Liver Disease
Brenda Beckett, PA-C
Liver
Large, 4 lobes
 Highly vascularized

– Nutrient-rich blood from GI tract with
products of digestion via portal vein
– Oxygen-rich blood via hepatic artery
Metabolism, detoxification, storage,
excretion
 Ability to regenerate

Mechanisms of disease
Hepatocyte damage
 Biliary tract obstruction
 Metabolic disorders
 Metallic deposition
 Fibrotic changes
 Neoplasms

Symptoms of Liver Disease

May be asymptomatic until advanced
– RUQ abdominal pain
– Pruritis – bile salts deposited below skin
– Fatigue
– Weakness
– Decreased libido
– Nausea
– Bleeding
Signs of Liver Disease
Gynecomastia
Diabetes
Testicular atrophy
Ataxia / Asterixis
Xanthomas,
xanthelasmas
Jaundice (icterus)
Spider angiomata
Palmar erythema
Hepatosplenomegaly
Ascities / anasarca
Encephalopathy
Fetor hepaticus
Caput medusa
Asterixis
Assessing for Liver Disease
Typical patterns in lab tests
 Many patients with abnormal labs are
asymptomatic (need for screening)

– Tests for hepatocellular damage
– Tests for liver function
Hepatocellular Damage

Aminotransferases – AST, ALT
– Present in hepatocytes. AST also in
cardiac muscle. Released with necrosis

Alkaline phosphatase
– Isoenzymes in liver, bone, gut

GGT
– Enzyme present in multiple tissues
– Nonspecific. Will help to locate liver source
Tests for Liver Function
Prothrombin time - measures synthesis
of factors II and VII
 Albumin – plasma protein. Maintains
oncotic pressure
 Cholesterol – Not specific, many
variables. May be decreased in endstage disease

Bilirubin
Hemoglobin heme biliverdin
unconjugated bilirubin.
 Combines with albumin
to liver.
 Conjugated and excreted as bile to
intestines
 Elevated in liver disease and hemolysis

Jaundice
Prehepatic - excess production
 Hepatic - impaired function (uptake
or conjugation)
 Posthepatic - obstruction

Jaundice
Unconjugated - (pre and hepatic)
 Excess production
– Hemolytic anemia, hemolysis
 Hepatic
– Causes
• Hepatocellular disease, Gilbert’s,
neonatal jaundice
Jaundice
Conjugated (posthepatic)
 Causes
– Obstruction
– Hepatocellular disease
– Drugs
– Sepsis
– Post surgical
Jaundice Evaluation

History
– Drugs – prescribed, otc, vit., herbs, etc
– Transfusions, IVs, tattoos, IV rec drugs,
sexual activity
– Recent travel, exposure to jaundiced,
alcohol intake
– Duration, constitutional symptoms, fever,
weight loss, RUQ pain
Jaundice Evaluation

Physical
– Nutrition, signs of chronic liver disease
– JV distention, liver and spleen
enlargement,
– Ascites, tender RUQ

Labs
– Bilirubin, Conj and Unconj. Liver
enzymes
Other diagnostic tools
Ultrasound

Obstruction:
– Biliary tract stones
– Intrahepatic biliary dilation
Texture of liver (fatty vs. cirrhosis)
 Cystic/solid tumors

17
CT Scan
Characterize/quantify lesions
 Enhancement with contrast
 Smallest detectable lesion is 1cm


Obstruction
18
MRI

Best for:
– Cystic lesions
– Hemangiomas
– Iron overload
19
PET Scan
Positron emission tomography
 FDG (Fluorodeoxyglucose) taken up by
active tissue and cancer cells
 Whole body scan
 Especially to rule out extrahepatic
disease in colon cancer patients

20
Percutaneous Biopsy
Can be safely done
 Use US or CT guidance
 Allows tissue diagnosis

21
22
Alcohol Related Liver Disease
Chronic alcohol intake can lead to fatty
liver, hepatitis and finally, cirrhosis
 Fatty liver and hepatitis (inflammation)
are reversible, but are precursors to
cirrhosis
 Exact mechanism unknown, but partially
due to toxicity and partially due to
nutritional deficits

