Liver Flashcards
Role of hepatocytes in anabolic vs. catabolic states
anabolic - hepatocytes store energy rich nutrients from portal circulation
catabolic - hepatocytes release glucose from glycogen/gluconeogenesis into the systemic circulation
How do hepatocytes make glycogen?
- import glucose via GLUT2
- phosphorylated into G6P via glucokinase (polymer of this is glycogen)
- G6P can also be made into pyruvate via glycolysis
- pyruvate can then enter the Krebs cycle and feed into lipid synthesis
*hepatocytes also import a.as for hepatocyte and plasma protein synthesis
How does glycogenolysis occur in hepatocytes?
- G6P converted back into glucose via glucose 6 phosphatase, then exported
- G6P can also be created from pyruvate via gluconeogenesis (precursors include lactate, a.a.s, glycerol from lipid catabolism)
When does ketogenesis occur?
- occurs during catabolism, comes from acetyl-CoA and is exported
Describe the Cori Cycle
- In the liver, lactate becomes pyruvate via LDH and pyruvate becomes glucose (also from gluconeogenesis)
- In muscle, glucose becomes pyruvate and pyruvate becomes lactate via LDH
Lactic Acidosis
- occurs when pyruvate enters the Krebs cycle and the ETC and conversion of pyruvate to glucose is inhibited
- this is caused by a lack of O2 (hypoxia, ischemia), impaired gluconeogenesis (liver failure), ETC disorder (HAART, ASA, genetics)
What are the plasma proteins made in the liver?
- albumin, transferrin, ceruloplasmin (transport)
- fibrinogen (coagulation)
- IgG (immunity)
- C3 (complement)
- alpha1-antitrypsin (protease inhibitor)
- miscellaneous peptide hormones
How are plasma proteins made in the liver regulated?
- all plasma proteins are produced at a faster rate with decreased plasma oncotic pressure
- Acute phase Reaction (IL-6 regulated) - positive regulation for A1AT/ceruloplasmin/C3, and negative regulation for albumin/transferrin
- estrogen increases A1AT, ceruloplasmin, coagulation proteins
Storage of nutrients in the liver
- carbohydrates (glycogen)
- lipids (triglycerides)
- vitamins (B12, folate, A)
- trace metals (iron, copper)
Lipid Metabolism
- uptake from intestine, synthesis with hepatocytes (FFAs, PGs, cholesterol), export into blood via lipoproteins (VLDLs, LDLs, HDLs), oxidation for energy
Diff between chylomicrons, VLDLs, LDLs, HDLs
Chylomicrons - intestine generated, deliver TGs to tissues, remnants deliver cholesterol to the liver
VLDLs - export TGs and cholesterol from liver to tissues
LDLs - derived from LDLs after they deliver TGs
HDLs - reverse transport of cholesterol from tissues to liver
Ammonia (NH4)
- byproduct of a.a. metabolism
- toxic but detoxified in the urea cycle (which produces urea, a non-toxic water soluble compound that can be excreted by the kidneys)
Bilirubin
- explain metabolism
- end product of heme metabolism, mainly made in RE cells from old erythrocytes, metabolized only in the liver
- transported in blood via albumin
- free bilirubin is TOXIC to cells
- uptake into hepatocyte, conjugated to glucuronic acid and excreted in bile
- enters SI via common bile duct, glucuronic acid is hydrolyzed, conversion to urobilinogens, reabsorbed from SI mostly taken up by the liver (enterohepatic circulation), re-excreted by the liver
- eventually eliminated in the urine/ feces
3 Categories of Jaundice Causes
