Liver and Biliary Flashcards
Liver and Biliary
What are the three causes of jaundice?
Pre-hepatic
Hepatic
Post-hepatic
What is pre-hepatic jaundice?
Excess bilirubin due to excessive haemolysis
liver is fine but can’t conjugate fast enough
What is hepatic jaundice?
Impaired hepatocellular uptake, defective conjugation, or abnormal secretion of bilirubin
What is post-hepatic jaundice?
Impaired excretion due to a mechanical obstruction of the biliary flow
Which serum markers will be elevated in pre-hepatic jaundice?
Unconjugated bilirubin only (normal ALP/AST/ALT)
Which serum markers will be elevated in hepatic jaundice?
AST + ALT = sign of hepatocyte damage
Conjugated + unconjugated bilirubin may also be elevated (backlog- impaired metabolism)
Which serum markers will be elevated in post-hepatic jaundice (biliary disease)?
ALP + GGT = sign of cholangiocyte damage
Conjugated bilirubin
What are some signs of portal hypertension?
Oesophageal varices Splenomegaly Caput medusae Ascites Haemorrhoids
What are some signs of liver failure?
Asterixis Bruising Clubbing Dupuytren's contracture Erythema (palmar) Fetor hepaticus (breath of the dead) Gynaecomastia Hypertension (portal) Itching Jaundice Spider naevi/testicular atrophy (ABC...)
Which hepatitides are transmitted through the faecal-oral route?
Hepatitis A, E (can also spread by sex/contaminated water)
Which hepatitides are transmitted through bodily fluids?
Hepatitis B, C, D
What is the incubation period of Hepatitis A?
2 weeks
What is the incubation period of Hepatitis B?
4-12 weeks
What is the incubation period of Hepatitis C?
2 weeks - 6 months
What is the incubation period of Hepatitis D?
4-12 weeks
What is the incubation period of Hepatitis E?
5-6 weeks
What are the risk factors for Hepatitis A?
Poor hygeine
What are the risk factors for Hepatitis B?
Health workers
IVDU
M-M sexual relations
What are the risk factors for Hepatitis C?
IVDU
M-M sexual relations
What are the risk factors for Hepatitis D?
Only co-infects with Hep B
What are the risk factors for Hepatitis E?
Immunocompromised Pts
Pregnancy
Which hepatitides are at risk of chronic development?
Hepatitis B (in children) Hepatitis C (60-80%)
What are some generic symptoms of viral hepatitis?
Reduced appetite N+V Abdo pain Pruritus Skin rash Joint pain Jaundice Hepatomegaly Recent travel from Africa/East Mediterranean
What investigations would you do on a Pt with viral hepatitis?
LFTs FBC U+Es Antibodies NAAT (nucleic acid amplification test can indicate viral load)
What is the interpretation of the following HBV antibodies?
Anti-HBc IgM: -ve
Anti-HBc IgG: -ve
HbSAg: -ve
Anti-HBs: -ve
Not infected
What is the interpretation of the following HBV antibodies?
Anti-HBc IgM: -ve
Anti-HBc IgG: -ve
HbSAg: -ve
Anti-HBs: +ve
Not infected, with prior vaccination
What is the interpretation of the following HBV antibodies?
Anti-HBc IgM: -ve
Anti-HBc IgG: -ve
HbSAg: +ve
Anti-HBs: -ve
Early acute HBV infection
What is the interpretation of the following Hep B antibodies?
Anti-HBc IgM: +ve
Anti-HBc IgG: -ve
HbSAg: +ve
Anti-HBs: -ve
Acute HBV infection
What is the interpretation of the following HBV antibodies?
Anti-HBc IgM: -ve
Anti-HBc IgG: +ve
HbSAg: -ve
Anti-HBs: +ve
Resolved acute HBV infection
What is the interpretation of the following HBV antibodies?
Anti-HBc IgM: -ve
Anti-HBc IgG: +ve
HbSAg: +ve
Anti-HBs: -ve
Chronic HBV infection
Notes for HBV antibody interpretation
HBsAg: surface antigens
If these are present, there is an infection
Anti-HBs: surface antigen antibodies
If these are present, body is successfully protected against virus
Anti-HBc IgM/IgG: core antigen antibodies
IgM precedes IgG, hence IgM indicates a more recent infection
What is the management for hepatitis A/E?
Supportive care
Avoid alcohol/excess paracetamol
What is the management for hepatitis B?
Supportive care if acute
Antivirals and peginterferon if chronic
What is the management for hepatitis C?
