenase IB (ADH)CYP2E1Catalase

CO2/ATP

Acetaldehyde dehydrogenase

enters

Acetyl-coenzyme A synthetase

Tetrahydroisoquinolines(TIQs)

Note: Disulfiram inhibits Acetaldehyde dehydrogenase

Alcohol & Acetaldehyde

Damage to embryonic neural crest cells = birth defects

If not metabolized,releases free radicals

Alcohol forms “Adducts” that activate immune system cell injury

Cytochrome CYP2E1 metabolizes ethanol to Acetate, releasing oxygen free radical radical induced injury

Antioxidants are Vit A,C,E, Superoxide dismutase, beta carotene, glutathione

Free Radicals:eg superoxide ( O2- ),hydrogen peroxide (H2O2), peroxynitrite

Alcohol ↑ gut permeability ↑ endotoxin Kupffer cells activation TNF a, IL6 Inflamation

Alcoholic liver Disease

• Beginning of Part 2………

ALD: Spectrum

• The pathology of alcoholic liver disease consists of three major lesions, with the injury rarely existing in a pure form:

(1) fatty liver, (2) alcoholic hepatitis, (3) cirrhosis.

Diagnosis of alcoholic liver disease

1. A thorough history of alcohol use. 2. CAGE:screening method for alcohol abuse or

dependency.3. A detailed P/E should be done, searching for signs of

CLD and staging its severity.4. A liver chemistry profile (including serum albumin,

bilirubin and transaminases [AST/ALT]). CBC & PT/INR.5. It may be necessary to perform a liver biopsy in

patients with suspected alcoholic liver disease when the diagnosis is unclear .

CAGE Questionaaire

• Have you felt the need to Cut down drinking?• Have you ever felt Annoyed by criticism of

drinking?• Have you had Guilty feelings about drinking?• Do you ever take a morning Eye opener ?

ALD:Fatty liver

• Fatty liver, also known as fatty liver disease (FLD), is a reversible condition wherein large vacuoles of triglyceride fat accumulate in liver cells via the process of steatosis (i.e., abnormal retention of lipids within a cell).

• AFL(steatosis) is rarely diagnosed clinically because most patients are asymptomatic.

• The only complaint may be mild, tender hepatomegaly.• DX: in pt with alcohol abuse/dependent with fatty

changes in imaging and excluding other causes. LFT may be normal/mild abnormal.

Microvesicular fat Macrovesicular fat

Alcoholic foamy degenerationAcute fatty liver of pregnancyReye's syndromeValproic acidTetracycline

AlcoholMalnutritionObesityDiabetes mellitusCorticosteroidsTotal parenteral nutrition

ALD: Alcoholic hepatitis

• The characteristic clinical features of alcoholic hepatitis are fever, hepatomegaly, jaundice, and anorexia.

• Patients can also present with right upper quadrant/epigastric pain, hepatic encephalopathy, and bleeding.

ALCOHOLIC CIRRHOSIS AND FIBROSIS

• The term "fibrosis" in this setting denotes the accumulation of scar or extracellular matrix (ECM), and is potentially reversible in the absence of continued alcohol abuse.

• In contrast, true cirrhosis is characterized by the presence of regenerative nodules and is irreversible even in the absence of further alcohol ingestion.

Acute liver failure

• Acute liver failure is an uncommon condition in which the rapid deterioration of liver function results in coagulopathy and alteration in the mental status (encephalopathy) of a previously healthy individual.

Liver failure: definitions

• Acute liver failure is a broad term that encompasses both fulminant hepatic failure and subfulminant hepatic failure (or late-onset hepatic failure).

• Fulminant hepatic failure is generally used to describe the development of encephalopathy within 8 weeks of the onset of symptoms in a patient with a previously healthy liver.

• Subfulminant hepatic failure is reserved for patients with liver disease for up to 26 weeks before the development of hepatic encephalopathy.

Next Part :• Clinical features………….

• End of Part two………….