Characterized pathologically as IRREVERSIBLE Chronic Injury of the Hepatic Parenchyma
Include extensive fibrosis in association with the formation of Regenerative Nodules
Central Event leading to Hepatic Fibrosis: Cytokine-Mediated (tgf-B) Activation of the Hepatic Stellate Cells producing Fibrin Forming Type-1 Collagen
Results from:
o Hepatocyte Necrosis
o Collapse of the supporting network with subsequent connective tissue deposition o Distortion of Vascular Bed, and Nodular Regeneration of remaining Liver Parenchyma I. ALCOHOLIC CIRRHOSIS
Excessive chronic alcohol use can cause different types of Chronic Liver Disease: Alcoholic Fatty Liver, Alcoholic Hepatitis, and Alcoholic Cirrhosis
Diagnosis requires an accurate history regarding amount and duration of alcohol consumption
Laboratory Tests can be completely normal in patients with Early Compensated Alcoholic Cirrhosis
In Advanced Liver Disease, patient may be:
o Anemic from either Chronic GI Blood Loss o Nutritional Deficiencies
o Hypersplenism related to Portal Hypertension
o Direct Suppressive Effect of Alcohol on the Bone Marrow II. CAUSES AND COMPLICATIONS OF CIRRHOSIS
III. LABORATORY FINDINGS IN CIRRHOSIS (from the Lecture)
Liver Insufficiency:
o Decreased Albumin: < 3.8 g/dL o Prolonged PT (INR > 1.3) o Increased Bilirubin: > 1.5 mg/dL
Portal Hypertension
o Decreased Platelet Count: < 175,000
AST / ALT Ratio > 1
Imaging (CT or UTZ) o Nodular Liver o Splenomegaly o Venocollaterals
Liver Biopsy: NOT always necessary if:
o 1) Decompensated Cirrhosis (Variceal Hemorrhage, Ascites, etc) o 2) Liver/Spleen imaging diagnostic of Cirrhosis
LIVER ENZYMES:
AST / ALT > 2 Alcoholic Liver Disease AST / ALT < 1 Viral
Alk Phos > Liver Enzymes Cholestatic
COMPLICATIONS OF CIRRHOSIS:
Portal Hypertension (Gastroesophageal Varices, Portal Hypertensive Coagulopathy (Factor Deficiency, Fibrinoysis, Thrombocytopenia) Gastropathy, Splenomegaly, Hypersplenism, Ascites / SBP Bone Disease (Osteopenia, Osteoporosis, Osteomalacia)
Hepatorenal Syndrome (Type 1, Type 2) Hematologic Abnormalities (Anemia, Hemolysis, Neutropenia, Thrombocytopenia)
Hepatic Encephalopathy Malnutrition
Portopulmonary Hypertension Hepatopulmonary Syndrome
CAUSES OF CIRRHOSIS
Alcoholism Cardiac Cirrhosis
Chronic Viral Hepatitis (Hep-B, Hep-C) Inherited metabolic Liver Disease
Autoimmune Hepatitis - Hemochromatosis
Non-Alcoholic Steatohepatitis - Wilson’s Disease
Biliary Cirrhosis - A1-Antitrypsin Deficiency
Primary Biliary Cirrhosis - Cystic Fibrosis
Primary Sclerosing Cholangitis Cryptogenic Cirrhosis
Autoimmune Cholangiopathy
IV. SEVERITY OF LIVER DISEASE:
Child Turcotte Pugh
MELD Score
A. Child Pugh Criteria for Hepatic Functional Reserve
A B C
Serum Bilirubin (mg/dL) (umol/L)
< 2.0
< 34
2.0-3.0 34-51
> 3.0
> 51 Serum Albumin (g/dL)
(g/L) > 3.5
> 35 3.0-3.5
30-35 < 3.0
< 30 Prothrombin Time Seconds Prolonged
INR
0-4
< 1.7
4-6 1.7 – 2.3
> 6
> 2.3
Ascites None Easily controlled Poorly controlled
Neurologic Disorder None Minimal Advanced Coma
B. MELD Score
o Estimates the Risk of 3 month Mortality (higher the MELD score likely to die in three months) o Three Laboratory Values used:
Serum Total Bilirubin
Serum Creatinine
INR
6.4 + 9.8 x log(INR) + 11.2 x log(Cr) + 3.8 x log(Bilirubin)
V. HISTORY OF CHRONIC LIVER DISEASE
Chronic Liver Disease Compensated Cirrhosis Decompensated Cirrhosis Death
VI. COMPLICATIONS OF CIRRHOSIS
Portal Hypertension Liver Insufficiency
Variceal Hemorrhage Encephalopathy
SBP
Ascites Jaundice
Hepatorenal Syndrome Encephalopathy
Compensated VS Decompensated: Presence of Complications!