Supportive care if acute
Antivirals if chronic
What is the prognosis for hepatitis A?
Nearly all resolve in 6 months
What is the prognosis for hepatitis B?
Viral suppression in 90% of chronic cases
What is the prognosis for hepatitis C?
79% mortality at 10 years for chronic cases
What is the cause of NASH/NAFLD?
Insulin resistance -> increased triglycerides -> steatosis -> inflammation -> steatohepatitis
What are the risk factors for NASH?
No alcohol Hx
Obesity (truncal) Insulin resistance/diabetes Hyperlipidaemia Hypertension Metabolic syndrome Short bowel syndrome TPN.
What is the triad for NASH?
RUQ pain
Hepatomegaly
Metabolic syndrome without alcohol
What are the investigations for NASH?
Liver function tests
- AST:ALT elevated <1 (>2 in alcoholic liver disease)
- FBC- thrombocytopaenia, elevated WCC, deranged clotting
- Metabolic profile (elevated glucose)
- Lipid profile- hyperlipidaemia
- Hepatic ultrasound
What is the management for NASH?
Diet and exercise
Correction of glucose and lipid levels (statins, metformin, thiazolidinediones)
Liver transplant if in liver failure
What is the prognosis for NASH?
1/3 reverse the condition
1/3 keep the condition
1/3 develops into cirrhosis
What are the complications of NASH?
Cirrhosis HCC Ascites Portosystemic thrombosis Haemorrhage
What is the cause for ALD?
Alcohol metabolism -> XS NADH -> inhibits gluconeogenesis -> increased fatty acid oxidation -> steatosis -> inflammation -> steatohepatitis
What is the triad for ALD?
RUQ pain
Hepatomegaly
Associated with a Hx of alcohol consumption
What are the investigations for ALD? What would you see?
Liver function tests (AST:ALT >2, raised GGT) = FIRST LINE
FBC- macrocytic anaemia
Clotting screen
Vitamin screen
Hepatic USS (cirrhotic PT to screen for HCC)
Liver biopsy (diagnostic, rarely needed) + histology
What is the management for ALD?
- Alcohol abstinence + withdrawal management (diazepam to prevent seizure)
- Nutrition (enteral preferred, calories and vitamins)
- Weight loss/stop smoking
- Steroids in severe alcoholic hepatitis
- Liver transplant if in liver failure
What is liver cirrhosis?
Scarring of the liver due to hepatocyte damage
Normal liver replaced with fibrosis and nodules of regenerating hepatocytes
Can be stable or decompensated (liver failure)
What are the symptoms of liver cirrhosis?
Abdominal distension
Pruritus
Coffee-ground vomit (due to gastro-oesoph varices)
What are the signs of liver cirrhosis?
Jaundice Ascites Asterixis Dupuytren's contracture Palmar erythema Caput medusae
What are the investigations for liver cirrhosis?
LFTs -low albumin -prolonged PT U+Es -hyponatraemia: ascites US/CT/MRI can see atrophy/fibrotic nodules
What is the management for liver cirrhosis?
Treat underlying cause
Liver transplant if in liver failure
What is Wilson’s disease?
Autosomal recessive disease of impaired copper excretion in the bile
ATP7B mutation
What are the signs and symptoms of Wilson’s disease?
IN A YOUNG PERSON:
Hepatitis symptoms (liver accumulation):
- Hepatosplenomegaly
- RUQ pain
- jaundice
- ascites
- portal HTN
Parkinsonism (basal ganglia accumulation):
- Ataxia
- Tremor
- Dysdiadochokinesia
- Dementia
Kayser-Fleischer rings
What investigations would you do for Wilson’s disease?
FIRST LINE:
- LFTs (raised transaminases/bilirubin)
- 24-hr urinary copper
- slit lamp examination
COPPER STUDIES:
- ↓ serum ceruloplasmin (copper transport protein)
- ↑ serum free copper
GOLD STANDARD/DIAGNOSTIC
- Genetic testing
- Liver biopsy and measurement of copper content
What is haemochromatosis?
Autosomal recessive multisystem disorder of dysregulated dietary iron absorption and increased iron release from macrophages
Commonly C282Y or H63D mutation
Due to HEPCIDIN abnormality so there is no inhibition of Fe uptake
What are the investigations for haemochromatosis?
FIRST LINE = Iron studies:
- high ferritin (non-specific as acute phase protein)
- low transferrin
- high transferrin saturation
Gene typing of HFE Liver biopsy (gold standard)
What is cholelithiasis?
