Hepatitis and Liver Disease Flashcards
AST/ALT levels leading to differentials
Toxic or ischemic injury when >1000
Acute Hep C, A, C >300-3000
EtOH
Chronic Hep B and C about 100
Liver disease with highest prevalence in US
Nonalcoholic fatty liver disease
Abnormal labs seen in hepatitis
Liver tests/LFTs: hepatocellular pattern (<10xULN)
Predominantly increased ALT and AST (liver transaminases)
Maybe elevated ALP (sometimes see in NASH)
What is hepatitis?
Inflammation of the liver
General guidelines to interpret increased AST/ALT
AST:ALT >2 (alcoholic liver disease)
ALT>AST (NASH and usually ratio is less than 1 and acute/chronic viral hepatitis)
What is a fatty liver?
Hepatic steatosis
What is non-alcoholic steatoheatitis (NASH)?
Fatty liver with inflammation of liver with hepatocyte injury (higher risk in developing fibrosis and cirrhosis)
Biopsy may show fibrosis (scarring of liver)
What is a non-alcoholic?
<20g ETOH/day (<2-3 drinks/day)
Subtypes of nonalcoholic fatty liver disease
Isolated steatosis (NAFL) Non alcoholic steatohepatitis (NASH)
What is isolated steatosis?
Fatty liver without injury or fibrosis of hepatocytes on bx
Minimal risk of progression to cirrhosis
What should be considered in all pts with NAFLD?
Aggressive modification of CVD risk factors (also DM)
Risk factors of NAFLD
Abd obesity DM2 (insulin resistance) Hyperlipidemia (high TG and low HDL) Metabolic syndrome Genetic factors-PNPLA3, TM6SF2 and age (less common)
Strongest predictor for NASH
Metabolic syndrome
What is seen on biopsy for NAFLD/NASH?
Steatosis (fat accumulation)
Inflammation and maybe fibrosis
(will see fatty infiltration on imaging)
*gold standard but not necessary for dx
Lab features of NASH
Hepatocellular pattern (mild elevation ALT/AST rarely above 300)
Normal bilirubin, albumin, INR
Ferritin elevated (marker for inflammation)
Hyperlipidemia
Glucose (elevated)
ALP elevated in 1/3 and maybe GGT
Cornerstone of management for NASH
Exercise and weight loss
How can weight loss help NASH?
> 3% improves steatosis
7-10% NASH resolution
10% fibrosis regression seen
Other management for NASH
Minimize alcohol, modify CVD risk factors, control DM and HLD, monitor LFTs, vaccinate Hep A and B (check for IgG Ab etc)
What is hereditary hemochromatosis?
Hereditary disorder of iron metabolism (genetic mutation results in increased GI absorption of iron and leads to accumulation in liver/pancreas/heart/other organs)
Clinical findings of hereditary hemochromatosis
FHx or incidental note increase AST/ALT
Caucasians or northern european origin
Fatigue, malaise, RUQ discomfort
Late manifestations of hereditary hemochromatosis
(generally seen in 4th-5th decade)
Hepatomegaly, hepatic insufficiency, cirrhosis, DM, impotence, arthralgia (2nd and 3rd MCPs), bronze pigmentation of skin, cardiomegaly with/without CHF
Bronze diabetes
Triad of DM, bronze pigmentation of skin and cirrhosis
Labs in hereditary hemochromatosis
Elevated LFTs (AST, ALT, alk phos) Screen with serum Fe and TIBC and ferritin (Fe/TIBC equals transferrin saturation)
What to do if transferrin sat >45 and/or ferritin >200 ng/mL in men or >150 ng/mL in women?
Proceed to GI (HFE mutation and analysis)
Tx is therapeutic phlebotomy
How to diagnose hereditary hemochromatosis
Genetic testing and maybe liver biopsy
Tx for hereditary hemochromatosis
Prevent cirrhosis from iron overload
Avoid vit C and iron supplements, uncooked shellfish and EToH
Do regular phlebotomy (therapeutic)
Cirrhosis screen q 6 mos (US and AFP)
What to do for all 1st degree relatives in hereditary hemochromatosis?
Genetic screening (HFE genotype) and iron testing
Who do you screen for hereditary hemochromatosis in (AASLD)?
Elevated liver tests (AST/ALT) Abnormal iron studies First degree relative dx with HH Evidence of liver disease Suggestive sxs of HH
What is Wilson’s disease?
