Liver Flashcards
What are the functions of the liver and what can go wrong?
-Oestrogen level regulation - spider navei, palmer erythema
-Albumin - ascites + oedema
-Clotting factors - bleeding disorders
-Storage of vits/Fe/Cu/fat -Wilsons, haemachromatosis
-Metabolism of carbs
-Immunity (Kupffer)-SBP
-Detoxification -hepatic encephalopathy
-Billirubin metabolism- jaundice
What are the markers of liver function that indicate liver damage?
Bilirubin- Conj/unconj =High
Albumin =Low
Prothrombin time =High
What enzymes are increased tat would suggest liver damage?
-ALT =Alanine transaminase
-AST =Aspartate aminotransferase
Both found in liver, heart, kidney and lungs
-GGT=Gamma glutamyl transferase
-ALP= Alkaline phosphate
What would AST:ALT typically suggest?
> 2:1. - ALD
4.5:1 -Wilosns or hyperthyroid
<0.9:1 - Suggest NAFLD
What would high GGT suggest?
High in ALD + helps differentiate high ALP as a hepatic or bony cause
What would high ALP suggest?
High in billiary tree specific damage + bony pathology
What is liver failure?
Liver loses its ability to repair and regenerate leading to decompensation
What is decompensation?
Characterised by abnormal bleeding, ascites, hepatic encephalopathy and jaundice
What is acute liver failure?
Liver injury accompanied with hectic encephalopathy, jaundice and coagulopathy(>1.5INR), and ascites in a patient with a previously normal liver
What is fulminant liver failure?
rare syndrome of massive hepatocyte necrosis (histologically = multiacinar necrosis)
- hyper acute (HE within 7 days of jaundice)
-acute (8-28 days HE within jaundice)
-Subacute (5-26 weeks)
What is the most common cause of fulminant liver failure?
Paracetamol overdose (50%case sin the UK)
What is acute on chronic liver failure?
Abrupt decline in patient with chronic liver Sx
What is Chronic liver failure?
Patient with progressive Hx of liver disease;
Hepatitis -> fibrosis-> compensated cirrhosis-> decompensated cirrhosis (ESLF)
What are the causes of acute liver failure?
-Viral = HEP A,B,E ; CMV;EBV
-Autoimmune hep
-Drugs - paracetamol, alcohol, ecstasy
-HCC
-Metabolic - Wilkinsons, haemochromatosis, A1ATD
-Budd Chiari
What is the presentation of acute liver failure?
Acute Px of Jaundice, coagulopathy, HE:
-spider naevi
-fetor hepaticus -breath
-caput medusae - distended abdo BVs
Dupuytren’s contracture - abnormal thickening of skin on palms of hands
What is West haven criteria grades 1-4?
- Severity of encephalopathy (HE)
1. altered mood, sleep issues
2. lethargy, mild confusion, asterixis
3.marked confusion
4. comatose
What is the diagnosis of acute liver failure?
Bloods: LFTs (high bilirubin, low albumin, Hugh PT/INR)
High serum AST/ALT, high ammonia, low glucose
Imaging - EEG- grade HE
USS abdo to check Budd chiari
Microbiology to rule out infections - blood culture, urine culture, ascitic tap
What is Budd Chiari?
an uncommon disorder characterized by obstruction of hepatic venous outflow.
What is the treatment for acute liver failure?
Acutely - ABCDE, fluid, analgesia
Tx underlying cause + complications
What are the complications and treatments of acute liver failure?
Increased ICP = IV Mannitol
HE= Lactulose (increase ammonia excretion)
Ascites = diuretics
Haemorrhage = Vit K
Sepsis = sepsis 6
What is chronic liver failure?
Progressive liver disease over 6+ months due to repeated liver insults
What are the causes of chronic liver failure?
ALD - mc
NALD
Viral - hep BC
+ metabolic, Budd chiari, drugs, autoimmune, PBC, PSC
What is the pathology of chronic liver failure?
Hepatitis/ Cholestasis –> fibrosis(reversible damage) –> cirrhosis (irreversible) -> either compensated or decompensated (ESLF)
What is the Child Pugh score?