Presence of solid concentrations in the gall bladder
What is choledocholithiasis?
Formation of solid concentrations in the gall bladder which exit the bile duct
What is the anatomy of the biliary tree, starting from the sphincter of Oddi?
Sphincter of Oddi -> hepatopancreatic ampulla of Vater
AoV -> common bile duct and pancreatic duct
CBD -> cystic duct and common hepatic duct
CHD -> left and right hepatic duct
What are the risk factors for gallstones?
Fair skinned Fat Female Fertile Family Hx Forty+ (6 F's)
What are the symptoms of gallstones?
RUQ pain- colicky, post-prandial (fatty meals)
Nausea
NO JAUNDICE- not obstructing biliary flow
What is Murphy’s sign and what pathology does it present in?
Palpate the costal margin mid-clavicular plane
Pain/wince upon inspiration
Gallstones
What is Boas’ sign and what pathology does it present in?
Pain radiating to below the scapula
Gallstones
What is Kehr’s sign and what pathology does it present in?
Pain radiating to the shoulder tip
Gallstones
What investigations would you do for gallstones/cholelithiasis?
LFTs (first line)
Abdo US of liver and biliary tree (diagnostic)
What is the management for cholelithiasis?
If asymptomatic- nothing
If biliary colic- elective cholecystectomy + analgesia
What is the management for choledocholithiasis?
(Analgesia) + ERCP
+ lap chole
What is ascending cholangitis?
choledocholithiasis + infection
Bile stasis- bacteria enter the hepatopancreatic duct
Leads to inflammation and infection
What is acute cholecystitis?
Gallstone in the gall bladder/cystic duct causing bile stasis, inflammation, and infection
What is Mirizzi syndrome?
Blockage of the cystic duct causing inflammation
Inflammation blocks CHD leading to obstructive jaundice
What are the signs and symptoms of acute cholecystitis?
Constant RUQ pain +/- Boas' sign Fever N+V Rebound tenderness Murphy's sign +ve
What are the signs and symptoms of ascending cholangitis?
Charcot’s triad- RUQ pain, fever, jaundice
If septic, Reynold’s pentad
What is Charcot’s triad?
RUQ pain
Fever
Jaundice
What is Reynold’s pentad?
RUQ pain Fever Jaundice Hypotension Confusion
What is primary biliary cirrhosis?
Autoimmune damage and destruction of the biliary epithelial cells lining the small intrahepatic bile ducts
What is the epidemiology of PBC?
55-65 yrs
F:M 10:1
What are the symptoms of PBC?
Pruritus
Fatigue
Sjogren’s (dry mouth and eyes)
What are the investigations of PBC?
LFTs
Anti mitochondrial antibodies
Abdo US/MRCP- rule out obstructive duct lesion
What is primary sclerosing cholangitis?
Inflammation and fibrosis of the intrahepatic and/or extrahepatic bile ducts, leading to diffuse, multi-focal stricture formation.
What is the epidemiology for PSC?
40-50s
Male
What are the symptoms of PSC?
RUQ pain
Pruritus
Fatigue
What are the investigations for PSC?
LFTs (elevated GGT)
MRCP: beading
AMA: -ve
What are the RF for pancreatic cancer?
65-75 yrs old Smoking FHx Obesity TD2M Chronic pancreatitis
What are the symptoms for pancreatic cancer?
Painless jaundice
Palpable gallbladder
FLAWS
Commonly delayed presentation due to non-specific signs (malaise, weight loss, abdo pain). Jaundice is later sign.
Hepatomegaly if hepatic metastasis
What are the investigations for pancreatic cancer?
FIRST LINE
- LFTs
- Abdominal USS- first line
- CT pancreas is first line if high suspicion of pancreatic cancer
GOLD STANDARD:
- Biopsy (via ERCP/EUS)
- Tumour marker: CA19-9
A 26 y/o male returns from holiday in India. He has had diarrhoea after eating at a seafood restaurant on his last night. He is feverish and nauseous. You notice that the whites of his eyes are yellow.
A. Hepatitis A B. Hepatitis B C. Hepatitis C D. Hepatitis D E. Hepatitis E
A. Hepatitis A
A 64 y/o male with thalassaemia is investigated under the two-week wait for jaundice and weight loss. His blood tests show a raised αFP. Which chronic infection is he most likely to have?
