Liver Flashcards
What is acute liver failure
Onset of liver injury, hepatic encephalopathy, and coagulopathy (INR >1.5) in patients w/ no prior h/o liver disease
Most acute liver cases arise from
massive hepatocyte necrosis; APAP overdose
-viral hepatitis, drugs, toxins, metabolic, vascular events, misc.
What are S/Sx of acute liver failure
AMS (encephalopathy) cerebral edema coagulopathy multiple organ failure ascites, anasarca, shrinking liver on PE
What are the stages of encephalopathy (AMS)
Early: personality change, reverse sleep pattern
Progressing: lethargy
Late: coma
What is acute hepatic failure
acute onset liver failure with coagulopathy (INR >1.5) and jaundice
Encephalopathy w/in 1-4 weeks of liver injury!
What is subacute hepatic failure
Acute liver failure with encephalopathy developing 12-24 weeks after onset of liver injury
What are lab findings in acute liver failure
Severe coagulopathy (high PT/INR)- bleed easy
CBC: leukocytosis
BMP: hyponatremia, hypokalemia, hypoglycemia
LFT: marked elevation of bilirubin, ALT, AST
How do you treat acute liver failure
Hospitalization
Continuous monitoring
Supportive care
If recovery seems unlikely, prep for liver transplant
What is hepatitis
Acute or chronic hepatocellular damage
What causes acute vs chronic hepatitis
Acute: Viral!
Chronic: Viral!
so basically… VIRAL!!
How are different hepatitis forms contracted
A&E: fecal oral route (E from Mexico). But they are self limited!
B, C, D: parenterally, mucous membrane (IVDU, tattoos, infected mom, transfusion). these progress to chronic
What are categories of acute hepatitis
Self limited
Acute liver failure
Cholestatic hepatitis (HAV)
Relapsing hepatitis (HAV)
What is the pathophys of acute viral hepatitis
Cell mediated mechanisms cause hepatocyte injury by degeneration or apoptosis; CD8 and CD4 respond, and cytokines are produced
What are S/Sx of acute viral hepatitis (self limited)
Prodrome: malaise, anorexia, N/V, flu-like Sx. Abrupt onset in A&E, insidious in B-D
Wen prodromal Sx subside, jaundice sets in w/ dark urine and pruritis
What will self limited acute viral hepatitis show on PE
mild enlargement and ttp of liver
mild splenomegaly
What are S/Sx of cholestatic hepatitis (HAV acute)
severe jaundice
pruritis
anorexia and diarrhea
-BUT a good prognosis
What are S/Sx of relapsing hepatitis (HAV acute)
Sx recur for wk-months arthritis vasculitis cryoglobulinemia -BUT, prognosis is excellent eventually
What are lab findings in acute viral hepatitis (self limited)
ALT/AST >500 Total bili: normal Alk Phos: normal Prolonged PT/INR: normal Albumin: normal WBC: normal \+/- lymphocytosis
What are cholestatic disease (acute viral) findings
Bilirubin 20+
Alk phos: high
ALT/AST: initially elevated, may decrease*
What are lab findings in relapsing acute viral hepatitis
ALT/AST: elevation after normalization
Bilirubin: elevation after normalization
-relapses usually don’t exceed previous levels
How do you treat acute viral hepatitis
Self limited and relapsing: outpt, unless severe dehydration. Plenty of fluids&kcal. No EtOH, rest, d/c non-essential drugs, if HCV doesn’t resolve in 3 months use antiviral, if HBV use tenofovir or entecavir if severe
How do you treat cholestatis acute viral hepatitis
Prednisone
Ursodeoxycholic acid
Cholestyramine for pruritis
Are HAV and HEV chronic
No, the virus can survive in bile and is shed in feces, but does NOT result in prolonged viremic or intestinal carrier states
What is the pathophys of hep A&E
Virus ingested, transported across intestinal epithelium, through mesenteric veins to liver
It enters hepatocytes, replicates, causes cell mediated injury, and is then shed into bile and travels to intestine
What are RF for Hep A
Live in Africa, Asia, or Latin America (poor sanitation, developing countries)
Close contact with infected person
MSM
Food outbreak (contaminated water, ice, shellfish)
What are S/Sx of HAV
28 day incubation: Fever, jaundice (2 weeks)
Cholestatic and relapsing hepatitis are common manifestations
Fulminant course NOT common
How can you diagnose Hepatitis A
IgM antibody to HAV (anti-HAV) 5-10 days before Sx. Stay high for 3-6 months
Lifelong IgG anti-HAV elevation means immunity**!