Alcohol Related Liver Disease
Mechanism not well understood
 mechanisms

– Direct toxicity to hepatocytes
– Malnutrition
– Immune reactivity after cell damage
– Inc risk of Hepatocellular Carcinoma (HCC)
Alcohol Induced Hepatotoxicity

Alcohol Dehydrogenase primary metabolic pathway
– Present in gastric mucosa and liver
– Women with less in stomach so more reaches liver

Fatty acid & triglyceride deposition 1st response
• Fatty Liver or Steatohepatitis in 80%+ EtOH abusers
• Usually reversible - may be due to obesity

EtOH metabolism products toxic to hepatocytes
– Pathologic changes cause hepatitis
•
•
•
•
Infiltrative PMNs
Inflammatory product cell changes
Fibrotic changes and cirrhosis
Partially reversible
Alcohol Related Liver Disease

Risk for EtOH disease fxn of quantity
and duration of abuse
– No correlation to type of beverage
– Women develop ARLD with less intake
EtOH
– 1 beer, 4 oz wine, 1 ounce whiskey has
about 12 g of EtOH
• Inc risk with intake of >60-80 g EtOH daily for
10 years by men, >20-40 g daily by women
Alcohol Abuse
Patient may not admit to overconsumption
 First clue may be liver failure/disease
 Use transaminase levels for clue, then
biopsy to definitively diagnose
 R/O other causes and comorbidities

– HBV, HCV, etc.
Cirrhosis

Inflammation activates lipocytes
– Lose Vit A and form collagen
Fibrotic bands form and replace normal
cellular architecture
 Lose compliance  firm liver
 Results in  liver function and Portal
Hypertension
 Treatment possible early in process

– Treat cause: EtOH, metals, infection, etc.
Causes of Cirrhosis

Alcohol
 Viral hepatitis
 Biliary obstruction
 Veno-occlusive disease
 Hemochromatosis
 Wilson disease
 Autoimmune
 Drugs and toxins
 Metabolic diseases
 Idiopathic
Cirrhosis
Manifestations - determined by
pathology
 Scarring and disruption of
architecture distorts vascular bed
 Inadequate blood flow and ongoing
damage disturbs hepatocyte function
 Initially: fatty infiltration
Alcohol Related Liver Disease

Signs and symptoms:
– Often asymptomatic until late.
– Hepatomegaly
– Anorexia, nausea
– Jaundice
– Abdominal pain, RUQ tenderness,
splenomegaly, ascites, fever,
encephalopathy
Dx: ARLD
Typical blood abnormalities: Incr GGT,
AST, ALT (AST>ALT), ALP, Bilirubin.
Decr Albumin. Anemia. Prolonged PT
 Liver biopsy to confirm

– Large fatty droplets in fatty liver
– Inflammatory changes in hepatitis
– Fibrosis with nodular formation, Mallory
bodies, destruction of liver architecture in
cirrhosis
DDX: ARLD
US and other imaging to r/o obstruction
 Hepatitis screening


NAFLD can be diagnosed AST/ALT
ratio, BMI, MCV and gender
Trt: ARLD
Abstain from alcohol!
 Maintain adequate coloric intake
 Thiamine and folate supplements
 Cirrhosis: often hospitalization

– Low protein diet, monitor lytes, remove
ascites, give clotting factors, lactulose to
decrease nitrogen absorption from gut
Complications of Cirrhosis
Chronic Liver Failure
 Portal hypertension. Causes:
– Esophageal varices
– Ascites
– Encephalopathy
Hepatorenal syndrome
 Hepatopulmonary syndrome

Ascites - fluid in abdomen

Total body water and sodium excess
 Cause unknown but 3 theories:
– Portal HTN causes sequestration fluid in
splanchnic bed  dec circulating blood volume
– Primary renal process causing retention H2O, Na+
– Portal HTN causes release NO  arterial
vasodilatation

All cause RAA system activation, worsening
problem
 Dec albumin levels dec oncotic pressure to
hold fluid in vascular space
Ascites





