Phase 2 - Liver Flashcards
What can acute and chronic liver injury lead on to?
Acute usually recovers but can lead on to liver failureChronic can lead to recovery but could also cause cirrhosis which can then lead to liver failure (including varices (usually oesophageal) and hepatoma)
What can cause acute liver injury
- VIRAL infection (Hep A/B/E esp; EBV, CMV)
- DRUGS (ALCOHOL, paracetamol)
- VASCULAR (Budd-chiari syndrome - hepatic vein thrombosis)
- Metabolic (Wilson’s, Haemochromatosis, A1ATD)
- OBSTRUCTION (gallstone)
- CONGESTION (e.g. from HF)
- Pregnancy (increased metabolic demand)
What can cause chronic liver disease
- ALCOHOL (common in inpatients)- VIRAL infection (esp Hep B/C)- AUTOIMMUNE- Metabolic (iron - haemachromatosis/copper - Wilson’s overload; A1ATD)- Ostruction/Congestion
Presentation of Acute liver injury
- MALAISE- NAUSEA- Anorexia (potentially)- JAUNDICE (eventually)Less common:- CONFUSION (ammonia in brain - encephalopathy)- BLEEDING (low clotting factors)- liver PAIN (consider obstruction/malignancy)- HYPOGLYCAEMIA (impaired gluconeogenesis/decreased insulin uptake)Abnormal LFTs
Presentation of chronic liver injury
- Congestion: - ASCITES (fluid backup/overload) -> hernia sometimes - Oedema - Haematemesis (VARICES - from portal HTN)- POOR ABSORPTION: - Malaise - Wasting/anorexia (poor absorption)- Easy bruising (low clotting) - vit K deficiency, - thrombocytopenia- SPIDER NAEVI (oestrogen)- Itching (bilrubin)- XANTHELASMA (fat deposits around eyes)- Hands: - CLUBBING - Dupuytren’s Contracture - Palmar erythema- Hepatomegaly (compensation)- Abnormal LFTs (normal if compensated)- Rarely jaundice/confusion (waste product accumulation)(Hypoglycaemia, gynaecomastia, impotence, amenorrhoea - happens later)
Serum liver funtion tests (LFTs)
Bilirubin (normally unconjugated) - high Albumin - low (or normal initially in acute) (but can also be low in infection/inflammation) - bad prognosisProthrombin time (sensitive - synthetic function) - increasesCholestatic enzymes:- alk phos - increased synthesis in intra/extrahepatic cholestatic disease (also - bone, intestine, placenta)- gamma-GT (may leak into blood and so increase)Hepatocellular enzymes: Serum transaminases - (high - leak when liver damaged):- ALT (only rises in liver disease) - AST (also in - heart, muscle, kidney, brain)
What deficiency can also cause high prothrombin time
Vit K deficiency- commonly occurs in biliary obstruction (Vit K need bile salts to absorb)
Types of jaundice
‘Pre-hepatic’ - unconjugated bilirubin- Haemolysis (too much made - not cleared quickly enough)- Gilberts (reduced UDP glucoronyl transferase activity) - Crigler-Najjar syndrome (still intrahepatic but NO UGT function at all) - v. rareIntrahepatic (mixed conjugated + unconjugated)- Liver disease (hepatic level) *Hepatitis (don’t forget drugs, esp if acute) * Ischaemia/Congestion * Neoplasm’Cholestatic’ - conjugated- Bile duct obstruction (post hepatic) * Gallstone: common bile duct, Mirizzi * Stricture: MALIGNANCY, ischaemia, inflammation, PBC, PSC
Pre-heptic vs cholestatic jaundice
Pre-hepatic:- NORMAL urine, stool and LFTs - urine: neg bilirubin, increased urobilinogen- NO ITCHINGCholestatic:- DARK URINE (because conjugated bilirubin is soluble in water so diffuses into blood) - decreased urobilinogen, bilirubin is present in urine (diffused into blood before it could get to GI due to cholestasis)- possibly PALE STOOL- ABNORMAL LFTs- MAYBE ITCHING
Symptoms of jaundice
Urine, stool, itching (varies depending on type)Biliary pain - RUQ, radiates to shoulderRigorsAbdomen swellingWeight loss