Positive anti-HAV IgG can indicate
Prior infection or recent disease
How do you treat Hep A
Supportive care
Nearly all will recover fully in 6 months
What info do you send the patient with Hep A home with
Wash hands after pooping and changing diapers
Dispose waste sanitarily
Safe food handling practices
Immunization if you are high risk
Avoid excess APAP and alcohol, eat a balanced diet
Kids: don’t go back to school until 1 week after illness onset
How can you prevent Hep A
HAV vaccination (inactive) for: **All kids 1 y/o (CDC says healthy ppl 1-40) kids 2-18 in high risk areas Traveling to endemic area MSM IVDU Occupational risk Hx of chronic liver dx Clotting factor disorder Household member has Hep A
What is Hep A prophylaxis
If you have been exposed to Hep A and are not vaccinated, Give prophylaxis w/in TWO WEEKS* of exposure
If <1 or >40, or immunocompromised, give immunoglobulin*
Key highlight on slide 42
Do it
What is the epidemiology of Hep E (where it’s found, how it’s spread, etc)
Endemic in: mexico, cuba, asia, africa, middle east
Spread by animals, MC swine and deer
Contaminated drinking water
What are Sx of Hep E
Abrupt onset prodromal Sx
Acute liver failure is common in pregnant ladies (esp in 3rd trimester)
How do you diagnose HEV
IgM anti-HEV detectable for 6 weeks
IgM replaced by IgG anti-HEV, detectable for 12-20 months (NOT immune longterm)
HEV RNA confirms presence of Hep E in serum or stool
How do you prevent Hep E
NO vaccine!! or immunoglobulin for prophylaxis! So:
Good sanitation
Avoid unpurified H2O
Avoid raw pork and venison (deer)
What is Hep B
a DNA virus that is transmitted by sex or mucosal route
Can develop limited (MC in adults) or chronically infected (MC in kids and perinatal) disease
Where is Hep B prevalent
West africa
South sudan
What are characteristics of Hep B
Outer envelope has: Hep B surface antigen (HBsAG)
In envelope: structural protein (HBcAg), non-structural (HBeAg), DNA polymerase (reverse transcriptase)
Hep B infection is influenced by
age genetic factors presence of other viruses HBV mutation level of immunosuppression
How does Hep B manifest in different individuals
Neonates: 95% become chronic ASx carriers
Adult primary infection: 70% are ASx and self limited
Chronic HBV: risk of cirrhosis esp in older pts, or if co-infected with HCV, HDV, or HIV
What is the pathophys of Hep B
Liver injury occurs 2/2 host immune response to Hep B virus
Immune response is against Hep B structural protein (HBcAg)
Strong RF for Hep B are
Perinatal exposure to Hep B mom Multiple sex partners MSM IVDU Asian, Eastern European, African FHx of HBV FHc of HCC Household contact with HBV
In order to diagnose Hep B you need
elevated clinical suspicion* in high risk individual
What are Sx of Hep B
Insidious onset
Serum sickness like syndrome: fever, chills, malaise, rash, n/v, arthralgias, arthritis
How does Chronic Hep B present
May be ASx OR signs of chronic dz:
Cirrhosis
HCC
liver failure
how do you diagnose acute Hep B
IgM antibody to Hep B core antigen (HBcAg) w/ Sx and elevated ALT
HBsAg and IgM anti-HBc 2wk-6mo after exposure
How do you know Hep B has resolved
ALT normalizes
No HBV DNA
Seroconversion to Anti-HBe and Anti-HBs, and IgG anti-HBc
How can you tell if someone has had a prior HBV infection
Will have both surface and core proteins!