pre-hepatic (unconjugated) - hemolysis, hematoma, inherited metabolic abnormality
hepatic (conjugated) - viral, drug, alcohol, cirrhosis, Gilbert’s
cholestatic (conjugated) - sex hormones, gallstones, bile duct or pancreatic cancer, drugs, alcohol, viral, sepsis, PBC
Heaptic Metabolism of Drugs
- Chemical modification (hydroxylation, oxidation, P450 system)
- Conjugation (sulfate, glucuronic acid)
- Excretion (water-soluble conjugate leads to biliary and renal excretion)
Bile
- production
- 3 main functions
- composition
- yellow/green/brown fluid excreted into bile canaliculi by hepatocytes
- drained by the hepatic duct and stored in the gallbladder
- digestion, excretion, hepatic cell signalling
- mainly bile salts, then electrolytes, phospholipids, cholesterol, bilirubin
Bile salts
- derived from cholesterol (conjugated to glycine and taurine)
- both hydrophilic and phobic surfaces to solubilize lipids
- reabsorbed in the terminal ileum and returned to the liver (enterohepatic circulation)
Risks for gallstone disease
- older age
- female, pregnant
- DM, dyslipidemia, obesity
- rapid weight loss
- family history
- SCI
- cirrhosis, hyperbilirubinemia
- Crohn’s
- Meds (ceftriaxone, fibres, OCPs)
Definition of:
Cholelithiasis
Choledocolithiasis
Cholecystitis
Cholangitis
Biliary Colic
- stones in the gall bladder or cystic duct
- stones in the common bile duct or SI opening
- inflammation of the gallbladder
- inflammation of the bile duct system
- abdominal pain often due to stone obstruction
Signs and symptoms of gallstones in the gallbladder vs. in the common bile duct
Gallbladder - asx, dull URQ/epigastric pain, nausea, diaphoresis, vomiting, fever, leukocytosis
- can see gallstones and sludge on U/S
CBD - fever, jaundice, pain, increased bilirubin/lipase/amylase/AST/ALT, mental changes, acute pancreatitis
- may see intrahepatic duct dilation on U/S along with gallstones and sludge in CBD
Which tests are more helpful for cholelithiasis vs. choledocolithiasis?
Cholelithiasis - HIDA scan helpful for cholecystitis, U/S
Choledocolithiasis - MRCP helps with anatomy and stones, ERCP helps with dx AND tx of stones
*only 10-15% of all gallstones have enough calcium to be visible on x-ray
Pros and Cons of U/S and CT for gallstones
U/S pros: cheap, no radiation, high sp/sn, can detect 1.5-2mm stones
U/S cons: operator dependent, scarring can lead to false negatives, can miss stones under 3mm, poor sensitivity in distal CBD
CT pros: useful to rule out other Dx, assess complications like perforation/cancer
What would you see on CT for acute cholecystitis? What is considered a dilated CBD on U/S?
- gallbladder distension, wall thickening, gallstones, mucosal hyper enhancement, pericholecystic fat stranding
- 6mm or more is considered dilated for CBD
HIDA Scan
MRCP
ERCP
HIDA Scan - use if diagnosis is unsure after U/S
- technetium label HIDA is IV injected and taken up via hepatocytes –> excreted into bile (allows tracing)
MRCP - magnetic resonance cholangiopancreatography and MRI with liver contrast
- helps evaluate biliary tree, non-invasive, no radiation
- good for CBD stones if no ECRP available or cancer
ERCP - scope, can diagnose and remove CBD stones
- can help stent and brush the CBD to rule out cancer
- could lead to bleeds, perforation, pancreatitis
What are indications for cholecystectomy?