A. Hepatitis A B. Hepatitis B C. Hepatitis C D. Hepatitis D E. Hepatitis E
C. Hepatitis C
aFP is raised in cancer. Hep C chronicity has a high risk of HCC.
A 32 y/o male returns from holiday in Thailand, feeling ‘under the weather’ with RUQ pain, fevers and nausea. He is jaundiced. He reveals he has used IV drugs and had unprotected sex with a stranger while on holiday. Which test is most likely to give the correct diagnosis?
A. Liver function tests B. HIV serology C. Hepatitis B serology D. Hepatitis C PCR E. CXR
C. Hepatitis B serology
A 43 y/o confused man is brought to A&E by police after being found wandering the streets. He is disorientated and unable to give a clear history. You notice brown rings in his eyes. What is he likely to have?
A. Alcohol intoxication B. Wilson’s disease C. Opiate overdose D. Haemochromatosis E. Hypoglycaemia
B. Wilson’s disease
72 y/o man with cirrhosis presents to A&E with diffuse abdominal pain and fever. He is nauseous and has vomited. His abdomen is distended and there is shifting dullness on examination. Which investigation would be most urgent?
A. Paracentesis B. Stool sample MC&S C. Abdominal USS D. LFTs E. Blood cultures
A. Paracentesis
Has signs of bacterial peritonitis, which needs to be treated more urgently than the cirrhosis
A 41 y/o female presents with a history of colicky, right sided abdominal pain. She states the pain is worse after eating fish and chips and Indian takeaways. On examination her abdomen is soft and non-tender. Which is the best investigation to confirm her diagnosis?
A. Abdominal X-ray B. ERCP C. Liver biopsy D. USS of biliary tree E. CT-KUB
D. USS of biliary tree
A 41 y/o female presents to A&E with a history of severe, continuous, RUQ pain. She feels feverish and complains of an occasional pain in her right shoulder. On examination she displays RUQ tenderness and a positive Murphy’s sign. What is the most likely diagnosis?
A. Biliary colic B. Ascending cholangitis C. Acute cholecystitis D. Primary biliary cirrhosis E. Cholangiocarcinoma
C. Acute cholecystitis
A 41 y/o female presents to A&E with a history of severe, continuous, RUQ pain. She feels feverish and complains of an occasional pain in her right shoulder. On examination she displays RUQ tenderness and a positive Murphy’s sign. While waiting to be admitted, her RUQ pain becomes worse and she starts shaking uncontrollably. You notice she now looks jaundiced. What is the most likely diagnosis?
A. Biliary colic B. Ascending cholangitis C. Acute cholecystitis D. Primary biliary cirrhosis E. Cholangiocarcinoma
B. Ascending cholangitis
A 35 y/o man presents with a two week history of jaundice and RUQ pain. He is taking mesalazine for a “bowel condition”. What is the most likely cause of his jaundice?
A. Autoimmune hepatitis B. Haemochromatosis C. Primary sclerosing cholangitis D. Primary biliary cirrhosis E. Drug side effect
C. Primary sclerosing cholangitis
A 39 year old female attends her GP for a routine check-up. She is obese and has type II diabetes, and been taking metformin and simvastatin for around 2 years. She complains of mild fatigue but has otherwise been well. She says she drinks around 8 units of alcohol per week. On examination there are no signs of chronic liver disease.
Investigations Albumin 38 g/L (35-51) ALT 178 IU/L (<40) AST 154 U/L (<40) ALP 57 U/L (35-51) GGT 19 U/L (11-42) Bilirubin 12 umol/L (<17)
What is the most likely diagnosis? Drug-induced hepatitis Non-alcoholic steatohepatitis Alcoholic hepatitis Viral hepatitis Cirrhosis
Non-alcoholic steatohepatitis
A 21 year old male student in London was well until 4 days ago when he developed diarrhoea, vomiting and RUQ pain. Yesterday morning, his flatmates noticed that his eyes had turned yellow. He has not lost any weight in the past few months and his stools are brown. LFTs revealed high transaminases, and a viral screen was ordered.
Viral screen Anti-HepA IgM/IgG Negative Hep C Virus RNA Undetectable HBsAg (HepB surface antigen) Positive Anti-HBcAg IgM Positive Anti-HBcAg IgG Negative Anti-HBsAg IgG Negative
Given the diagnosis, what is the most likely prognosis for this patient?
