GASTROINTESTINAL Last edited: 3/4/2024

7. CIRRHOSIS
I. PATHOPHYSIOLOGY III. COMPLICATIONS IN CIRRHOSIS IV. DIAGNOSTIC APPROACH TO CIRRHOSIS V. TREATMENT OF CIRRHOSIS
II. CAUSES OF CIRRHOSIS: A. PORTAL HYPERTENSION RELATED A. ASSESS FOR CIRRHOSIS LABORATORY EVIDENCE: A. TREATMENT OF ASCITES
A. PARENCHYMAL DISEASES COMPLICATIONS B. ASSESS FOR LIVER FIBROSIS IMAGING EVIDENCE B. TREATMENT OF SPONTANEOUS BACTERIAL PERITONITIS
B. VASCULAR DISEASES B. ↓LIVER FUNCTION RELATED C. ASSESS FOR DECOMPENSATED CIRRHOSIS C. TREATMENT OF HEPATIC ENCEPHALOPATHY:
C. BILIARY TRACT DISEASE COMPLICATIONS D. TREATMENT OF HEPATORENAL SYNDROME:
E. TREATMENT OF ESOPHAGEAL VARICES
F. SURVEILLANCE OF HEPATOCELLULAR CARCINOMA:
G. LIVER TRANSPLANT IN SEVERE CIRRHOSIS:

I. Pathophysiology
o Repeated hepatocyte injury → Chronic Hepatocyte damage → Hepatic Fibrosis →
Chronic loss of hepatic function and Portal HTN develops

II. Causes of Cirrhosis:

A. Parenchymal Diseases 00:39

1. Alcoholic Liver Disease 4. Metabolic Liver Disorders

Chronic Alcoholism a) Hemochromatosis

→ Steatohepatitis ↑Iron buildup in the liver → Chronic hepatocyte damage
o Look for AST > ALT or AST/ALT ratio > 2 o Hemochromatosis also associated with hyperpigmentation,
diabetes mellitus, and restrictive cardiomyopathy
2. Viral Injury
b) Wilson’s Disease
Hepatitis B and C Virus Infection ↑Copper buildup in the liver→ Chronic hepatocyte damage
Hepatitis virus → Hepatocyte infection→ Hepatocyte o Wilson’s disease is also associated with Kayser-Fleischer rings
destruction/damage occurs in order to replicate and spread the and movement disorder
virus
c) Alpha-1-Antitrypsin Deficiency
o HBV and HCV are seen in IVDA or sexual transmission
↑Misfolded alpha-1-antitrypsin buildup in the liver→ Chronic
hepatocyte damage
3. Antibody-Mediated Injury o Alpha-1-Antitrypsin deficiency is also associated with pan-
Autoimmune Hepatitis lobular emphysema
ANA, ASMA, IgG, Anti-LKM1 antibodies directed against d) Nonalcoholic Fatty Liver Disease (NAFLD)
hepatocytes → Hepatocyte damage
↑Fatty deposition into the liver→ Steatohepatitis
o NAFLD is also associated with obesity/metabolic syndrome
+ Inflammation + Fibrosis o Look for AST/ALT ratio < 1

Parenchymal Damage
Normal Liver Hepatitis Cirrhosis Drug induced
Autoimmune Hepatitis
-Alcohol (M/ C)
ANA
AST ALT ASMA
IgG
Anti-LKM1

Viral induced Metabolic induced

-HBV -Hemochromatosis Fe ++
-HCV -Wilson’s Dx Cu
+

- 1
AT
-NAFLD Steatosis

Cirrhosis GASTROINTESTINAL : Note #7 1 of 10

 B. Vascular Diseases 11:01 C. Biliary Tract Disease 13:39

a) Right Heart Failure a) Primary Biliary Cholangitis (PBC)

