19. Hepatitis Flashcards
What is the liver’s dual blood supply, and what comprises the portal triad?
Describe the hepatic venous drainage.
How many anatomical segements does the liver have?
What does bile contain?
Hepatic artery (provides 30-40% O2 to liver) and portal vein.
Portal triad: common hepatic duct, portal vein, hepatic artery
Hepatic vein drains to IVC
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Water, electrolytes, cholesterol, bile acids, phospholipids, conjugated bilirubin
What are the 7 functions of the liver?
- *1. Protein synthesis** (e.g. for antibodies, nutrition, albumin - oncotic pressure!)
- *2. Carbohydrate mechanism** (glycogen storage, gluconeogenesis)
- *3. Lipid metabolism
4. Bile production** - *5. Immunological function** (reticuloendothelial (macrophage) system, abs)
- *6. Hormone and drug metabolism/excretion
7. Detoxification**
What are the 4 liver enzymes often tested for?
What tests liver function?
- *ALT (alanine aminotransferase):** liver specific. ALT > AST = hepatitis/liver damage etc.
- *AST (aspartate aminotransferase):** mitochondrial enzyme, in heart/muscle/kidney. AST>ALT = alcoholic liver disease.
- *ALP (alkaline phosphatase):** in bile cannalicular + sinusoidal membranes, and bone/placenta. Rises in cholestasis - intra/extrahepatic.
- *GGT (gamma glutamyl transpeptidase):** hepatocellular, more sensitive marker to cholestatic damage than ALP. If isolated ALP increase and GGP also increased = chronic alcohol toxicity
PT time, albumin, bilirubin. Also serum sodium and creatinine (in terms of medications e.g. diuretics)
List things to include in a liver patient history.
What are some cholestatic, systemic and decompensation (later stage) symptoms of liver disease? (Or may be asymptomatic - most)
What are some compensated, general and decompensated signs of chronic liver disease?
Past hx of hepatitis/jaundice. Alcohol hx. Ilicit drug use. Medication. Sexual and travel hx. Professional. Family hx. Co-morbidity.
Cholestatic: jaundice, pruritis, pale stools/dark urine (obstructive symptoms)
Systemic: wt loss, muscle loss, fatigue
Decompensation: fluid retention, abdo distension, drowsiness/confusion, wt loss (poor nutrition), bleeding (variceal)
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What related imaging techniques might you use (and for what conditions)?
What are the 3 possible ways of taking a liver biopsy?
- US** - biliary tree (could be obstructed if jaundiced), liver lesions, ascites, spleen (size indicates portal HTN*)
- *CT triple phase** (looks at vasculature)
- MRI/MRCP** (magnetic resonance cholangiopancreatography*) (looks at bile duct)
- *1. Fibroscan** (using it more, US probe, gives amout of liver stiffness. Better for staging)
- *2. Percutaneous liver bx** (dx + staging, bleeding risk, 0.02% mortality) [Pic]
- *3. TJ (transjuglar) liver bx** (reduced risk esp. if pts have clotting problems, less pain, smaller core, pressure readings)
Compare the hepatitis viruses in terms of class, genome (DNA/RNA), transmission route, incubdation (d), and chronicity.
Where are areas of highest hep B prevalence?
What fraction of the world’s population is infected with hep B at some stage?
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NB. A & E are self-limiting. B & C most common, mainly transmitted via infected blood, chronic inefction -> cirrhosis, liver cancer. D acquired as either simultaneous co-infection with B, or as superinfection in those with existing B infection. There is a vaccine for A and B
Middle east, South Asia, Far East and sub-saharan Africa.
1/3 (with 350-500 million chronic infection). High risk populations screened. Vaccination
Describe 3 ways hep B can be transmitted
Where does HDV most occur, and what does it need?
Describe the natural history of HBV infection.
Mother to child (born outside UK, child more likely to remain chronically infected), blood contact, sexual contact (acute infection usually with jaundice and clearance)
IVDU, population specific. Requires HbsAg (Hep B ag) If a pt has HBV check for HDV too b/c diff tx
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What do the following things mean in a HBV serology?
a) HbsAg
b) HbsAb
c) HbcAb - IgG or IgM
d) HbeAg/Ab
e) HBV DNA
f) HDV IgG
g) HDV RNA
a) Active inflammation (>6/12 = chronic)
b) Active immunisation (vaccine)
c) IgG = past exposure; IgM = acute infection/recent exposure
d) If +ve, virus is actively replicating = v. infectious
e) Viral load, if >20,000, treat
f) and g) = check for hep D
How is HBV treated?
Where is hep C most common in?
What are some high, moderate and low risk factors for HCV infection?