anti-HBs, IgG anti-HBc, and anti-HBe
How do you diagnose chronic Hep B
HBsAg present for >6 months
HBeAg and HBV DNA persistence
Inactive carrier: ASx, normal ALT, low HBV DNA, anti-HBe
How do you treat chronic Hep B
Acute: self limiting
Fulminant: liver transplant
Chronic: anti-viral therapy
What are first line therapy options for chronic viral Hep B
*Peginterferon alfa-2a: weekly subQ injection for 48 weeks (best for young, non-cirrhotic, low HBV-DNA level) Nucleoside analogues (Entacavir, Tenofovir) to inhibit HBV replication: daily PO indefinitely
Goal of Hep B antiviral Tx is
Sustain low or undetectable HBV DNA
Seroconvert HBeAg and HBsAg and normalize ALT
How can you prevent Hep B
Hep B vaccine given once, then repeat 6 months later
Part of universal infant immunization, and for high risk individuals
What Hepatitis has vaccines
A and B!!!
NONE OTHERS
How can you prevent Hep B
Hep B immunoglobulin
Postexposure prophylaxis then HBV vaccine if sex w/ casual partner with HBV
Newborn w/ Hep B + mom: HBIG and HBV vaccine immediately after birth
What is secondary prevention of Hep B
Chronic HBV not immune to Hep A: Hep A vaccine
Chronic HBV: Avoid heavy alcohol
HBsAg positive: use barrier protection, don’t share toothbrush or razor, cover open cuts, clean blood with bleach, no blood, organ, or semen donation
What is the prognosis of Hep B
5 year risk for:
Cirrhosis= 10-20%
HCC= 5-10%
decompensated cirrhosis= 15%
Key highlights on slide 78
Go look
When should you suspect Hep D
Fulminant Hep B infection
Acute Hep B infection that improves then relapses
Progressive chronic HBV w/o active HBV replication
How do you get Hep D
You can only get it if you also have Hep B!
HDV is specific only in the presence of HBsAg
What do Hep D labs show
anti-HDV and HDV RNA
Co-infection: IgM anti-HBc
Superinfection: IgG anti-HBc
How do you treat Hep D
High dose interferon alpha and PEG IFN
therapy is not optimal 2/2 high risk of relapse
What is Hep C
a flavivirus
Per CDC, when should you screen for Hep C
If high risk for infection
If born between 1945-1065 regardless of risk
What is the pathophys of Hep C
Acute: self limited, most develop antibodies
Persistent viremia: hepatic inflammation and fibrosis. weak CD4 and CD8 cells can’t control viral replication
Chronic: liver damage 2/2 local immune response (inflammation) by hepatic stellate cells
In Hep C, cirrhosis is accelerate by
Chronic alcohol consumption
Coincidental viral infection
What are the types of Hep C
6 genotypes!
U.S.: Genotype 1
Middle east: genotype 4
South africa/asia: genotype 5&6
How is Hep C transmitted
Blood exposure, MV in IVDU
less common but still possible: sex, perinatal, accidental blood contact
Strong RF to Hep C are
IVDU
Blood transfusion before 1992
Clotting factor transfusion before 1987
HIV (more likely to progress to liver dz, esp w/ low CD4)
What is literally the worst news a hypochondriac could receive about Hep C
It can live outside the body for 3 weeks
YOU CAN GET HEP C FROM DRIED BLOOD!!!