↑↑CVP→ Severe hepatic congestion→ Poor hepatic venous AMA → Intrahepatic duct inflammation → Intrahepatic duct
drainage→ Liver Ischemia→ Hepatocyte damage strictures→↑Narrowing of hepatic ducts → ↑Bile backflow →
↑Bile acid buildup in hepatocytes → Chronic Hepatocyte
b) Budd-Chiari Syndrome damage→ Chronic Inflammation and Fibrosis → ↓Hepatic
Polycythemia, malignancy, hypercoagulable state→ Hepatic vein function and portal hypertension
clots → Severe hepatic congestion→ Poor hepatic venous o PBC is often associated with Jaundice and Pruritus
drainage→ Liver Ischemia→ Hepatocyte damage o Given the presence of AMA, PBC is often associated with
Autoimmune diseases such as Hashimoto’s or Scleroderma

Vascular Disease b) Primary Sclerosing Cholangitis (PSC)

p-ANCA → Intrahepatic and extrahepatic duct inflammation →
Right Heart Intrahepatic and extrahepatic duct strictures → ↑Narrowing of
Failure hepatic ducts → ↑Bile backflow → ↑Bile acid buildup in
CVP hepatocytes → Chronic Hepatocyte damage → Chronic
Inflammation and Fibrosis → ↓Hepatic function and portal
hypertension
Budd-Chiari Syndrome o PSC is often associated with Jaundice and Pruritus
Malignancy o PSC is often associated with Ulcerative Colitis (UC)

Polycythemia

Biliary Tract Disease

Primary Biliary Cholangitis (PBC)

IHD inflammation
Associated with A.M.A.

Primary Sclerosing Cholangitis(PSC)

IHD inflammation
EHD inflammation
Associated with U.C.

Hepatocyte Injury

Bile backflow

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 III. Complications in Cirrhosis
A. Portal Hypertension Related Complications 17:18

1. Ascites 2. Spontaneous Bacterial Peritonitis:

Pathophysiology: Pathophysiology:
o Liver Fibrosis → Portal venule compression from fibrosis → o Bacterial translocation from intestines to nearby lymph nodes
Portal pressure builds up in portal venous system → Portal to the ascitic fluid→ Activates neutrophil migration to ascitic
hypertension → Portal hydrostatic pressure increases → fluid→ Inflammatory reaction occurs in ascites and nearby
Albumin/protein-deficient fluid leaks into the peritoneal cavity peritoneal lining → Peritonitis
→ Ascites formation develops Presentation:
 Splanchnic vasodilation from portal HTN also contributes to o Diffuse abdominal pain and distention
Ascites → Triggers the RAAS system → Sodium and water o Fevers and Leukocytosis
retention → Worsened ascites
Presentation: Spontaneous Bacterial
o Abdominal Distention Ascites Peritonitis
o Shifting Dullness
o Fluid wave test (+)

Bacterial translocation

+ PMN’s
+ (>250/mm3)
SAAG>1.1

Cytokines Fever

Abdominal distention Abdominal pain

Shifting dullness
Fluid Wave test +

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3. Esophageal Varices 5. Hepatic Encephalopathy
Pathophysiology: Pathophysiology:
o Liver fibrosis → Portal venule compression from fibrosis → o Liver fibrosis→ Portal venule compression from fibrosis→
Portal pressure builds up in portal venous system → Portal Portal pressure builds up in portal venous system→
hypertension → Portal hydrostatic pressure increases → Portal hypertension→ Various portosystemic shunts form to
Esophageal vein dilate and become torturous → Esophageal divert blood around the liver → These shunts lead to less
varices form processing of substances such as ammonia and other
Presentation neurotoxins → ↑Ammonia in blood → Encephalopathy and
o Massive UGIB secondary to rupture of esophageal varices Cerebral edema
 Hematemesis o Triggers for this process include the following:
 Melena  SBP
 Anemia • ↑Production of ammonia
 Hypovolemic shock secondary to blood loss  GI Bleeding
• ↑Production of ammonia
Esophageal Varices  TIP’s procedure
• ↓Clearance of ammonia
UGIB  Hypovolemia
Hematemesis • ↓Clearance of ammonia
Melena Presentation:
o Encephalopathy
4. Hepatorenal Syndrome
 Confusion, delirium, lethargy, comatose state
Pathophysiology: o Asterixis
o Liver fibrosis →  Flapping tremor occurs during extension
Portal venule compression from fibrosis→ o Cerebral edema
↑Portal pressure in portal venous system→  If severe cerebral edema occurs → Can potentially lead to
Portal hypertension → ↑ICP, brain herniation, death
Vasodilators are produced as a response→
Splanchnic vasodilation occurs in an attempt
to reduce portal pressure →
↓↓Systemic Blood pressure occurs from
massive vasodilation→
Renal vasoconstriction occurs in response to
↓systemic blood pressure →
Poor renal perfusion → AKI
 This can be made worse by events that further
↓Systemic perfusion and renal perfusion:
• SBP
• Large volume paracentesis not repleted
with albumin
• Over-Diuresis/Dehydration
Presentation:
o ↓↓Urine output
o ↑↑Creatinine
o FeNa < 1%

