1
Q
Liver - palpation
A
- lowermost edge lies approximately parallel with the costal margin (lower edge of the ribcage)
- enlargement of liver occurs in an inferior direction
- normal liver is impalpable or palpated close to the costal margin
2
Q
Liver - functions
A
- removes toxic byproducts eg drugs, alcohol
- produces most proteins
- produces bile
- produces clotting factors and vitamin K
- metabolizes nutrients to produce energy, when needed eg gluconeogenesis
- stores glycogen, vitamins (A, D, K, B12), iron, copper
- breaks down ammonia
- helps fight infections (kupffer cells) by removing bacteria
3
Q
Alcohol-related liver disease - clinical features
A
- RF = prolonged heavy alcohol consumption, presence of hepatitis C, and female gender
- RUQ pain
- hepatomegaly
- less common: haematemesis/melaena, jaundice, ascites, weight loss, pruritus, confusion - these are more common in cirrhosis
4
Q
Alcohol-related liver disease - investigations
A
- LFTs = raised AST, ALT. Classically AST > ALT (ratio of AST/ALT >2)*. Raised bilirubin and GGT. ALP may be raised. Low albumin
- FBC = anaemia, leukocytosis, thrombocytopenia, high MCV
- serum electrolytes = normal or low sodium, potassium, magnesium, phosphorus
- U+Es = normal or high urea and creatinine
- PT, INR = normal or prolonged
- hepatic US = may show hepatomegaly, fatty liver, liver cirrhosis, liver mass, splenomegaly, ascites, evidence of portal hypertension
*if ALT was more raised it’d probably be NAFLD
5
Q
Alcohol-related liver disease - next step after bloods and US?
A
- consider liver biopsy to assess need for corticosteroid treatment
biopsy can show: steatosis, inflammation-neutrophil infiltrate, ballooning hepatocytes, Mallory hyaline bodies, pericellular fibrosis
- use Maddrey discriminant function (DF) score to assess - score based on PT and bilirubin levels
score > 32 suggests need for Rx
6
Q
Alcohol-ralated liver disease - management
A
- conservative = alcohol abstinence, weight reduction, smoking cessation
- alcohol withdrawal Rx = oxazepam or lorazepam
- enteral nutrition and offer multivitamins
- check imminisations are up to date
- corticosteroids = prednisolone 1st line
- control renal function = sodium restriction + diuretics
- 2nd line = liver transplant
- monitor for complications
7
Q
Alcohol-ralated liver disease - complications
A
- hepatic encephalopathy
- portal HTN
- GI bleeding
- coagulopathy
- renal failure
- hepatorenal syndrome
- hepatocellular carcinoma
- sepsis
8
Q
Alcoholic liver disease - When to refer for liver transpantation?
A
- still have decompensated liver disease after best management and 3 months’ abstinence from alcohol
and
- are otherwise suitable candidates for liver transplantation.
9
Q
Cirrhosis - definition
A
Cirrhosis is a diffuse pathological process, characterised by fibrosis and conversion of normal liver architecture to structurally abnormal nodules known as regenerative nodules. It can arise from a variety of causes and is the final stage of any chronic liver disease.
10
Q
Cirrhosis - causes
A
- Chronic viral hepatitis: hepatitis C, hepatitis B
- Alcoholic liver disease
- Metabolic disorders: NAFLD, obesity, haemochromatosis, Wilson’s disease, A1ATd
- Cholestatic and autoimmune liver diseases: PBC, PSC, autoimmune hepatitis.
- Biliary obstruction: mechanical obstruction, biliary atresia, cystic fibrosis.
- Hepatic venous outflow obstruction: Budd-Chiari syndrome, right-sided heart failure.
- Drugs and toxins: amiodarone, methotrexate.
11
Q
Compensated vs decompensated cirrhosis
A
- compensated = biochemical, radiological, or histological findings with preservation of hepatic synthetic function and no evidence of complications
- decompensated = development of complications of liver dysfunction with reduced hepatic synthetic function and portal HTN including ascites, gastro-oesophageal varices and variceal bleeding, hepatic encephalopathy, and/or jaundice.