- biliary colic, cholecystitis, cholangitis, pancreatitis
*most gallstones do not need to be treated unless they are symptomatic
Courvoisier’s Sign
- jaundice with non-tender palpable RUQ mass
- unlikely to be a stone
General investigation steps for jaundice
- CBC/ liver panel/ lytes/ kidney/ blood
- CT and U/S as initial imaging
- biopsy/brush
- stage with CT chest/abdo/pelvis and possibly MRI/PET
Pancreatic Adenocarcinoma
- often too far gone by diagnosis
- vascular invasion and extra pancreatic spread common
Gallbladder Cancer
- tx
- incidence is about as common as the prevalence of cholelithiasis
- often found late as an incidental finding
- tx - cholecystectomy and resection of the gallbladder fossa
Cholangiocarcinoma
- sx
- tx
- arises from the epithelial cells of bile ducts
- mostly extrahepatic
- biliary obstruction, abdominal pain, weight loss, fever
- tx - NO chemo, liver transplant
Whipple Surgery
- remove most of pancreas, gallbladder, part of stomach and SI, bile duct
- some pancreas left for digestion and insulin
Gallstone Ileus
- fistula from the biliary tract to intestine (most commonly the duodenum)
- obstruction if stone is over 2.5cm (often terminal ileum)
- will see distended SI loops, SBO, ectopic calcified gallstone, nausea, vomiting, pain, constipation
Mirizzi Syndrome
- sx
- dx
- tx
- obstructive jaundice from stone in the neck of gallbladder or CD, narrowing CHD
- epigastric pain, jaundice, increased enzymes on liver fxn test
- Dx: ERCP
- Tx: open cholecystectomy
These clinical pictures point to:
- RUQ pain, high WBC, normal liver function, presence of cholelithiasis on U/S w or w/out CBD dilation
- Fever, Jaundice, Hypotension, Upper Abdominal Pain, Tachycardia
- also: biliary duct dilation w shadowing in the CBD on U/S
- Cholecystitis
- Reynold’s Pentad (Cholangitis)
When would gallbladder resection not be appropriate?
- metastases, involvement of vital structures (portal vein), other comorbidities (HF, CKD)
Risks of chronic alcohol abuse?
How is alcohol metabolized?
- fatty liver, cirrhosis, cancer, acute hepatitis
- alcoholic hepatitis has high mortality if severe
- acetaldehyde causes cell injury, oxidative stress, mitochondrial dysfunction due to increased NADH/NAD ratio, hypoxia of centrilobular area
- ADH is primary if lower [EtOH], CYP2E1 is induced by higher [EtOH]
- metabolized from EtOH - acetaldehyde - acetate - CO2 and water
What is the common presentation of alcoholic liver disease?
- history of alcohol use
- RUQ pain
- increased AST compared to ALT (alcohol inhibits pyridoxal 5-phosphate which is more important for ALT synthesis) *BUT if AST over 400 consider other causes
- hyperbilirubinemia
- hepatic encephalopathy
- coagulopathy
- leukocytosis
What would you see on biopsy for someone with alcoholic liver disease?
- macro vesicular steatosis
- hepatocellular ballooning
- neutrophil/lymphocyte infiltration
- Mallory-Denk bodies (condensed cytokeratin filaments/ ubiquitin)
- cholestasis
- bile duct proliferation
- fibrosis with perivenular/sinusoidal/ cellular distribution (chicken wire)
What are tx options for someone with alcoholic liver disease?
- prednisone
- pentoxyfilline
- nutritional support and abstinence
Intrinsic vs. Idiosyncratic Drug-Induced Liver Injury (and three subtypes of idiosyncratic)
*worsened by alcohol and malnutrition
Intrinsic - predictable, prototype is acetominaphen but also alcohol, tetracycline
Idiosyncratic - variable presentation, affects susceptible individuals, most common
- Non-immune - no features of hypersensitivity, metabolites bind and cause oxidative stress, bad metabolism
- amiodarone, diclofenac, isoniazid - Immune - rash, fever, joint pain, eosinophilia, SJS, prompt recurrence after rechallenge, covalent binding of drugs with protein, activation of immune cells
- amoxicillin, diclofenac, phenyotin - Autoimmune-Like - increased IgG/ANA/ASMA, eosinophilia or granulomas on biopsy, responds to corticosteroids, NO relapse
- minocycline, nitrofurantoin
Hepatocellular Injury (i.e. hepatitis) vs. Cholestatic Injury
Hepatocellular - transaminases (ALT/AST) much higher than alkaline phosphatase
- acetaminophen, macrolides, isoniazid
Cholestatic - alkaline phosphatase much higher than transaminases
- amoxicillin, chlorpromazine
*bilirubin may be increased in both cases
* a mixture of both can be caused by anabolic steroids, amiodarone, flavocoxib
What is the R value?
- ALT/ULN divided by ALK/ULN
- if over 5, hepatocellular
- if under 2, cholestatic
Liver biopsy will rarely show a pathognomonic pattern, but what do these suggest?
