Lecture 4 - Liver 1 Flashcards
LFTs commonly include?
hepatic panel = LFT
Bilirubin Albumin ALT AST ALP Total Protein
Less commonly included in LFTs?
GGT
LDH
PTT/INR
Platelets
Review: ALT is found primarily in the liver whereas AST is found in skeletal muscles and erythrocytes. So?
ALT elevations are generally more specific for hepatic injury
Transaminitis?
Elevation of transaminases (ALT/AST), often discovered on routine labs in otherwise asymptomatic pt
DDx is vast (so requires a thorough history, PE, repeat labs, hepatitis panel, hepatitis US, GI referral)
2:1 elevation in AST:ALT often indicates what? (particularly in light of elevated GGT)
alcohol-related liver disease
AST/ALT catalyze transfer of a-amino groups from aspartate/alanine to a-keto group of ketoglutaric acid to generate oxalacetic/pyruvic acids.
Both enzymes require what?
pyridoxal-5’-phosphate (Vit B6) (a deficiency which has a greater effect on ALT, hence the 2:1 ratio)
(alcoholic liver disease = pyridoxal-5’-phosphate deficiency)
GGT is an enzyme that is present in hepatocytes, biliary epithelial cells, renal tubules, pancreas, intestine (mechanisms of alteration are similar to ALP).
Note that GGT levels can also be observed in a variety of non-hepatic diseases as well
Many diseases of the liver, regardless of cause, may be responsible for altered GGT serum levels.
Because of lack of specificity, but HIGH SENSITIVITY, GGT can be useful for IDing causes of altered ALP levels
GGT elevated, with AST/ALT ratio > 2, may support the diagnosis of alcoholic liver disease
Disproportionate elevation in alkaline phosphatase (ALP) compared to ALT/AST…
LFT w/ cholestatic pattern
Most common causes of pathological elevation of ALP?
Liver/bone disease
Hepatic ALP is present on the surface of bile duct epithelium. Cholestasis enhances the synthesis and release of ALP, and accumulating bile salts increase its release from the cell surface
Pathologic increase in portal pressure indicated by?
pressure gradient b/w portal vein and IVC > 10 mm HG
Most common etiology of portal HTN?
Cirrhosis
Jaundice is result of accumulation of bilirubin in body tissue but isn’t clinically apparent until what level?
greater than 2 mg/dL
Unconjugated bilirubin (+albumin) is found where?
Found in the blood… then… arrives at the liver where it becomes conjugated and moved through the biliary system to the small intestine for excretion
Prehepatic jaundice is shown by elevated levels of unconjugated (indirect) bilirubin, most commonly due to?
- overproduction of bilirubin
- impaired bilirubin uptake by the liver
- abnormalities of bilirubin conjugation
Unconjugated hyperbilirubinemia causes?
Increased bili production: Hemolytic anemias, hemolytics rxns, hematomas, pulm infarct
Impaired bili uptake/storage: posthepatitis hyperbilirubinemia, Gilbert syndrome, Crigler-Najjar syndrome, drug rxns (TMP-SMX)
Plasma elevation of BOTH unconjugated and conjugated bilirubin can be to?
(this is often referred to as conjugated hyperbilirubinemia, even though both fractions of bilirubin are elevated)
Hepatocellular disease
Impaired canalicular disease
Biliary obstruction
Conjugated hyperbilirubinemia from hepatocellular dysfunction could be caused by?
hepatitis
cirrhosis
Examples of conditions of biliary obstructions causing hyperbilirubinemia are?
choledocholithiasis
biliary atresia
carcinoma
Clinical findings of unconjugated hyperbilirubinemia (prehepatic jaundice)?
Mild jaundice (maybe only scleral icterus)
Normal stool/urine color
Splenomegaly if etiology is hemolytic disorder (note that sickle cell anemia will likely NOT present w/ splenomegaly)
Clinical findings of hepatic/conjugated jaundice (hepatocellular disease)?
So, cirrhosis and hepatitis
Malaise, anorexia
Low grade fever
RUQ pn
Dark urine
amenorrhea
enlarged/tender liver
spider teleangiectasias
palmar erythema
ascites
gynecomastia
Clinical findings of conjugated jaundice from cholestatic syndromes?
Jaundice
Pruritus
light colored stool
Clinical findings of conjugated-biliary obstruction jaundice?
(post hepatic)
RUQ pn
wt loss (suggestive of carcinoma)
pruritus
dark urine
light-colored (acholic)
- Lab studies for jaundice?
- Radiographs for jaundice?
- What else can you do, for bile ducts maybe?
- Hepatic labs, CBC, CMP, UA
- Hepatic US
- ERCP, if biliary obstruction is suspected
Endoscopic technique in which a specialized side-viewing upper endoscope is guided into duodenum, allowing for instruments to be passed into the bile and pancreatic ducts…
Indicated for?
