Lvr
Cirrhosis
search
Cirrhosis
, Laennec's Cirrhosis, Portal Cirrhosis
Pathophysiology
Irreversible liver injury and inflammation leads to hepatic fibrosis and altered hepatic architecture
Diffuse fibrotic bands
Nodular regeneration (Micronodular and Macronodular)
Decreased hepatic metabolic and synthetic function
Decreased
Clotting Factor
s and
Thrombocytopenia
Increased
Bilirubin
Results in increased
Portal Hypertension
See
Portal Hypertension
Cirrhotic Ascites
Esophageal Varices
Epidemiology
Twelvth leading cause of death in United States
Cirrhosis deaths: 12.8 per 100,000 U.S. population
Alcohol
was previously most common cause of Cirrhosis in U.S., but has been surpassed by
Viral Hepatitis
(esp.
Hepatitis C
)
Gene
tic predisposition
Incidence
greatest in middle aged males
More common in non-hispanic black and mexican americans in U.S.
Risk Factors
Progression from Hepatitis to Cirrhosis (
Alcohol
,
Viral Hepatitis
,
NAFLD
)
Advanced Age
Medical Comorbidities (esp. comorbid HIV and
Hepatitis C
)
Male gender (except for women in
Alcoholic Hepatitis
, who may rapidly progress to Cirrhosis)
Causes
Common
Viral Hepatitis
(most common cause of Cirrhosis)
Hepatitis B
(and
Hepatitis D
)
Progresses to Cirrhosis in 20-30% of cases
Hepatitis C
Leading cause of Cirrhosis in U.S.
Progresses to Cirrhosis in 5-20% of cases
Alcohol Abuse
(20%)
Surpassed by
Viral Hepatitis
(esp.
Hepatitis C
) as most common cause of Cirrhosis
Progresses from
Alcohol
ic
Steatosis
to
Alcoholic Hepatitis
Ultimately results in hepatocellular necrosis and Cirrhosis
Nonalcoholic Fatty Liver Disease
(
NASH
)
Increasing
Prevalence
and is trending to become the most common cause of liver transplant by 2035
Primary Biliary Cirrhosis
Hemochromatosis
(5-10%)
Biliary obstruction (5-10%)
Congenital: Biliary atresia, biliary cysts
Cystic Fibrosis
Causes
Less Common
See
Hepatotoxin
(e.g. Amiodaron,
Methotrexate
)
Autoimmune Chronic Hepatitis
Venoocclusive Disease (Budd-Chiari Syndrome)
Gene
tic Disorders
Wilson's Disease
Alpha-1-Antitrypsin Deficiency
Inborn Errors of Metabolism
Glycogen Storage Disease
Galactosemia
Congestive Heart Failure
Sarcoidosis
Infections
Brucellosis
Tertiary Syphilis
Echinococcosis
Schistosomiasis
Symptoms
Often asymptomatic in compensated Cirrhosis
Gene
ral
Weakness
Fatigue
Weight loss
Anorexia
and decreased appetite
Gastrointestinal
Nausea
and
Vomiting
Diarrhea
Endocrine
Loss of libido
Gynecomastia
Impotence
Infertility
Amenorrhea
Signs
Eyes
Scleral Icterus
Kayser-Fleischer Ring (
Wilson's Disease
)
HEENT
Sublingual juandice
Parotid hypertrophy
Chest
Gynecomastia
Pleural Effusion
Abdomen
Liver
span
Initial:
Hepatomegaly
Large firm, nontender palpable liver
Later:
Liver
shrinks in size
Splenomegaly
Ascites
Testicular atrophy
Skin
Jaundice
Purpura
Palmar erythema
Spider
nevi or Caput Medusa
Superficial veins dilate on
Abdomen
and chest
Telangiectases
Nail changes
Muehrcke's Line
s
Terry's Nail
s
Digital Clubbing
Loss of Axillary and pubic hair
Musculoskeletal
Lower extremity edema
Dupuytren's Contracture
Muscle Wasting
Neurologic
Asterixis (hand
Tremor
into wrist extension)
Tremor
Altered Mental Status
(drowsy, confusion,
Delirium
to coma)
Genitourinary
Testicular atrophy
Other
Fetor hepaticus (sweet, pungent breath odor due to dimethyl sulfide)
Labs
Initial
Complete Blood Count
(CBC)
Microcytic Anemia
from blood loss
Macrocytic Anemia
from
Folate Deficiency
Pancytopenia
from hypersplenism
Thrombocytopenia
(<160,000 sensitive for Cirrhosis)
Liver Function Test
s
See
Liver Function Test Abnormality
Prolonged
Prothrombin Time
(INR)
Hypoalbuminemia (
Serum Albumin
<3.5 g/L)
Bilirubin
elevated
Alkaline Phosphatase
elevated
Gamma-Glutamyltransferase (GGT) increased
Alanine transaminase (ALT)
Aspart
ate transaminase (ALT)
Most cost effective screening for Cirrhosis
Electrolyte
s
Hyponatremia
Hypokalemic alkalosis
Glucose
disturbance
Labs
Elucidate Cirrhosis Causes
Review
Hepatotoxin
exposure history
Alcohol Abuse
Hepatotoxic Medication
s
Viral Hepatitis
Studies
HBsAg
xHBc IgM
xHBs IgG
xHCV IgG
xHDV IgG
Non-
Alcohol
ic
Fatty Liver
Risk Factors (
NAFLD
)
Fastin
g
Lipid
Panel
Hemoglobin A1C
Iron
Studies (Rule out
Hemochromatosis
)
Serum Iron
Total Iron Binding Capacity
