Liver disease Flashcards
Define what chronic liver disease is
- It is a disease process of the liver lasting over 6 months that involves a process of progressive destruction and regeneration of the liver parenchyma leading to fibrosis and cirrhosis.
- It consists of a wide range of liver pathologies
What does chronic liver disease eventually result in ?
Compensated cirrhosis and then decompensated cirrhosis/chornic liver failure or acute on chronic liver failure
List the different causes of chronic liver disease
- Chronic Alcohol abuse
- NAFLD
- Hepatitis C or B
- Autoimmune disorders - Primary Biliary Cholangitis (PBC), Primary Sclerosing Cholangitis (PSC), Autoimmune Hepatitis
- Genetic disorders - Haemochromatosis, Wilsons Disease, alpha 1anti-trypsin
- Budd-Chiari
- Drugs - Methotrexate, amiodarone, methyldopa
What are the clinical features of liver cirrhosis (compensated and decompensated)?
May be none (just increased LFT’s) but as cirrhosis progresses signs eventually show
Chronic liver disease signs:
- Leuconychia (white nails due to hypoalbunaemia)
- Clubbing
- Palmar erythema
- Duputyrens contracture
- Jaundice
- Hepatomegaly
- Easy burising
- Weight loss & loss of appetite
- Fatigue & weakness
- Spider naevi
- Xanthelasma
- Testicular atrophy & hair loss
- Complications may develop
Then will eventually become decompensated (bascially liver failure):
- Liver failure Acute –on-chronic; Infection, SIRS
- Jaundice, Ascites, Encephalopathy, Bruising
Good to look over
What clinical sign of cirrhosis is shown here ?
Spider naevi
What complications may develop in someone with liver cirrhosis ?
- Hepatic failure - encephalopathy & ascites etc
- Portal hypertension - ascities, splenomegaly, Portosystemic shunt (oesophageal varices, caput medusae & haemorrhoids)
- Hepatocellulcar carcinoma
How is liver cirrhosis diagnosed ?
Offer transient elastography to diagnose cirrhosis for:
- People with hepatitis C virus infection
- Men who drink >50 units of alcohol & women who drink > 35
- People diagnosed with alcohol-related liver disease.
Offer either transient elastography or acoustic radiation force impulse imaging (whichever is available) to diagnose cirrhosis for people with NAFLD and advanced liver fibrosis (as diagnosed by a score of 10.51 or above using the enhanced liver fibrosis [ELF] test).
2nd line = Consider liver biopsy to diagnose cirrhosis in people for whom transient elastography is not suitable.
What is the general treatment of liver cirrhosis ?
- Avoid alcohol, NSAID’s, sedatives & opiates
- Colestyramine for pruritus
- Specific treatment then depending on the cause and complications
What is the only cure for liver cirrhosis ?
Liver transplantation
What screening tests are recommended to be done in patients with diagnosed liver cirrhosis ?
- An upper endoscopy to check for varices in patient’s with a new diagnosis of cirrhosis
- Liver US every 6 months (+/- alpha-feto protein) to check for hepatocellular cancer
What is NAFLD?
It is a spectrum of disease ranging from:
- Steatosis - fat in the liver
- Steatohepatitis - fat with inflammation, non-alcoholic steatohepatitis (NASH), see below
- Progressive disease may cause fibrosis and liver cirrhosis
What is the primary cause of NAFLD?
Obesity
What are the risk factors for development of NAFLD?
- obesity
- type 2 diabetes mellitus
- hyperlipidaemia
- jejunoileal bypass
- sudden weight loss/starvation
What are the features of NAFLD?
- Usually asymptomatic
- Hepatomegaly
- ALT is typically greater than AST
- Increased echogenicity on ultrasound
Should people at risk of NAFLD be screened for it ?
No
If NAFLD is found incidentally (usually on liver US) what should be done ?
Enhanced liver fibrosis (ELF) blood test to check for advanced fibrosis
If the ELF blood test shows someone is likely to have advanced liver fibrosis what should be done ?
- 1st line = transient elastography or ARFII
- 2nd line = liver biopsy
What is the treatment of NAFLD ?
Lifestyle changes (particularly weight loss) and monitoring
What is primary biliary cholangitis ?
It is a chronic autoimmune liver disorder where interlobular bile ducts become damaged by a chronic inflammatory process causing progressive cholestasis which may eventually progress to cirrhosis and portal hypertension.