Very rare hereditary disorder of copper metabolism
Autosomal recessive
Genetic defect results in decreased excretion of copper into bile and accumulation of copper in liver (when exceeds that it builds up everywhere else)
Findings of Wilsons disease
Predominantly hepatic, neuro or psychiatric findings
Neuro/psych sxs (tremor, dysarthria, incoordination, ataxia, parkinsonism, personality changes)
Pathognomonic for Wilsons disease
Kayser Fleischer ring and neuro manifestations
What is a Kayser Fleischer ring?
Fine pigmented granular deposits in the cornea (brownish or gray-green)
Get ophtho exam
How to diagnose Wilson’s disease?
Mild elevation AST/ALT and alk phos (normal or low)
Screen with serum cerulospasmin (low in most pts)– <5 is strong evidence
Can also do 24 urinary copper (increased) after ceruloplasmin
Confirm with liver biopsy adf molecular testing (rare)
Tx for Wilsons disease
Chelating agents (D-penicillamine and trientine GI)
Alpha 1 antitrypsin deficiency
Genetic disorder with decreased levels of alpha 1 antitrypsin production (protects against tissue injury in lungs or liver)
Severe forms of alpha 1 antitrypsin below 11 micromole/L
At risk for severe lung disease and chronic liver disease (increase risk with cig smoking and onset is accelerated)
Infants and kids can present with severe liver disease
When do you want to suspect alpha-1 antitrypsin deficiency?
Suspect in non-smoker with emphysema at young age (<45 yrs) or in neonatal cholestasis or childhood cirrhosis
Who to screen in adult population for alpha 1 antitrypsin deficiency?
Emphysema in young pt, non/minimal smoker or predominant basilar changes on CXR
Adult onset asthma
Clinical findings or history of unexplained chronic liver disease (LFTs or cirrhosis)
Family hx of emphysema and/or liver disease
Hx of panniculitis
What is panniculitis?
Skin manifestation of alpha-1 antitrypsin deficiency
Labs in alpha 1 antitrypsin deficiency
Mild elevation of AST/ALT
Serum alpha 1 antitrypsin (decreased)–(might be false neg if increased with inflammation) and ALSO get alpha 1 antitrypsin phenotype/genotype
Treatment of alpha 1 antitrypsin deficiency
Liver transplant (get genetic counseling too)
Presentation of autoimmune hepatitis
Asymptomatic with elevated liver enzymes
Acute hepatitis and maybe liver failure
Cirrhosis
Non specific sxs (fatigue, malaise, anorexia, pruritus, abd pain, arthritis)
What is the presentation of acute severe liver disease associated with autoimmune hepatitis?
Hepatomegaly and tenderness
Jaundice, splenomegaly, fever
Serological markers for autoimmune hepatitis
Antinuclear antibodies (ANA), anti smooth muscle antibodies (ASMA), liver kidney microsomal antibody (LKMA) or antibody to liver cytosol (LKC-1 IgG) in adults!! Anti-soluble liver antigen (SLA) and anti-liver pancreas antigen (LPA) in kids!!
Other clinical findings depending on severity of autoimmune hepatitis
Elevated bilirubin
Elevated ALP
Elevated PT/INR
Albumin (decreased)
Important labs for acute autoimmune hepatitis
AST,ALT 7-10 times ULN ASMA positive (sometimes ANA) IgG (high titer) ANA LKC and maybe LKMA SLA/LPA (kids)
Management for autoimmune hepatitis
Depends on disease activity
Prednisone and maybe azothioprine (combo!)–continue until remission (take off ASAP and on lowest dose)
Monitor DEXA
Liver transplant in liver failure
What to remember for viral hepatitis
Only AcutE (no chronic) fEcal-orAl ABle to get vaccine C=Chronic (most do) Hep D is Dependent on hep B Hep E can be fatal in prEgnancEEEE
When do you see acute hepatitis?
Areas with inadequate sanitation and limited clean water
Asia and Africa
Fecal or oral transmission (person to person or contaminated food or water)
Recent outbreaks in homeless populations
Acute presentation of hep A
Children <6 more likely to be asymptomatic (incubation 15-50 days)
Prodrome of Hep A
Flu like (fever, malaise, anorexa, n/v, RUQ pain)
Icteric phase of Hep A
Jaundice, dark urine, pruritus, light colored stool (look yellow)
Hepatomegaly and jaundice most common seen
Labs in Hep A
Increased AST/ALT (>1000 or 15x ULN), increased bilirubin and increased ALP
+IgM anti-HAV at onset
Antibodies in hep A
IgM anti-HAV is for acute infection (positive for 4 mos)
IgG anti-HAV implies immunity
Management for hep A
Supportive (fluids, rest, full recovery in about 6 mos)
Infection precautions (hand wash, food prep, chlorine)
Notify local health dept
When to hospitalize with hep A
Elderly
Multiple comorbidities
Underlying liver disease
Fulminant liver failure
Leading cause of cirrhosis and hepatocellular carcinoma worldwide
Hep B
How to get hep B
Blood to blood by body fluids (DNA virus)
Sexual contact
Parenteral contact
Peri-natal transmission
Sxs of acute hep B
N/v, RUQ pain, jaundice, malaise, arthralgias, fever
Labs for acute hep B
Increased bilirubin and ALP
Significantly increased transaminases (>15 x)
Who becomes chronic in hep b
Most infants will (only some adults will)
Management of acute hep B
Supportive b/c most adults recover with immunity
Antiviral therapy if acute liver failure or protracted course
When should you admit to hospital with acute hep B?
