Functional Liver Tests and Treatment of Chronic Hepatitis Flashcards
what can cause Prolongation of PT (INR)
Significant hepatocellular dysfunction
Vitamin K deficiency
how can you differentiate liver Dysfunction vs. Vit K deficiency?
Administer subcutaneous vitamin K and assess response
No correction = liver dysfunction
Normalization = vitamin K deficiency
predominately elevated AST and ALT would indicate what pattern of disease?
Hepatocellular Injury or Necrosis
predominately elevated alk phos would indicate what pattern of disease?
Cholestatic Pattern
where in AST located in the hepatocyte?
Cytosol and mitochondria
where is ALT located in the hepatocyte?
Cytosol
what organs express AST?
liver, heart, muscle, blood
what organs express ALT
Liver only
what is a Typical AST:ALT ratio
<1
AST:ALT Ratio >1 is seen in _____
cirrhosis
AST:ALT Ratio >2 is suggestive of ________
alcoholic liver disease
what is alkaline phosphatase
Hydrolase enzyme responsible for removing phosphate groups from nucleotides, proteins and alkaloids
alkaline phosphatase can be elavated in
Cholestatic or infiltrative diseases of liver
Obstruction of biliary system
Bone disease
Pregnancy
what do glutamyltransferase (GGT) lab values represent
GGT is Not present in bone
so if GGT is elevated and alk phos is elevated then you know the origin is the liver
Is Elevated after alcohol consumption and almost all types of liver disease
what are 7 hepatobiliary causes of increased alk phos?
Bile duct obstruction Primary biliary cholangitis (PBC) Primary sclerosing cholangitis (PSC) Medications Hepatitis Cirrhosis Infiltrating disease
what are 6 non-hepatic causes of elevated alk phos?
Bone disease Pregnancy Chronic renal failure Lymphoma and other malignancies Congestive heart failure Infection and inflammation
what are 3 things that can cause Unconjugated (indirect) hyperbilirubinemia
Gilbert’s syndrome
Hemolysis (increased heme breakdown)
Crigler-Najjar syndrome
what 4 things can cause conjugated hyperbilirubinemia
Extrahepatic obstruction of bile flow
Intrahepatic cholestasis
Hepatitis
Cirrhosis
what is HBsAg and what does it indicate?
Hepatitis B surface antigen
Marker of active infection
Presence for >6 months defines chronic hepatitis B infection
what is HBsAb (or anti-HBs) and what does it indicate?
Antibody to HBsAg
Marker of immunity to hepatitis B
what is HBcAb and what does it indicate?
Hepatitis B core antibody
Marker of active or prior infection
what is HBeAg and what does it indicate?
Hepatitis B “e” antigen
Surrogate marker of high viral load
what is HBeAb (or anti-Hbe) and what does it indicate
Antibody to hepatitis B “e” antigen
Associated with lower viral load
what does HBV DNA indicate on lab tests
Presence means active viral replication
what are the goals of HBV treatment?
HBeAg seroconversion -> Loss of HBeAg and development of HBeAb associated with negative HBV DNA when treatment stopped.
Prevention of decompensated cirrhosis in those with advanced fibrosis
what are the 3 indications for treatment of chronic HBV
1) HBsAg(+) > 6 months*
2) Serum HBV DNA >105 copies/mL
3) Persistent or intermittent elevation in ALT and AST levels
Likelihood of HBeAg seroconversion with normal ALT is very low
what are 2 treatment options for HBV
1) Interferon
Finite duration of therapy (1 year)
Absence of resistant mutations
More durable response
2) Nucleoside/tide analogues
Fewer side effects
Resistant mutations
Chronic HCV defined as presence of HCV RNA in blood ____ months after infection
> 6
Goal of antiviral therapy is to clear HCV RNA such that they remain HCV RNA negative ______ after stopping therapy.
12 weeks
what is a current Tx option For HCV
NS5B polymerase inhibitor (SOFOSBUVIR)
+
NS5A inhibitor (LEDIPASVIR)
For 12 weeks
what is hereditary hemochromatosis
Inherited disorder resulting in increased intestinal iron absorption
what is the treatment of hereditary hemochromatosis
Therapeutic phlebotomy
500 mL of whole blood = 200-250 mg iron
Endpoint is serum ferritin 50 ng/mL
Maintenance phlebotomy to keep ferritin 50-100
ng/mL
what is the tx for hereditary hemochromatosis in anemic patients not able to tolerate phlebotomy?
chelation therapy with desfuroxamine
for diagnosis of hereditary hemochromatosis, Initial iron studies are ordered; what results would make you proceed with a gene test?
% iron saturation is >45% OR
ferritin (>500 ng/mL)
what is the mutation seen in hereditary hemochromatosis
HFE Gene mutation -> C282Y, H63D, S65C
If gene testing comes back positive for hereditary hemochromatosis, what should be the next step?
Evaluate for end organ involvement
Liver -> MRI
Heart -> Cardiac MRI
Pancreas, gonads, thyroid, joints
Primary Biliary Cholangitis
Immune mediated disease causing damage to small intrahepatic bile ducts
what is the treatment for Primary Biliary Cholangitis
ursodeoxycolic acid (UDCA) -> Improves bile acid transport, “detoxifies” bile and providing cytoprotection
what is Primary Sclerosing Cholangitis
Inflammatory disease of the intra- and EXTRAHEPATIC large bile ducts -> Leads to strictures and obstruction of bile ducts and can ultimately result in cirrhosis
what is the Tx of Primary Sclerosing Cholangitis
Treatment focused on management of complications of bile duct obstruction
1) Stenting strictures
2) Antibiotics for cholangitis
what is wilsons disease?
Autosomal recessive disorder
Decreased hepatocullar copper excretion resulting in hepatic copper accumulation and injury
what is the Tx of wilson’s disease
copper chelation -> D-penicillamine, Trientine
Maintenance therapy with zinc
what is Non-Alcoholic Steatohepatitis (NASH)
NASH is presence of hepatic steatosis and inflammation with hepatocyte injury (ballooning with or without fibrosis
what is the Tx of Non-Alcoholic Steatohepatitis (NASH)
Treatment focused on modifying risk factors
Obesity
Diabetes mellitus type 2
Dyslipidemia