Note - used to be called ‘primary biliary cirrhosis’
Who is typically affected by primary biliary cholangitis ?
Middle-aged women
What conditions is primary biliary cholangitis associated with ?
Autoimmune conditions
- Sjogren’s syndrome (seen in up to 80% of patients)
- rheumatoid arthritis
- systemic sclerosis
- thyroid disease
How is primary biliary cholangitis diagnosed ?
- 1st line = LFTs will demonstrate a cholestasis (obstructive picture) - Increased ALP & GGT + midly increased ALT & AST
- 2nd line = A liver screen is done (includes US abdo, autoantibodies tested for & immunoglobulins (IgM will be increased). Sometimes liver biopsy done but rarley needed)
If the liver screen demonstrates AMA or smooth muscle antibodies then PBC diagnosed.
What autoantibody is the hallmark of primary biliary cholangitis ?
Antimitochondrial antibodies (AMA)
What are the clinical features of primary biliary cholangitis ?
Early:
- Often asymptomatic (e.g. raised ALP on routine LFTs)
- Fatigue and pruritus (itch) may then preceed jaundice by many years
Mid:
- Cholestatic jaundice - this will have itch
- Skin hyperpigmentation, especially over pressure points
- xanthelasmas, xanthomata
- clubbing, hepatosplenomegaly
Late:
- may progress to liver failure
What are the potential complications of primary biliary cholangitis ?
- Malabsorption of fat soluble vitamins (ADEK): osteomalacia, coagulopathy
- Sicca syndrome (Sjogren syndrome)
- Portal hypertension: ascites, variceal haemorrhage
- Hepatocellular cancer
What should be checked due to the increased risk of hepatocellular cancer in patients with primary biliary cholangitis ?
AFP twice per year
What is the treatment of PBC ?
- Pruritus: cholestyramine
- Fat-soluble vitamin supplementation
- Ursodeoxycholic acid
- Liver transplantation e.g. if bilirubin > 100
What is primary sclerosing cholangitis ?
A biliary disease of unknown aetiology characterised by inflammation and fibrosis of intra and extra-hepatic bile ducts.
What conditions is primary sclerosing cholangitis associated with ?
- UC - 4% of patients with UC have PSC, 80% of patients with PSC have UC
- Crohn’s (much less common association than UC)
- HIV
What are the clinical features suggestive of primary sclerosing cholangitis ?
- Cholestasis = jaundice and pruritus
- RUQ pain
- Fatigue
What complications can develop due to primary sclerosing cholangitis ?
- Ascending cholangitis
- Cirrhosis and end-stage hepatic failure
- Cholangiocarcinoma
- Colorectal cancer
How is primary sclerosing cholangitis diagnosed ?
Via MRCP (ERCP less preferred due to being invasive)
- LFTs - ALP & GGT elevated, AST & ALT mild-moderately elevated
- AMA negative but may be positive for ANCA, ANA & SMA
What is the treatment of primary sclerosing cholangitis ?
- Colestyramine for puritis
- Liver transplantation is they develop end-stage disease
- Monitor for cholangiocarcinoma and colorectal cancer
What is autoimmune hepatitis ?
It is an inflammatory liver disease of unknown cause characterised by suppressor T-cell defects with autoantibodies directed against hepatocyte surface antigens
What are the 3 types of autoimmune hepatitis and what are they based on ?
Classification is based on the autoantibodies present:
- Type I = ANA &/or SMA present
- Type II = Anti-liver/kidney microsomal type 1 antibodies (LKM1) present. ANA & SMA -ve
- Type III = Soluble liver-kidney antigen (SLA) present. ANA & SMA -ve
Who is affected by each of the 3 types of autoimmune hepatitis ?
- Type I affects both adults & children
- Type II affects children only
- Type III affects middle aged adults
Who is most commonly affected by autoimmune hepatitis ?
Young females (10-30)
What are the clincal features of autoimmune hepatitis ?
40% present with Acute hepatitis: fever, jaundice etc and signs of autoimmune disease e.g. malaise, uticarial rash, polyarthritis, pleurisy, pulmonary infiltration or glomerulonephritis
The remainder may present with signs of chronic liver disease:
- Hepatomegaly
- Jaundice
- Stigmata of chronic liver disease
- Splenomegaly
- Elevated AST and ALT, Elevated PT
- Non-specific symptoms: malaise, fatigue, lethargy, nausea, abdominal pain, anorexia
Amenorrhoea (common)
ANA/SMA/LKM1 antibodies, raised IgG levels
How is autoimmune hepatitis diagnosed ?