Assessing prognosis and extent of Tx required for chronic liver failure; essentially decompensated cirrhosis
-Classes scores ABC
What consists of the child Pugh score?
- billirubin
-ascites presence
-serum albumin
-PT/INR
-Hepatic encephalopathy
What are the ABC Child Pugh class system?
A = 100% 1year survival
B=80% 1 year survival
C=45% 1 year survival
What is Meld score?
Model for end stage liver disease, stratifies severity of ESLD for transplant planning
What is a risk factor for developing HCC?
ESLF - decompensated cirrhosis
What is the presentation of decompensated ESLF?
- jaundice
-HE
-Coagulopathy
-Ascites
-Portal HTn +oesophageal varices
-low serum albumin
What are the patient symptoms of chronic liver failure?
- jaundiced
-Ascites
-HE
-Portal HTN+ oesophageal varices
-Caput medusae
-Spider nave
-Palmar erythema
-clubbing
-fetor hepaticus
What is the diagnosis of chronic liver failure?
Liver biopsy - GS - needed to determine extend of CLD (fibrosis vs cirrhosis)
-LFT,Imaging,USS, ascitic tap culture
What is the treatment of chronic liver disease?
-Prevent progression - lifestyle modifying (low alcohol, low BMI, avoid drugs)
-Consider liver transplant (if decompensated liver)
-Manage complications
HE- lactulose
Ascites- diuretics
Oesophageal varices rupture
What is alcoholic liver disease?
Liver disease caused by excessive alcohol intake - most common cause of liver failure
What are the risk factors of alcoholic liver disease?
-chronic alcohol
-obesity
-smoking
What is the pathology of alcoholic liver disease?
Steatosis (fatty liver, undamaged) -> alcoholic hepatitis (with mallory bodies) -> Alcoholic cirrhosis (micro nodular)
What is the presentation of alcoholic liver disease?
-Early stages may show very little symptoms/ signs
-Later more severe stages = chronic liver failure Sx + alcohol dependency
- Jaundice, hepatomegaly, palmar erythema, Dupuytren contracture , ascites, HE, spider naevi, caput medusae, easy bruising
What does an alcohol dependency questionnaire include ?
CAGE and audit
- 10 questions alcohol use disorder test
-2 or more = dependent
What is the diagnosis of alcoholic liver disease?
Bloods - LFT= high bilirubin, low albumin, high PT, high GGT(AST:ALT >2)
-FBC = macrocytic non megaloblastic anemia
Biopsy needed confirm extent of cirrhosis
- inflammation, necrosis, mallory cytoplasmic inclusion bodies
What is the conservative treatment of alcoholic liver disease?
Conservative = stop alcohol - give diazepam for delirium tremors + with drawl Sx
-healthy diet, low BMI
What are the withdrawal Sx of alcohol?
Tremors
Agitation
ataxia
Disorientation
What is the pharmacological treatment for alcoholic liver disease?
Steroids short term
B1 + folate supplements
Maddrey’s discriminant - severity of ALD + treatment requirements
What is the surgical treatment for ALD?
Liver transplant for ESLF cases- abstain for 3+ months from alcohol before consideration
What are the complications and treatments for ALD?
Pancreatitis = IgE smashed
HE - lactulose
Ascites- diuretics
HCC- chemo/surgery
Mallory weiss tear
Wernicke Korsakoff syndrome
What is Wernicke Korsakoff syndrome?
Combined B1 deficiency (alcohol causes B1 deficiency ) and alcohol withdrawal Sx - ataxia, nystagmus, encephalopathy
What is the treatment for wernicke Korsakoff syndrome?
IV Thiamine
What is non alcoholic liver disease?
Chronic liver disease not due to alcoholism, results from fat deposition
What are the risk factors of NAFLD?
obesity
HTN
Hyperlipidemia
T2DM
FHx
Endocrine disorders
Drugs - NSAIDs/amiodarone
What is the pathology of NAFLD?