Full recovery
This patient currently has acute hepatitis B infection (evidenced by presence of Hep B surface antigen, and IgM antibodies against Hep B core antigen, but no IgG). The most common outcome of an acute hep B infection in adults is natural clearance of the virus and full recovery. For this reason there is no need to treat acute hep B patients with antivirals
A 59 year old man with a history of long-standing alcoholism and previous episodes of hepatic encephalopathy presents to ED with altered mental status, fever and worsening abdominal distension and tenderness. An ascitic tap shows neutrophil concentration of 345 cells/mm3
Given the most likely diagnosis, how would you manage this patient?
Reassure and discharge IM chlordiazepoxide and IV rifaximin Large volume paracentesis IV Cefotaxime and oral lactulose IV vancomycin and IV albumin
Both SBP and HE require treatment so this is not a suitable option
Chlordiazepoxide is a sedative, and sedatives should generally be avoided in hepatic encephalopathy
Paracentesis can be used as an adjunct in uncomplicated SBP, although IV antibiotics are first line. However, this patient clearly has SBP complicated by HE so this may not be appropriate
This option provides broad spectrum antibiotics to treat the SBP empirically. Furthermore, the oral lactulose would aid to reduce ammonia production in the gut. IV fluids along with short-term protein restriction are likely to be indicated in this patient
IV vancomycin is typically used for hospital acquired SBP (whereas this patient has been brought into ED without mention of another recent hospital stay) due to a wider range of potential causative agents. IV albumin is indicated in SPB only when there is concurrent renal dysfunction, of which there is no sign here.
Briefly explain bilirubin metabolism
- reticuloendothelial cells in spleen break down RBCs into haem and globin
- haem oxygenase breaks down haem into iron and biliverdin
- bilviderin –> unconjugated bilirubin
- In blood, unconjugated bilirubin binds to albumin and travels to liver
- glucuronyl transferase conjugates bilirubin (soluble)
bilirubin excreted into the duodenum in bile - in colon, bacteria deconjugate bilirubin into urobilinogen
-20% –> absorbed and excreted in kidneys
- 80% further oxidised to stercobilin + excreted in faeces
Causes of pre-hepatic jaundice
- Haemolysis
- Gilbert’s
Causes of post-hepatic jaundice
Anything blocking the bile duct:
- Gallstone
- Pancreatic cancer/(bile duct cancer)
- PSC/PBS
- Drugs
Causes of hepatic jaundice
Hepatitis
Cirrhosis
Liver mass
Haemochromatosis
Usually issues with
Compare urine and stools for the different types of jaundice
pre-hepatic = normal urine hepatic = dark urine (conjugated bilirubin absorbed into blood) post-hepatic = dark urine, light stools (no stercobilin)
Cause of pruritis
excess bile acids in blood due to blockage of the bile ducts
Think POST-HEPATIC causes of jaundice`
Causes of hepatitis
- Autoimmune
- Viral
- Alcoholic
- Non-alcoholic Steatohepatitis (NASH)
- Drugs
Hepatitis signs and symptoms
- RUQ pain
- Jaundice
- Hepatomegaly
- Joint pain
- Nausea
- Fatigue
- Dark urine
Can’t differentiate causes based on symptoms as these are generally similar
Stages of progression of alcoholic liver disease
- Steatosis (fatty)- after a few days of heavy drinking
- Alcoholic Hepatitis (inflammation)- due to chronic alcohol abuse
- Cirrhosis- irreversable scarring
LFTs in alcoholic hepatitis
AST/ALT ratio >2 ↑bilirubin -/↑ALP ↑GGT ↓ albumin
Which 2 markers represent the functional capacity of the liver?
CLOTTING FACTORS- INR: ↑ prothrombin time = sensitive marker of significant liver damage
ALBUMIN: ↓ albumin
What would liver biopsy show in ALD?
Ballooning
Mallory bodies indicates hepatitis
When can Hep E cause chronic hepatitis?
Immunosuppressed (post-transplant, HIV)
When can Hep E cause liver failure?
pregnancy
What serology would you do for HEV/HAV? How would they differ?
IgM and IgG antibodies
HEV: IgM lasts 6 weeks + IgG persist for LIFE
HAV: IgM lasts 2 months + IgG last a few YEARS
What is the commonest cause of HCC ?
UK = HCV Worldwide = HBV (less carcinogenic BUT much more common)
What percentage of HBV becomes chronic?
B usually stays acute (10% chronic)
Which hepatitis most commonly becomes chronic?
HCV
As can be chronic, risk of cirrhosis/HCC
What increases risk of liver failure in HBV?
hepatitis D coinfection/superinfection
How does ACUTE management of HBV and HCV differ?