No lab test is pathognomic so depends on ruling out other causes:
- Elevated AST and ALT
- Elevated IgG
- Presence of autoimmune antibodies
- Liver biopsy - interface hepatitis and marked piecemeal necrosis and lobular involvement
Rule out other causes:
- Wilsons disease
- Alpha 1 antitrypsin deficiency
- Viral hepatitis (A, B, C)
- Drug induced liver disease (alcohol, minocycline, nitrofurantoin, INH, PTU, methyldopa, etc)
- NASH
- PBC, PSC, autoimmune cholangitis
What is associated with autoimmune hepatitis ?
- Autoimmune disorders e.g. thyroiditis, graves disease, chronic UC, pernicious anaemia, autoimmune haemolysis, glomerulonephritis etc
- Hypergammaglobulinaemia
- and HLA B8, DR3.
What is the treatment of autoimmune hepatitis ?
- 1st line = Prednisone + Azathioprine
- 2nd line = liver transplantation if decompensated cirrhosis or failure to respond to medical therapy
Note Hepatitis B&C is covered in the hepatitis deck
What is hereditary haemochromatosis (HH)?
An autosomal recessive disorder of iron absorption and metabolism resulting in iron accumulation and deposition in the heart, liver, pancreas, pituitary, adrenals, joints & skin
What mutation causes HH?
C282Y or H63D mutations in both copies of the HFE gene on chromosome 6
What are the clinical features suggestive of HH?
Early on - symptoms may be nil or faitgue, arthralgia (esp the hands) & erectile dysfunction
Later on:
- Bronze skin pigmentation
- Signs of chronic liver disease
- Cardiac failure - 2° to dilated cardiomyopathy
- Diabetes mellitus - 2° iron deposition in pancreas
- Hypogonadism (2nd to cirrhosis and pituitary dysfunction - hypogonadotrophic hypogonadism)
- Arthritis (especially of the hands)
How is HH diagnosed ?
- 1st = check serum ferritin (>300 in men and >200 in women) and % tranferrin (>50%) & low TIBC - this is suggestive of iron loading
- 2nd = Diagnosis then made by testing for HFE mutation
Liver biopsy using Perl’s stain only done only if uncertain about iron loading or to assess tissue damage
What do joint X-rays in someone with HH typically show ?
Chondrocalcinosis
What is the treatment of haemachromatosis ?
- 1st = Initially weekly venesections to exhaust iron stores continue this until - serum ferritin <20 µg/L
- 2nd = Then carry out maintance venesections 3-4 times per year - to keep serum ferritin below 50 µg/l
When we discover someone has hereditary haemachromatosis, what is offered to 1st degree family members ?
Testing for HFE mutation and iron status checked with serum Ferritin and % transferrin saturation
What is wilsons disease ?
An autosomal recessive disorder characterised by excessive copper deposition in the tissues (liver & CNS) due to increased copper absorption from the small intestine and decreased hepatic copper excretion.
What causes wilsons disease ?
Defect in the ATP7B gene located on chromosome 13.
When does the presentation of wilsons disease usually arise ?
- Usually between 10 - 25 years.
- Children usually present with liver disease whereas the first sign of disease in young adults is often neurological disease
What are the clinical features suggestive of wilsons disease?
- Liver disease - hepatitis, cirrhosis, liver failure
- CNS signs: tremor, dysarthria, dysphagia, dyskinesias, dystonias, purposless stereotyped movements e.g. hand clapping, dementia, parkinsonism, micrographia, ataxia/clumsiness
- Kayser-Fleischer rings
- renal tubular acidosis (esp. Fanconi syndrome)
- haemolysis
- blue lunulae (blue nails)
How is wilsons disease diagnosed ?
No one test is diagnostic - Copper studies mainly:
- Reduced serum caeruloplasmin
- Reduced serum copper (counter-intuitive, but 95% of plasma copper is carried by ceruloplasmin)
- Increased 24hr urinary copper excretion
May also do:
LFTs, liver biopsy, MRI, slit lamp for KF rings and genetic testing
If someone is diagnosed with wilsons disease what should be done ?
Genetic testing of 1st degree relatives via analysis of the ATP7B gene
What is the treatment of wilsons disease?
- 1st line = penicillamine (chelates copper)
- 2nd line = trientine hydrochloride (alternative chelating agent)
What is Alpha-1 antitrypsin deficiency?