Variceal Hemorrhage
Ascites
Encephalopathy
Jaundice
VII. INVESTIGATING ASCITES
CONDITION GROSS APPEARANCE PROTEIN
(g/L)
SAAG (g/dL)
CELL COUNT OTHER TESTS
RBC,
>10,000u/L WBC, per uL Cirrhosis Straw colored or bile stained < 25 (95%) > 1.1 1% < 250 (90%)
Predominantly Mesothelial Neoplasm Straw colored, hemorrhagic,
mucinous, or chylous
> 25 (75%) < 1.1 20% > 1000 (50%) Variable Cell types
Cytology, cell block, peritoneal biopsy TB Peritonitis Clear, Turbid, Hemorrhagic,
Chylous
> 25 (50%) < 1.1 7% > 1000 (70%) Usually > 70% L
Peritoneal Biopsy, Stain and Culture for AFB Pyogenic
Peritonitis
Turbid or purulent If purulent,
> 25
< 1.1 Unusual Predominantly PMN Leukocytes
Positive Gram Stain, Culture
CHF Straw-colored Variable
(15-53)
Variable Amylase in Ascitic Fluid & Serum A. SAAG: Serum to Ascites Albumin Gradient
o Serum Albumin [minus] Albumin in Ascitic Fluid (Gradient) o The gradient correlates DIRECTLY with Portal Pressure
1. If SAAG is > 1.1g/dL (or 11 g/L)
Cause of Ascites is PORTAL HYPERTENSION with (97% Specificity):
Cirrhosis
Cardiac Ascites
Budd Chiari Syndrome
Portal Vein Thrombosis
Veno-Occlusive Disease
Fatty Liver of Pregnancy 2. If SAAG is < 1.1g/dL (or 11 g/L)
Peritoneal Carcinomatosis
Infection (Peritonitis, TB)
Nephrotic Syndrome
Pancreatic or Biliary Ascites B. Absolute WBC Count (PMN) > 250/mm3
o Infection
o When Mononuclear Cells are predominant: TB, Fungal C. RBC Count > 50,000/mm3 = Hemorrhagic Ascites
o Malignancy o TB
o Trauma D. Others:
Amylase Increased in Pancreatic Ascites
TAG Increased in Chylous Ascites
Cytology Positive in Malignancy Gram Stain or Culture Bacterial Infections pH < 7 Bacterial Infection E. Management of Ascites
o Removal of > 1 L at a time (Paracentesis) may lead to Hypovolemia, Shock
o
Unless 10grams Albumin is replaced IV for each 1 L Ascitic Fluid removedManagement of Ascites:
Dietary Salt Restriction (2g Salt/day)
Diuretic Therapy
Paracntesis
TIPS
Spontaneous Bacterial Peritonitis:
Infectious complication of Portal HPN-Related Ascites
Abdominal Pain & Distention, Fever, Decreased Bowel Sounds, Worsening of Hepatic Encephalopathy
Diagnosis is likely when Ascitic Fluid has >
250 neutrophils/u/L
VIII. HEPATIC ENCEPHALOPATHY: Grading System for Hepatic Encephalopathy:
Disorientation from time, amnesia, decreased inhibitions,
aroused, confused Disorientation for place, aggressive Asterixis, Hyperactive Reflexes,
Babinski’s Sign. Muscle Rigidity Slowing Triphasic Waves
4 Coma Nil Decrebrate Slowing Delta Waves
**NOTE: Asterixis is POSITIVE in Stage I, II, and III – but Negative on IV!
o There will be NO Asterixis when patients is already in COMA o First Manifestation is the Reversal of the Sleep-Wake Pattern
A. Pathogenesis (Most Important):
o SEVERE Hepatocellular Dysfunction and/or Intrahepatic & Extrahepatic Shunting of Portal Venous Blood into the Systemic Circulation BYPASSING the Liver (There is FAILURE to DETOXIFY the substances)
B. Common Precipitants of Hepatic Encephalopathy:
o Increased Nitrogen Load: Gastrointestinal Bleeding, Excess Dietary Protein, Azotemia, Constipation o Electrolyte and Metabolic Imbalance: Hypokalemia, Alkalosis, Hypoxia, Hyponatremia, Hypovolemia o Drugs: Narcotics, Tranquilizers, Sedatives, Diuretics
o Miscellaneous: Infection, Surgery, Superimposed Acute Liver Disease, Progressive Liver Disease, Portal-Systemic Shunts C. Aims of Treatment:
o 1) Eliminate or Treat the Precipitating Factors
o 2) Lower Blood Ammonia (and other Toxins): Decreases Absorption of Proteins and Nitrogenous Products from the Intestine D. Approach to the Patient with Hepatic Encephalopathy, BUN (Blood Urea Nitrogen)
Initial Evaluation:
Exclude other Causes of Disordered Mentation, Identify Precipitants and Correct Determine Electrolytes, BUN, Creatinine, NH3 (Optional), Glucose
Protein Restriction
Inadequate Response (?)
Laxative (eg. LACTULOSE 30-120mL, 1 to 4x daily until 4 stools/day)
Broad-Spectrum Antibiotics
(eg. Neomycin 500-1000mg qid; or Metronidazole 250mg tid)
Inadequate Response (?)
Consider Liver Transplantation
Portosystemic Encephalopathy is a serious complication of chronic liver disease and is broadly defined as an alteration in mental status & cognitive function occurring in the presence of liver failure.
Encephalopathy is more commonly seen in patients with chronic liver disease. Gut-derived neurotoxins are not removed by the liver because of vascular shunting and decreased hepatic mass get to the brain
& cause symptoms. Ammonia levels are typically elevated in patients with hepatic encephalopathy.
Treatment is multifactorial and includes management of the precipitating factors.
Sometimes hydration & correction of electrolyte imbalance is all that is necessary.
Mainstay of Treatment (in addition to correction of precipitating factors) is to use Lactulose, which result in Colonic Acidification. Catharsis ensues, contributing to the elimination of waste products in the gut. Goal: 2-3 Stools per day.
Treatment of Hepatic Encephalopathy (Washington)
Treat Precipitating Factors
Dietary Protein Restriction (Controversial)
Non-Absorbable Disaccharide (Lactulose, Lactitol)
Neomycin
Metronidazole (250mg PO q8h)