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 B. ↓Liver Function Related Complications 34:22

Liver Function Related Complications

Conjugation/Excretion Jaundice
of Bilirubin
Bilirubin
Estrogen
metabolism

Albumin II/VII/IX/X Hyper-

(procoagulant)
estrogenism
TPO NH3 clearance

INR

PLTS

Hepatic
Coagulopathy Encephalopathy

ICH Mucocutaneous
bleeding GIB

1. Jaundice 3. Coagulopathy
Pathophysiology: Pathophysiology:
o Hepatocyte damage → ↓Conjugation and excretion of o Hepatocyte damage → ↓Synthetic function of Factors
conjugated bilirubin → ↑Mixed hyperbilirubinemia→ II/VII/IX/X and TPO → ↓Procoagulants and ↓Platelets →
Deposition into skin and sclera ↑Risk of Bleeding
Presentation Presentation
o Jaundice of sclera and skin o Thrombocytopenia and ↑INR (> 1.5)
o Bleeding
2. Hyperestrogenism  GI bleeding
Pathophysiology:  Intracranial hemorrhage
o Hepatocyte damage → ↓Estrogen metabolism→↑Estrogen  Mucocutaneous bleeding (e.g., gingival bleeding, epistaxis,
levels petechiae, purpura)
Presentation
4. Hepatocellular Carcinoma (HCC) 41:16
o Testicular Atrophy
o Gynecomastia in males Pathophysiology:
o Spider angiomas o Chronic liver inflammation →
o Palmar erythema Hepatic dysplasia →
↑Risk of Hepatocellular Carcinoma
Presentation
o Commonly → Asymptomatic
o Therefore, must monitor for ↑↑AFP levels
(released from tumor cells) and RUQ U/S to
assess for hepatic masses

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 42:10
IV. Diagnostic Approach to Cirrhosis

A. Assess for Cirrhosis Laboratory Evidence B. Assess for Liver Fibrosis Imaging Evidence
1. Obtain LFTs 1. Obtain RUQ U/S with Elastography
The presence of ↑Bilirubin and ↑AST/ALT suggests → The presence of nodularity and ↑Liver stiffness highly suggests
Hepatocellular Injury the presence of cirrhosis, especially in the context of the above-
mentioned lab findings
2. Obtain PT/INR
The presence of ↑INR (> 1.5) suggests a coagulopathy related to
↓Liver function. This becomes especially true if the patient is not
on anticoagulation (Warfarin)

3. Obtain Albumin
The presence of ↓Albumin suggests ↓Liver function, especially
if the patient does not have any evidence of heavy albuminuria
(Nephrotic syndrome)

4. Obtain CBC 2. Liver Biopsy

The presence of a chronic ↓Platelets suggests a decline in the If the definitive diagnosis of cirrhosis is required → Obtain a
livers ability to produce TPO, especially in combination with all of liver biopsy which would show definitive evidence of nodular liver
the above abnormalities fibrosis
o Additionally, if there is any question of the cause of cirrhosis
that is unable to be elucidated with history, labs and imaging
→ A biopsy may aid in the diagnosis (e.g. Autoimmune
hepatitis, PBC, Hemochromatosis, Alpha-1 antitrypsin
deficiency, Wilson’s disease)

