Liver Flashcards
What are the functions of the liver and the consequences of this with liver failure?
1) Stores carbohydrate and glucose homeostasis - therefore hypoglycaemia
2) Albumin production - hypoalbuminemia - oedema, ascites and leukonuchia
3) Ferritin production - macrocytic anaemia
4) Drug metabolism via cp450 system - therefore altered drug metabolism
5) Bilirubin metabolism and secretion - jaundice and pruritus
6) Oestrogen breakdown
- gynaecomastia, loss of male pattern hair, palmar erythema, dupretrons contracture, spider naevi, testicular atrophy and ED
7) completement cascade
- infections
8) clotting factors
- bruising and bleeding easily
9) ammonia excretion
- encephalopathy, asterixis and hepatic foetor
10) portal hypertension - splenomegaly, oesophageal varices, caput medusae
Causes of hypoglycaemia
EXPLAIN
Exogenous drugs - insulin/hypoglycaemics, quinolones, quinines, alcohol, pentamidine
P - pituitary insufficiency - no GH or cortisol
L - liver failure
A - adrenal insufficiency - no cortisol
I - insulinomas - immune hypoglycaemia
N - non-pancreatic neoplasms
Malaria
Symptoms of acute liver disease?
Symptomatic is often viral
Generalised symptoms of malaise, anorexia and fever
Jaundice may appear as illness progresses
Symptoms of chronic liver disease?
Right hypochondrial pain due to liver distension
Ascites
Ankle swelling
GI haemorrhage - haematemesis or melaena
Pruritus
Signs of hyper-oestrogen
Encephalopathy signs
Signs of liver disease?
Jaundice, xanthelasmas, spider naevi, loss of body hair, gynaecomastia, liver (small or large), splenomegaly, caput medusae, ascites
Palms - erythema, clubbing, duputrens and xanthomas
Scratch marks from pruritus. Bruising
Oedema
Testicular atrophy
Liver flap, confusion - encephalopathy
Hepatic foetar
What serum bilirubin is needed for jaundice to be detectable clinically?
> 50umol/L
3 types of jaundice
Pre-hepatic - usually haemolytic
Hepatic - hepatitis (alcohol, drugs, viruses, ischaemic, cirrhosis)
Post-hepatic - obstructive - cholestatic
Causes of obstructive jaundice x5
Gall stones Sclerosing cholangitis (PSC) Biliary stricture Carcinoma of bile duct, pancreas head, ampulla of vater Pancreatitic pseudocyst
Presentation of intra and post-hepatic jaundice
Pale stools and dark urine - conjugated
Questions to ask if Hep B jaundice suspected?
Country of origin Generally a shorter history of presentation IVDU, tattoos, injections Male-male sex Female sex workers Blood transfusion
Questions to be asked if Hep C jaundice suspected?
IVDU, injections, tattoos, blood transfusion
Question to ask if Hep A jaundice suspected?
Recent consumption of shellfish, recent outbreak of jaundice in the community
Recent travel as regions have high risk Hep A
Other questions to ask jaundice for non-hepatitis causes?
Recent anaesthetic - halothane Family history Recent biliary tract/carcinoma surgery Environment Fevers or rigours - cholangitis/liver abscess Alcohol history
Different types of hepatomegaly
Smooth tender liver - hepatitis with extrahepatic obstruction
Knobbly irregular - metastases
USS when is it useful
In jaundice
Shows bile ducts and sizes
Level of obstruction
Cause of obstruction in virtually all tumour patients and 75% of gallstones
Way to approach jaundice in an older patient with no risk factors for hepatitis + weight loss
USS (also do liver biochem and viral markers)
If USS is normal - do viral markers. If positive then treat hepatitis.
If USS and viral markers are negative - re-check drug history, autoantibodies test and possible biopsy
If USS shows infiltration, tumour or mets - do liver biopsy
If USS shows CBD dilatation - treat gallstones if found or if other biliary obstruction then do MRCP
Way to approach jaundice in a young patient with risk factors for hepatitis
Viral markers (liver biochem) If negative then do USS - treat same as in elderly with CBD dilatation or nothing on USS - autoantibodies and recheck drug history
If viral markers positive then treat hepatitis
Liver biochemistry high in obstructive liver disease
ALP and ggt
Liver biochemistry high in hepatitis
AST and ALT
Definition of hepatitis
Inflammation (swelling) of the liver
Why do you get dark urine in jaundice?