Hepatosteatosis (NAFLD) -> non alcoholic steatohepatitis -> fibrosis -> cirrhosis
What is the presentation of NAFLD?
typically aSx; any findings are incidental initially
- if very severe present with signs of liver failure
What is the diagnosis of NAFLD?
Bloods -deranged LFTs
(high PT/INR, low albumin, high bilirubin)
FBC - thrombocytopenia, hyperglycaemia
Imaging- 1st line for suspected NAFLD = USS abdomen
Assess risk of fibrosis with non invasive scoring system therefore avoid invasive biopsy
What is the treatment for NAFLD?
Lose weight (low BMI) and control risk factors :
-statins
-metformin
-ACEi
VITAMIN E - improves steatotic/ fibrotic liver appearance
What are the complications of NAFLD?
- HE
-Ascites
-Portal HTN
-Oesophageal varices
What is viral hepatitis?
Inflammation of the liver as a result of viral replication within the hepatocytes
What is hepatitis A?
-Acute, mild, positive strand RNA
-Faeco-oral spread
-Picornavirus
-associated with travel, endemic in Africa
-notifiable disease
What are the risk factors of HEP A?
- overcrowding
-poor saturation
-shellfish
-travel
What is the pathology of HepA?
incubation for 2 week - replicated in liver and excreted in bile
- then self limiting within 6 weeks
What is the presentation of hep A?
- prodomal phase (1-2weeks)- malaise, n+v, fever
-Then jaundice, dark urine, pale stools, hepatosplenomegaly
What is the diagnosis of hep A?
Bloods = raised ESR + leukopenia
LFT= raised bilirubin when icteric
HAV serology = HAV IgM = acutely infected
What is the treatment for HepA?
Supportive - travellers vaccine available
What is a complication of hep A?
Fulminant liver failure
What is HEP E?
-Acute, ssRNA
-faecal-oral spread
-calcivirus
What is the epidemiology of HEP E?
- commoner than HAV in UK
- associated with undercooked pork
-common in inso-china
what is the presentation of of hep E?
usually aSx
Self limiting
What are the complications of HEP E?
- can cause chronic disease in immunosuppressed
-can cause fulminant liver failure
-normal mortality 1-2%
-in pregnant ladies 10-20%
What is the diagnosis of HEPE?
HEV IgM- acutely infected
What is the treatment for hep E?
supportive
self limiting
vaccine only in china
What is HEP D?
Acute + chronic , SSRNA
Blood Bourne - sex/IVDU
What is the pathology of hep D?
unable to replicate on its own, requires HBV for assembly
- manifests as a co-infection
What is the diagnosis of hep D?
serology = IgM HDV +IgM HBV
What is the treatment for Hep D?
Same as Hep B
What is Hep B?
-Acute + chronic
-dsDNA
-bloodbourne
-hepadnavirus
What is the epidemiology of Hep B?
-presents worldwide
what is the transmission of Hep b?
needles
sexual
vertical - mother to child
horizontal - between children
HBV found in semen and saliva
What are the risk factors for hep B?
IVDU
MSM
Dialysis patients
Healthcare workers
What is the presentation of hep B?
1-2 week prodome
- jaundice, dark urine , pale stools, hepatosplenomegaly , urticaria, arthralgia
-incubation 1-6months
What is the diagnosis of hep B?
serology = HBV DNA - direct count of viral blood
- HBVsAg = present for 1-6 months of infection
-HBsAB= present after 6 months -denotes immunity
HBcAg= exposed to hep B at some point
HBcIgM = acute infection
HBCIgG = chronic infection/carrier
HBeAg = marker of patient infectiousness - acutely infected
HBeAb= in all ironically affected patients or if they have cleared
AntiHBsAg = cleared/ vaccine
What are the complications of hep B?
- 5-10% cases will progress to chronic liver failure +HCC risk
-90% cases in children become chronic decompensated = poor prognosis and need a transplant
What is the treatment for Hep B?
SC Pegylated interferon alpha 2a -stimulates immune response
Antiviral treatment - tenofovir
What is HEP C?
- acute + chronic
-ssRNA
Blood bourne -IVDU - flavivirus
What are the risk factors of hep c?