Underlying liver disease
Multiple comorbidities
Signs of liver failure need to go to liver transplant center
Older or elderly (more severe when >60 YO)
What antibodies seen with vaccine or infection?
Antibody to surface antigen (anti-HBs)
What antibodies are seen in an infection?
Exposed to both surface and core antigens so have anti-HBc and Anti-HBs
What do you have in current or previous hep b infection?
Hep B core antibody
Lab findings for chronic hep B
Hep B surface antigen positive > 6 mos Elevated transaminases (mild or normal)
Complications of chronic hep B
Cirrhosis
Hepatocellular carcinoma can occur without cirrhosis (higher than any other liver disease)
When does Hep B become chronic more often?
In immune compromised adult or if exposure as an infant of child <5 YO
Labs for hep B
Hep B surface antigen (HbSAg)– active disease acute or chronic
anti-HBs–immunity so vaccine or resolved infection
IgM anti-HbC–acute exposure
IgG anti-HbC and total anti-HBc–previous exposure
What is the first detectable marker of hep B infection?
Hep B surface antigen (HBsAg)- because rises before onset of sxs
What is a hallmark of active hep B infection?
Hep b surface antigen
When might IgM anti-Hbc also be seen?
In pt who cleared HBsAg but have not yet developed surface antibody (can persist about 4 months)
What indicate end of acute infection phase?
Antibody to surface antigen
What does hep B vaccine give you?
+ anti-HBs/HBsAb
Prior infection with resulting immunity to hep B
Hep B surface antibody positive
Hep B core antibody IgG (anti-HBc IgG) positive
Prior vaccination with resulting immunity to Hep B
Hep B surface antibody positive
Hep B core antibody IgG negative
What is the hep B e antigen used for?
Index of infectivity (marker of replication)
What does antibody to hep b e antigen with HB e Ag negative status?
Indicates lower levels of HBV DNA
Positive anti-HBe is a predictor of long term clearance o f HBV
Chronic Hep B management
Vaccinate for hep A
HCC surveillance b/c increased risk
Who needs monitoring for HCC?
All pts with cirrhosis
Pts without cirrhosis (US and AFP–African Americans?)
Transmission of hep C
Blood/blood derived body fluids
Most common cause of liver transplantation
Hep c
Risk factors for hep C
IV drug use, tattoos and piercings at unregulated facililty
Recipient of clotting factors, blood transfusion, HIV infection, hemodialysis, known exposure, children born to HCV mother, sexual contact
Presentation of acute hep C
HCV asymptomatic in most cases
Some experience jaundice, fatigue, fever, n/v, RUQ discomfort
Labs for hep C
AST/ALT usually in 100s (<300)
Bilirubin elevated
- Hep C Ab with + RNA viral load OR + hep C Ab prior had - Hep C Ab
Chronic HCV presentation
Most develop this and cirrhosis
Most asymptomatic and diagnosed with increased LFTs and liver tests (mild)
Fatigue, wt loss, anorexia, nausea, RUQ discomfort
IVDU!!!
Recommendations for hep C screening
Persons born 1945-1965 w/o prior assessment of risk is big time!
How to diagnose chronic hep C
Elevated transaminases (varying ALT patterns–AST can be greater than ALT in cirrhosis)
LFTs can rise and fall
Present late in disease course (signs of cirrhosis)
Management for Hep C
Avoid ETOH Screen for HAV and HBV and vaccinate Discuss non infected sexual partner testing Cure Screen for HIV etc
Meds for hep C
New oral meds (8-12 wks usually)
Check for co-infection with HBV (meds can reactivate)
When do you see Hep D?
Only in conjunction with hep B
Acute hepatitis sxs
How to diagnose hep D
Delta virus RNA with +HBsAg
How to manage hep D
Eradicate hep B
Presentation of hep E
Acute hepatitis sxs similar to hep A (travel in last couple months)
How to diagnose hep E
Hep E RNA