Pumps in small bile ducts are defective in the liver disease which cause jaundice
Conjugation is easily done - therefore this continues even in damaged liver
For bilirubin to appear in urine it must be conjugated because unconjugated bilirubin is bound to albumin which is not secreted in the urine
When small bile duct pumps are damaged, bilirubin passes into the bloodstream and then gets cleared by the kidneys in the urine - this can also happen if obstructive
Which viruses can cause viral hepatitis?
CMV, EMV, Hep A-E
Which virus is CMV?
Herpes virus 5 - DNA virus
How many people infected by CMV in UK?
90% by age of 16 - lifelong infection
Presentation of CMV infection?
Often asymptomatic in immunocompetent
Can get glandular fever type symptoms with mild hepatitis (deranged LFTs)
More dangerous in infants or immunosuppressed
What do IgG and IgM mean on serology?
IgG - infection has occured
IgM - recent infection or reactivation
Which virus is EBV?
Herpes virus 4 - DNA virus lifelong infection
Proportion of EBV infection?
50% of 5 year olds and 90% of adults
Presentation of EBV infection?
Immunocompetent - glandular fever illness - on first infection
Immunosuppressed
- PUO - post transplant lymphoproliferative
What cancers are EBV associated with?
Burkitt’s lymphoma, Hodgkin’s lymphoma, nasopharyngeal carcinoma, oral hairy leukoplakia in HIV
Hep A transmission and incubation period
Faecal oral or shellfish, 15-50 days
Once showing symptoms - no longer infective
Presentation of Hep A infection
Usually children get it, asymptomatic, build up immunity and not come back
In adult, very bad presentation of fever, malaise, anorexia, nausea - followed by jaundice, hepatosplenomegaly and adenopathy
Tests in Hep A infection
AST and ALT rise 22-40 days after exposure and ALT very high >100
Will return to normal over 5-20 weeks
Mortality with Hep A
Low
Treatment of Hep A
Supportive, avoid alcohol
Vaccination Post exposure prevention in Hep A
HAV vaccine (Havrix monodose) given if travelling to endemic areas and for people with chronic liver disease, haemophilia or those who work in contact with people with hep a
Vaccinate someone if within 2 weeks of exposure
Hep B number of deaths per year
1 million
Where is Hep B endemic?
Far east, africa and mediterranean
Incubation period for Hep B
1-6months
Transmission of Hep B
IVDU, tattoos, sex, blood exposure (transfusions)
Mother to child and child to child transmission is most common cause of it in endemic areas
Acute hep B presentation
Similar to hep a - nausea, anorexia, fever, malaise
- Most people get unwell, ALT rise, jaundice and body fights within 6 weeks
Will remain okay unless immunosuppressed
Chronic Hep B pathology and presentation
Have infection (can be mild or symptomatic initial infection) but body doesn’t clear it
As you get older body will recognise virus and try and fight it
Get infection and fibrosis and vicious circle
Therefore it is not cytopathic but immune response causes damage
Consequences of Hep B
Directly oncogenic - HCC - 80% of all HCC in Asian Americans
Also causes cirrhosis and liver disease
How infectious is Hep B?
50-100x more infectious than HIV
Hep B markers
HbsAg - Hep B surface antigen - diagnostic test - present 1-6months after exposure and >6 months is carrier status
E antigen - AbeAG - virus makes it, does nothing to human host but implies they are very infective
Hep B DNA and viral load - another indication of infectivity
Surface antibodies - show that person has been shown antibody and built up immunity
Chance of reactivation of Hep B
If chemotherapy - will reactive
Also with steroids
Risk continues 6 months post-treatment
Treatment of Chronic Hep B - if liver damage
Interferon for a year - increase immune control
Tenofovir/entecavir - viral control - may be needed life long
Places Hep C most prevelant
North Africa, Central Asia and Middle East
Egypt and Pakistan have epidemics because of poor vaccination programs
Transmission of Hep C
Blood bourne therefore percutaneous exposure
IVDU, unsafe vaccination, tattoos
Presentation of Hep C virus
Most do not get symptoms (similar to HAV and HBV)- if they do it means clearing it
85% develop chronic hepatitis
Risk with Hep C