So watch the damn tamp box in the bathroom, ya nasty
How does Hep C present
MC: ASx
Prodromal jaundice
Young women can spontaneously clear, but most develop chronic infection
Black are least likely to clear infection
What are acute function tests for Hep C
8 wks after exposure: HCV RNA (needed to Dx acute infection)
6-12 wks after: ALT and AST elevated
8 wks-months after: anti-HCV (hep C antibody) detectable
Who is more likely to spontaneously clear hep C (self limited dz)
IL28B genotype CC
IL28B CT&TT are LESS likely
How can you diagnose chronic infection of HCV
HCV RNA in blood for min 6 months
Screening test by EIA detects Abs against virus. If +, it’s active
ASx
Likely have chronic liver disease, decompensated cirrhosis, and HCC
What factors influence development of chronic progressive liver disease 2/2 HCV
Older age Male Concurrent Hep B HIV high alcohol intake
How do you use Hep C tests
Qualitative studies confirm viremia and have low limits of detection (RT-PCR detects 40-50 IU, TMA lower limit is 5IU)
Quantatitave tests give a wide dynamic range of viral loads
What is a baseline HCV workup
Confirm HCV viremia (quantitative)
Eval for coexisting liver disease and HIV
Vaccinate for Hep A and B
Get viral genotype
Goal in treating Hep C is
Clear virus from blood stream
Stabilize or improve liver histology
Sx control
Prevent complications (HCC, cirrhosis, decompensated dz)
If already cirrhotis: avoid passing to new liver, haver fewer complications, have less mortality
What is NEW Hep C treatment
Telaprevir and Boceprevir: protease inhibitors that bind protease of HCV genotype 1 and inhibit replication
Sofosbuvir was more effective than any other medications
Direct acting antivirals: Simeprevir, Paritaprevir, Grazoprevir (second gen NS3-4 inhibitors)
-Can use ribavirin
What determines Tx regimen for Hep C
HCV genotype
Has the patient been treated before
Do they have cirrhosis
(she said basically Sofosbuvir + another med)
How can you tell Hep C is responding to Tx
RVR: HCV DNA undetectable by week 4 of Tx
EOT response: HCV DNA undetectable by end of Tx
SVR: sustained virologic response (best) means no HCV RNA 12 weeks after Tx is over
(Non-response means you have detectable RNA, Relapse means you were undetectable and now you are again)
What reduces likelihood of achieving SVR
Cirrhosis
Previous nonresponse
HCV genotype 3
-In these, continue Tx by 24 weeks and add Ribavirin
Hep C patient education is
Dont share toothbrush or razors Cover bleeding wounds Don't donate organs or blood Use barrier protection Avoid IVDU
Go over key highlights slide 128
do it
this was a shit show
What drug classes are known to cause toxic hepatitis
Antimicrobials* CNS agents Immunomodulators Analgesics Lipid lowering meds
What specific drugs are known to cause toxic hepatitis
APAP NSAIDs, ASA Augmentin, Sulfonamides Isoniazid, Rifampin Interferon, antiretrovirals for HIV OCP Carbamazepine, phenytoin, valproic acid Amiodarone TZD, Metformin Statins Methotrexate, Azathioprine Chemo Herbals Mushrooms Cocaine
How does toxic hepatitis present
LFT elevation +/- acute liver failure
Liver injury w/in days-weeks of ingestion
Labs can look like hepatotoxic injury, cholestatic, or mixed
How do you diagnose toxic hepatitis
H&P!
Exclude other causes
How do you treat toxic hepatitis
Remove causative agent
+/- liver transplant for severe acute liver failure
What is the MCC of acuute liver failure and drug induced liver injury
Tylenol!!!