Potential sources of viral hepatitis
irregular sex (Hep B esp)IV drug use (Hep C esp)Exotic travel
Diagnosis/tests for Jaundice
LFTs: Very high AST/ALT suggest liver disease - ULTRASOUND (1st line): Biliary obstruction -> dialated INTRAhepatic bile ducts- CT if cancer suspicion- Magnetic resonance cholangiogram (- if intrahepatic suspision?)Endoscopic retrograde cholangiogram (ERCP) - if stones in bile duct
Classification of bile stones
Bile pigment stones - more likely to be intrahepaticCholesterol - more likely from gallbladder (more common)Mix of both
What is biliary colic
Pain from temporary obstruction of cystic/common bile duct by gall stoneSudden onset, severe, CONSTANT, crescendo characteristic (worse in waves) - initially epigastric -> RUQ (related to peritoneal involvement) -> radiates to back (right shoulder/sub scapular region - unusual in colic)- if severe -> possible nausea/vomitingAssociated with tenderness and muscle guarding/ridgityCommonly affects mid-evening -> early morningRelated to increased fatty food consumptionNOT INFLAMMATORY
Causes/risk factors for gall stone
- Obesity/rapid weight loss - diet: HIGH animal fat; LOW fibre- DM- FEMALE (esp caucasian)- Fertile (more kids = increased risk)- Contraceptive pill- Age- Liver cirrhosis- Smoking- NOT FAMILY HISTORY
Pathophysiology of cholesterol stone formation
If bile has relative EXCESS cholesterol (relative deficiency of bile pigments/phospholipids) - cholesterol is held in solution (by detergent action of bile salts/phospholipids) -> forms micelles/vesicles -> crystalises IF cholesterol crystalising vs solubilising factors UNBALANCEDTypically forms large, solitary stones
Examples of when supersaturated (relative excess cholesterol) bile would be present
DMHigh cholesterol diet (also decreases bile salt synthesis so further unbalanced)
Pathophysiology of bile pigment stones
2 types black and brown. Mainly composed of calcium.Black:- Composed of CALCIUM BILIRUBINATE, network of MUCIN GLYCOPROTINS that interlace with salts- glass-like cross-sectional surface- related to HAEMOLYTIC ANAEMIASBrown:- Composed of CALCIUM SALTS (bicarbonate, bilirubinate and fatty acids)- muddy: alternating brown/tan on cross-section- ALMOST ALWAYS present with bile stasis/biliary infection- common cause of recurrence after cholecystectomy
Presentation of gallstones
- MAINLY ASYMPTOMATIC- symptoms linked to recurrence- BILIARY COLIC- Acute cholecystitis related symptoms (if stones obstruct gallbladder emptying) - RUQ pain radiating to RIGHT SHOULDER - Fatigue (inflam) - FEVER - Murphy’s sign (pain on inspiration when palpating right subcostal region)- Cholangitis (if stone blocks common bile duct) - RUQ pain radiating to R shoulder - FEVER + rigors - JAUNDICE (common bile duct blocked) - Murphy’s sign - May be septic: REYNOLD’S PENTAD (triad + confusion + hypotensive shock)- Pancreatitis if gallstones blocking drainage of pancreasNOT ASSOCIATED WITH: fat intolerence, indegestion, bowel upset etc (vague upper gi symptoms)
Pathophysiology of acute cholecystitis
- Gallbladder emptying blocked - usually by stones- Leads to increased gallbladder glandular secretion (compensation?) and distension (may compromise blood supply).- Retained bile -> TRANSMURAL inflammatory response (infection can occur secondarily to vascular/inflammatory events)- Inflammation can irritate parietal peritoneum -> local peritonitis (cause of localised RUQ pain)
What occurs in Mirizzi
Impacted stone in cystic duct/infundibulum of gallbladder -> extrinsic compression of common hepaticCan present with cholestatic jaundice, biliar pain, cholecystitis.
