Liver Flashcards
AST:ALT >2 means
alcoholic hepatitis
SSSSSIpping
ALT>AST means
viral/toxic/inflammatory processes
AST and ALT > 1000 means
acute viral hepatitis (A and B mostly)
increased ALP + GGT suggests
hepatic source or biliary obstruction
Increased ALT, + ANA, and + smooth muscle antibodies
responding to steroids
means
autoimmune hepatitis
which acute hepatic illnesses are associated with chronicity?
HBV, HCV, HDV
Fatigue, weakness, sleep disturbance, anorexia, unintentional weight loss, N/V
RUQ pain, vague abdominal discomfort
Pruritus, jaundice, bleeding
PE: muscle wasting, spider telangiectasias, petechiae/ecchymoses, palmar erythema, caput medusae, hepatomegaly, nodular liver edge, splenomegaly, dupuytren contractures, edema, delirium, AMS, asterixis
Enlarged abdomen with small extremities (ascites), gynecomastia
cirrhosis
RF for —:
Cholestatic disease
Autoimmune disease
Metabolic disease
Hepatic biliary obstructive disease
Hepatic venous outflow obstruction (RHF)
cirrhosis
Diffuse fibrosis of the liver, secondary to ongoing, chronic liver injury
Loss of normal structure of the liver due to scarring and “regenerative nodules” → loss of function
Irreversible → compensated or decompensated phases
Downstream complications related to ½ root causes:
Synthetic dysfunction (liver insufficiency)
Dysregulated circulatory dynamics (portal HTN)
Alcoholic liver disease, chronic hepatitis C, NAFLD, NASH (metabolic syndrome), chronic hepatitis B
cirrhosis
What are the two types of cirrhosis?
compensated and decompensated
Consider in anyone with chronic liver disease
Compensated = may not be detectable, hinging on liver biopsy/histology “gold standard” —
Labs: increased INR, bilirubin, low albumin
Thrombocytopenia most sensitive and specific
Imaging: US/CT/MRI: enlarged liver, splenomegaly, collateral vessels
Decompensated = complications in setting of chronic liver disease is essentially diagnostic
varices/hemorrhage
Ascites
Hyponatremia
Portal venous thrombosis
Encephalopathy
jaundice
cirrhosis
What signs indicate decompensated cirrhosis?
varices/hemorrhage
Ascites
Hyponatremia
Portal venous thrombosis
Encephalopathy
jaundice
— is the most sensitive and specific for cirrhosis
thrombocytopenia
what is gold standard for cirrhosis?
liver biopsy
MELD-Na score → 3 month mortality risk
Bilirubin
Cr
Na+ level
INR
>17 = liver transplant
Child-Pugh class → 1 year survival rate, likelihood of developing complications
Bilirubin
Albumin
PT
Ascites, encephalopathy
Class A = 100%, B = 80%, C = 45%
cirrhosis
how do you treat cirrhosis?
Ascites + edema: sodium restriction, diuretics
Pruritus: cholestyramine
US every 6 months
Prodrome of anorexia, nausea, vomiting, malaise, aversion to smoking, URI symptoms
Spiking fever, enlarged and tender liver, jaundice (after 5-10 days)
Abdominal pain mild and constant in RUQ or epigastric aggravated by jarring or exertion
After 5-10 days = dark urine, pale, acholic stools → jaundice, icteric sclera, pruritus
acute hepatitis A
crowding and poor sanitation, and international travel are RF for
acute hep A
hep A is spread through
Fecal-oral route - person-person, or ingestion of contaminated food/water w/ incubation ~30 days
LABS: Normal-low WBC
Markedly elevated aminotransferases
Bilirubinuria
Strikingly elevated AST or ALT early (ALT>AST) → bilirubin/ALP elevation
anti-HAV +
PE: Hepatosplenomegaly, RUQ tenderness to palpation, jaundice
IgM anti-HAV only for symptomatic persons
Past exposure = IgG HAV Ab with negative IgM
acute hep A
how do you treat acute hep A
Bed rest
N/V → IV glucose
Avoid strenuous exertion, alcohol, hepatotoxic agents
does Hep A have risk of chronic liver disease?
no
Onset abrupt or insidious with low grade fever, fall in pulse rate w/ jaundice, anorexia, malaise, N/V, aversion to smoking
Dark urine, pale, acholic stools, jaundice + pruritus
acute hep B
acute hep B is associated with
glomerulonephritis, polyarteritis nodosa, Guillain-Barre syndrome
Healthcare workers have a risk of
hep B
Hep B is spread through
Infected blood products or sexual contact (in saliva, semen, vaginal secretions) ~ 6 weeks - 6 months
Percutaneous, sexual, parenteral, perinatal
Similar to acute hepatitis A
Serum aminotransferases higher on average
Utilize serologic patterns: + HBsAg, Anti-HBc, HBeAg (chronic)
hep B infection
how can you prevent hep B?