A common inherited condition caused by a lack of A1AT normally produced by the liver. It commonly affect the lungs (emphysema) & the liver (cirrhosis & hepatocellular carcinoma)
What is the role of A1AT ?
To protect cells from enzymes such as neutrophil elastase.
What genetic mutation causes A1AT deficiency?
Defect located on chromosome 14 and the degree of A1AT def is classified as:
- normal = PiMM
- homozygous PiSS (50% normal A1AT levels)
- homozygous PiZZ (10% normal A1AT levels)
What are the clinical features of A1AT deficiency ?
What patients with A1AT def usually manifest disease?
Usually those with the PiZZ genotype
What are the clinical features suggestive of A1AT defiency ?
- Lungs: dysponea from emphysema (COPD)
- Liver: cirrhosis and hepatocellular carcinoma in adults, cholestasis jaundice in children
What is the classical presentation of someone with A1AT def ?
Emphysema (i.e. chronic obstructive pulmonary disease) in patients who are young and non-smokers.
How is A1AT def diagnosed ?
- 1st line = serum A1AT concentrations (if low diagnosed)
- 2nd line if low conc = Genetic testing to see the variation of the faulty A1AT gene a person has
spirometry: obstructive picture to see how severly someone is affected
What is the treatment of A1AT def?
1st line = no smoking + supportive: bronchodilators, physiotherapy
What is budd-chiari syndrome ?
This is hepatic vein obstruction caused by thrombosis or a tumour. It results in congestive ischaemia & hepatocyte damage
What causes budd-chiairi syndrome ?
Hypercoagulative states:
- polycythaemia rubra vera
- thrombophilia: activated protein C resistance, antithrombin III deficiency, protein C & S deficiencies
- pregnancy
- oral contraceptive pill
Tumours - liver, renal or adrenal
What are the clinical features suggestive of budd-chiairi syndrome ?
- Abdominal pain: sudden onset, severe
- Ascites
- Tender hepatomegaly
- Increased ALT
How is budd-chiairi syndrome diagnosed ?
US with Doppler flow studies
What is the treatment of budd-chiairi syndrome ?
Recanalization via angioplasty or TIPS
What are the clinical features suggestive of methotrexate (or the other drugs) causing liver fibrosis and potentially chronic liver disease?
- Clinical- no signs, monitor fibrosis
- Tx = stop the drug
What is cardiac cirrhosis ?
Liver cirrhosis secondary to cardiac dysfunction, common causes include:
- Incompetent tricuspid valve
- Congenital
- Rheumatic fever
- Constrictive pericarditis
What are the clinical features suggestive of cardiac cirrhosis ?
CCF, with too much ascites and or liver impairment
What is the treatment of cardiac cirrhosis ?
Treat the cardiac condition
What is alcoholic liver disease?
It is the term used to describe the manifestations of alcohol overconsumption, leading to inflammation and scarring of the liver tissue
The spectrum of alcoholic liver disease includes 3 subtypes:
- Alcoholic fatty liver disease
- Alcoholic hepatitis
- Cirrhosis.
As alcoholic liver disease progresses what do people develop symptoms/signs of ?
Chronic liver disease
What are the LFT results suggestive of alcoholic liver disease ?
Ratio of AST:ALT is normally >2, a ratio of >3 is strongly suggestive of acute alcoholic hepatitis
- AST: typically 100-200IU/L
- ALT: May be normal or only mildly raised, even in severe cases.
GGT raised in association with chronic heavy alcohol comsumption
In alcoholic fatty liver disease (AFLD), normally there is a solitary mild increase in AST and ALT.
What is the treatment of alcohol liver disease ?
- Alcohol absitence & weight loss & nutrition (high protein diet)
- Hep A & B vaccinations
- Prednisolone given for acute alcoholic hepatitis
- End-stage ALD (cirrhosis with decompensation), liver transplantation can be considered usually must be alcohol free for >6 months
What can drinking during pregnancy cause?
- Foetal alcohol syndrome
What are the clinical features of foetal alcohol syndrome?
- Baby may show symptoms of alcohol withdrawal at birth e.g. irritable, hypotonic, tremors
Features:
- short palpebral fissure
- thin vermillion border/hypoplastic upper lip
- smooth/absent filtrum
- learning difficulties
- microcephaly
- growth retardation
- epicanthic folds
- cardiac malformations