25% get cirrhosis and 4% get HCC
Tests in Hep C
LFT changes with cirrhosis - exclusion of other viruses
Anti-HCV antibodies confirms exposure - usually positive 8 weeks from infection
HCV RNA can be detected 1-8 weeks after infection on HCV-RNA PCR
Treatment of Hep C virus
Stop alcohol
Interferon
Sofosbuvir - RNA polymerase inhibitor
Lots of new drugs coming out
Features of Hep A and E infection
faecal-oral transmission
don’t really get chronic phase - unless immunocompromised and then you can
Hep D virus features
Small RNA virus - requires Hep B to replicate
Co-infection - two at the same time, clinically indistinguishable from acute HBV infection
Superinfection if you get the two at the same time - acute flare up of Hep B
Hep D transmission
Blood bourne therefore mostly IVDU in Uk but can affect any at risk of Hep B
Chronicity of Hep D
Relatively infrequent but spontaneous resolution is rare - most develop cirrhosis more rapidly than with Hep B alone
in 15% rapidly progressive to cirrhosis
Treatment for Hep B patients with active liver disease
Detected from raised ALT or inflammation on biopsy
Given interferon and adefovir
Hep E virus features
RNA virus causing hepatitis clinically very similar to hep A
Enterally transmitted usually by infected water
Endemics in many developing countries and some developed countries where patients had contact with farm animals
Other viral hepatitis with liver failure but more with liver abnormalities
Malaria, dengue, yellow fever
Infections with deranged LFTs
Avian flu
Q fever, legionella, mycoplasma
Leptospirosis
Rickettsial illness
Female to male ratio of autoimmune hepatitis
F:M = 4:1
Presentation age of autoimmune hepatitis
Bimodal - 10-30 years and post-menopausal
Presentation of autoimmune hepatitis in young population - teens and early 20s
Acute hepatitis with jaundice and very high ALT and AST
- Clinical features of cirrhosis with hepatosplenomegaly, acne, hirsutes, bruises and sometimes ascites
Can also have features of autoimmune disease
Presentation in peri/post-menopausal group
Asymptomatic and found over liver biochemistry
Or because of fatigue
Or because of signs of chronic liver disease on routine examination
Biochemical findings on autoimmune hep
ALT and AST raised - lesser elevations in ALP and bilirubin
IgG high
Normochromic, normocytic anaemia with thrombocytopenia and leucopenia
Even before portal hypertension and splenomegaly
Two types of autoimmune hepatitis
AH1 = Type 1 with antibodies - 80% - Anti-nuclear antibody (ANA) - Anti-smooth muscle (ASMA) - Soluble liver antigen (SLA) - More common in women and adults Good response to immunosuppression
AH2 - more common in children - europe >usa
LKM-1 +ve (anti-liver kidney microsomal type 1 antibodies)
ANA and ASMA -ve
More commonly progresses to cirrhosis and less treatable
Management of autoimmune hep
Immunosuppression treatment
Budesonide fewer side effects than prednisolone and now favoured
OR
Prednisolone - 30mg/day for 1 month
then slowly decrease it to a maintenance dose of 5-10
Can be stopped after 2 years but relapse common
Azothioprine - steroid sparing
Liver transplantation if really bad
Most common cause of cirrhosis in the west and worldwide?
West = alcohol Worldwide = viral infection
What are the characteristic pathological features of cirrhosis?
Regenerating nodules of inflammation, necrosis and fibrosis.
Nodules separated by fibrous septa and loss of normal lobular architecture within the nodules
What are the two types of cirrhosis which have been described?
Micronodular cirrhosis - regenerating nodules usually
What level of albumin is considered to be associated with poor outcome?
Liver biochem in compensated not very severe cirrhosis and in decompensated cirrhosis
If not very severe can be normal but usually at least a slight elevation in serum ALP and ALT, AST
In decompensated cirrhosis - all biochemistry is deranged
What serum creatinine is associated with worse prognosis?
> 130umol/L
What is scoring system in cirrhosis?
Child-Pugh classification
Grade A 10
Risk of variceal bleeding much higher if >8
Bilirubin
50 = 3 points
Albumin
- >35 = 1 point
- 28-35 = 2 points
-
When is endoscopy indicated in cirrhosis?