- Steatosis
- Acute cholestasis
- Chronic cholestasis
Steatosis - methotrextae
Acute cholestasis - amoxicillin/ OCPs
Chronic cholestasis - amoxivcillin
What are management options for drug-induced liver disease?
- stop offending agent
- supportive
- do not suggest a rechallenge
- antidotes (i.e. acetaminophen is N-acetylcysteine)
Acetaminophen Injury
- signs
- what is fatal?
- nomogram
- will see severe transaminitis (ALT > 1000)
- fatal if over 15g, unless also an alcoholic then 2-6g
- also at higher risk if fasting, CYP promoter medications
- nomogram is used to determine [serum] related to time since ingestion
Drugs of Concern:
Anabolic Steroids
Antibiotics
Methotrexate
Steroids - cholestasis without hepatitis, bilirubin more than 20x ULN, very slow resolution to normal
- ABX - cholestasis WITH hepatitis, onset of sx can be delayed by weeks
- amox-clav, fluoroquinolone
- MTX - increased risk if over 60/ alcoholic/ obesity/ DM/ NSAIDs/ vitamin A
- possibly greater in psoriatic arthritis
*also need to worry about “-Mabs” and herbal supplements
Lab Values and Signs of:
- transaminitis
- acute hepatitis
- acute severe hepatitis
- acute liver failure
- acute on chronic liver failure
Transaminitis - high enzymes
Acute hepatitis (under 6 months) - very very high enzymes, high bilirubin
Acute severe hepatitis - high enzymes, high bilirubin, high INR (coagulopathy), jaundice
Acute Liver Failure - high enzymes, high bilirubin, high INR (over 1.5), altered mentation (encephalopathy)
Acute on Chronic Liver Failure - high enzymes, high bilirubin, high INR, possible altered mentation, pre-exisiting liver disease
*only see encephalopathy with failure, NOT hepatitis
* acute hepatitis can be managed outpatient, failure needs hospital
What can cause cirrhosis?
What can cirrhosis lead to?
What is the pathophys?
- inflammation, infections (HAV/BV/CV/EBV/CMV), hereditary (hemochromatosis), toxins (EtOH, acetaminophen), vascular (Budd-Chiari)
- portal HTN, which (if decompensated) can lead to fluid overload, variceal bleeds, hepatic encephalopathy, heptocellular carcinoma
- hepatocellular damage - macrophages - hepatic stellate cells - myofibroblasts - fibrosis - cirrhosis
Portal HTN
- pathophys
- consequences
- destruction of sinusoidal architecture leading to increased resistance in the portal vein/ feeding venous structures
- as resistance increases through the liver, there is development of venous collaterals for blood to return to the heart
- systemic vasodilation (ascites, hyponatremia, edema)
- hematemesis, hemorrhoids
- splenomegaly, anemia (will have low platelet count)
- gynecomastia, testicular atrophy
- jaundice, asterixis, fetor hepaticus
- coma
How to manage varices?
- want to decrease portal pressures
- ABCs (IV fluids)
- IV octreotide and PPI
- correct coagulopathy (platelet infusion), transfuse RBCs ub to Hb100
- endoscopy
- ABX to prevent spontaneous bacterial peritonitis (Ceftriaxone and Cipro)
Ascites
- different forms and their causes
- presinusoidal - portal vein thrombosis
- post sinusoidal - heart failure, Budd-Chiari
- sinusoidal - cirrhosis, liver metastases
- portal HTN - splanchnic vasodilation –> low ECF –> RAAS –> ascites and renal vasoconstriction leads to hepatorenal syndrome
What is SAAG?
- what do diff values mean?