Toxic dose is 10-20g (lower in alcoholics)
How does APAP toxic hepatitis present
30 min-24 hours after ingestion: GI Sx
2 d after: R side abd pain and oliguria, elevated LFT, prolonged PT/INR
3-5 d after: hepatic necrosis w/ elevated aminotransferase, renal failure or acute liver failure
5-10 d after: recovery phase
What increases the likelihood of death or need for liver transplant in an APAP OD
pH <7.3
Stage 3-4 encephalopathy w/ PT/INR >6.5 and Cr >3.4
Factor V level 10% or less
How do you manage APAP OD
Get a serum APAP level
IV NAC
Charcoal w/in 1 hr of ingestion
Gastric lavage w/in 4 hours
What are the types of alcoholic liver disease
Steatosis: fatty liver
Steatohepatitis: alcoholic hepatitis
Cirrhosis: fibrogenesis/scarring
What are Sx of alcoholic liver disease
Portal HTN
Fever, anorexia, nausea, RUQ pain, tender hepatomegaly, jaundice
What are lab findings in alcoholic liver disease
AST high (AST>ALT) Alk phos: high Other LFT: normal Tg: high K, Phos, Mag: deficient Glucose: high
How do you diagnose alcoholic liver disease
Hx of significant alcohol abuse
Exclude other forms
Liver biopsy
How do you manage alcoholic liver disease
Abstinence can stop progression +/- reverse damage!
What is Maddrey’s Discrimination function
A way to calc short-term prognosis in pts w/ worsening alcoholic hepatitis:
4.6 x (diff btwn pt’s PTT and control PTT) + SrBili
If DF >32, pt has 50% mortality during current hospitalization
How do you manage acute worsening of alcoholic hepatitis
Stop drinking EtOH
Naltrexone, Acamprosate, or Baclofen lessen effects of withdrawal and decrease desire to drink
Counseling
Give carbs and calories (promote gluconeogenesis, prevent hypoglycemia)
Ntr support
Give folic acid, thiamine (prevent werneke’s), and zinc
Methylprednisolone PO x 1 month (reduce DF)
Pentoxifylline: PDE inhibitor to enhance circulation, reduce 4 week mortality
What is NAFLD (hepatic steatosis)
Accumulation of Tg droplets in hepatocytes.
Can be benign if no significant inflammation or fibrosis on biopsy
What is NASH
necroinflammatory change on liver biopsy, can progress to cirrhosis
Lipotoxic injury to hepatocytes
RF for NAFLD are
Insulin resistance Obesity DM2 Lipid abnormalities Meds like Tamoxifen, and corticosteroids
What increases the likelihood of death or need for liver transplant in an APAP OD
pH <7.3
Stage 3-4 encephalopathy w/ PT/INR >6.5 and Cr >3.4
Factor V level 10% or less
How do you manage APAP OD
Get a serum APAP level
IV NAC
Charcoal w/in 1 hr of ingestion
Gastric lavage w/in 4 hours
What are the types of alcoholic liver disease
Steatosis: fatty liver
Steatohepatitis: alcoholic hepatitis
Cirrhosis: fibrogenesis/scarring
What are Sx of alcoholic liver disease
Portal HTN
Fever, anorexia, nausea, RUQ pain, tender hepatomegaly, jaundice
What are lab findings in alcoholic liver disease
AST high (AST>ALT) Alk phos: high Other LFT: normal Tg: high K, Phos, Mag: deficient Glucose: high
How do you diagnose alcoholic liver disease
Hx of significant alcohol abuse
Exclude other forms
Liver biopsy
How do you manage alcoholic liver disease
Abstinence can stop progression +/- reverse damage!
What is Maddrey’s Discrimination function
A way to calc short-term prognosis in pts w/ worsening alcoholic hepatitis:
4.6 x (diff btwn pt’s PTT and control PTT) + SrBili
If DF >32, pt has 50% mortality during current hospitalization
How do you manage acute worsening of alcoholic hepatitis
Stop drinking EtOH
Naltrexone, Acamprosate, or Baclofen lessen effects of withdrawal and decrease desire to drink
Counseling
Give carbs and calories (promote gluconeogenesis, prevent hypoglycemia)
Ntr support
Give folic acid, thiamine (prevent werneke’s), and zinc
Methylprednisolone PO x 1 month (reduce DF)
Pentoxifylline: PDE inhibitor to enhance circulation, reduce 4 week mortality
What is NAFLD (hepatic steatosis)
Accumulation of Tg droplets in hepatocytes.