Anasarca less common form of same
pathophys
Inc abdominal girth, weight
Dyspnea as fluid restricts diaphragmatic
excursion
Shifting dullness and US to confirm diagnosis
Treat the root cause: fix the liver
–
–
–
–
Na+ restrict 1500 mg/d
Spironolactone initially, add furosemide prn
Paracentesis (up to 4-6L)
Beware of spontaneous bacterial peritonitis
Other Complications

Hepatorenal syndrome: cause unknown
– Azotemia, hypernatremia, oliguria in presence of
histologically normal kidneys
• No urinary sediment indicating nephritis
– Dx by failure to resolve with hydration
– No known treatment

Hepatopulmonary syndrome causes
hypoxemia
– Pulmonary hypertension and R-to-L
intrapulmonary shunts
– Confused with co-morbid COPD
Hepatic Encephalopathy

Change in mental status in presence of liver
disease
– Spectrum from subtle personality changes to
confusion to coma

EEG changes noted
 Can cause coma and death
 Usually follows precipitating event:
– GI bleed, sepsis, electrolyte disturbance, shock,
sudden inc dietary protein intake
Hepatic Encephalopathy

Pathophysiology unknown
 Theory: hepatocellular damage and cirrhosis
cause extrahepatic shunting of venous portal
blood
– Toxic substances not removed from blood

Increased serum ammonia level
 Treat with lactulose up to qid to cause
diarrhea (decr nitrogen absorption)
Portal Hypertension
Classified as:
1) Sinusoidal: Alcoholic cirrhosis
2) Presinusoidal: Splenic/portalvein
thrombosis, hepatitis, hepatic fibrosis
3) Postsinusoidal: Vascular outflow
problem
- Budd-Chiari syndrome:
Thrombosis of hepatic veins
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Portal Hypertension

Signs:
– Ascites
– Caput medusa
– Splenomegaly
– Variceal bleeding
– Encephalopathy
Management of Portal HTN
1)
2)
Medical: Ascities, encephalopathy,
coagulopathy
Surgical: TIPS (Transjugular
Intrahepatic Portosystemic Shunt),
other shunting procedures
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Acute Liver Failure
Acute massive loss of hepatocyte
function
 No pre-existing liver disease or portal
HTN
 Acetaminophen overdose, viral
hepatitis, drug toxicity, herbal and
dietary supplements

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Acute Liver Failure
Extremely elevated transaminases
 Bilirubin may be normal
 Coagulopathies
 Increased ammonia


Acetaminophen overdose: treat with
acetylcysteine
Acute Liver Failure

Can progress to fulminant hepatic
failure with encephalopathy
– Sepsis
– Cerebral edema

High mortality rate
– May need transplantation
No long term sequelae in survivors
 Uncommon

46
Benign Solid Liver Tumors
Hepatic Adenoma
- Reproductive age females on OCPs
- Sheets of hepatocytes with no
parenchymal cells
- Risk of rupture and malignant
transformation
47
Hepatic Adenoma
DX: Difficult to distinguish from FNH
(Focal Nodular Hyperplasia)
- CT/MRI: to differentiate
Can rupture and bleed
48
Hepatic Adenoma
Management:
<4cm: cessation of OCPs, can regress
>4cm, no regression; resection
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Malignant Tumors of Liver
Hepatocellular Carcinoma (HCC)
- Associated with cirrhosis, hepB, C
- Weight loss, weakness, abdominal
pain, hepatomegaly, mass
DX: CT scan, perc. biopsy
- Will have elevated Alk Phos, AFP
50
HCC
Tx: surgical resection - difficult
Prognosis: Poor – depends on stage
4-6 months
5 year survival 25%
- Death due to cachexia, hepatic
failure, mets, bleeding
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Metastatic Lesions to Liver
- Most common neoplasm of liver
- Reach liver by portal venous
circulation, hepatic artery, direct
extension or lymphatic spread
- Colon, breast, lung, pancreas,
stomach, others
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Metastatic Lesions
DX: CT, labs, PET scan
TX: Resection of mets, segments, lobe
- Hepatic arterial infusion
chemotherapeutic agents
- New: Portal vein embolization,
radiofrequency ablation
53
Hepatic Resection
- Can remove up to 80%
- Albumin, synthetic capability by 3rd
week
- Regeneration by hypertrophy of
remaining tissues
54
Wilson Disease
Genetic disorder of copper metabolism
 Impaired biliary excretion of Cu
 Age 14-30, unless caught in screening
 Neuro Sx: tremor, ataxia, anxiety, MS 
 Liver: cirrhosis, hepatitis
 Renal, cardiac involvement