- serum ascites albumin gradient
= serum albumin - ascites albumon - if over 11, portal HTN or cardiac cirrhosis
- if under 11, hypoalbuminemia (malnutrition, nephrotic syndrome) or interruption of peritoneal lining (infection, malignancy, pancreatitis)
Managing ascites
- restrict sodium to under 2g/day
- spironolactone, furosemide, amiloride
- paracentesis, TIPS if refractory
Spontaneous Bacterial Peritonitis
- sx
- tx
- prophylaxis
- infection of ascitic fluid, growth of bacteria
- often asx but can have pain/ Lower LOC/ AKI
- Tx - paracentesis to dx, cefotaxime/ceftriaxone
- prophylaxis - cipro/septra, do if presenting with GI bleed/ prior SBP/ fluid protein under 10g/L
Hepatic Encephalopathy
- altered mentation from cirrhosis due to toxins in blood
- precipitants include infection, acidosis, constipation, GI bleeds, opioids/benzos/NSAIDs, hypoNA/hyperK/hyperCa, renal failure, dehydration
Hepatic Encephalopathy
- precipitants
- sx
- tx
- prophylaxis
- altered mentation from cirrhosis due to toxins in blood
- precipitants include infection, acidosis, constipation, GI bleeds, opioids/benzos/NSAIDs, hypoNA/hyperK/hyperCa, renal failure, dehydration
- lowered memory/concentration, confusion, somnolence, day/night reversal, coma (grade IV)
- tx - lactulose (acute), flatly, PEG, CANNOT DRIVE
- prophylaxis - lactulose, rifaximin, avoid opioids/ benzos/ NSAIDs
Clues for Advanced Liver Disease
- AST > ALT (AST is found more in extra hepatic tissues)
- more than 1g increase (less Kuppfer cell mass, increased liver vascular shunting)
- leukopenia and thrombocytopenia (due to splenomegaly)
*dupuytren’s contractions can be a sign of chronic liver disease
What do these suggest?
- ANA+, ASMA+, anti LKM+, higher IgG
- higher IgA
- very high GGT
- very high ferritin
- AMA+, ANA+, higher IgM
- increased ferritin, increased TSAT
- low ceruloplasmin, increased urinaey copper
- decreased alpha-1 antitrypsin
- autoimmune hepatitis
- fatty liver
- induced by drugs/alcohol/fat
- induced by steatosis, alcohol, inflammation
- primary biliary cholangitis
- hemochromatosis/alcohol/fatty liver
- Wilson’s
- alpha1 antitrypsin deficiency
Alcoholic Hepatitis
- active inflammation and hepatocyte damage
- non-cirrhotic portal hypertension (inflammation around central veins)
- presents as acute severe dysfunction
- women have less ADH
- abstinence is the only determinant of longterm survival, steroids and nutrition for longterm
Metabolic Associated Fatty Liver Disease (MAFLD)
Non Alcoholic Fatty Liver Disease (NAFLD)
Secondary Fatty Liver Disease
- visceral fat (not peripheral) is the problem - waist circumference over 35 for women and 40 for men
- treat by losing 10% weight in one year
- PNPLA3 gene, often have features of metabolic dysfunction, exclusion of other causes
- genetic syndromes, rapid weight loss, celiac’s, drugs
Primary Biliary Cholangitis
- tx
- chronic progressive cholestatic liver disease
- more common in women
- destruction of small and medium intrahepatic bile ducts
- tx: ursodeoxycholic acid (#1), obeticholic acid, bezafibrate/fenofibrates
Autoimmune Hepatitis
- inflammation affecting hepatocytes of an unknown cause
- more common in women
- IgG, ANA, ASMA are most common markers, anti-LKM if pediatrics
- tx: prednisone, budesonide (if no cirrhosis or portal HTN), tacrolimus, azathioprine
Primary Sclerosing Cholangitis
- screening?