Differential diagnosis for biliary colic
IBS/IBD, carcinoma on right side of colon, renal colic, pancreatitis, GORD, peptic ulcers
Differential diagnosis for acute cholecystitis
acute episode pancreatitis, peptic ulcer, pneumonia, intrahepatic abscess
Diagnosis of gallstones
1ST LINE - FBC + CRP:- raised WCC and CRP in inflammation (NOT COLIC)LFTs:- raised alk phos in biliary COLIC - Serum transaminases (ALT normally higher than AST) also RAISED in CHOLESYSTITIS/cholangitis - Serum bilirubin also raised in CHOLANGITISBlood cultures/MC&S - for infectionsABDO ULTRASOUND (1st line imaging):- no major changes in bloods or images for biliary colic except STONES + duct dilationAcute cholecystitis/cholingitis US:- thick walled, shrunken gallbladder (bile can’t enter from liver)- pericholecystic fluid (fluid around gallbladder)- STONESMRCP (higher resolution but less accessible)ERCP potentially for CHOLANGITISContrast enhanced dynamic CT - excludes pancreatic carcinoma- EASIER TO SPOT PIGMENTED STONES in cholingitis- Amylase - Exclude Pancreatitis
What is Murphy’s sign
Pain on deep inspiration when 2 fingers placed in RUQ (push under ribs)- because diaphragm pushing down on gallbladder
Treatment for gallstones
LAPROSCOPIC CHOLECYSTECTOMY (GOLD for all SYMPTOMATIC gallstones - avoid in >80s)- try conservative FIRST - NSAIDs/ANALGESIAIf FEBRILE/SEPTIC need to treat INFECTION FIRST:- nil by mouth (can’t consume anything)- AGGRESSIVE FLUID RESUS (IV fluids)- Opiate analgesia- IV antibiotics (e.g. CEFUROXIME, CEFTRIAXONE)- Cholecystectomy after symptoms subside- ERCP if small stones at bottom of hepatic duct (involves sphinterectomy; use basket or balloon to remove; mechanical or laser to crush)put in stent (pigtail stent)))??If pure/near-pure cholesterol stones: - STONE DISSOLUTION by increasing bile salt content- ORAL URSODEOXYCHOLIC ACID (UDCA)- can give statins (simvastatin) to lower cholesterolShock wave lithotripsy - shock wave fragments stones so they can be passed (only works if duct still patent)
What can cause ascending/acute cholingitis
Infection of biliary tree - usually secondary to PROLONGED common bile duct obstruction by stones- Bacteria CLIMB up from DUODENUM -> biliary tree infection + consolidation - SURGICAL EMERGANCY (sepsis = high mortality)benign biliary STRICTURES from biliary SURGERYCANCER of pancreas head compressing bile ductPARASITES in Far East/Mediterranean
Treatment of cholingitis specifically
- IV ANTIBIOTICS (e.g. CEFOTAXIME/METRONIDAZOLE) continued after drainage till SYMPTOM RESOLUTION - IV FLUIDSBiliary drainage - Endoscopic Retrograde Cholangio-Pancreatography with sphincterotomy- basket or balloon to remove- mechanical or laser to crush- pigtail stent- UNSAFE FOR LARGE STONE -> REQUIRE SURGERY
Complication of gallstones
- In the gallbladder & cystic duct:* Biliary colic* Acute cholecystitis* Empyema - gallbladder fills with pus* Carcinoma* Mirizzi’s syndrome - stone in gallbladder presses on bile duct casing jaundice- In bile ducts:* Obstructive jaundice* Cholangitis (inflammation of bile duct)* Pancreatitis
How can drugs cause liver injury
Disrupt intracellular Ca2+ homeostasisDisrupt bile canalicular transport mechanismsInduce apoptosisInhibit mitochondrial function -> prevents fatty acid metabolism -> acummulation of lactate and reactive oxygen species
When do most DILI occur
within 3 months/12 weeks of starting drug- usually after at least 1 weekcan occur weeks after stopping drugusually resolves within 3 months of stopping drug but prolonged injury (over 6 months) -> long term damage
Which drugs DO NOT typically cause liver injury
Low dose aspirinNSAIDs other than DiclofenacHRTBeta BlockersACE InhibitorsThiazidesCalcium channel blockers
How do you differentiate between hepatocellular and cholistatic injury based on LFTs