Can be benign if no significant inflammation or fibrosis on biopsy
What is NASH
necroinflammatory change on liver biopsy, can progress to cirrhosis
Lipotoxic injury to hepatocytes
What is Wilson’s disease
Auto recessive genetic abnormality leads to impaired copper transport
Results in hepatolenticular degeneration and cirrhosis, impaired biliary copper excretion, neuro complications
How does NAFLD/NASH present
ASx!
+/- RUQ pain, hepatomegaly
Elevated eminotransferase levels
How do you diagnose NASH/NAFLD
Macrovesicular steatosis w/ or w/o inflammation and fibrosis on liver bx
4 or less EtOH drinks x day
How do you treat NASH/NAFLD
Weight loss
Dietary fat restriction
Exercise
What is autoimmune hepatitis
Chronic hepatitis w/ high serum globulins
Presents w/ + ANA or amooth muscle antibosy
What does autoimmune hepatitis respond to
Corticosteroids!
Prednisone and Azathioprine improve Sx and decrease:
Sr bili, Aminotransferases, gamma-globulin levels, reduce hepatic inflammation
What are S/Sx of autoimmune hepatitis
Insidious onset
Fatigue, jaundice, hepatomegaly
+/- acutely severe or fulminant
What lab findings indicate autoimmune hepatitis
Aminotransferase >1000
Total bili: increased
Alk Phos: increased
Sr gamma globulin: increased
What do you need to diagnose autoimmune hepatitis
Autoantibodies: ANA or smooth muscle >1:40- anti-LKM1 if >1:40- anti-SLA +
High gamma globulin
No evidence of viral hepatitis
Liver bx
Standard Tx for autoimmune hepatitis is
Prednisone taper from 30mg to 10mg in 1 month PLUS Azathioprine 50mg
or
Prednisone taper from 60mg to 20mg in 1 month, then 20mg maintenance
When do you stop treating autoimmune hepatitis (end point for steroids)
Remission ideally: No Sx, nl AST/ALT, ULN), nl liver tissue (no hepatitis)
BUT- Tx can fail, you can have incomplete response, or drug toxicity
When do you follow up on autoimmune hepatitis if remission is achieved
Hepatologist q3-6 months 2/2 high likelihood of recurrence
Where does copper tend to accumulate in Wilson’s disease
Liver
Brain
Cornea (Kayser-Fleischer rings)
Wilson’s disease has what specific lab findings
Decreased ceruloplasmin
How do you treat Wilson’s disease
D-Penicillamine
Liver transplant if: fulminant hepatitis, hepatic insufficiency unresponsive to medical therapy, severe neuro Sx
What is hereditary hemochromatosis
Inherited disorder w/ impaired intestinal iron absorption causing iron to deposit in multiple organs
GFE gene mutation
Suspected 2/2 FHx ot Hx of elevated iron saturation or Sr ferritin
What is primary sclerosing cholangitis
Chronic thickening of bile duct walls leading to cholestatic liver disease
Inflammation, fibrosis, and stricturing of intra- and extra-hepatic bile ducts
Unknown pathogen, may be autoimmune
M>F, avg age 41
How do you treat hemochromatosis
Serial phlebotomy to achieve iron depletion
If not Tx, can cause cirrhosis and HCC
What is alpha-1 antotrypsin (AAT) deficiency
AAT is a protease inhibitor of proteolytic enzyme elastase
Deficiency manifests in lungs, liver, and rarely, skin
How does AAT present in kids
Liver disease (elevated LFT, cholestasis)
How do you diagnose AAT deficiency
Decreased AAT level
Genotypic Z protein (PiZZ is severe, PiMZ is intermediate)
How do you treat AAT deficiency
No Tx!