- chronic inflammation/ fibrosis of intra and extra hepatic bile ducts, leads to strictures/ cirrhosis/ portal HTN
- likely immune (common with IBD), ANCA in 80%
- increased risk of cancers
- every 5 years with a colonoscopy if no IBD
- every 1-2 years with a colonoscopy if IBD
- multiphase MRI+MRCP annually if no cirrhosis
- alternate US/MRI 6 months if cirrhosis
Hereditary Hemochromatosis
- tx
- type I autosomal recessive (over 90% homozygous C282Y mutation of HFE gene), high incidence in celtic
- systemic iron overload, leads to hepatitis/cirrhosis/ risk of HCC and many other co-morbidities
- will see increased ferritin, TSAT over 45% if female or over 50% if male, echogenic liver in U/S, ferriscan (MRI)
tx: phlebotomy until ferritin 50mcg/L, avoid vitamin C supplements
Wilson’s Disease
- uncommon autosomal recessive
- excessive copper deposition in organs
- neuropsychiatric symptoms, Kayser Fleisher ring in eyes, low ceruloplasmin, increased 24 hour urine copper, increased hepatic copper on biopsy
- tx: D-penicillamine (chelation), zinc, low copper diet
Liver Cysts
- common, may be multiple, bile duct origin
- usually asymptomatic, but can be large
- simple - smooth, thin walls, solid (no internal septa/nodules)
- complex - separations, nodules, thick walls (i.e. daughter cysts within a main cyst is suggestive of parasites)
Hemangioma
- most common liver tumor
- endothelial origin, may be multiple, collagen scaffold
- usually asymptomatic
- peripheral in-filling is diagnostic on radiology
Focal Nodular Hyperplasia
- second most common liver tumor
- hyperplasia of normal liver cells, possible due to AVM/scar
- usually of no clinical significance and rarely symptomatic
Liver Cell Adenoma
- benign neoplasm, less common
- hepatocyte origin, may be symptomatic/large/fleshy, risk of rupture (especially in pregnancy) which can lead to death, treat with surgery if large
- will look the same throughout contrast imaging
- more common in women (may regress with cessation of OCPs)
- hard to distinguish from well-differentiated hepatocarcinoma
Hepatocellular Carcinoma
- dx
- tx
- may be multifocal, usually associated with cirrhosis (hepB/C/hemochromatosis)
- may arise from dysplastic regenerative nodules
- Dx: tumor marker is alphaFP, tumor will have less contrast than liver later on
-Tx: surgical resection (#1), treat underlying disease, ablate if small tumor/ radiate (chemo injected directly into tumors)/ transplant
Cholangiocarcinoma
- risk factors
- tx
- less common and harder to treat (close to portal triad so can spread easily), malignant
- from bile duct epithelium (usually major ducts)
- risk factors: PSC, choledochal cysts, clonorchis infection
- tx: surgical resection, stenting, biliary bypass
- poor results with chemo!
Liver Metastasis
- more common than primary cancers in the west
- will see alpha FP increase (tumor marker)
- can be hypo OR hyper vascular
tx: resection, ablation, chemo
transplant is not an option
When is systemic chemo a viable treatment option?
- metastases (5-FU, oxaliplatin, bevacizumab)
- moderate benefit for HCC (sorafenib, lenvatinib)
- do NOT give for cholangiocarcinoma
What are considered markers of liver cell injury?
- AST (90% released from liver)
- ALT (small amounts also in kidney and muscle)
*both key for converting a.a.s into high energy molecules for gluconeogenesis
*both intracellular enzymes - means cells are DYING (markers of hepatocellular injury)
What are considered markers of hepatic secretory function?
- ALP (also see rise in GGT), mostly on canalicular membrane of the hepatocyte, induced by bile acids due to duct obstruction or hepatocyte injury
- total bilirubin - increases due to over production (hemolysis), under secretion (obstruction, liver injury), or impaired metabolism (Gilbert’s)
*known as cholestatic enzymes, markers that something is wrong post-hepatically
What are considered markers of impaired synthetic function?
- albumin - only made in the liver, half life of 14-21 days, production inhibited by physiological stress (surgery, infxn, disease, advanced chronic liver disease)
- INR (PT) - extrinsic clotting pathway (2,5,7,10) all made in liver, increased INR suggests deficient production of at least one of the cofactors
- factor 7 has shortest half-life so reasonable measure of immediate liver function
What is a broad differential of things that can cause elevated AST or ALT?
Elevated ALP or GGT?