ERCP
indicated in jaundiced patient suspected of having biliary obstruction
Tx approach for jaundice?
Aimed at underlying etiology
SHould be referred (GI) for underlying etiology
Parameters for acute liver failure?
Severe acute liver injury w:
encephalopathy
AND
impaired synthetic fx (INR>1.5)
(w/in 8 weeks of onset of dz, in a pt w/o preexisting liver dz)
Most common cause of acute liver failure?
Acetaminophen (45%)
risk increased in pts w/ DM
By definition, pts w/ acute liver failure have severe acute liver injury (hepatic encelopathy, INR>1.5)
Other ssx?
Fatigue/malaise/lethargy anorexia N/V RUQ pn pruritus jaundice abd distension (from ascites)
Lab finding for acute liver failure?
- INR>1.5
- markedly elevated aminotransferase levels
- Elevated bilirubin and ALK PHOS
- Low platelet count (<150,000)
elevated ammonia
elevated amylase/lipase
elevated BUN/Cr
Acute liver failure admission/in patient mgmt parameters?
IV fluid/electrolyte replacement
Dietary monitoring
Gastroprotective measures (IV PPI, H2 to prevent stress gastropathy)
(and of course other tx as indicaated by etiology)
Most common causes of viral hepatitis in US?
Hep A
Hep B
Hep C
The hepatropic viruses follow a similar pathologic pattern… what is it?
Viral replication
Prodromal
Icteric
Convalescent
What would you see during phase 1 of viral hepatitis?
(viral replication phase)
Pts typically asymptomatic
Labs show serologic and enzyme markers of hepatitis
What would you see during phase 2 of viral hepatitis?
Prodromal phase
Anorexia/Nausea/Vomiting Arthralgias Malaise/Fatigue Urticaria Pruritus Alterations in taste (aversion to cig smoke)
What would you see during phase 3 of viral hepatitis?
(Icteric phase)
Predominant GI symptoms
Jaundice
Dark urine -> pale-colored stools
Malaise
(maybe RUQ w/ hepatomegaly)
What might you see during phase 4 of viral hepatitis?
Convalescent phase
symptoms/jaundice resolve
liver enzymes return to normal
Most common cause of viral hepatitis in US?
Route/transmission?
Hep A (fecal oral transmission)
Associated w/ localized outbreaks/contaminated food/water
30 day incubation period
Viral shedding in feces of infected host for up to two weeks prior to onset of clinical syndrome
Low mortality (progression to fulminant disease is rare unless?)
acute hepatitis A
unless coinfection w/ HCV
Acute Hep A ssx:
Malaise/myalgia/arthralgia easy fatigability Upper resp. ssx Nausea/Vomiting Anorexia (smokes develop distaste for cigs) Low grade fever
When do the ssx start and what’s the deal with the fever?
Ssx begin ~4 weeks post-exposure (so, get a good hx)
Low grade fever… once it breaks expect an onset of jaundice 5-10 days after
(presentation may be initially mistaken for viral gastroenteritis or viral URI)
In acute Hep A, what can you expect to see when jaundice develops?
How long is Hep A course of illness typically?
Dark urine ->acholic stools
Clinical ssx initially worsen, followed by progressive improvement
Course of illness is typically 2-3 weeks (self-limiting w/ no progression to chronic carrier state)
Lab findings for Acute Hep A?
Markedly elevated AST/ALT
Moderately elevated bilirubin/ALP
Anti-HAV antibodies appear
The presence of what is diagnostic for acute Hep A illness?
presence of IgM anti-HAV
Tx for HAV?
Bedrest if needed
Symptomatic care (antiemetic, antidiarrheals, fluids)
Avoid strenous work/exercise
NO ALCOHOL/HEPATOTOXIC MEDS
Mode of infection for HBV?
Inoculation of infected blood
Sexual contact (saliva, semen, vaginal secretions)
HBsAg positive mothers may transmit to newborn during delivery
Acute Hep B has variable presentation, but has a risk of?
conversion to chronic hepatitis
Groups at risk for Hep B?
Healthcare workers (including staff at hemodialysis centers)
IV drug users
Prisoners
Incubation period for Hep B?
6 weeks to 6 months
Chronic Hep B patients have a substantial risk for?
cirrhosis and hepatocellular carcinoma
men moreso than women
Ssx of acute Hep B?
Simiilar to Hep A… (see below)
Malaise/myalgia/arthralgia easy fatigability Upper resp. ssx Nausea/Vomiting Anorexia (smokes develop distaste for cigs) Low grade fever
Ssx begin ~4 weeks post-exposure
Low grade fever… once it breaks expect an onset of jaundice 5-10 days after
(presentation may be initially mistaken for viral gastroenteritis or viral URI)
Lab findings for Acute Hep B?
Similar to HAV
Greater elevations in AST/ALT
(serology findings are imprtant markers for different clinical states of HBV…. see next notecards)
Serologic hallmark of HBV INFECTION?