Handle disposable needles carefully and NOT recap
Screening of donated blood
ALL pregnant women undergo testing for HBsAG
Immunoprophylaxis reduces risk of perinatal transmission, mother may get antiviral treatment in 3rd trimester
HBIG is protective + HBV vaccine
How do you treat hep B?
Bed rest
N/V → IV glucose
Avoid strenuous exertion, alcohol, hepatotoxic agents
Hospitalize if:
Encephalopathy or severe coagulopathy = acute liver failure
Liver transplant
elevated aminotransferase levels for 3-6 months + and in majority of infected infants and immunocompromised adults
chronic hepatitis
Incubation 6-7 weeks with clinical illness – prodrome of anorexia, N/V, malaise, aversion to smoking, fever, enlarged and tender liver, jaundice
Asymptomatic, waxing and waning of symptoms
acute hepatitis C
What are RF for hepatitis C
IV drug use
Body piercing, tattoos, hemodialysis
Lower risk = sex and maternal-neonatal transmission
HIV
Transmission through injection of drugs
MCC of chronic liver disease, cirrhosis, and liver transplantation
hepatitis C
Liver biopsy = hepatocellular necrosis and mononuclear infiltrate
LABS: Markedly elevated aminotransferases
Antibodies to HCV (confirm with assay for HCV RNA)
anti-HCV = antibodies, previous infection
hepatitis C
all adults 18-79 and all pregnant women should be screened for
HCV
How do you treat HCV?
Eradicate infection and prevent disease progression (defined as absence of HCV RNA in serum 12 weeks following completion of antiviral therapy
Sofosbuvir + velpatasvir x 12 weeks
OR glecaprevir + pibrentasvir x 8 weeks
does chronic hepatitis develop in hep C?
yes – VERY OFTEN
Does chronic hepatitis occur in hep B?
yes
Most are asymptomatic; fatigue, myalgia, nausea, RUQ pain, jaundice, dark urine
In chronic hepatitis B = worse short term prognosis → acute liver failure, severe chronic hepatitis rapidly progressing to cirrhosis
hepatitis D
what are RF for hepatitis D?
Drug injectors
High-risk sexual behavior
HIV/HCV co infections
Can you only have HDV without HBV
no
You only have an HDV with –
HBsAg
Dx: detection of antibody to hepatitis D antigen (anti-HDV), HDAg or HDV RNA in serum
Check for presence of HBV virus (HBsAg)
HDV
How do you treat HDV?
Pegylated interferon alfa 2b
Prodrome of anorexia, N/V, malaise, aversion to smoking
Extrahepatic manifestations: arthritis, pancreatitis, thyroiditis, myocarditis, glomerulonephritis, monoclonal gammopathy, thrombocytopenia, aplastic anemia, Guillain-Barre syndrome
hepatitis E
Hepatitis E is prevalent in
international traveling to endemic areas
FULMINANT in pregnant women
What’s the MCC of acute viral hepatitis? (and how is it transmitted)?
Hepatitis E - fecal-oral transmission
PE: jaundice, scleral icterus, hepatomegaly, RUQ tenderness
IgM anti-HEV in serum
ALT>AST, >1000
Past immunity = IgG HEV Ab with - IgM
hep E
How do you treat hep E?
3 month course of oral ribavirin (severe)
chronic hepatitis is often
asymptomatic
Chronic infection for longer than 3-6 months: viruses, autoimmune hepatitis, alcohol-associated, metabolic dysfunction-associated steatohepatitis, certain meds (isoniazid and nitrofurantoin), Wilson disease, antitrypsin deficiency, celiac disease
chronic hepatitis
Risk for reactivation = male sex, HBV genotype C, immunosuppression, advanced age, alcohol use, smoking, coinfection
chronic hepatitis B
What are the 5 phases of chronic hepatitis B?