Hep B: Acute = supportive
Hep C: Acute = antiviral
State some antiviral treatments for HCV
Sofosbuvir (NS5B inhibitors)
Ledipasvir (NS5A inhibitors)
Grazoprevir (NS3/4 protease)
Prognosis HCV
80% progresses to chronic if left untreated
Directly-acting antivirals mean that HCV can be cured in nearly 100% of cases, with short treatment regimens and minimal side effects
Management of HBV
ACUTE = supportive
CHRONIC = antivirals:
- if no decompensated cirrhosis = peginterferon-a-2a
- if poor liver function = tenofovir / entecavir
Management of HBV with HDV coinfection
peginterferon-a-2a
AND
tenofovir/entecavir
if HBV surface antigen is present, what does this mean?
the patient is currently infected with HBV (active infection)
NOT PRESENT IN CLEARED INFECTION
What does it mean is someone has antibodies to HBsAg?
either:
- vaccinated (if nothing else)
- cleared infection
NOT PRESENT IN ACTIVE INFECTION
What does it mean is someone has antibodies to HBcAg?
SIGN OF PAST OR ONGOING INFECTION
Means that patient has either:
- acute (IgM)
- chronic (IgG)
Serological markers- vaccinated against HBV
HBcAg IgM: -ve
HBcAg IgG: -ve
Hb S antigen: -ve
anti-HBs: +ve
Serological markers- past HBV infection
HBcAg IgM: -ve
HBcAg IgG: +ve
Hb S antigen: -ve
anti-HBs: +ve
Serological markers- acute HBV infection
HBcAg IgM: +ve
HBcAg IgG: -ve
Hb S antigen: +ve
anti-HBs: -ve
Serological markers- chronic HBV infection
HBcAg IgM: -ve
HBcAg IgG: +ve
Hb S antigen: +ve
anti-HBs: -ve
Which serological marker is positive in both cleared and current HCV infection?
anti-HCV antibodies
Which serological marker is positive in current HCV infection only?
HCV RNA
if very high for >6 months = chronic
Serological markers for acute and chronic HDV
if acute:
- positive HDV RNA
- positive HDV IgM
- positive HDV antigen
- negative IgG
if chronic:
- positive HDV RNA
- positive HDV IgG
- negative HDV antigen + IgM
RF for Hep A
Asia and Africa travel
MSM
Shellfish- improperly cleaned shellfish from contaminated water
Symptoms of HAV/HEV
Acute onset, lasts 8 weeks max: Nausea Vomiting (+ Diarrhoea) Fever Jaundice Abdominal pain (particularly RUQ)
What type of virus is HCV
RNA flavivirus
HEV treatment in immunocompromised
Ribavirin
Predominant mode of transmission HCV
Blood product spread (IVDU/transfusion)
Predominant mode of transmission HBV
Sexually transmitted; IVDU; vertical
What are the symptoms of HCV?
most commonly ASYMPTOMATIC
implications for chronic disease progression
In terms of blood investigations, compare the 5 main causes of hepatitis
ALCOHOLIC
- AST:ALT >2
- ↑GGT
NASH
- AST:ALT <1
VIRAL
- AST + ALT in 1000s
- serology
DRUG
- AST + ALT in 1000s
- serum drug conc
AUTOIMMUNE
- AST + ALT in 1000s
- ANA / ASMA / AMA positive
Tx paracetamol overdose
N-acetyl cysteine
Define haemochromatosis
condition leading to abnormal iron deposition in certain organs
(liver, pancreas, skin, pituitary, heart, joints)
How can haemachromatosis be classified?
PRIMARY
Hereditary- autosomal recessive- defect in the HFE gene
Cannot stop iron absorption from GI tract
SECONDARY
Iron overload e.g., multiple transfusions
Pathophysiology primary haemachromatosis
Defect in the HFE gene
Transferrin binds poorly to its receptor, causing the liver to reduce hepcidin production.
Hepcidin usually inhibits ferroportin (the enterocyte iron transporter).
With reduced hepcidin production, ferroportin activity in the enterocytes is unregulated
More iron is transported across the enterocytes, and
Results in iron accumulation and damage to the affected organs.