(
TIBC
)
Ferritin
Autoimmune factors
Antimitochondrial
Antibody
Smooth Muscle Antibody
Antinuclear Antibody
(ANA)
Miscellaneous Cause evaluation
Ceruloplasmin (
Wilson's Disease
)
Alpha-1-Antitrypsin
Labs
Noninvasive Staging of Hepatic Fibrosis
AST to Platelet Ratio Index Score
Score <0.5: Good
Negative Predictive Value
(80% for
Hepatitis C
Virus
related fibrosis)
Score >2.0:
Test Specificity
for Cirrhosis 91% (but only 46%
Test Sensitivity
)
Fibrosis 4 Score
See
Fibrosis Probability Score
(Fib-4 Score)
Score <1.45: Good
Negative Predictive Value
(80% for
Hepatitis C
Virus
related fibrosis)
Score >3.25 (>2.67 in
NAFLD
):
Positive Predictive Value
>80%
FibroTest/FibroSure
Score <0.30: Good
Negative Predictive Value
(90% for
NAFLD
related fibrosis)
Score >0.70 (>0.48 in
Viral Hepatitis
):
Positive Predictive Value
>80%
NAFLD
Fibrosis Score
Score <-1.455 has 88%
Negative Predictive Value
for advanced fibrosis in
NAFLD
Score >0.676 has 82%
Positive Predictive Value
for advanced fibrosis in
NAFLD
Imaging
Abdominal Ultrasound
with Doppler
Preferred first line imaging (preferred over CT)
Efficacy
Steatosis
(94%
Test Sensitivity
, 84%
Test Specificity
)
Fibrosis or Cirrhosis (<57%
Test Sensitivity
)
Gene
ral findings suggestive of Cirrhosis
Liver
nodularity, irregularity
Increased echogenicity
Liver
Atrophy
Findings suggestive of advanced disease and
Portal Hypertension
Liver
small and nodular
Ascites
Decreased portal circulation by doppler flow
Portosystemic collateral vessels
Splenomegaly
Repeat
Ultrasound
every 6 months in Cirrhosis and
Hepatitis C
Evaluate for
Hepatocellular Carcinoma
Transient Elastography (via
Ultrasound
Fibroscan)
Office based point-of-care procedure performed in 5 minutes
Liver
stiffness evaluated in kilopascals via measured velocity of low frequency elastic shear waves through liver
Efficacy
Negative Predictive Value
>90%
Test Sensitivity
: 81%
Test Specificity
: 88%
False Positive
s in
Bone Marrow
disease,
Hemolysis
, medications
Less accurate in obese patients, excessive
Alcohol
, extrahepatic cholestasis
Advanced imaging: CT Scan or MRI of liver
Poor sensitivity for early Cirrhosis
Identifies
Nodule
s, lobar atrophy
Diagnostics
Liver
Biopsy
Indicated where no cause on noninvasive evaluation
Contraindicated in severe
Coagulopathy
Check CBC with platelets, INR before proecdure
No
NSAID
s or
Aspirin
for 7-10 days before procedure
Benefit outweighs risk: Diagnosis improves course
Test Sensitivity
and
Specificity
: 80-100%
However error rate in fibrosis staging still occurs in 20% of cases
Portal Venography
Wedged hepatic vein pressure management
Staging
See
Child-Pugh Score
See
MELD Score
See Metavir Scoring System
Evaluation
Complication Screening
Endoscopic screen for
Esophageal Varices
q1-2 years
Hepatocellular Carcinoma
screening
Serum
Alpha-fetoprotein
every six months
Liver
Ultrasound
every 6 to 12 months
Evaluation
Coagulation abnormalities
Pathophysiology
End-stage liver disease patients have mixed
Coagulation Disorder
s (both hypocoagulable and
Hypercoagulable
)
Liver
failure results in deficiency of pro-coagulant factors (increasing risk of bleeding)
Procoagulant Factors: I (
Fibrinogen
), II (prothrombin), V, IX, X (thrombin) and XI
Increased risk of
Gastrointestinal Bleeding
(especially
Variceal Bleeding
)
Liver
failure also results in deficiency of
Anticoagulant
factors (increasing risk of clotting)
Anticoagulant
Factors: Protein C, protein S and
Antithrombin
Increased risk of
Portal Vein Thrombosis
,
Deep Vein Thrombosis
INR is a poor marker for bleeding risk in liver failure
INR is specific for
Warfarin
which affects all
Vitamin K
dependent factors (II, VII, IX and X) equally
Liver
failure, in contrast, affects both procoagulants and
Anticoagulant
s inconsistently
More accurate markers of bleeding risk in liver failure
Fibrinogen
Thromboelastogram (limited availability)
Active bleeding management
Replace blood losses with
Packed Red Blood Cells
Aim for systolic
Blood Pressure
>90 mmHg (permissive
Hypotension
)
Exercise
caution with blood replacement in
Variceal Bleeding
May increase bleeding due to increased pressure
Villanueva (2013) N Engl J Med 368(1):11-21 [PubMed]
Manage bleeding source (e.g.