Detection and treatment of varices and portal hypertension gastropathy
Monitoring in patients with decompensated cirrhosis
6 monthly ultrasound to detect early development of HCC
Management of a patient with compensated cirrhosis
Restrict salt intake Avoid aspirin and NSAIDs Avoid alcohol (although if not due to alcohol or viral hep then can be had in small amounts)
Indications for liver transplant general
Patients with fulminant hepatic failure
Chronic liver disease - cirrhosis no longer responsive to therapy
All with Child grade C should be referred to transplant clinic
Indications for liver transplant - PBC
Serum bilirubin persistently >100umol/l
Or intolerable symptoms eg. itching
Indications for liver transplant Chronic Hep B
If HBV DNA negative or levels falling under therapy
Prevent recurrence with hep B immunoglobulin and nucleoside analogues
Indications for liver transplant Chronic Hep C
Most common indication for transplant
Reinfection and cirrhosis occurs in 10-20% at 5 years - can give antivirals to delay progression
Indications for liver transplant autoimmune hepatitis
Failed to respond to medical therapy or major side-effects of corticosteroid therapy
Can reoccur
Indications for liver transplant - alcoholic liver disease
Well-motivated patients who have stopped drinking
Contraindications for liver transplant
Patients with active sepsis outside hepatobiliary tree Malignancy outside liver Liver mets Not psychologically committed Age >70 not usually transplanted HCC recurrence rate is high unless
Rejection in liver transplantation
Acute/cellular rejection - usually seen 5-10 days post transplant . Can be asymptomatic or can be a fever. Responds to immunosuppresive therapy
Chronic ductopenic rejection - seen 6 weeks-9 months post-transplant, disappearing bile ducts (vanishing bile duct syndrome) and an arteriopathy with narrowing and occlusion of arteries. Early may be reversed with immunosuppression but often requires retransplantation
Prognosis with liver transplantation
Require lifelong immunosuppression
90% 1 year survival
70-85% 5 year
Most disease recurrence in HCV cirrhosis, PSC and HCC
Main sites of collaterals following portal hypertension? (and cause)
Venous system dilates following increase in portal pressure - collaterals occur within the systemic venous system
Gastro-oesophageal junction - most likely to give symptoms
Rectum
Left renal vein
Diaphragm
Retroperitoneum
Anterior abdominal wall via umbilical vein - caput medusae
Cause of prehepatic portal hypertension?
Portal vein thrombosis - cause often unidentified but some due to congenital/inherited defects - eg. prothrombotic conditions
Intrahepatic causes of portal hypertension?
Usually cirrhosis
Schistosomiasis
Other rarer causes exist
Post-hepatic causes of portal hypertension
Budd-Chiari syndrome
Prolonged severe heart failure
Clinical presentation of portal hypertension
Features of chronic liver disease
Splenomegaly
Often asymptomatic
Variceal haemorrhage
Occurrence of variceal haemorrhage
90% of cirrhosis patients get gastro-oesophageal varices over 10 years - but only 1/3 will bleed from them
Management of acute active bleeding episode in variceal bleeding
Resus - IV line for bloods, restore blood volume with plasma expander or blood transfusion
Only target HB of 80g/l
Ascitic tap
Monitor alcohol withdrawal - thiamine
Start prophylactic ab’s - cephalosporins eg. cefotaxime - treat and prevent infection and early rebleeding - reduce mortality
Send for urgent endoscopy to confirm diagnosis - banding or injection sclerotherapy
Give vasoconstrictor therapy - restrict portal inflow by splanchnic arterial constriction Terlipressin or somatostatin if first is contraindicated
Two options for stopping bleeding with endoscopy
Variceal banding - Band on tip of endoscope - suck varix in and then put band on
Scleropathy - inject varices with sclerosing agent
Two other therapies to control bleeding if banding/sclerosing is ineffective
Balloon tamponade or stenting
What to do if variceal bleeding can’t be stopped or early rebleeding occurs within 5 days
Transjugular intrahepatic portocaval shunt (TIPS)
Guidewire passed from portal vein to hepatic vein - total shunt past the liver - therefore reduces pressure
Long-term management of variceal bleeding
Beta-blockade - non-selective - propanolol
Should also be given to patients who have not bled but have cirrhosis and varices - do not prevent development of varices but prevents bleeding
Repeated courses of banding at 2 week intervals -obliterates varices (30-40% return per year therefore follow-up needed)
3 factors involved in ascites pathogenesis
1) Sodium and water retention - peripheral vasodilatation by nitric oxide, ANP and prostaglandins = activates sympathetic nervous system and renin-angiotensin system therefore sodium and water retention promoted
2) Portal hypertension - exerts local hydrostatic pressure - increased hepatic and splanchnic production of lymph and transudation of fluid into peritoneal cavity
3) Low serum albumin - reduction in plasma oncotic pressure - draws water out into abdomen
3 things as a result of accumulating fluid
1) Shifting dullness
2) Peripheral oedema
3) Pleural effusion - passage of ascitic fluid through congenital diaphragmatic defects
What would be found on ascites fluid aspirate if spontaneous bacterial peritonitus?
Neutrophil count >250 cells/mm3
Target of management in ascites?
Reduce sodium intake and increase renal excretion of sodium
This should produce net reabsorption of fluid from ascites into circulating volume
Maximum mobilisation of ascites is 500-700ml in 24hour
Management of ascites?