What is primary biliary cirrhosis
T cell attack on bile ducts causes gradual bile duct loss and portal scarring= cirrhosis
Commin in middle aged women
How does primary biliary cirrhosis manifest
ASx
+/- fatigue and pruritis
Jaundice, cirrhosis, xanthelasma, xanthoma, steatorrhea
What will primary biliary cirrhosis labs show
Alk phos: elevated
+ AMA
IgM: elevated
Cholesterol: elevated
How do you diagnose primary biliary cirrhosis
Normal biliary imaging
Characteristic liver biopsy
What are complications of ESLD
Jaundice Fibrosis- then cirrhosis Palmar erythema Spider angioma Encephalopathy w/ asterixis (hands tremor when pointed up) Portal HTN Ascites, muscle wasting
What is hepatic encephalopathy
Neuropsych abnormalities (I-short attention, II-personality change, III-confusion, IV-coma) 2/2 hepatocellular dysfxn causing increased ammonia levels (liver can’t convert ammonia to urea so ammonia crosses the BBB)
How does PSC present
Pruritis, jaundice
Fatigue, weight loss, RUQ pain
Hepatomegaly, splenomegaly
What do PSC labs look like
Cholestatic pattern: elevated alk phos and bilirubin, mild ALT/AST elevation (<300)
Atypical P-ANCA +
How do you diagnose PSC
MRCP/ERCP: multifocal stricturing and dilation of intra/extrahepatic bile ducts (ERCP can also retrieve stones and place stents!)
Liver bx: support Dx and tells you level of cirrhosis
How do you manage PSC
Stent for strictures (ERCP)
Ursodiol: reduce secretion of cholesterol from liver, may help Sx
What is spontaneous bacterial peritonitis
Infection in abd ascites fluid or pleural fluid
Presents w/ fever, abdominal pain, AMS, or can be ASx
What is the prognosis of PSC
Progress to cirrhosis, require liver transplant
10-12 year survival w/o transplant
Screen for cholangiocarcinoms q6-12 mo (CA 19-9, CT, or MRI)
If pt has UC: screen for colon cancer (CEA, colonoscopy)
What diseases can lead to ESLD (cirrhosis) that have elevated ALT/AST
HCV, HBV EtOH Steatohepatitis/NASH/NAFLD Autoimmune hepatitis Hemochromatosis Wilsin's disease AAT deficiency
What diseases can lead to ESLD that have elevated Alk phos and Bili
PSC
primary biliary cirrhosis
What are complications of ESLD
Jaundice Fibrosis- then cirrhosis Palmar erythema Spider angioma Encephalopathy w/ asterixis (hands tremor when pointed up)
What is hepatic encephalopathy
Neuropsych abnormalities (short attention, personality change, coma) 2/2 hepatocellular dysfxn leading to increased ammonia levels
How do you treat hepatic encephalopathy
Grade I-II: Lactulose (want 2 BM/d) or Rifaximin
Grade III-IV: admit for Lactulose via NG tube until mental status improves
What is portal vein thrombosis
Diminished blood flow in portal vein and changes in clotting factors that are normally cleared by liver causes thromboembolism
How do you diagnose and treat portal vein thrombosis
Doppler US, CT, or MRI
Tx with anticoags (heparin or LMWH)
How do you treat ESLD
1st line: Furosemide&Spironalactone (40mg:100mg)- compression stockings for LE edema
2: Paracentesis, thoracentesis
3: Transjugular intrahepatic Portosystemic Shunt (TIPS) creates channel between hepatic and portal vein to reduce portosystemic pressure to <12
What is MELD (model of ESLD)
Determine transplant eligibility
3.8 (Srbili) + 11.2 (INR) + 9.6 (SrCr) + 6.4
MELD - Na - (0.025 x MELD x [140-Na]) +140
Total bili, INR, Cr, and Na are used bc they are strong predictors of 3 month mortality
Mortality decreases starting at MELD 15 (0 is least likely to die)
What serology indicted ESLD
Low Albumin and globulins (<6.3) High PT/INR Low Sodium High Creatinine Thrombocytopenia
What is albumin
60% of protein in serum! Should be 3.5-5
Carries small hydrophobic molecules (fatty acids, bili, drugs) and maintains osmotic pressure of blood
If low, think: nephrotic syndrome, malntr, chronic liver dz
What is PTT
Thromboplastin +CaCl added to plasma to measure time to clot
Norm is 12-15 seconds
Need vitamin K for liver synthesis of thromboplastin!