Immune tolerant (common in infants/children)
Immune active
Inactive HBsAg carrier state
Reactivated chronic hepatitis B phase
HBsAg-negative phase
HBeAg+ and HBV DNA present
Serum aminotransferase levels normal
Little necroinflammation in liver
chronic hep B immune tolerant
HBeAg+ with aminotransferase AND HBV DNA levels elevated
Necroinflammation present in liver
Low-level IgM anti HBc present
chronic hep B immune active
HBeAg- with immune clearance and cirrhosis not developed
chronic hep B inactive HBsAg carrier
HbeAg- with rise in serum HBV DNA levels, progression to cirrhosis may occur
reactivated chronic Hep B
rarely patients reach this phase with Anti-Hbe detectable and everything else normal
HBsAg- hep B
How do you treat hep B?
Nucleoside or nucleotide analogs → lower HBV DNA and normalize ALT and histologic improvement
Entecavir or tenofovir
85% of acute hep C becomes
chronic
chronic hep C is confirmed with
detection of anti-HCV by EIA
How do you treat hep chronic hep C
20% progress to cirrhosis
Antivirals: glecaprevir and pibrentasvir
Sofosbuvir and velpatasvir
Insidious onset with some presenting with acute liver failure, following viral illness or exposure to drug/toxin
Amenorrhea, frequency of depression
Arthritis, Sjogren syndrome, thyroiditis, nephritis, UC, Coombs+ anemia
commonly young, middle-aged women
autoimmune hepatitis
PE: spider telangiectasias, cutaneous striae, hirsutism, hepatomegaly
LABS: serum aminotransferase >1000
Total bilirubin elevated
autoimmune hepatitis
autoimmune hepatitis tx
Prednisone +/- azathioprine
factors that predict need for liver transplantation
Age 20+ or 60+
Low albumin
Cirrhosis
anti-SLA presence
Incomplete normalization of serum AST after 6 months
Fever, RUQ pain, tender hepatomegaly, jaundice, anorexia and nausea
May be asymptomatic
History
Abdominal pain/tenderness, splenomegaly, ascites, fever, encephalopathy
Infection is common
alcohol-associated liver disease
MC precursor of cirrhosis
alcohol-associated liver disease
Chronic alcohol intake >80/day for men and 30-40/day in women
alcohol-associated liver disease
AST > ALT often by a factor of 2 or more (SIPPING)
LABS: anemia (macrocytic), leukocytosis with left shift, thrombocytopenia, mild liver enzyme elevation, ALP, bilirubin increased
Gamma-globulin increased
Folic acid deficiency
Imaging: CT w/ IV contrast or MRI
Liver biopsy: Mallory bodies, fibrosis, infiltration
alcohol-associated liver disease
How do you treat alcohol-associated liver disease?
Abstinence from alcohol (acamprosate, naltrexone, baclofen, topiramate, gabapentin)
Nutritional support, supplement nutritional deficiencies
Steroids
Admit when:
-Hepatic encephalopathy is present
-INR >1.6
-Total bilirubin 10+
-Inability to maintain hydration
stool and urine color normal, mild jaundice, no bilirubin in urine, splenomegaly with hemolytic disorders
unconjugated hyperbilirubinemia
hereditary or intrahepatic (asymptomatic)
Hepatocellular disease = malaise, anorexia, low-grade fever, RUQ pain, pruritus, dark urine, jaundice, amenorrhea, hepatomegaly/tenderness, spider telangiectasias, palmar erythema, ascites, gynecomastia, sparse body hair, fetor hepaticus, asterixis
Biliary obstruction = RUQ pain, weight loss, jaundice, pruritus, dark urine, light “clay” stools, stones, occult blood
conjugated hyperbilirubinemia
malaise, anorexia, low-grade fever, RUQ pain, pruritus, dark urine, jaundice, amenorrhea, hepatomegaly/tenderness, spider telangiectasias, palmar erythema, ascites, gynecomastia, sparse body hair, fetor hepaticus, asterixis
hepatocellular disease –> hyperbilirubinemia
RUQ pain, weight loss, jaundice, pruritus, dark urine, light “clay” stools, stones, occult blood
biliary obstruction –> hyperbilirubinemia
What can predispose someone to hyperbilirubinemia?