Monitor fluid chart
Restrict dietary sodium to 40mmol in 24hour - maintain protein intake
Stop drugs which contain sodium (antacids, antibiotics, effervescent tablets)
Avoid sodium retaining drugs - NSAIDs and corticosteroids
Diuretic - spironolactone - 100mg daily
If response poor - can increase spironolactone up to 400mg daily
Can also add furosemide
Non-medical management of ascites? x2
1) Paracentesis - no more than >5l removal because can cause hypovolaemia and renal dysfunction
Can overcome hypovolaemia but infusing albumin - 8g/l of ascitic fluid removed
2) Shunts - TIPD for resistant ascites - if no encephalopathy and minimal disturbance of renal function
Features of spontaenous bacterial peritonitis in ascites? Presentation and treatment
Complication of ascites with cirrhosis
Occurs in approx 8%
Pain and pyrexia frequently absent but suspect in ascites patient who clinically deteriorates
Treat with cephalosporin, eg. cefotaxime, ceftazidime
What is the chronic neuropsychiatric syndrome secondary to cirrhosis and why does it occur?
Portosystemic encephalopathy
Occurs due to shunting - either due to collaterals from portal hypertension or in patients with TIPS
This increases circulating levels of toxic metabolites such as ammonia, FFAs, amino acids, false neurotransmitters
Alters brain neurotransmitter balance
Presentation of PSE - acutely
Acute onset often has precipitating factor (high dietary protein, GI haemorrhage, constipation, infection, TIPS, drugs, development of HCC ) patient becomes increasingly drowsy and comatose
Presentation of PSE - chronically
Disorder of mood, personality and intellect
N+v, weakness
Signs: - fetor, flap, apraxia, decreased mental function
Diagnosis of PSE
Clinical
Management of PSE
Remove precipitating cause
Lactulose and enemas to empty bowel of nitrogenous substances
Maintain nutrition - do not restrict protein for >48hour
Antibiotics - rifaximin (metronidazole in acute setting)
Stop/reduce diuretic therapy
Increase protein in diet to the limit of tolerance as encephalopathy improves
When do you get hepatorenal syndrome? What sort of renal failure is it?
In patients with advanced cirrhosis, portal hypertension with jaundice and ascites
Functional renal failure - decreased renal output and low sodium concentration
Mechanism of hepatorenal syndrome
Similar to that of ascites
Peripheral vasodilatation activates homestatic mechanisms (symp NS and renin-angiotensin)
Cause sodium and water retention
There is also a decreased CO inappropriate to degree of vasodilatation
2 Pulmonary manifestations in cirrhosis
1) Hepatopulmonary syndrome - hypoxaemia occuring in patients with advanced liver disease - due to intrapulmonary dilatation
Normally no resp symptoms but cyanosis - low saturation of arterial blood - can become breathless on standing
2) Porto-pulmonary hypertension - pulmonary hypertension secondary to portal hypertension - occurs in 1-2% of patients
What happens in Primary Biliary Cirrhosis?
Interlobular bile ducts are damaged by chronic autoimmune granulomatous inflammation
This causes cholestasis
Can also lead to fibrosis, cirrhosis and portal hypertension
Prevalence of PBC
F:M = 9:1
Age range usually 40-50 years at presentation
7/100,000
What causes PBC?
Genetic predisposition but also unknown environmental triggers
Antimitochondrial antibodies (AMA) - M2 is specific to PBC
Clinical features of PBC?
Often asymptomatic and discovered on routine examination or screening
Pruritus and fatigue often precede jaundice by a few years
Hepatomegaly will be present by the time jaundice appears
Signs of high cholesterol can also be seen
Tests in PBC
Mitochondrial antibodies seen in 95% -M2 specific
ALP raised may be only liver biochem abnormality originally
High serum immunoglobulins - IgM and cholesterol
Low albumin and high bilirubin
Ultrasound
Liver biopsy not needed but would show histological features of a portal tract infiltrate
DDX of PBC
Autoimmune hepatitis
Extrahepatic biliary obstruction
Schistosomiasis
Treatment of PBC
Ursodeoxycholic acid/Ursodiol - improves bilirubin and ALT + AST values but no symptomatic improvement
Vitamin supplementation of fat soluble vitamins - A, D, E, K
Cholestyramine for pruritus
Naltrexone and rifampicin may help pruritus
Liver transplant
What is Primary sclerosing cholangitis? PSC
Chronic cholestatic liver disease characterised by fibrosing inflammatory destruction of both the intra- and extrahepatic bile ducts
What is PSC associated with?