- association with IVDU limited vertical + sexual transmission
What is the presentation of hep C?
often acutely aSX
- can be influenza like symptoms
- present later with chronic liver signs + hepatosplenomegaly
What is the diagnosis of hep C?
Serology:
HCVRNA =current infection
HCVAB =presents within 4-6 weeks of infection
What is the treatment for hep C?
Direct acting antivirals (DAA)
- oral ribavirin + NS5A/B inhibitors - needed for viral replication
What is the complication with Hep c?
30% cases progress to chronic liver failure - cirrhosis + HCC risk
What is autoimmune hepatitis ?
- aka lupus hepatitis
-rare
-causes lupus like rash
-adaptive immunity mounts autoimmune response vs hepatocytes
What are the risk factors of autoimmune hepatitis?
- females
-other autoimmune diseases
-viral hepatitis
-HLADR3/4
What is type 1 autoimmune hepatitis?
Type 1= Adult females 80% cases :
- ANA (anti nuclear antibody - found in other autoimmune diseases)
-ASMA( anti smooth muscle Ab)
What is type 2 autoimmune hepatitis?
Type 2 =young females - rare
-ALC-1 (anti liver cytosol)
-ALKM-1 (anti liver-kidney microsomal)
What is the presentation of autoimmune hepatitis?
-25
-aSx
-many = jaundice, fever, hepatosplenomegaly
What is the diagnosis of autoimmune hepatitis?
Serology (ANA,ASMA +/- ALC-1/ALKM-1)
What is the treatment for autoimmune hepatitis?
Corticosteroids (prednisolone) + azathioprine
-Hep A/B vaccination
- transplant = last resort
What is jaundice?
AKA icterus - yellowing of skin, eyes due to accumulation of conj/unconj bilirubin. Sign of liver dysfunction.
What are the causes of jaundice?
Pre hepatic
Intrahepatic
Post hepatic
what is pre hepatic jaundice?
- unconjugated hyperbilirubinemia due to increase in RBC breakdown;
Haemolytic anemias:
-sickle cell
-G6PDH def
-Autoimmune haemolytic anemia
-Thalassemia
-MAlaria
What is intra hepatic jaundice?
conjugated/ unconjugated hyperbilirubinemia, may be mixed
Parenchymal disease( failure of hepatocytes to take up metabolise or excrete bilirubin):
-HCC
-ALD/NAFLD
-Hepatitis
-Hepatotoxic drugs
-Gilbert syndrome
-crigler nijjar syndrome
What is Gilbert syndrome?
-Auto recessive mutation of UGT1A1 gene; low UGT enzyme therefore low conj billirubin and high unconj so sometimes classed as pre hepatic
Typical patient = young male with painless jaundice, sudden onset
-Okay without treatment
What is crippler nijjar syndrome?
Auto recessive absence of UGT, more rare than Gilberts
More severe - Jaundice with N+V
Can die from kernicterus - accumulation of bilirubin in basal ganglia causing neurological deficits
Tx= phototherapy - breaks down unconj bilirubin
What is post hepatic jaundice?
Conjugated hyperbilirubinemia due to biliary obstruction :
Biliary tree pathology:
-Choledocholithiasis (stone stuck in cBD)
-pancraetic cancer
-cholangiocarcinoma
-PBC/PSC
Pale stool + dark urine
Why is there pale stools and dark urine in obstructive?
As conjugated bilirubin affects stool and urine
- conj -hyperbilirubinamia high in blood and low in intestine therefore less effect on stool -stercobilin
pee - urobilin
What is Courvoisier sign?
painless jaundice + palpable gall bladder
- most likely in pancreatic cancer
What is charcot’s triad?
Fever
RUQ pain
Jaundice
What is Reynold pentad?
present in ascending cholangitis
-Fever, RUQ pain, Jaundice, confusion , hypotension
What is Murphy signs?
RUQ tenderness, ask patient to take a breath in while pressing on RUQ; will see them whince - cholecystitis
What is the diagnosis for jaundice?
