Liver Disease Brenda Beckett, PA-C. Liver Large, 4 lobes Highly vascularized –Nutrient-rich blood from GI tract with products of digestion via portal.

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 end-stage 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

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Ultrasound

Obstruction:– Biliary tract stones– Intrahepatic biliary dilation

Texture of liver (fatty vs. cirrhosis) Cystic/solid tumors

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CT Scan

Characterize/quantify lesions Enhancement with contrast Smallest detectable lesion is 1cm

Obstruction

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MRI

Best for:– Cystic lesions– Hemangiomas– Iron overload

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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

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Percutaneous Biopsy

Can be safely done Use US or CT guidance Allows tissue diagnosis

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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 over-consumption

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)

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Portal Hypertension

Classified as:1) Sinusoidal: Alcoholic cirrhosis2) Presinusoidal: Splenic/portalvein

thrombosis, hepatitis, hepatic fibrosis3) Postsinusoidal: Vascular outflow

problem- Budd-Chiari syndrome:

Thrombosis of hepatic veins

Portal Hypertension

Signs: – Ascites– Caput medusa– Splenomegaly– Variceal bleeding– Encephalopathy

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Management of Portal HTN

1) Medical: Ascities, encephalopathy, coagulopathy

2) 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

Acute Liver Failure

Extremely elevated transaminases Bilirubin may be normal Coagulopathies Increased ammonia

Acetaminophen overdose: treat with acetylcysteine

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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

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Benign Solid Liver Tumors

Hepatic Adenoma

- Reproductive age females on OCPs

- Sheets of hepatocytes with no parenchymal cells

- Risk of rupture and malignant transformation

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Hepatic Adenoma

DX: Difficult to distinguish from FNH (Focal Nodular Hyperplasia)

- CT/MRI: to differentiate

Can rupture and bleed

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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

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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

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Hepatic Resection

- Can remove up to 80%

- Albumin, synthetic capability by 3rd week

- Regeneration by hypertrophy of remaining tissues

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 co-

morbidities 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 right-

sided 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