IBD - usually UC - in 75% of patients
PSC can predate onset of UC
PSC more common in women or men?
Men
PSC age of onset
40 years
Presentation of PSC
Increasing frequency of being found incidentally in screening of UC patients
Pruritus, fatigue, jaundice
Can also get cholangitis
Diagnosis of PSC
Can be made with MRCP
Tests in PSC
ALP raised, then bilirubin raised
AMA -ve
But may be ANA, SMA, ANCA +ve
Treatment of PSC
Only proven treatment is liver transplant
Colestryramine might help pruritus
Treat cholangitis with antibiotics
When does secondary biliary cirrhosis occur?
Cirrhosis can occur after prolonged duct obstruction - bile duct strictures, gall stones and sclerosing cholangitis
Increased risks associated with PSC?
Bile duct, gall bladder, liver and colon cancers are all more common
Therefore yearly screening needed
Cholangiocarcinoma - occurs in 15%
What is hereditary haemochromatosis?
Inherited disorder of iron metabolism which results in excess deposition of iron in liver and pancreas
Also in joints, heart, pituitary, adrenals and skin
What causes hereditary haemochromatosis?- pathologically
HFE gene - interacts with receptor in intestine - transferrin receptor 1 - which mediates iron absorption
Also alters hepcidin protein - synthesised in the liver which controls iron absorption from gut. Increased in iron deficient states and vice versa.
Altered expression of this gene results in iron overload
Iron in liver causes fibrosis
Difference between men and women in HH?
Men present earlier with more overt disease - likely women protected by menstrual loss of iron
Prevalence of HH
Carrier rate of 1 in 10
Homozygosity = 1 in 200-400
Early presentation of HH
Nil or tiredness + arthralgia
Triad of severe HH presentation
Bronze skin pigmentation (melanin deposition), hepatomegaly and DM
Other HH symptoms
Pit dysfunction - hypogonadism
Heart - arrhythmia’s and HF
Arthropathy
Complications of HH
30% develop HCC
Tests in HH
LFTs often normal even with severe disease
Serum iron raised
Serum ferritin raised
Transferrin saturation >45%
High glucose (DM)
Imaging - joint deposition & MRI - iron overload
Liver biopsy
Management of HH
Venesection (removal of blood) needed for life every 2-3months
If can’t have venesection (anaemia, severe cardiac disease) can give deferoxamine - iron chelator
Low iron diet
Tea, coffee or red wine with meals helps decrease iron absorption (fruit juice or white wine - increase absorption)
What is Wilson’s disease?
Very rare inborn error of copper metabolism resulting in copper deposition in various organs (liver, basal ganglia)
Normally copper incorporated into apocaeruloplasmin forming caeruloplasmin - this then secreted into blood, rest excreted in faeces and bile
This incorporation doesn’t happen leading to decreased serum caeruloplasmin
But precise cause of copper deposition unclear
Presentation of Wilson’s disease
Children - hepatic problems
Young adults - more neurological problems - of basal ganglia - tremor, involuntary movements
Kayser-Fleischer rings - copper deposition in corneal membrane
Tests in Wilson’s disease
Serum copper and caeruloplasmin usually reduced but can be normal
Urinary copper increased usually
Liver biopsy - high copper levels
Treatment of Wilson’s disease
Lifetime treatment with penicillamine - chelating copper
1-1.5g daily
Monitor urine copper
What are the three pathological causes of the changes seen in alcoholic liver disease?