Clinical features of haemachromatosis
75% asymptomatic- takes years for iron to accumulate
- hepatomegaly
- diabetes mellitus onset
- bronze skin
- arthralgia
- male impotence
M experience before F
May progress to cirrhosis and HCC
Why do females experience haemachromatosis later than males?
females have an additional method of excreting iron through menstruation, whereas this is not possible in males so iron accumulates more quickly
Investigations for haemachromatosis
FIRST LINE: Transferrin saturation (raised) and serum ferritin (raised, non-specific as acute phase protein)
Gene typing of HFE
Liver biopsy (gold standard)
Epidemiology of Wilsons
Autosomal recessive genetic disorder
Age of onset 5-35 years
Causes of cirrhosis
Alcohol misuse viral hepatitis (B/C) autoimmune hepatitis haemochromatosis NASH chronic biliary disease
causes of macro/micro nodular cirrhosis
MACRO = viral MICRO= alcoholic
signs of of chronic stable liver disease
clubbing spider naevi dupuytren’s contracture palmar erythema gynaecomastia bruising
Define portal hypertension
↑ pressure in portal vein due to cirrhosis (of any cause)
Blood flows from portal to systemic circulation (porto-systemic anastamosis)
sites of porto-systemic anastamosies
Lower eosophagus
Anal canal
Umbilicus
Splenorenal
leads to varices
Signs of portal hypertension
caput medusae
ascites
oesophageal varices
What causes hepatic encephalopathy?
Impaired liver function in decomponesated cirrhosis means that ammonia is not metabolised in liver
Toxins + ammonia make their way into the systemic circulation (intrahepatic shunting + extrahepatic via anastamoses)
Travels to brain impacting neurotransmission and causing confusion
Precipitating factors for hepatic encephalopathy
- high protein diet
- GI bleed
- Infection
- Benzodiazepines
protein –> ammonia (gut flora)
Management of cirrhosis
Treat cause + avoid hepatotoxic drugs (alcohol, sedative, opiates, NSAIDs etc.)
Monitor risk of complications (MELD score, 6-monthly
USS, endoscopy upon diagnosis and every 3 years)
Manage complications- ascites, encephalopathy, SBP, varices
Management of hepatic encephalopathy
Treat precipitating event (GI bleed, infection etc.) + short term protein restriction
Oral lactulose, phosphate enema
Avoid sedatives
Management of ascites
Sodium restriction ±
Diuretics (furesomide + spironolactone) ±
Large volume paracentesis
Management of SBP
Abx (cefuroxime + metronidazole)
Define SBP
On ascitic drain:
>250 neutrophils per mm3ascitic fluid
….with no obvious cause of infection
Commonest pathogen causing SBP
E.Coli
Management of varices
Non-selective β-blocker (if small) = propanolol
Endoscopic variceal band ligation (if large)
If this doesn’t work:
Transjugular intrahepatic portosystemic shunt (TIPS)
Management of bleeding varices
A-E, IV fluids + blood (when Hb<7g/dL)
Terlipressin (reduce blood flow to gut, reduce pressure on portal system)
Antibiotics
Uncontrollable bleeding use balloon tamponade/metal mesh stent
When stable: endoscopic variceal band ligation
Define liver failure
severe liver dysfunction leading to jaundice, encephalopathy and coagulopathy
most common causes of ALF
paracetamol overdose (transaminitis +++) (50% of ALF) viral hepatitis
acute on chronic: acute decompensation in patients with chronic liver disease
How can liver failure be categorised?
Hyperacute: Encephalopathy <7 days after onset of jaundice
Acute: Encephalopathy 1-4 weeks after onset of jaundice
Subacute: Encephalopathy 4-12 weeks after onset of jaundice
Acute on chronic: acute decompensation in patients with chronic liver disease
Treatment for ALF
treat cause
liver transplant
Define liver abscess + give 4 main types
Liver infection –> walled off collection pus/cyst fluid
- Pyogenic
- Amoebic
- Hydatid cyst
- TB
most common pathogen in pyogenic abscess
most polymicrobial
- S. Aureus (kids)
- E. Coli (adults)
most common pathogen in amoebic abscess
Entamoeba histolytica infection (faeco-oral spread)
Associated with amoebic dysentery (profuse bloody diarrhoea)
most common pathogen in hydatid cyst
Tapeworm Echinococcus granulosis infection
Commonest causes of pyogenic abscess
60% related to biliary disease
e.g., gallstones, strictures
symptoms of liver abscess
Fever malaise weight loss RUQ pain (referred shoulder pain) jaundice Foreign travel.