Variceal Bleeding
)
Reversal of
Coagulopathy
is based on expert opinion only
Increased INR reversed with
PCC4
or FFP is commonly used but may not alter bleeding risk
Cryoprecipitate
indications
Fibrinogen
<150 mg/dl
Fibrinogen
increases 100 mg/dl with 10 units of
Cryoprecipitate
Platelet indications
Platelet Count
<50,000
Invasive procedures
Bleeding complications are most reduced when procedure is performed by most skilled provider
In contrast to risk based on degree of
Coagulopathy
Deloughery (1996) Transfusion 36(9): 827-31 [PubMed]
Anticoagulation
Consult hepatology and adjust regimen for severe liver disease (e.g.
Child-Pugh
C),
Esophageal Varices
Decreasing portal pressure (e.g.
Beta Blocker
s) may reduce bleeding risk on
Anticoagulation
Warfarin
may be used if baseline INR (before
Warfarin
) is <1.7
Direct Oral Anticoagulant
s or
DOAC
S (e.g.
Apixaban
) may be used in
Child-Pugh
A, and some
Child-Pugh
B cases
References
Orman and Deloughery in Herbert (2014) EM:Rap 14(4): 1
Tripodi (2011) N Engl J Med 365(2): 147-56 [PubMed]
Management
See
Prevention of Liver Disease Progression
Vaccination
Hepatitis A Vaccine
Hepatitis B Vaccine
Annual
Influenza Vaccine
Polyvalent pneumococcal Vaccine
Avoid exacerbating medications and substances
See
Hepatotoxic Medication
s
Acetaminophen
is safe (max 2000 mg total per day)
Avoid
Alcohol
In
Alcohol
cessation, avoid
Naltrexone
and acomprosate in
Child-Pugh
Grade C Cirrhosis or worse
Baclofen
5-10 mg three times daily is safe at any stage of liver disease
Avoid
NSAID
S
Risk of
Upper GI Bleed
ing
Risk of
Renal Failure
Avoid raw fish consumption and brackish or salt water exposure
Risk of
Vibrio vulnificus
infection
Avoid unpasteurized dairy
Risk of Listeria infection
Review medications needing adjustment in
Child-Pugh Class
B and C (moderate to severe Cirrhosis)
Drugs primarily metabolized by the liver
Highly Protein bound medications (increased effects in hypoalbuminemia)
Maintain adequate nutrition
Optimize
Diabetes Mellitus
management
Weight loss of 10% is recommended if obese with
NAFLD
Limit
Sodium
intake to <2 grams per day
Frequent, high calorie meals and bedtime snack
Check fat soluble
Vitamin
s and zinc
Adequate protein
Early Cirrhosis: 1 to 1.5 grams/kg/day
Advanced Cirrhosis: 1 gram/kg/day
Previously tried to treat Cirrhosis (most ineffective)
Penicillamine
(inhibits collagen cross-links)
Propylthiouracil
(reduces hepatic hypermetabolism)
Interferon
alpha (inhibits liver fibrogenic activity)
Manage complications specifically
See
Esophageal Varices
Acute bleeding from
Esophageal Varices
ICU Admission with acute stabilization (
pRBC
,
Soma
tostatin)
Compensated Cirrhosis with large
Varices
Non-selective
Beta Blocker
(
Propranolol
,
Nadolol
)
Consider endoscopic variceal ligation
Compensated Cirrhosis with no
Varices
Upper endoscopy screening for
Varices
q2-3 years
Targeted screening of those with findings suggestive of
Portal Hypertension
is replacing general screening
Compensated Cirrhosis with small
Varices
Upper endoscopy screening for
Varices
every 1-2 years
See
Cirrhotic Ascites
Salt restriction and
Diuretic
s
Paracentesis
(Treat if subacute
Bacteria
l peritonitis identified)
See
Spontaneous Bacterial Peritonitis
See
Hepatic Encephalopathy
Disaccharides or Rifaximin (Xifaxan)
Do not drive
Paracentesis
(Treat if subacute
Bacteria
l peritonitis identified)
Acute
Hyponatremia
See
Hypervolemic Hypoosmolar Hyponatremia
Results from splanchnic vasodilation with renin-
Angiotensin
activation