Hepatocellular:- ALT >2 ULN, ALT/Alk Phos ratio >=5Cholestatic:- ALT >2, ratio <=2Alk phos higher in cholestatic
Pathophysiology of paracetamol overdose
too much paracetamol over-saturates the Phase II reaction (glucoronidation and sulphate conjugation pathway -> Glucoronide + sulfate metabolites)Normally if metabolised via phase 1 reaction (oxidation) makes reactive compund (NAPQI) which is made non-toxic by CONJUGATION with GLUTATHIONE (anti-oxident -> cystein conjugate) - in over dose GLUCTATHIONE DEPLETES so INCREASED NAPQI-> hepatotoxicity + kidney injury
Presentation + diagnosis of paracetamol overdose
First 24 hours - Usually asymptomatic then:- SUDDEN ONSET SEVERE RUQ pain- N + V- ANOREXIA- Jaundice- ConfusionLFTs show liver damage at 18 HOURS AFTER- RAISED ALT72-96hrs after - PEAK ALT and Prothrombin timeAcute liver injury symptoms:- JAUNDICE AND ENCEPHALOPATHY- HYPOglycaemia (overdose inhibits gluconeogenesis)- Coagulation defects, electrolyte imbalancesPotential kidney injury from ACUTE TUBULAR NECROSIS:- METABOLIC ACIDOSIS (lactic acid)- Raised creatinineDIAGNOSED on:- History- Raised ALT- Serum Paracetamol conc
Treatment for paracetamol overdose
ACTIVATED CHARCOAL - to prevent absorption in stomach (only works if given within 1 hour)- IV N-ACETYLCYSTEINE (give immediately - non-toxic form is a cystein conjugate so giving a cystine pushes it in that pathway) - replenishes cellular GLUTATHIONE - rash common side effect -> treat with CHLORPHENAMINE - don’t stop unless anaphylactoid
What is a serious complication of acute liver failure
Hepatic encephalopathyPresents with CONFUSION, COMA or FLAPPING TREMOR (ASTERIXIS - flapping tremor with wrist extended) Caused by build up of ammonia passing to brain (neurotoxic - halts Krebs cycle - irreparable/irriversible damage)Also, astrocytes try to clear ammonia by converting glutamate to glutamine but EXCESS GLUTAMINE causes OSMOTIC SHIFT INTO CELLS -> CEREBRAL OEDEMA(risk of oedema decreases the more delayed the onset of encephalopathy)- TREAT WITH IV MANNITOL or LACTULOSE - reduces ammonia)Can also get Wernicke-Korsakoff syndrome - memory disorder due to B1 deficiency (thiamine) (damages neural/supporting cells)- ATAXIA, NYSTAGMUS- MEMORY IMPAIRMENT, confusion, behavioural changes- TREAT WITH IV THIAMINE
Causes of ascites
Local inflammation:- pritonitis, PANCREATITIS- TB- Abdo CANCERS (esp OVARIAN)Low Protein:- NEPHROTIC syndrome (kidney disease), kidney failureFlow stasis:- CIRRHOSIS/chronic liver disease (MAIN)- Budd-chiari (hepatic vein thrombosis), portal thrombosis- HF, constrictive pericarditis
Investigations for ascites
SHIFTING DULLNESS exam (resonant at top when lying on back but dull at sides as bowels/gas floats; site of resonance changes to flank when on side)- fluid wave/thrill (can feel tapping through fluid on other side of abdomen)ASCITIC TAP/aspiration (peritoneocentesis - 10-20ml fluid)- cytology (WCC) + cultures- proteins + amylase * if TRANSUDATE (pushed out - increased hydrostatic pressure) - CLEAR fluid - <30g/L protein (LOW), Serum albumin-ascitic gradient <11g/L(SAAG - serum albumin-albumin in ascitic fluid) * if EXUDATE (leaks out due to inflammations) - CLOUDY - >=30g/L protein (HIGH), SAAG >= 11g/LIMAGING: - XR (worst sensitivity)- US- CT (best sensitivity)
Treatment for ascites
SODIUM/fluid restrictionSPIRONALACTONE (aldosterone antagonist) (furosimide works better on oedema - combined is effective but may contribute to kidney failure (electrolyte imbalance))PARACENTESIS (draining); pleuric/indwelling drain (smaller volumes)TIPS (transjugular intrahepatic portosystemic shunt)Treat underlying cause:Stop alcohol (usually not viable)Liver transplant (esp if getting peritonitis)
Treatments for varices