Dubin-Johnson Syndrome (conjugated)
Gene mutation of MRP2 (Dubin, Direct, Dark liver) with mild icterus, flares with pregnancy, OCPs, illness
Formation, transport, metabolism, or excretion abnormalities of bilirubin – overproduction of bilirubin, impaired hepatic uptake due to drugs, impaired conjugation (hemolysis?)
unconjugated hyperbilirubinemia
impaired excretion of bilirubin, hepatocellular injury, biliary obstruction (viral?)
conjugated hyperbilirubinemia
Normal = <1
→yellowish discoloration of sclera and mucous indicates >2.5
Palpable gallbladder (Courvoisier sign) = pancreatic head tumor
Hepatocellular jaundice labs = increased bilirubin, ALP, AST, ALT, low albumin, unresponsive to Vitamin K
Obstruction = increased bilirubin, albumin, ALP, responsive to Vitamin K
hyperbilirubinemia
Dubin, Direct, Dark liver → asymptomatic/mild icterus, flares with pregnancy, OCPs, illness
dubin johnson syndrome
gene mutation of MRP2 → decreased hepatocyte excretion of conjugated (direct) bilirubin
black liver on biopsy
DJS
Type I: neonatal jaundice with severe progression in 2nd week that can lead to encephalopathy
Type II: asymptomatic
Crigler-Najjar syndrome
autosomal recessive disorder Type I (no activity), Type II Arias Syndrome (limited activity) of enzyme conversion (inability to convert indirect → direct)
Crigler-Najjar syndrome
Dx: elevated total bilirubin, no elevation in LFTs
→ Type I: 20-50
→ Type II: 7-10
Crigler-Najjar syndrome
How do you treat CN syndrome?
Type I: phototherapy, criss = plasmapheresis, liver transplant
Type II: phenobarbital if needed
asymptomatic to transient episodes of jaundice during stress, fasting, ETOH, illness
gilbert’s syndrome
hereditary reduced UGT activity/production → decreased unconjugated bilirubin uptake
Gilbert’s syndrome
Dx: elevated bilirubin, no elevation in LFTs
gilbert’s syndrome
Do GS or DJS need treatment?
no
Abdominal distention, recent weight gain, vague abdominal discomfort, dyspnea
common in cirrhotic patients
ascites
Accumulated fluid in the peritoneal cavity
Most common decompensation from cirrhosis
ascites
Clear on PE – US, imaging
→ all new ascites should undergo diagnostic paracentesis (check if SBP is present)
SAAG gradient </>1.1g/dL
SAAG >1.1 = cirrhosis or cardiac ascites (more protein)
SAAG <1.1 = infection, malignancy (less protein)
ascites
SAAG > 1.1
cirrhosis or cardiac ascites (more protein)
SAAG <1.1
infection, malignancy (less protein)
How do you treat ascites?
Na+ restriction <2g/day, diuretics
Spironolactone + lasix
Refractory = large volume paracentesis
>5L removed = add albumin replacement
Wide range of neuropsychiatric changes → subclinical to comatose
Grade 1: altered consciousness, sleep-wake reversal, memory impairment
Grade 2: drowsy, confusion, bizarre behavior, disorientation
Grade 3: lethargic/stuporous, another planet
Grade 4: coma
Asterixis, AMS
hepatic encephalopathy
GI bleeding, constipation, infection, hypovolemia, opioids/sedatives, TIPS
hepatic encephalopathy
AMS/cognitive impairment secondary to cirrhosis from toxic accumulation → increased ammonia → upregulation of GABA with more dysregulation
hepatic encephalopathy
elevated ammonia
hepatic encephalopathy
how do you treat hepatic encephalopathy
Decrease intestinal ammonia production/increase excretion
– lactulose - neutralizing ammonia
– rifaximin
eat!
Often asymptomatic, mild RUQ discomfort
Hepatomegaly
Signs of portal HTN = liver fibrosis/cirrhosis
fatty liver/ non-alcoholic fatty liver disease, (MDAS)
What predisposes someone to fatty liver?
Obesity
Diabetes
Hypertriglyceridemia
– psoriasis, soft drink/red meat consumption, ambient air pollutants, cholecystectomy
Excess hepatic fat = steatotic liver disease
M =
Overweight or obesity, Type 2 diabetes, impaired glucose regulation, HTN, dyslipidemia
Extremely common cause of mildly abnormal LFTs
Nonalcoholic fatty liver = benign accumulation of TGs, unassociated with malignant potential
Nonalcoholic steatohepatitis (NASH) = liver cell injury and death, inflammation, fibrosis
fatty liver disease
Elevated aminotransferase levels, elevated ALP, hepatomegaly, steatosis
Liver biopsy = macrovesicular steatosis w/ or w/o inflammation and fibrosis
FIB-4 score, NAFLD score
fatty liver disease
what’s the treatment for fatty liver disease?