signs of liver abscess
Jaunice
tender hepatomegaly
dullness to percussion/↓ breath sounds at right
lung base
Investigations for liver abscess
Bloods (FBC- mild anaemia, leukocytosis, eosinophilia for hydatid cyst
Liver USS- hyperechoic
Stool microscopy: For Entamoeba histolytica or Echinococcus granulosis
Aspiration and culture of abscess: pyogenic (most polymicrobial), amoebic (anchovy sauce with necrotic hepatocytes/trophozoites)
2 associations of raised GGT
bile duct damage
chronic alcohol abuse
Name some common drugs that cause drug induced cholestasis
Co-amoxiclav
Nitrofurantoin
OCP
cause a paralysis of the biliary system (ileus).
common characteristic of pancreatic cancer
painless palpable gallbladder (Courvoisier’s law) and jaundice
typical presentation of acute cholangitis
RUQ pain, fever and jaundice.
Acute cholangitis is typically extremely painful
typical presentation of cholangiocarcioma
Gradual onset obstructive pattern
UC is associated with which bile duct disease?
PBC
Primary Biliary Cholangitis
Management of acute cholangitis
Clear fluids only. Analgesics, fluid resus, broad IV Abx if infection.
Definitive: Lap cholecystectomy (within 1 week if uncomplicated)
what is ascending cholangitis
Choledocholithiasis + infection
Difference between ascending cholangitis and acute cholecystitis
Ascending cholangitis: may be jaundice/raised ALP/GGT- obstruction to biliary flow
acute cholecystitis = no obstruction
management of abscess in gall bladder
cholecystostomy
What are the 2 key complications of choledocolithiasis?
Ascending cholangitis
Pancreatitis
Management of ascending cholangitis
Clear fluids only. Analgesics, fluid resus, broad IV Abx
+ ERCP
Lap cholecystectomy
What are most gallstones formed from?
Mostly mixed (20–80% cholesterol, calcium carbonate, bile salts, bilirubin)
What causes pigment stones?
Haemolysis
Calcium bilirubinate
Severe RUQ pain, +ve murphy’s sign without jaundice strongly points to what?
acute cholecystitis
compare definitions/location of PBC and PSC
Both inflammatory conditions of the bile ducts causing cholestasis
PBC = intrahepatic ducts, F>M PSC = intra and extra hepatic ducts, M>F
Think PSC-ary- generally worse condition
What are the associations of PBC and PSC?
PBC: Sjorgen’s, RA
PSC: associated with IBD (esp UC)
compare complications of PSC and PBC
PBC: granulomas
PSC: cirrhosis, cholangiocarcinoma
Both can increase risk of HCC
compare histology of PSC and PBC
PBC: florid ductal lesions
PSC: concentric onion skin fibrosis
compare diagnosis of PSC and PBC
PBC: presence of AMA antibodies
PSC: MRCP shows beaded appearance- segmental fibrosis with saccular dilation.
Most prevalent serum antibodies= p-ANCA, then ANA
What is the tumour marker for pancreatic cancer?
CA19-9
CEA (les common)
What is the most common cause of liver tumours?
SECONDARY TUMOURS Metastasised commonly from: bowel breast oesophagus stomach pancreas
What are the 2 main types of primary liver tumour?
Hepatocellular carcinoma (90%) Cholangiocarcinoma
RF for HCC
HBV- commonest worldwide HCV- commonest in europe ALD AIH haemochromatosis NAFLD aflatoxin PBC Smoking Obesity
Signs and symptoms of HCC
Malaise, FLAWS RUQ pain Jaundice scites (due to chronic liver disease) Cachexia Hepatomegaly
Investigations for HCC
FIRST LINE:
- Liver USS (6 monthly USS for high risk PTs)
- LFTs
- Tumour markers - AFP
- Viral serology
GOLD STANDARD
- Liver CT
- Liver biopsy
Most common type + location of pancreatic cancer
Mostly adenocarcinoma from exocrine tissue
75% in head of pancreas
Define cholangiocarcinoma
adenocarcinomas of bile duct epithelium
RF cholangiocarcinoma
PSC, worm infections and cirrhosis
Investigations for cholangiocarcinoma
Abdo USS (dilated intrahepatic ducts, mass lesion) Gold standard- biopsy (using ERCP)
signs and symptoms cholangiocarcinoma
same as pancreatic cancer
-distinguished by imaging/histology
Pancreatic cancer more common
Presence of anti-smooth muscle antibodies is a feature of which disease?
autoimmune hepatitis
appearance of PSC on MRCP
BEADS ON A STRING
segments of fibrotic bile duct, followed by dilated bile duct