- TIPS - transjugular intrahepatic portosystemic shuntstent connects portal veins to adjacent vessels with lower BP -> relives pressure in liver -> help stop fluid back upINCREASED RISK OF ENCEPHALOPATHY (as blood bypasses liver) - give prophylaxis- CONTRAINDICATED if multiple previous episodes of ENCEPHELOPATHY- VARICEAL BANDING - rubber band ligation if at risk of rupture- TERLIPRESSIN (vesopressin analogue -> SPLANCHNIC VASOCONSTRICTION)
Progression of AFLD from normal liver
- Normal- Steatosis/fatty liver (smooth; fat-filled hepatocytocytes on cytology) - can be reversed- Alcoholic fibrosis with inflammation -> can progress to alcoholic hepatitis (talk about this if we get asked about stages of AFLD)- Cirrhosis (nodular - irreversible) - compensated or uncompensated- Hepatocellular carcinoma (HCC)
Risk factors for AFLD
- Binge/chronic drinking- Obesity- Smoking- FEMALE sex
Presentation of AFLD
early - almost asymptomaticmore severe -> chronic liver failure/alcohol dependancy- jaundice- hepatomegally- ascites- spider naevi- Hepatic encephalopathy (HE)- palmar erythema, dupuytren contracture (painless, finger bent to palm, maybe cord in palm)- easy bruising
Diagnosis of AFLD
FBC: macrocytic, non-megaloblastic anaemiaLFTs: - Raised AST/ALT- PARTICULARLY RAISED GGT (gamma-glutamyl transferase)- raised bilirubin- low albumin- raised prothrombin time (CLOTTING PROFILE)Biopsy to confirm cirrhosis or hepatitis:- inflammation, necrosis- MALLORY BODIES (hyaline (from degeneration of connective tissue - looks darker) cytoplasmic inclusions in hepatocytes)
Treatment for AFLD
conservative:- STOP ALCOHOL * DiAZEPAM/LORZEPAM for Delireum tremens- lower fat diet, lower BMI- detox regiempharm:- short term steroids (only if necessary)- B1 (thiamine)/folate supplements - give prophylactically as alcohol prevents thiamine absorption in gut -> deficiency(may give low/slow opiate analgaesia if viable)surgical:- liver transplant if end-stage (only if abstains for 3 months; Lille score)Treat complications e.g. ascites
Complications of AFLD
- Pancreatitis (increased ethanol)- Encephalopathy- Ascites- ALCOHOL withdrawal - DELERIUM TREMENS- HCC- Mallory Weiss tear (lower oesophageal tear - violent coughing/vomiting)- Wernicke-Korsakoff syndrome (B1 deficiecy/alcohol withdrawal) - treat with IV B1 (thiamine)
Progression of NAFLD from normal liver
NormalHepatosteatosis (fatty liver - deposited in hepatocytes)Non-alcoholisc steatohepatitis (NASH - fatty+fibrotic)FibrosisCirrhosis
Symptoms of NAFLD
Usually asymptomatic (picked up incidentally)If severe - chronic liver failure symptoms- N+V- Diarrhoea- Hepatomegaly
Diagnosis of NAFLD
Deranged LFTs:- RAISED PT/INR and BILIRUBIN- LOW ALBUMIN- Enhanced Liver Fibrosis Test (if you suspect fibrosis)1ST LINE : ULTRASOUND liver/abdomen (shows fatty liver)CT/MRI2nd line: Assess risk of fibrosis (non-invasive scoring system - FIB-4)BIOPSY - DIAGNOSTIC- (may find Mallory bodies if biopsy done)
Treatment for NAFLD
Conservative + control risk factors- lower BMI/weight- EXERCISE- Stop SMOKING- avoid ALCOHOL- control risk factors - diabetes, HTN, cholesterol ( statins, metformin, ACE-I) - consider pioglitazone to improve insulin sensitivityvitamin E can reduce fibrotic appearance (improves liver function)
Complications of NAFLD
HCC!portal HTN, varicesencephalopathyascites
Risk factors for NAFLD
SAME AS CVD and DM:- hyperlipidaemia/HIGH CHOLESTEROL- OBESITY - Poor diet/low activity - HTN - T2DM - insulin resistence- MIDDLE AGE ONWARDS- SMOKINGFamily historyEndocrine disordersDrugs (NSAIDS, amioderone)(- past bypass)
What can cause a sudden decline in patients with chronic liver disease
ConstipationDrugs GI bleedInfectionHYPO: natreamia, kalaemia, glycaemiaAlcohol withdrawalOther (cardiac/intercranial)ALWAYS DO ABCDE first