- AST/ALT - viral, bacterial, fungal, parasites, toxins (drugs, alcohol), shock, right heart failure, hepatic vein thrombosis, Wilson’s, Celiac’s, hemochromatosis, sacred/amyloidosis, fat
- ALP/GGT - stones, strictures, malignancy (CCA/HCC), drugs, lymphoma, metastases, viral
What you test for with:
- Hep C
- Hep B
- Hemochromatosis
- Wilson’s Disease
- A1AT
Hep C - anti-HCV Ab, HCV RNA by PCR and genotype if positive
Hep B - HBsAg, anti-Hb core, HBeAg/HBeAb/HBV-DNA by PCR if positive
Hemochromatosis - Fe TIBC, ferritin, HFe genetic testing if positive
Wilson’s - ceruloplasmin, 24h urine copper, ATP7b genetics if positive
A1AT - A1AT, A1AT phenotypic if positive
NASH
- non-alcoholic steatohepatitis (happens if you have NAFLD)
- ALT over 150, dyslipidemia, obesity, DM2
- check ferritin, IgA, U/S
What is Hy’s law?
- serum bilirubin over 2x ULN with transaminases over 3x ULN will have a worse prognosis than isolated increased transaminases
DDx of high ferritin
- hemochromatosis
- HCV
- NASH
- alcoholic liver disease
- any inflammatory disease (acute hepatitis)
*high ferritin and high enzymes is NOT always indicative of hemochromatosis (need genetics and biopsy)
How are Hep A/B/C/D/E transmitted, and what are risks of longterm infection?
Hep A/E - food-borne, usually no long-term infection
Hep B/C/D - body fluids, can cause a chronic infection
Hepatitis C
- what kind of virus?
- sx
- consequences
- dx
- staging
- RNA virus (cannot integrate in our genome)
- only 15% are symptomatic - malaise, fever, abdominal pain, jaundice, dark urine, clay stools
- increase in ALT/AST 6-8 weeks after exposure
- 75% develop chronic exposure, 20% of those develop cirrhosis after 20 years and further risk of ascites/encephalopathy/HCC/variceal bleeds
- Dx: HCV Ab - if positive either an ongoing or resolved infection
- order additional HC RNA PCR
- repeat in 6m for spontaneous clearance
- can stage using fibroscan - measures liver stiffness via vibration velocity (slow if more fibrous)
- can also stage with APRI:
((AST/AST ULN)/platelet count) x 100
- if over 0.7, significant fibrosis
- if over 2, cirrhosis
Treatment for Hep C
- Direct-Acting Antiviral (DAA) therapy
- anyone with detectable RNA is eligible, goal is HCV clearance (RNA negative 3 and 6m after therapy)
- target NS3/4A protease inhibitors, NS5A inhibitors (replication and assembly), NS5B inhibitors (polymerase)
- different combos of sofosbuvir/velpatasvir/ ledipasvir depending on pa-genotype/ genotype 1 specific, re-tx
Hepatitis B
- type of virus
- consequences
- tx
- enveloped DNA virus, can form mini-chromosome in nucleus
- 30-50% have sx, only 5-10% progress to chronic (unless infant, then 90%)
- 20-30% of chronic get cirrhosis/HCC/failure within 5 years
- tx: only intervene if signs of inflammation/damage (follow enzymes and fibroscan)
- nucleoside analogues
- lamivudine, entecavir, tenofovir (most potent) are all first line
- goal is longterm viral suppression and reversal of liver damage (can rarely get seroconversion)
- HBV vaccine (synthetic surface Ag) - part of standard BC vax at 0/2/6m
- immunity is lifelong, better response if young
Process of Diagnosing Hep B
- HBV surface Ag (HBsAg) - marker of active infection (acute or chronic)
- HBV surface Ab (antiHBs) - marker of immunity (infection or vaccine)
- HBV Core Ab (anti HBc) - suggests acute infection or re-activation of viral replication
- HBV eAg - seen in active infection, marker of viral replication and infectivity
- HBV eAb - marker of some degree of immunity, usually recovery phase
- HBV DNA - measuring replication in active infection/ response to tx
- Hep Delta Ab - check for co-infection
*HBsAG (+) antiHBc (+) IgM antiHBC (+) antiHBs (-) –> acutely infected
(igm only rises in acute phase)
*HBsAG (+) antiHBc (+) IgM antiHBC
(-) antiHBs (-) –> chronically infected
- HBsAG (-) antiHBc (+) antiHBs (+) –> immune from natural infection
- HBsAG (-) antiHBc (-) antiHBs (+) –> immune due to vaccination