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 C. Assess for Decompensated Cirrhosis
1. Obtain a Paracentesis 3. Obtain Basic Metabolic Panel (BMP)
if concerned about SBP if concerned about Hepatorenal Syndrome (HRS)
Indications: Indications:
o New onset Ascites o Oliguria in a patient with Cirrhosis
o History of Cirrhosis and being hospitalized with Ascites o Triggers to be suspicious for HRS:
Findings suggestive of SBP:  Recent diagnosis of SBP
o SAAG > 1.1→ Suggests a Portal HTN-Related Ascites  Recent large-volume paracentesis
o PMN’s > 250 PMNs/mm3 → Highly suggestive of SBP  Hypovolemia/Hypotension
o Fevers, leukocytosis, and abdominal pain also aid in the Findings suggestive of HRS:
diagnosis. This may trigger the decision for a paracentesis if a o ↑↑Creatinine
history of cirrhosis and ascites are present o FENa < 1%, ↑Urine osmolality → Suggest Pre-Renal AKI
o Triggers to be suspicious for HRS:
 AKI is not responsive to IVF and history of cirrhosis

2. Obtain an EGD 4. Obtain Ammonia Level

if concerned about Variceal Bleeding if concerned about Hepatic Encephalopathy
Indications: Indications:
o Upper GI bleeding (e.g. Hematemesis and Melena) in a patient o Patient with new onset encephalopathy with a history of
with a known history of Cirrhosis cirrhosis
Findings suggestive of Variceal Bleeding: Findings suggestive of Hepatic Encephalopathy:
o Presence of bleeding varices witnessed on EGD o ↑↑Ammonia levels
 However, normal ammonia levels DO NOT exclude hepatic
encephalopathy as there may be other neurotoxic
substances we are unable to measure to determine their
effect on encephalopathy
 The presence of new-onset confusion, lethargy, delirium,
and asterixis in the presence of cirrhosis → Highly suggests
Hepatic encephalopathy, rather than ammonia levels alone

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 48:35
V. Treatment of Cirrhosis
A. Treatment of Ascites
a) Spironolactone & Furosemide Therapy c) TIPS:
Any cause of portal HTN→ Splanchnic vasodilation → Stimulates Transjugular Intrahepatic Portosystemic Shunting (TIPS)
the RAAS → Worsens ascites by retaining more sodium and water Indications for TIPS:
in the body o Ascites refractory to medical therapy and require frequent
Spironolactone works by suppressing the RAAS→ Which leads to large-volume paracentesis
less sodium and water retention → Less ascites formation, o Treatment of refractory variceal bleeding and prevention of
whereas furosemide helps with removing any excess volume from variceal bleeding associated with portal HTN
the body Complications of TIPS:
o This coupled with sodium and water restriction may help to o In patients with cirrhosis, the TIPS procedure can allow
reduce ascites ammonia and other neurotoxic substances to enter the
bloodstream through portosystemic shunts, potentially causing
Spironolactone/Furosemide severe hepatic encephalopathy

Spironolactone Transjugular Intrahepatic Portosystemic Shunt (TIPS)

-
Renal artery 4
vasoconstriction RAAS
+
3 5
+
Vasodilators Furosemide
-
1 6 Hepatic vein
2
Na/H2O retention
Portal HTN +
Splanchnic Stent
+ vasodilation
Ascites
Liver

Portal vein

Gallbladder

b) Large Volume Paracentesis (LVP)

Indications for LVP:
o Large ascites, despite sodium and water restriction and
Spironolactone/Furosemide therapy
o Symptomatic ascites
Use of Albumin in Large-Volume Paracentesis
o If more than 5 liters of ascitic fluid are removed, administering
IV albumin is crucial to prevent volume depletion, which can
impair kidney function and lead to hepatorenal syndrome