Why are liver patients vulnerable to infection
- impaired reticulo-endothelial function- reduced opsonic activity (normally tag pathogens)- leucocyte function- permeable gut wall
What can cause renal failure secondary to liver failure
Drugs: - Diuretics - NSAIDS - ACE Inhibitors - Aminoglycosides (DON’T GIVE)InfectionGI bleedingMyoglobinuria (muscle brakdown -> too much in blood + urine)Renal tract obstruction
Causes of coma in liver disease patients
Hepatic encephalopathy (ammonia) - infection - GI bleed - constipation - hypokalaemia - drug (sedatives, analgesics)Hyponatraemia / hypoglycaemiaIntracranial event
Bedside tests for encephalopathy
Serial 7’sWORLD backwardsAnimal counting in 1 minuteDraw 5 point starNumber connection test
Which investigations should you do for chronic liver disease
Viral serology - hepatitis B surface antigen, hepatitis C antibody, hep E IgG antibody, (EBV, CMV, hep A (IgM))Immunology - autoantibodies - AMA, ANA, ASMA (smooth muscle) - coeliac antibodies - immunoglobulinsBiochemistry - iron studies - copper studies - caeruloplasmin (serum copper transport protein) - 24 hr urine copper - α1-antitrypsin level - lipids, glucoseRadiological investigations - USS / CT / MRIBiopsy if possible/required
Risk factors for autoimmune hepatitis
- Female- Other autoimmune conditions (e.g. SLE)- Viral hep- HLA DR3/DR4 (also linked to T1DM)
Presentation of autoimmune liver disease
usually asympother wise - liver failureCOMPLICATION = Cirrhosis
Diagnosis/treatment of autoimmune liver disease
Raised IgGAutoantibodies (not diagnostic):- Type ONE - OLDER women * Anti-nuclear (ANA) * Anti smooth muscle (ASMA) * Anti soluble Liver Antigen (Anti-SLA)- Type 2 - YOUNGER females (rarer) * Anti liver cytosol (ALC-1) * Anti liver kidney micrsomal (ALKM-1)BIOPSY - diagnostic!- presence of plasma cells and other lymphocytes- INTERFACE HEPATITIS (affects hepatocytes around portal tracts); inflammationTREAT WITH STEROIDS (prednisolone) + IMMUNOSUPPRESSANTS (AZATHIOPRINE)- or liver transplant
Risk factors for Primary Biliary cholangitis (PBC)
FEMALE40-50 y/oOther autoimmune/rheumatoid diseaseSmoking
Pathophysiology of PBC
T cell mediated immune response causes intralobular (small, in lever) bile duct damage leading to:- Outflow obstruction (Cholestasis)- Chronic, GRANULOMATOUS INFLAMMATIONCHOLESTASIS -> back-pressure:- fibrosis- chirrhosis- portal HTN- infection- jaundice- reduced secretion of cholesterol via bile ducts causes it to build up in skin and blood vessels -> XANTHELASMAAutonomic neuropathy -> correlates to fatigueAutoantibodies are also present.
Presentation of PBC
usually asymp- early - PRURITIS + FATIGUE- GI disturbance/abdo pain- JAUNDICE- xanthelesma (yellow growths around eyelids - cholesterol deposits)/xanthoma- HEPATOMEGALY (+ other signs of CIRRHOSIS/FAILURE)Complications:- cirrhosis -> HCC- MALABSORPTION of fats/ADEK (due to lack of bile) -> steaorrhoea, OSTEOMALACIA or OSTEOPOROSIS- coagulopathy (from vit K def)- Hypothyroid- Distal renal tubular acidosis (build up of acids)
Diagnosis of PBC
- Deranged LFTs - ALP, GGT, BILIRUBIN RAISED; - ALBUMIN LOW- Rule out viral - check antibodies/antigens- SEROLOGY - ANTI MITOCHONDRIAL ANTIBODY (AMA) - most specific to PBC, (high specificity) - raised IgM - ANA present in 35%USS - exclude extrahepatic cholestasisBIOPSY - PORTAL TRACT LYMPHOCYTIC INFILTRATE + fibrosis- granulomatous- determines staging/diagnosis
Treatment for PBC
1ST LINE - URSDEOXYCHOLIC ACID (UDCA) lifelong- dampens immune; decreases cholestasis (it’s a bile acid analogue - slows down progression); - reduces portal pressure + varices - doesn’t reduce itching or fibrosis- reduces cholesterol absorption in gut -> less risk of xanthoma/CVDCHOLESTYRAMINE for pruritis (RIFAMPICIN also, but can DAMAGE LIVER)- it’s a bile acid sequestrate that binds to bile acid to prevent absorption in gut (reduces pruritis)Immunosuppressants (e.g. steroids) in some patientsADEK vit supplementLiver transplant