If high think: chronic liver dz, acute liver failure, obstructive jaundice, vitamin K deficiency
What is INR
Used to standardize PT
Why is sodium low in ESLD
Indirect marker of portal HTN (chronically overloaded)! Marker of mortality
If w/ hyponatremia may lead to cerebral edema and neuro changes
Added to MELD score
Why is Creatinine high in ESLD
Indicates worsening renal fxn
Vasodilation 2/2 portal HTN decreases blood flow to kidneys
Why is thrombocytopenia present in ESLD
Coagulopathy of liver, TPO is dependent on liver function
Splenomegaly 2/2 portal HTN
Score the progression of fibrosis
0: none
1: portal fibrous expansion
2: Thin fibrous septa
3: Septa bridge central veins
4: Cirrhosis
What is MELD (model of ESLD)
Determine transplant eligibility
How do you screen for cirrhosis complications
EGD to r/o varicies
Abdominal imaging to r/o HCC
What is the serum marker for HCC
AFP!
Imaging you can do are CT/MR every 6 months
MC RF for HCC is
Cirrhosis**
Other: chronic HBV, hereditary tyrosemia, Aflatoxin, Thorotrast
How do you decide to transplant
MELD >15 is on the list
Ensure disease is not amenable to meds/surgery
Must have diminished QoL
Non-hepatic disease that would benefit from transplant (Amyloidosis)
What is the epidemiology of HCC
one of MC malignancies worldwide
Highest in Asia an sub-saharan africa
Median age is 40
M>F
How do you diagnose HCC
Screen: US or CT, AFP
confirm: Liver biopsy
how do you manage HCC
No mets: liver transplant
Monitor growth w/ CT/MRI q6 months
Prevent growth w/ radiofrequency ablation and TACE
What is cholangiocarcinoma
Cancer arising from bile duct epithelium
Intrahepatic (Klatskin tumors, perihilar) or Extrahepatic (distal)
Most are adenocarcinomas**
What is the epidemiology of cholangiocarcinoma
MC in 50-70 y/o*
M>F
What are some causes of cholangiocarcinoma
chronic liver disease alcoholic liver dz Cirrhosis bile duct disease UC Choledocolithiasis HIV PSC chronic typhoid carrier heavy drinking exposure to: OCP, radionuclide, isoniazid
How does cholangiocarcinoma present
Painless jaundice weight loss abdominal pain pruritis palpable gallbladder hepatomegaly dark urine pale stools Triad*: fever, jaundice, RUQ pain
How do you treat cholangiocarcinoma
Resect if candidate
If non-resectable: liver transplant w/ chemo +/- radiation
Chemotherapy +/- radiation, palliative care (if not transplant candidate)
How do you decide to transplant
MELD >15 is on the list
What are some post-transplant issues
Can pt survive post-op?
Can pt comply w/ complex med regimen s/p transplant?
Does pt have other comorbidities that will compromise the donor liver?
Contraindications to liver transplant arw
Active EtOH or drug abuse extrahepatic HCC Mets bile duct cancer non-hepatic malignancy Severe cardiopulmonary disease Co-morbidities reducing chance of survival (BMI >35) Unfavorable psych issues
Who needs to eval patient for transplant
Hepatology Social worker Psych ID, cardiology Transplant surgery Selection committee
Who gets the liver first
Patient with most severe disease get it sooner than those w/ less severe disease!