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 B. Treatment of SBP D. Treatment of Hepatorenal Syndrome:
a) Antibiotics (Ceftriaxone) a) Systemic Vasoconstriction Agents
Indications: Midodrine → Outpatient/Non-ICU | Norepinephrine → ICU
o Diagnostic Evidence of SBP Mechanism:
Monitoring: o Systemic vasoconstriction →↑SVR → ↑MAP→ ↑Renal
o Monitoring for an improvement in abdominal pain, fevers, perfusion
leukocytosis, and normalization of paracentesis findings Monitoring:
(normal PMNs) o Improvement in urine output and creatinine

b) Splanchnic Vasoconstrictors
C. Treatment of Hepatic Encephalopathy: Octreotide
Mechanism:
a) Lactulose and/or Rifaximin: o Splanchnic vasoconstriction→ Prevents drop in Systemic BP→
Mechanism of Lactulose: Prevents renal artery vasoconstriction→ Improves renal
o Lactulose is metabolized by bacteria into acid metabolites that perfusion
bind up ammonia converting it into ammonium which is easily Monitoring:
excreted o Improvement in urine output and creatinine
Indications:
o Hepatic encephalopathy c) Plasma Volume Expanders
Monitoring: Albumin
o Monitor ammonia levels for normalization Mechanism:
o Monitor for improvement in mental status o ↑Albumin→ ↑Oncotic pressure→ ↑Plasma blood volume →
↑Renal perfusion
Bacteria NH4+
Lactic acid
( Toxic) Monitoring:
Lactulose H+ +
Acetic acid
NH3 o Improvement in urine output and creatinine

b) Osmotherapy
(Mannitol or Hypertonic Saline)
Indications:
o Cerebral edema with ↑ICP
Monitoring:
o Monitor for improvement in ICP
o Monitor for improvement in neurologic status

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 E. Treatment of Esophageal varices F. Surveillance of Hepatocellular Carcinoma:
a) Splanchnic Vasoconstrictors a) Abdominal U/S Every 6 Months
Octreotide Purpose:
Mechanism: o Allows the identification of an abnormal appearing hepatic
o Splanchnic vasoconstriction→ ↓Splanchnic blood flow→ mass in patients with cirrhosis
↓Portal blood pressures→↓ Blood flow across the bleeding
varices→ ↓Variceal bleeding b) AFP Levels Every 6 Months
Monitoring: Purpose:
o Improvement in UGIB o ↑↑AFP levels are suggestive of HCC

G. Liver Transplant in Severe Cirrhosis:

Prognostic Indicators for Liver Transplant:
Child-Pugh Score → Predicts one-year survival rate and the
likelihood of complications
o Factors affecting score:
 Albumin↓↓
 Bilirubin↑↑
 Coagulation abnormalities (INR↑↑)
 Distended abdomen (Severe ascites)
b) Antibiotics (e.g. Ceftriaxone)  Encephalopathy
Benefit/Purpose: MELD-Na Score → Predicts 3-month mortality rate
o ↓Risk of Infections (e.g. SBP) o Factors affecting score:
 Bilirubin↑↑
c) Endoscopy (Ligation)  INR↑↑
Indications:  Sodium (Hyponatremia is a poor indicator)
o All bleeding esophageal varices  Dialysis (Hepatorenal syndrome requiring dialysis is a poor
 Slight Drawback: Massive Bleeding and HD instability indicator)
• In this scenario the varices should be temporarily  Creatinine (Hepatorenal syndrome is a poor indicator)
compressed via the use of a Blakemore Tube to achieve
HD stability → Transferred to endoscopy suite for
ligation of varices
 Benefits:
• Resolution of UGIB via the use of Banding or sclerotherapy
of the varices

d) TIPS:
Transjugular Intrahepatic Portosystemic Shunting (TIPS)
Indications:
o Refractory Esophageal varices
o Refractory Ascites
Complications:
o Hepatic encephalopathy may occur from the portosystemic
shunt leading to ammonia bypassing the liver and unable to be
metabolized and cleared

e) Propranolol Therapy
Indications:
o Prophylaxis in patients with known esophageal varices
Mechanism:
o Splanchnic vasoconstriction→ ↓Splanchnic blood flow→
↓Portal blood pressures→↓ Blood flow across the bleeding
varices→ ↓Variceal bleeding

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