- Aims: reduce viral replication and improve immunological response; v. effective = progression to cirrhosis can be halted/fibrosis reduced.*
- *PEG-IFN** - mostly for acute hep B
- *Nucleoside/nucleotide analogues (RTi)** - mostly for chronic hep B e.g. entecavir, tenofovir, lamivudine, adefovir
Central and East Asia, North Africa, Middle East = highest prevalence
High: IVDU, recipients of clotting factors before 1987
Moderate: haemodialysis pts, recipients of blood/solid organ transplant before 1992, persons with undiagnosed liver problems, infants born to infected mothers
Low: occupational exposure, sexual practices
What is the estimated global prevalence of HCV?
Describe disease progression in hep C
What investigations would you do for HCV?
~3% (170 million) [UK prevalence 466,000]
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HCV IgG (if +ve do RNA level), HCV RNA, Genotype (1-6), LFT (ALT:AST \<1:1 until cirrhosis develops), HCC screen (USS, AFP), Liver bx (stage fibrosis via fibroscan). *_Comorbidities:_ ETOH, BMI, psychiatric/mood disorder, autoimmune, lifestyle*
How is HCV treated?
24-48w response guided therapy. Aim sustained virological response (SVR). Side effect profile.
Genotype 1 (4): triple therapy - PEG-IFN + ribavirin + protease inhibitor (telaprevir/boceprevir)
Genotype 2/3: dual therapy - PEG-IFN + ribavirin (beware cirrhotic)
New therapies: sofosbuvir, simeprevir, daclatisvir, ledipasvir
HCV is the major indication for liver transplantation. Also new gen of hep C tx curing ~100%
How many g in one unit of alcohol? How much wine/beer is this equivalent to?
What is the UK drink drive limit? What is the advised maximum alcohol intake/week?
How many people die/yr in the UK from alcohol-related liver disease?
List the progressive stages of alcoholic liver disease.
7g of alcohol. 1 small glass of wine, 1/2 pint of 3.5 - 4% beer
80mg per 100mL blood. 14 units/week
28,000 - commonest indication for liver transplantation in the UK
Steatosis (accumulation of fatty acids in liver cells), severe steatosis, alcoholic hepatitis (hepatocyte inflammation), cirrhosis (inflammation, fibrosis, and damaged membranes preventing detoxification of chemicals in the body, ending in scarring and necrosis)
What are some extra-hepatic manifestations of alcohol-related liver disease?
What are classic features of alcoholic hepatitis?
How is it diagnosed?
CVS: dilated cardiomyopathy, dysarrhythmias, HTN
Neuro: peripheral neuropathy, cerebellar syndrome, dementia, Wernicke’s encephalopathy (opthalmoplegia + confusion + ataxia) /Korsakoff’s syndrome (anterograde amnesia + variable presentation of retrograde amnesia + one of: aphasia/apraxia/agnosia/deficit in executive functions)
GI: pancreatitis
Endocrine
Dependence syndrome
Acute jaundiced illness (affects sinusoids -> obstruction -> coagulopathy) +/- cirrhosis. Liver decompensation leads to ascites, renal impairment, encephalopathy, variceal bleed
Dx: hx of significant alcohol intake, worsening LFTs incl. elevated bilirubin and ALT & AST, AST:ALT usually 1 or more, changes on liver bx important for dx confirmation
How would you manage alcoholic hepatitis?
Describe the spectrum of progressive fatty liver disease that comprises NAFLD (non-alcoholic fatty liver disease) (4 stages).
What can you see in the following 3 liver histologies?
Sepsis treatment, nutrition (NG feed)
Maddrey’s Criteria (if DF > 31 + encephalopathy then severe alcoholic hepatitis) - steroids (prednisolone). Liver transplant?
Long term prognosis - ETOH abstinence
Steatosis (fatty accumulation in liver) -> steatohepatitis (steatosis + inflammation + fibrosis) -> fibrosis -> cirrhosis (irreversible liver damange, bridging fibrosis and nodular regeneration)
Top L: macrovesicular steatosis; Top R: lobular inflammation; Bottom: pericellular fibrosis
What are some risk factors for steatosis in NAFLD?
What is the pathogenesis for NAFLD?
How is NAFLD diagnosed?
How is NAFLD treated?
Obesity, diabetes, insulin resistance, metabolic syndrome (at least 3 from: obesity, high serum trriglycerides, low HDL, HTN, DM, , hyperlipidaemias)
Hepatic triglyceride accumulation, free FAs released from lipid stores, oxidative stress, inflammatory mediators. Inflammatory cascade. Progressive fibrosis. Cirrhosis. Liver failure and HCC
Dx: ALT and GGT increase, USS fatty liver, risk factors, exclude other causes, liver bx
Tx: Wt loss (?bariatric surgery), treat metabolic factors (HTN, DM, lipid lowereing drugs), specific (metformin/glitazone, vit E?), antifibrotic?