12
Q
Cirrhosis - pathological changes
A
- activation of hepatic stellate cells
- accumulation of collagen types I and III in the hepatic parenchyma and space of Disse (perisinusoidal space)
- capillarisation of the sinusoids = lose their fenestration altering exchange between hepatocytes and plasma
- increased pressure within the portal venous system, as well as shunting blood away from the liver
- loss of normal protein production leading to malnutrition and reduction in clotting factors
- loss of ability to detoxify substances
13
Q
Cirrhosis - Risk factors
A
- alcohol misuse
- IVDU
- unprotected intercourse
- obesity
- blood transfusion
14
Q
Cirrhosis - symptoms
A
- pruritus and jaundice (reduced hepatic excretion of conjugated bilirubin)
- coffee-ground vomitus*
- black stool (melaena)*
- altered mental status/confusion (uncommon)
- 2ary to GI haemorrhage from gastro-oesophageal varices in portal HTN
15
Q
Cirrhosis - hand and nail signs
A
- leukonychia (white nails due to hypoalbuminaemia)
- palmar erythema
- spider naevi
- polished nails - excessive scratching in pruritus
- finger clubbing
- Dupuytren contracture - alcoholic liver disease
- asterixis (hepatic flap - sign of encephalopathy)
16
Q
Cirrhosis - facial signs
A
- telangiectasia
- spider angiomata
- jaundiced sclera
- xanthelasma (yellow plaques on eyelids secondary to lipid deposition) in PBC
- red tongue in alcoholic liver disease
17
Q
Cirrhosis - abdominal signs
A
- collateral circulation of the abdo wall around umbilicus
- hepatosplenomegaly
- distension - particularly flanks with shifting dullness due to ascites, bruising)
- caput medusa
- loss of sexual hair and testicular atrophy in men
18
Q
Cirrhosis - complications
A
- ascites / peripheral oedema
- gastro-oesophageal varices
- HCC
- spontaneous bacterial peritonitis
- Hepatic encephalopathy
- hepatorenal syndrome
- hypogonadism
- hepatic osteodystrophy (osteoporosis and osteomalacia)
19
Q
Cirrhosis - investigations
A
- LFTs = raised ALT and AST (ALT is more elevated than AST)*, raised GGT, reduced albumin
- FBC = reduced platelet count
- U+E = reduced sodium
- PT = prolonged
- positive antibodies to hepatitis C is indicative of chronic hepatitis C infection
- hepatitis B surface antigen indicative of chronic hepatitis B infection
- abdominal US or CT = liver surface nodularity, small liver, ascites, increased diameter of the portal vein
- Upper GI endoscopy - gastro-oesophageal varices
*except for alcoholic liver disease (AST > ALT)
NICE: Transient elastography is now the investigation of choice to detect liver cirrhosis
20
Q
Cirrhosis - management
A
- conservative = avoidance of alcohol and other hepatotoxic drugs (e.g NSAIDs, high doses of paracetamol), immunisation against hepatitis A and B for susceptible patients, weight loss, adequate nutrition, regular exercise.
- treat underlying cause eg direct-acting antiviral agents for hep C
- monitor for Cx (abdo US, upper GI endoscopy, CT/MRI for HCC)
- sodium restriction and diuretic therapy for ascites eg furosemide and spironolactone
- 2nd line = liver transpantation
21
Q
Acute liver failure - features
A
- hepatic decompensation + encephalopathy, coagulation distrubance and jaundice within 6 months of onset
- drugs (70-80%) = paracetamol overdose (toxin = NAPQI), NSAIDs, antidepressants
- hepatitis (5%) = A-E
- Budd-chiari syndrome (occlusion of hepatic veins)
- ## Other causes = wilson’s, Reye’s syndrome, shock
22
Q
Wilson’s disease - main features
A
- autosomal recessive, Chr 13
- decreased caerloplasmin (copper binding protein) so high copper in liver, brain, other
- hepatic involvement = chronic active hepatitis, cirrhosis, liver failure
- other = neuropsychiatric (tremor, psychosis, dysarthria, dementia), renal tubular acidosis, kayser-fleischer rings (brown deposits at corneal edge)
23
Q
Autoimmune Hepatitis - features
A
- female 8:1 male
- T cell infiltration (inflammation from portal tracts to liver parenchyma)
- high titres of antinuclear antibody (ANA) or smooth muscle antibody(SMA) are diagnostic
- anorexia, abdo and joint pain, hepatomegaly, jaundice
- high ALT, high IgG and high globulin
24
Q
Haemochromatosis - features
A
- common in northern europeans
- autosomal recessive, gene HFE (Chr 6)
- HFE protein in small intestine villi regulates iron absorption. Mutation: increased total body iron
- tetrad of manifestations =
1. cirrhosis
2. DM
3. cardiac failure
4. hyperpigmentation of skin (leaden-grey) - increased iron, transferrin sat and ferritin with decreased total iron binding capacity
4 H’s = hepatic failure, heart failure, hyperpigmented skin, hyperglycaemic
25
Liver cancer - main features
- common site for metastatic spread
- haemangiomata = most common benign, bright on US (blood content and calcified), asymptomatic
- hepatic adenoma = a/w OCP, get collection of hepatocytes w/o portal tracts. RUQ pain + haemorrhage
- hepatocellular carcinoma = malignant, often background of cirrhosis caused by HBV or HCV, haemochromatosis or alcohol. Weight loss, fever, RUQ discomfort, ascites. High serum alpha-fetoprotein
26
Primary Biliary Cholangitis (or cirrhosis) - features
- female 9:1 male, unknown aetiology
- antibodies to mitochondria (esp PDC-E2) known as anti-mitochondrial antibodies (AMAs)
- chronic granulomatous inflammation of smaller bile ducts with portal infiltration of lymphocytes and plasma cells - bile leaks through tight junctions in liver
- leads to liver fibrosis and cirrhosis
- pruritus and jaundice (late)
- Jaundice, cholesterol leaks, xanthomas (yellow patch in skin), arthropathy
27
Ischaemic Hepatitis
Ischaemic hepatitis is a diffuse hepatic injury resulting from acute hypoperfusion (sometimes known as 'shock liver'). It is diagnosed in the presence of an inciting event (e.g. a cardiac arrest) and marked increases in aminotransferase levels (exceeding 1000 international unit/L or 50 times the upper limit of normal). Often, it will occur in conjunction with acute kidney injury (tubular necrosis) or other end-organ dysfunction.