Antidiuretic Hormone
released with secondary free water retention
Management
See
Hyponatremia Management
Free water restriction limited to 1 to 1.5 Liters daily
Avoid rapid correction outside severe acute
Hyponatremia
Hepatocellular Carcinoma
screening
Ultrasound
liver every 6-12 months
Also consider alpha fetoprotein test every 6-12 months
Comorbid conditions and symptoms
Leg Cramp
s are common (esp. with
Diuretic
use)
Monitor serum
Electrolyte
s
Baclofen
5-10 mg up to three times daily
Major Depression
SSRI
medications appear safe in Cirrhosis
Management
Peri-operative risk assessment
Peri-operative risk factors
High
Child-Pugh Score
(see below)
Cirrhotic Ascites
Increased
Serum Creatinine
Cirrhosis cause other than primary biliary Cirrhosis
History of
Upper Gastrointestinal Bleeding
Abdominal surgery risk associated with
Child-Pugh Score
Child-Pugh Class
A: 10% peri-operative mortality
Child-Pugh Class
B: 30% peri-operative mortality
Child-Pugh Class
C: 82% peri-operative mortality
Mansour (1997) Surgery 122:730-5 [PubMed]
Management
Liver
Transplantation
Indications for evaluation
MELD Score
>15 (or significant complications)
Fulminant
Liver
Failure
Decompensated Cirrhosis
Hepatorenal Syndrome
Cirrhotic Ascites
Child-Pugh
Stage B
Hepatocellular Carcinoma
No single lesion >5 cm
No more than 3 lesions (largest 3 cm or less)
Contraindications
Hepatocellular Carcinoma
>5 cm
Other active malignancy
Active
Alcohol Abuse
or other
Substance Abuse
Chronic infection
Advanced cardiopulmonary disease
Availability
Candidates: 18,000 per year for 4000 available livers
Wait time for liver
Transplantation
: 2-3 years
Efficacy
One year survival: 85%
Five year survival: 75%
Post-transplant care
Expect on average up to 2 emergency department visits post-transplant (with 70% admission rate)
Typical post-transplant ED presentations are related to gastrointestinal or infectious symptoms
Complications
Portal Hypertension
Esophageal Varices
with bleeding
Hemorrhagic Gastritis
Cirrhotic Ascites
Spontaneous Bacterial Peritonitis
Hepatic Encephalopathy
Liver
Failure
Coagulation Abnormalities
Hepatorenal Syndrome
Hepatocellular Carcinoma
(
Relative Risk
: 22.9)
Cholelithiasis
Pericardial Effusion
Hyposplenism
Osteoporosis
Abdominal Wall
Hernia
Prognosis
Advanced Cirrhosis
See
Child-Pugh Score
See
Model for End-Stage Liver Disease
(
MELD Score
)
Progression from compensated to decompensated Cirrhosis (e.g.
Ascites
, encephalopathy)
Ranges from 4-10% per year (variable depending on cause, treatment, ongoing liver injury)
Compensated Cirrhosis is associated with a 12 year median survival (contrast with 2 years once decompensated)
Overall mortality
Two year mortality: 50%
Five year mortality: 65%
Factors associated with worse prognosis
Unfavorable signs
Hematemesis
Jaundice
Ascites
Additional Risk factors for worse prognosis
Black race
Mortality in 90 days based on
MELD Score
MELD Score
>40: 71.3%
MELD Score
30-39: 52.6%
MELD Score
20-29: 19.6%
MELD Score
10-19: 6.0%
MELD Score
<9: 1.9%
Kamath (2001) Hepatology 33(2): 464-70 [PubMed]
References
Swencki (2015) Crit Dec Emerg Med 29(11):2-10
Habib (2001) Postgrad Med 109(3):101-13 [PubMed]
Heidelbaugh (2006) Am Fam Physician 74(5):756-76 [PubMed]
Mcguire (1998) Postgrad Med 103(2):209-224 [PubMed]
Menon (2000) Mayo Clin Proc 75(5):501-9 [PubMed]
Riley (2001) Am Fam Physician 64(10):1735-40 [PubMed]
Smith (2019) Am Fam Physician 100(12):759-70 [PubMed]
Starr (2011) Am Fam Physician 84(12): 1353-9 [PubMed]
Type your search phrase here