What is Charcot triad
shows BILE DUCT OBSTRUCTIONRUQ pain, fever, jaundice
Risk factors for Primary Sclerosing Cholangitis
- MALE (atypical)- FHx- 30-40 y/o- UC (in 70%)
Pathophys of PSC
- auto antibodies attack intra AND/OR extrahepatic bile ducts- Biliary tree becomes STRICTURED/FIBROTIC (lining stiffens) - OBSTRUCTION- chronic obstruction -> HEPATITIS, fibrosis, cirrhosis
Presentation + Complications of PSC
usually asymp- PRURITIS + FATIGUE- Chronic RUQ PAIN- Charcot triad (typically - JAUNDICE regardless)- Hepatosplenomegaly- IBDCOMPLICATIONS:- acute bacterial cholangitis- cholangiocarcinoma- colorectal cancer- CIRRHOSIS/FAILURE- BILIARY STRICTURES- FAT soluble VIT DEFEICIENCY
Diagnosis of PSC
Deranged LFTsU&E, FBCSEROLOGY - no viral, - no AMA, - USUALLY pANCA POSITIVE (anti neutrophil cytoplasmic - non-specific but present 94%)- ANA (77%)- aCL (anticardiolipin)Biopsy - ONION SKIN fibrosis around ductsGOLD STANDARD - MRCP (may show bile duct lesion/strictures - ERCP too invasive)
Treatment for PSC
Conservative:- Cholestyramine (pruritis)- ADEK vit supplement- monitor for complications- ERCP can dilate/stent strictures- consider liver TRANSPLANTUDCA can also be used
Acute vs chronic hepatitis
Acute - less than 6 monthschronic - lasting >6 months
fulminant hepatitis
liver failure in acute hepatitis
Infectious causes of hepatitis
Viral:- Hep A-E (B and D infect together - D can only infect with B, B can infect alone)- Human herpes viruses (either in first case or on reactivation)-Others like flu, covid etc can cause abnormal LFTsNon-viral:- Spirochaetes, e.g. leptospirosis, syphilis- Mycobacteria, e.g. M. tuberculosis- Bacteria, e.g. bartonella- Parasites, e.g. toxoplasma
Infectious causes of chronic hep
Hep B+D (D can only infect alongside B, B can infect alone), C, (E)
signs and symptoms of acute hepatitis
Can be asympNon-specific (malaise, lethargy, myalgia)GI upset, Abdo painJaundice + pale stools/dark urineSigns:- Tender hepatomegaly, potentially jaundice- signs of fulminant hepatitis (acute liver failure) * bleeding, ascites, encephalopathyAbnormal LFTs- ALT/AST»_space; GGT/ALP
Signs/symptoms of CHRONIC hepatitis
asymp/non-specific symptomsPotentially signs of chronic liver disease:- CLUBBING, palmar erythem, Dupuytren’s contracture, spider naevi etc.LFTs normal if COMPENSATED.DECOMPENSATED:- coagulopathy, jaundice, low albumin, ascites (potentially spontaneous bacterial peritonitis), encephalopathycomplications: HCC, portal HTN -> bleeding
Hep A epidemiology/spread
- FAECO-ORAL TRANSMISSION (fAEco = A/E)- contaminated food/drink (SHELLFISH)- linked to access to safe resources/socioeconomic indicators - Close contacts - Homelessness- typically in low income countriesin high income countries:- Travel- Sex (MSM)- Injecting drug use
Incubation period of Hep A
SHORT: 15-50 days (usually 14-28)- incubation period normally lasts ~ 1-6m
Hep A presentation
USUALLY SYMPTOMATIC in adults:- PRODROMAL (no jaundice) - 1-2 weeks: * constituational symptoms e.g. FEVER, fatigue, NAUSEA, MALAISE * RUQ abdo PAIN- ICTERIC phase (jaundice) - few days - 1 week after pre-icteric starts - 3m: - JAUNDICE - dark urine, pale stools - pruritisSELF-LIMITING - no chronic disease
Hep A immunity after infection
100% immunity
Diagnosis of Hep A
Acute Hep signs/symptoms- LFTs - RAISED ALT- RAISED total BILIRUBIN- SEROLOGY: Presence of anti-HAV antibody - IgM high if acute - IgG present shows ImmunityCan’t test IgG by itself so know past infection has occured if Total anti-HAV antibody is positive but IgM is negative.