Wilson Disease Dx
Inc transaminases
 Dec ceruloplasmin <20 mg/dl
 Inc urinary copper excretion >100
g/24h
 Inc liver copper deposition >250 g/g
 Kayser Fleischer rings

Kayser Fleischer rings
Wilson Disease Tx
Usually lifetime of chelating agents
 Penicillamine, trientine, zinc
 Liver transplant for fulminant liver failure
 Important to catch early

Hereditary Hemochromatosis
Excess Fe absorption and deposition
 Caucasians, us. Northern European
 Early: fatigue, arthralgias, abd pain,
impotence
 Later: diabetes, hepatitis, cirrhosis,
cardiomyopathy

– Usually age 40-60 depending on comorbidities

Screening iron studies
HHC Dx
Sl. elevated transaminases
 Incr iron, Transferrin saturation >50%
 Serum ferritin elev but less specific
 Genotyping for C282Y and H63D
mutations
 Liver biopsy gold standard but not
necessary

HHC Tx is Phlebotomy
To prevent irreversible end organ
damage
 Phlebotomy 500 cc weekly until mild
anemia and ferritin <50 ng/ml
 May take 2 years initially
 Maintenance: phlebotomy quarterly
 Can improve quality of life in patients
with liver disease
 May need transplant

Vascular Diseases

Acute ischemic injury due to shock, CHF
 Injury due to chronic congestion from rightsided heart failure
– Retrograde elevated venous pressure dilates
sinusoids
– Poor perfusion results in ischemic injury, loss of
metabolic function
– Centrilobar fibrosis and cirrhosis
– Firm, large liver, other signs liver failure
Vascular Diseases

Budd-Chiari Syndrome
– Occlusion of hepatic veins
– Venous thrombosis
• Polycythemia Vera, hypercoagulable states,
myeloproliferative diseases (cause
hypercoagulable state)
– Mass or tumor
– US or MRI to diagnose
– Anticoagulate or TIPS
Granulomatous Liver Disease
Granuloma: Nodular inflammatory
lesion
 Usually asymptomatic
 Multiple causes

Granulomatous Liver Disease

Causes:
– Drugs: Allopurinol, quinidine, quinine, etc
– Infections: Bacterial, fungal, parasitic, viral
– Cirrhosis
– Systemic: Hodgkin’s, polymyalgia
rheumatica, connective tissue disorders,
sarcoidosis
Granulomatous Liver Disease

DX:
– Labs: elevated ALP, GGT
– Imaging: US, CT, MRI show calcifications
– Biopsy
– Often found during imaging for other
reasons
Granulomatous Liver Disease

Treatment:
– Treat the cause (stop meds, treat infection,
etc)
Pyogenic Hepatic Abscess

Multiple routes of entry of bacteria
– Common bile duct (ascending cholangitis)
– Portal vein
– Hepatic artery
– Direct extension from infection
– Trauma
Pyogenic Hepatic Abscess

Most common bacteria
– E. coli
– K. Pneumoniae
– P. vulgaris
– Enterobacter
– Multiple anaerobes
Pyogenic Hepatic Abscess

Signs/Symptoms:
– Fever almost always present
– RUQ pain
– Jaundice
Pyogenic Hepatic Abscess

Labs:
– Leukocytosis, shift to the left
– Liver tests nonspecific
– Positive blood culture

Imaging
– CXR: elevated diaphragm on R
– US, CT, MRI
Pyogenic Hepatic Abscess

Treat:
– IV antibiotics (3rd gen cephalosporin plus
metronidazole. 3-6 weeks
– Possible abscess drainage
– Treat underlying source