1) Acetaldehyde (breakdown product of alcohol) cannot be broken down due to ALDH saturation - powerful chemical agent - leads to production of neo-antigens on hepatocyte cell surface - immune-mediated hepatocyte killing
2) Increased NADH/NAD ratio - increased fatty acid synthesis & decreased fatty acid oxidation therefore hepatic accumulation of fatty acids
3) Impaired oxidation-reduction also impair carb and protein metabolism - cause necrosis of hepatocytes - tumour necrosis factor release leads to release of reactive oxygen species - tissue injury and fibrosis
4 stages of liver damage in alcoholic liver disease
1) Big liver - cell hypertrophy due to increase demand on liver
2) Fatty liver - Cells can become swollen with fat = steatosis
No liver cell damage yet, fat disappears if stop alcohol
3) Alcoholic hepatitis - leukocyte infiltration and hepatocyte necrosis. Can see Mallory Bodies sometimes
4) Alcoholic cirrhosis - classically micronodular regeneration - continued necrosis
Clinical features of fatty liver
Often no symptoms or signs
Can have hepatomegaly and some other features of chronic liver disease
Clinical features of alcoholic hepatitis
Mild-moderate symptoms of ill-health
Occasionally mild jaundice
Chronic liver disease signs
Liver biochem deranged
Can get jaundice and ascites if patient gets ill - abdominal pain and fever also
Clinical features of alcoholic cirrhosis
Final stage of liver disease but can be quite well
Usually signs of chronic liver disease and other alcoholic systemic features
Diagnosis of alcoholic hepatitis and cirrhosis
Biopsy
Investigations in fatty liver
MCV elevated often indicates heavy drinking
Liver biochem mild abnormalities
Gamma gt good for recent alcohol
Ultrasound or CT will show fatty infiltration
Investigations in alcoholic hepatitis
Leucocytosis - markedly deranged LFTs
Raised bilirubin, AST, ALT, ALP, PT
Low serum albumin may be found
Management of alcoholic liver disease
Stop alcohol
Treat delirium tremens with diazepam
IV thiamine to prevent Wernickes
Bed rest with high protein diet and vitamin supplements (may need to limit dietary protein if encephalopathy)
Steroid therapy might help alcoholic hepatitis
Treat encephalopathy and ascites
What is Budd-Chiari syndrome?
Obstruction of venous outflow of the liver - occlusion of the hepatic vein
Cause of BC syndrome
1/3 causes unknown
Can be hypercoagulablity states, thrombophilia, OCP, leukaemia
Compression from tumours (post abdo wall sarcoma, renal or adrenal tumour, HCC)
Hepatic infection
Presentation of acute BC syndrome
Abdominal pain
Nausea & vomiting
Tender hepatomegaly
Ascites
Chronic presentation of BC syndrome
Enlargement of the liver Mild jaundice Ascites Negative hepatojugular reflex Splenomegaly
Investigations in BC syndrome
High protein count ascitic fluid
Histology - congestion, haemorrhage, fibrosis and cirrhosis
Ultrasound, CT or MRI will show occlusion and abnormal parenchyma but caudate lobe spared because of independent blood supply and venous drainage
Doppler sonography
Treatment of BC syndrome
Acute - thrombolytic therapy
Treat ascites
TIPS
Chronic - liver transplant
Two types of liver abscess
Pyogenic abscess - bacteria
Amoebic abscess - amoeba
Previous most common cause of pyogenic liver abscess?
Portal pyaemia from intra-abdominal sepsis eg. appendicitis or gut perforations
Now many cases aetiology not known
Common cause of pyogenic abscess in elderly?
Biliary sepsis
Common organism for pyogenic abscess?
E.coli
Streptococcus milleri
Bacteroides
Can also be enterococcus faecalis, proteus vulgaris and staph aureus
Presentation of pyogenic abscess
Some can have malaise lasting months
or
Fever, rigours, anorexia, vomiting, weight loss, and abdominal pain
Patient can be jaundiced and have tender hepatomegaly
Investigations in pyogenic abscess
Often investigated as PUO
- will have raised ALP as only sign it is liver origin
Bilirubin may be raised
Raised ALP, ESR and CRP
Serum B12 is very high as vitamin B12 is stored in and subsequently released from the liver
Ultrasound and CT useful for diagnosis
Management of pyogenic abscess
Aspiration and antibiotics
Prognosis of pyogenic abscess
Depends on nature of pathology
Unilocular abscess better prognosis
Multiple scattered - very high mortality, 1 in 5 survive
When should you consider amoebic abscess?
Patient travelling from abroad
How do amoebic abscess occur?
Carried from bowel to liver via portal venous system
Presentation of amoebic abscess
Fever, anorexia, weight loss and malaise
Often no hx of dysentery
Tender hepatomegaly
Investigations for amoebic abscess
Same as pyogenic - bloods (ALP, CRP and ESR raised) serum B12 raised, ultrasound and CT
Serological tests for amoeba - always positive
Treatment of amoebic abscess
Metronidazole 800mg 3x day for 10 days
Aspiration in patients who fail to respond and large abscess
Complications of amoebic abscess
Rupture, secondary infection and septicaemia
What is the most common liver tumour?
Secondary metastatic tumour
Where to metastatic liver tumours usually come from?
GIT, breast, bronchus
Clinical presentation of liver mets
Weight loss & malaise
Upper abdominal pain
Hepatomegaly
+/- jaundice
Diagnosis of liver mets
Ultrasound
CT or MRI (look for primary)
ALP usually always raised
Treatment of liver mets
Depends on site and burden of liver mets
Chemotherapy or radiofrequency ablation of tumours
Are primary liver tumours usually benign or malignant?