Vitamin E
Thiazolidinediones reverse insulin resistance (leads to weight gain)
Metformin
Pentoxifylline
semaglutide/liraglutide
ACEI
Surgery if BMI > 35, liver transplant
Weight loss, dietary restriction, increased fiber, moderate exercise, Mediterranean diet, fasting
Paradox – intrahepatic vasoconstriction and resistance with extrahepatic vasodilation increasing blood flow
portal HTN
Insidious onset of upper abdominal pain, hepatomegaly, new/worsened ascites
Classic triad: ascites + hepatomegaly + RUQ abdominal pain developing rapidly
hepatic vein obstruction (Budd-Chiari syndrome)
What are RF for hepatic vein obstruction
Hereditary
Hypercoagulable states (disorder, pregnancy, surgery, meds), intra abdominal malignancy, surgery, inflammation, cirrhosis
obstruction/narrowing of hepatic veins as a portal vein DVT – NONcardiac hepatic outflow blockage → decreased liver drainage
MCC of portal HTN in children
hepatic vein obstruction (Budd-Chiari syndrome)
MCC of portal HTN in children
hepatic vein obstruction (Budd-Chiari syndrome)
Dx: Doppler US of liver, CT, MRA
PE: tender, painful hepatic enlargement
Biopsy = “nutmeg” liver
hepatic vein obstruction (Budd-Chiari syndrome)
How do you treat hepatic vein obstruction (Budd-Chiari syndrome)?
Manage hypercoagulable conditions, ascites
Antigulation x 3 months
-> lifelong in Budd Chiari syndrome
Angioplasty, stenting, TIPS
Undetected until new decompensation or deterioration - often asymptomatic
Malaise, weight loss, jaundice, abdominal pain, hepatosplenomegaly
hepatocellular carcinoma
Viral cause of cirrhosis (HCV, HBV) is a huge RF for
hepatocellular carcinoma
Cirrhosis-associated
hepatocellular carcinoma
CT/MRI with contrast enhancement
US for nodules
Dx: tissue biopsy of liver
hepatocellular carcinoma
How do you treat hepatocellular carcinoma?
Eradicate viral infection, chemo, surgical resection, local treatments, transplant
what’s the surveillance for hepatocellular carcinoma?
with chronic HBV infection, cirrhosis with HCV, HBV, ETOH use
Alpha-fetoprotein levels elevated
Standardly monitor with US + AFP levels 6 months for high risk patients
GI symptoms, systemic inflammatory response, kidney dysfunction, adrenal insufficiency, subclinical MI, jaundice
acute liver failure (fulminant hepatitis)
Acetaminophen and idiosyncratic drug reacts are MCC
fulminant hepatitis
Fulminant = hepatic encephalopathy within 8 weeks after onset of liver injury (INR 1.5+)
Subfulminant = 8 weeks - 6 months
Acute on chronic = deterioration in liver function often caused by infection
Viral hepatitis, heat stroke, malignancy, Budd-Chiari, Wilson, Reye, fatty liver, autoimmune, parvovirus
liver failure
AST + ALT elevated >5000
Blood ammonia level elevated and correlated with development of encephalopathy and intracranial HTN
AKI
liver failure
how do you treat liver failure?
Achieve metabolic and hemodynamic stability
Intravascular volume preservation (but avoid large-volume infusions)
Norepinephrine vasopressor, + vasopressin if persistent
Prevent hypoglycemia
Intermittent renal replacement therapy
Preserve muscle mass = enteral administration of protein (monitor ammonia)
H2 receptor or PPI prophylaxis
Broad spectrum antibiotic prophylaxis
Acetylcysteine for acetaminophen toxicity
Liver transplantation
When are AST and ALTs elevated
hepatocyte injury
When are ALPs elevated
injury to bile ducts
albumin decreases in — — and is associated with
liver disease, chronic
deficient clotting can result from
liver disease (usually acutely)
evaluate:
HBsAg+
Anti-HBc IgM+
HBeAg+
acute hepatitis B
evaluate:
Anti-HBs +
vaccination
evaluate:
Anti-HBs+
Anti-HBc IgG+
Anti-HBe+/-
recovery/immunity
evaluate:
HBsAg+
Anti-HBc IgG+
HBeAg+
chronic hepatitis B
Prolonged appearance of HBeAg increases the likelihood of what?
chronic hepatitis B
HCV RNA +
anti HCV+/-
acute hep c
anti-HCV +/-
HCV RNA -
resolved hep c
HCV RNA +
anti-HCV +
chronic hep c
HCV RNA is more
specific
with HBeAg+ or HBeAG- chronic Hep b, risk of cirrhosis and HCC correlates with
serum HBV DNA level