Hepatitis B surface Antigen (HBsAg)
Appears in most individuals AFTER CLEARANCE of HBsAg and after successful vaccination against Hep B?
anti-HBs (antibody to HBsAg)
Intracellular antigen expressed in infected hepatocytes
NOT DETECTABLE IN SERUM
Hepatitis B core antigen (HBcAg)
Appears shortly after HBsAg is detected
During acute infection, this antibody is predominantly of IgM class…?
Anti-HBc
Detection of what is typically regarded as an indication of acute HBV infection?
IgM anti-HBc
What persists in patients who recover from acute HBV and those who progress to chronic HBV?
IgG anti-HBc
A secretory protein that is processed from the pre-core protein…
Indicates viral replication and infectivity
HBeAg (hepatitis B e antigen)
Persistence of ____ beyond 3 months indicates increased likelihood of chronic HBV?
HBeAg
HBV DNA parallels the presence of HBeAg
Treatment for acute HBV?
Supportive (as in HAV)
Antiviral tx is reserved for those who develop severe disease
In acute HBV, what indicates severe disease requiring inpatient mgmt?
encephalopathy or coagulopathy
Acute HBV timelines for illness and recovery?
clinical illness lasts 2-3 weeks
complete recovery by 16 weeks
Prevention measures for HBV?
screening of donated blood
serologic testing in pregnancy
safe sex practices
safe handling of blood/body fluids/contaminated material
vaccination
What would you administer for known exposure?
Hep B immune globulin
followed by vaccination series
HCV modes of infection?
50% by injection drug use
Transfusion
Body piercing/tattoo/hemodialysis
(STI/maternal transmission possible, but low risk)
Vaccine available for HCV?
Negative
(co-infection in HIV positive pts is common)
(also, high risk of conversion to chronic state w/ an accompanying increase in risk of cirrhosis and carcinoma)
Incubation period for Hep C?
6-7 weeks
clinical illness is mild, or can be totally asymptomatic
Lab findings for Acute Hep C?
What is confirmatory for Hep C?
Hep Panel similar to HAV, HBV
If Anti-HCV EIA is positive or ambiguous, obtain HCV RNA test…presence of HCV RNA is confirmatory
If HCV is confirmed… obtain renal panel and UA to observe for what?
Observe for proteineuria, hematuria, and/or reduction of GFR
Medical treatment for Acute Hepatitis C is typically initiated after sufficient time to evaluate for for spontaneous clearance.
Recheck HCV RNA when?
12 weeks after exposure
or after diagnosis if exposure is uncertain
Tx decision for acute HCV are made by a hepatologist and are based on pt risk factors
A typical course of pharmacotherapy might include?
peginterferon weekly for 12-24 weeks (depending on viral genotype)
Acute HCV pts typically recover in?
3-6 mos
Up to 80% covert to chronic disease
30% develop cirrhosis (meaning an increased risk of hepatocellular carcinoma)
Causes infection only in assocation with HBV infection, specifically the HBsAg?
Hepatitis D
should therefore test in patients w/ acute HBV infxn
(usual route = IV drug use)
Hep E is a major cause of hepatitis in what areas?
and therefore should be a consideration in patients who have traveled to these areas
Central/SE Asia, middle east, North Africa
fecal-oral transmission, water-borne outbreaks
Hep E is a mild-moderate illness, but in certain patients it commonly progresses from severe to fulminant hepatitis?
Pregnant patients
Chronic viral hepatitis is an infection w/ HBV or HCV for greater than 3 mos, with what parameters?
Persistent elevated AST/ALT
Persistent presence of HBsAg/anti-HBc or anti-HCV
Or histologic findings on liver biopsy
(in the absence of concomitant cirrhosis, pts may be asymptomatic)
Treatment of chronic HBV (and HDV) is?
[not super important… GI doc will do this]
Nucleoside or nucleoside analogs: Lamivudine Adefovir Telbivudine Tenofovir Entecavir
OR
pegylated interferon
chronic HCV tx?
Direct-acting and host-targeting antiviral agents (with regimens based upon viral genotype)
Ledipasvir + sofosbuivir (super expesnive though)
Form of chronic hepatitis due to autoantibodies, more common in whom?
more common in women
varying clinical presentation (may be incidental finding)
Autoimmune hepatitis has varying clinical presentation (may be incidental finding)… ssx may include?
Transaminitis
fatigue/lethargy/malaise/anorexia/nausea/abd pain/itching/small joint arthralgia
More severe = profound jaundice, elevated PT, marked AST/ALT (>1000)
WHat are some common extrahepatitic manifestions of autoimmune hepatitis?
(increased risk of cirrhosis and cancer)
Arthritis
Sjogren syndrome
thyroiditis
nepthritis
UC
Coombs-pos hemolytic anemia