Imaging USS - 1st line
Bloods + LFTs = bilirubin, albumin, PT/INR,AST,ALT,GGT,ALP
Urine bilirubin =normally negative , positive (dark urine)in obstruction /hepatic disease
Urine urobillinogen = normally positive - high in haemolysis/pre, low in intra/post hepatic
What is pancreatic cancer?
Adenocarcinoma of exocrine pancreas of ductal origin typically affecting head
What is the epidemiology of pancreatic cancer?
- males, 60+
-head -60%
-body-25%
-tail -15%
What are the risk factors of pancreatic cancer?
smoking
alcohol
DM
FHx
Chronic pancreatitis
Genetic predisposition - PRSS-1 gene mutation
What is the pathology of pancreatic cancer?
Head= courvoiser sign (painless jaundice, palpable GB) with pale stool and dark urine
Body +tail. =epigastric pain radiating to back, relieved by sitting forward
May show trousseau sign of malignancy - episodes of vessel inflammation + clots in parts of body
What is the diagnosis of pancreatic cancer?
suspected pancreatic cancer = pancreatic CT - GS/diagnostic
1st line abdo USS
CA19-9 tumour marker positive = monitor disease progression
What is the treatment of pancreas cancer?
-poor prognosis - 5y survival - 3%
- surgery+post op chemo if no mets
-otherwise palliative
What are the types of liver cancers?
primary - least common. :
- hepatocellular carcinoma
-cholangiocarcinoma
-benign
Secondary - most common:
-GIT, breast, bronchial
What is hepatocellular carcinoma?
- arise from liver parenchyma
-90% all primary liver cancers
-males
What are the risk factors of hepatocellular carcinoma ?
-chronic hepatitis virus c+b
-cirrhosis from ALD/NAFLD/haemochromatosis
What is the pathology of HCC?
- metastases to lymph nodes, bones, lungs via haematogenous spread (hepatic/portal vein)
What is the presentation of HCC?
- signs of decompensated liver failure. - jaundice, ascites, HE and cancer signs - weight loss, fatigue
-irregular hepatomegaly
What is the diagnosis of liver HCC?
may show high serum AFP
Imaging. = 1st line USS
GS CT
biopsy avoided prevent seeding of tumour
What is the treatment of HCC?
surgical resection of tumour
When develop cirrhosis/ decompensated = liver transplant
Prevention - HBV vaccination
What is cholangiocarcinoma?
arises from biliary tree, typically adenocarcinomas
- 10% of all liver cancers
What are the risk factors of cholangiocarcinoma?
parasitic fluke worms , biliary cysts, IBD, PSC
What is the presentation of cholangiocarcinoma?
- abdopain , jaundice , weight loss, pruritus, fevers, may be courvoiser sign
Late constellation of Sx as slow growing tumour
What is the diagnosis of cholangiocarcinoma?
1st line imaging - abdo USS +CT
GS = ERCP (imaging of biliary tree) - obtain sample for biopsy/ diagnostic
can also stent strictures present in biliary tree
-High CEa/ high CA19-9
-LFT = high bilirubin, high ALP
What is the treatment for cholangiocarcinoma?
Majority of cases unrepairable as patients present very late
What are primary benign liver tumours?
Haemangioma (mc seen in infants as ‘strawberry mark on skin”
Hepatic adenoma
What are the secondary liver tumours?
- more common than primary tumours
- from GIT,Lungs, breast so Px variable depending on site of primary tumour
What is the diagnosis of secondary tumour ?
High serum ALP
Imaging - 1st line USS
GS CT/MRI for staging and primary tumour
What is the treatment of secondary lung tumours?
surgical resection if possible , chemo
What are the biliary tract diseases?
- gallstones
-cholecystitis
-ascending cholangitis
What are the risk factors of biliary tract disease?
fat, female, forty, fertile , FHx,, T2DM, NAFLD
What are gallstones?
stones made from supersaturation of bile made of cholesterol, pigment or both
What is the presentation of gallstones?
-RUQ ‘biliary colic’(constant severe episodes of pain 30+ minutes)
-worse after a fatty meal
What is the diagnosis of gall stones?
1st line - Abdo USS - iD gallstones
What is the treatment for gall stones?