Malignant
Prevalence of HCC
5th most common cancer worldwide
M>F
Risk of HCC
Cirrhosis in 95% of cases of HCC
HBV, HCV (risk higher with HCV than HBV - even higher with both)
Cirrhosis of other cause - alcohol, non-alcoholic fatty liver disease, haemochromatosis
Pathology of HCC
Can be single or multiple nodules throughout liver
Where does HCC metastasise to?
Lymph nodes, bones and lungs
Clinical features of HCC
Weight loss Anorexia Fever RUQ pain Ascites
Enlarged irregular tender liver may be felt
Investigations in HCC
Serum alpha-fetoprotein may be raised (normal in 1/3)
Ultrasound
CT and MRI
Tumour biopsy
Treatment of HCC
Resection of isolated lesions
What is a cholangiocarcinoma?
Cancer of mutated epithelial cells of bile ducts
Can be intra or extrahepatic
Associations of cholangiocarcinoma
Not associated with cirrhosis or Hep B
Presentation of cholangiocarcinoma
Similar to HCC - malaise, weight loss, RUQ pain, ascites
But also jaundice and cholangitis is more frequent
Prognosis of cholangiocarcinoma
Resection is rarely possible
Patients usually die within 6 months
Most common benign liver tumour
Haemangioma - of endothelial cells which line blood vessels
Usually small and single but can be large and multiple
Usually discovered incidentally on ultrasound, CT or MRI
Require no treatment
What causes increased risk of hepatic adenoma? Features and management
OCP
Present with abdominal pain or intraperitoneal bleeding
Resection for symptomatic patients, tumours >5cm or when stopping OCP doesn’t make it shrink
Prevalence of gallstones
Can be present at any age, unusual before 30’s
Increase prevalence with age
60-70s = 25-30%
90% remain asymptomatic
F>M
3 different types of gallstones
1) Cholesterol - 80% of those in western world
- Risk factor is age and obesity
- Usually large and solitary
2) Pigment stones
What is biliary colic?
Pain from temporary obstruction of cystic or CBD by a stone
Despite term “colic” - is severe but constant - crescendo characteristic
Symptoms of biliary colic?
Most common mid-evening lasting until early hours of morning
Usually epigastrium pain originally, may be RUQ
Radiation may go over right shoulder or to right sub-scapular region
N+V frequent with severe attacks
Cessation after several hours or with opiate analgesia
What causes acute cholecystitis?
Obstruction to gall bladder emptying, increased gall bladder glandular secretion and progressive distension
Inflammatory response to retained bile within the gall bladder
Presentation of acute cholecystitis?
Initially similar to biliary colic
Progresses to severe localised RUQ pain, tenderness and muscle guarding/rigidity
Complications of cholecystitis
Gall bladder can become distended with pus = empyema
Rarely an acute gangrenous cholecystitis develops - can perforate causing generalised peritonitis
Investigations in acute cholecystitis
Moderate leucocytosis and raised inflammatory markers
ALP and bilirubin raised
Abdominal USS - most useful investigation (can see gallstones and thickening of gall bladder wall)
DDX of biliary colic
IBS with hepatic flexure spasm Carcinoma of right side of colon Peptic ulcer disease - atypical Renal Colic Pancreatitis
DDX of acute cholecystitis
Pancreatitis
Perforated peptic ulceration
Intrahepatic ulcer
MI
Management of gall bladder stones
Cholecystectomy - lap chole
If acute cholecystitis - NBM, IV fluids, opiate analgesia and IV antibiotics - wait for inflammation to settle
If symptoms eg. due to empyema not improving can do radiologically placed gall bladder drain
If cholecystectomy is contraindicated
Can try stone dissolution - increase bile salt content of bile
Chenodeoxyocholic acid and ursodeoxycholic acid
Will require long-term therapy
Features of CBD stones
Biliary colic, fever and jaundice - triad only present in a number of patients (with cholangitis)
Usually just pain - sometimes jaundice
Investigations in CBD stones
Cholangitis - raised neutrophil count and raised ESR, CRP
Complete CBD obstruction - bilirubin >200, raised ALP and gamma gt
AST and ALT mildly raised, may be more if complete obstruction
Amylase high if stone related pancreatitis
Imaging for CBD stones
Ultrasound, CT, Endoscopic ultrasound scanning
Management of acute cholangitis
High mortality and morbidity especially for elderly
IV antibiotics and urgent bile drainage
Sphincterotomy + ERCP
Lap chole with exploration of CBD to remove stones