Management of Hep A
SUPPORTIVE - anti-emetics, restMonitor liver functionFULMINANT HEP VERY RARELY- consider liver transplantVaccines to close contacts within 1 week (or human normal immunoglobin within 14 days)
Primary preventation of Hep A
vaccines to high risk groups- travels, MSM, injecting drug users1 dose - immune for 12 months; 2 dose at 6-12 months - immune for at least 20 years
Epidemiology/spread of Hep E
FAECO-ORAL TRANSMISSION (fAEco = A/E)4 genotypes:- G 1/2: contaminated food/WATER- G 3/4: UNDERCOOCKED meat from mammals (particularly PORK)G3 most common in UK (endemic)- typically only ACUTE - usually SELF-LIMITING (chronic risk in immunocompromised with G3)TRANSPLANT RECIPIENTS
Presentation of Hep E
Usually ASYMPTOMATICExtra-hepatic manifestations esp neurological (meningoencephalitis, Guillian-Barre etc - confusion, coma, muscle weakness/paralysis) - may be main presentationMore common but still rare fulminant hep- esp G1/2 in pregnancy (esp 2/3 trimesters)- risk of CHRONIC in IMMUNOCOMPROMISED (G3/4 only)Occassional acute-on-chronic liver failure (ie fulminant in someone who already had chronic) - high mortality
Who are at risk of HEV complications
Immunosupressed with G 3/4 -> more risk of chronicPregnant ppl (esp 2nd/3rd trimester) with G1/2 -> more risk of fulminant hep
Investigations for Hep E
SEROLOGY:ACUTE - anti-HEV IgM + HEV RNAPast infection - anti-HEV IgG- unreliable in immunocompromisedHEV RNA - measure/monitor in SERUM/STOOL- if it persists for >6 months - chronic
Hep E management
ACUTE:- SUPPORTIVE (usually self limiting)- Monitor for liver failure * consider transplant or RIBAVIRIN (antiviral)CHRONIC:- Reverse immunosuppression if possible- if HEV RNA persists - treat with RIBAVIRIN >= 3 months- (2nd line: pegylated interferon-a)
Preventation of Hep E
- Avoid eating undercooked meats (especially if immunocompromised)- Screening of blood donors(Vaccine available in China only (HEV 239 (Hecolin®) against HEV genotype 1)
Epidemiology/spread of hep B
Most common - BLOOD-BORNE (and bodily fluids)- MOTHER-TO-CHILD (usually during birth, can occasionally get in-utero transmission if mother acquires acute hep B in pregnancy) - VERTICALHorizontal:- SEXUAL- injecting drug use (SHARING NEEDLES)- iatrogenic/occupational (needles) - also DIALYSIS- household contact (esp siblings)- blood products (medical)
Hep B natural historypresentation in immunocompetent adult (presentation + complications)
Mostly SYMPTOMATIC with SPONTANEOUS RESOLUTION (tho genome stays in host so may reactivate if later immunocompromised)- PRODROMAL phase (1-2 weeks) - malaise, RUQ pain, N+V, Fever- ICTERIC phase: jaundice phase - usually few weeks; can last up to 6 months (longer than hep A) - JAUNDICE (with stool/urine change) - PRURITIS - ARTHRALGIA - ascites, encephalopathy, coagulopathy, hypoalbuminaemia, varcies/bleeding (typical more severe hepatic symptoms/signs)<5% -> chronic HBV infection -> 25% progress to cirrhosis -> decompensation (might progress from chronic/cirrhosis to HCC)- some also get fulminant Hep
Hep B natural history in neonates/immunocompromised
MUCH MORE LIKELY TO BE CHRONIC - HCC, Cirrhosis
Investigations for Hep B
SEROLOGY:Total anti- HB core antibody (IgM + IgG - again no specific IgG test) (Anti Hb C Ag)- IgM if acute (at ~ sign as ALT)- IgG - previous exposure/chronic - HB SURFACE ANTIGEN (Hb S Ag) - CURRENT infection (1st to become positive)- Anti Hb S Ag - indicates IMMUNITY/VACCINATION - 1-3 months after exposureHb E Ag = INFECTIVITY/viral REPLICATION (2nd)Anti Hb E Ag = LOW activity/infectivityHBV DNA - indicates viral load (2nd)