- elective laparoscopic cholecystectomy if symptomatic
- until then - NSAIDs/ IM diclofenac
-lifestyle change , reduce fats
What is cholecystitis?
inflammation of the gall bladder
What is the presentation of cholecystitis?
-RUQ pain + fever , tender gall bladder
- may have referred pain to tip of right shoulder ; phrenic
-murphy sign positive ; press on GB and ask patient to inhale = whince
What is the diagnosis of cholecystitis?
FBC - leukocytosis + neutophilia
LFT- normal
Abdo USS shows thickened GB wall >3mm
What is the treatment for cholecystitis?
- surgery within one week - typically done within 72hr
-laproscopic cholecystectomy
Until then = IV fluid, analgesia, Abx if needed
What is ascending cholangitis?
Inflammation of the bile duct system - bile isn’t flushing out due to blockage so bacteria can climb up the ducts
What is the presentation of ascending cholangitis?
RUQ pain ,Fever, jaundice - charcot’s triad
- dark urine + pale stool
Reynolds pentad - confusion , altered mental state , hypotension
What is the diagnosis of ascending cholangitis?
FBC - leukocytosis + neutrophilia
LFT = high conjugated hyperbilirubinemia
Abdo USS - 1st line= CBD dilation +gall stones
MRCP - GS= diagnostic and best pre intervention management
What is the treatment fir ascending cholangitis?
ERCP (bile duct clearance) then laparoscopic cholecystectomy once stable
- consider risk of sepsis - biliary obstruction , E.coli from intestines can climb up through AOV and colonise biliary tree
What is MRCP?
magnetic resonance cholangio pancreatography
What is ERCP?
Endoscopic retrograde cholangio - pancreatography
What is Primary biliary Cholangitis/ Cirrhosis? (PBC)
Intrahepatic autoimmune jaundice affecting interlobular bile ducts
Women , typical autoimmune
What are the risk factors of PBC?
Female
40-50 year old
Other autoimmune disease -SLE, Sjorgens
Smoking
- more common than PSC
What is the pathology of PBC?
Autoantibodies cause interlobular bile duct damage ; chronic autoimmune granulomatosis inflammation
Resulting in cholestasis -> fibrosis, cirrhosis, portal HTN, infection
What is the presentation of PBC?
initially often aSx, routine test shows high AMA (anti mitochondrial Ab’s)
- pruritus + fatigue earliest , then jaundice , then hepatomegaly, Xanthelasma
What is the diagnosis of PBC?
USS - 1st line to exclude extrahepatic cholestasis
LFT = high ALP, high Conj bile, low albumin
Serology = AMA
Liver biopsy - granulomatosis/ portal tract infiltrate, portal tract fibrosis
What is the treatment for PBC?
1st line - improves Sx- ursdeoxycholic acid lifelong (bile acid analogue, dampens immune response and decreases cholestasis)
For pruritus - colestyramine
Vit ADEK supplements
What are the complications of PBC?
cirrhosis, malabs of fats +ADEK therefore stearrhoea , osteomalacia , coagulopathy
What is pruritus?
excess conj bilirubin excess concentration so can leak out + cause skin to itch
What is Primary sclerosing cholangitis? (PSC)
Autoimmune destruction of intra and extra lobular hepatic duct
- men (atypical)
What are the risk factors of PSC?
male, 40-50, strong link to IBD (UC)
What is the pathology of PSC?
Same as PBC but affects more ducts..
Autoantibodies cause extra/ interlobular hepatic duct damage ; chronic autoimmune granulomatosis inflammation
Resulting in cholestasis -> fibrosis, cirrhosis, portal HTN, infection
What is the presentation of PSC?
initially aSx, then pruritus, fatigue, jaundice , Charcot triad (if CBD involved ), hepatosplenomegaly , IBD
What is the diagnosis of PSC?
LFT
Serology : AMA neg - coeliac neg
pANCA positive
GS imaging - MRCP
What is the treatment for PSC?
Conservative Sx management
- Colestyramine for pruritis
-Fat soluble ADEK
-consider liver transplant
