Liver Disease

Question 1

Liver - palpation

Answer 1

• 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

Question 2

Liver - functions

Answer 2

• 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

Question 3

Alcohol-related liver disease - clinical features

Answer 3

• 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

Question 4

Alcohol-related liver disease - investigations

Answer 4

• 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

Question 5

Alcohol-related liver disease - next step after bloods and US?

Answer 5

• 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

Question 6

Alcohol-ralated liver disease - management

Answer 6

• 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

Question 7

Alcohol-ralated liver disease - complications

Answer 7

• hepatic encephalopathy
• portal HTN
• GI bleeding
• coagulopathy
• renal failure
• hepatorenal syndrome
• hepatocellular carcinoma
• sepsis

Question 8

Alcoholic liver disease - When to refer for liver transpantation?

Answer 8

1. still have decompensated liver disease after best management and 3 months’ abstinence from alcohol

and

2. are otherwise suitable candidates for liver transplantation.

Question 9

Cirrhosis - definition

Answer 9

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.

Question 10

Cirrhosis - causes

Answer 10

• 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.

Question 11

Compensated vs decompensated cirrhosis

Answer 11

• 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.

Question 12

Cirrhosis - pathological changes

Answer 12

• 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

Question 13

Cirrhosis - Risk factors

Answer 13

• alcohol misuse
• IVDU
• unprotected intercourse
• obesity
• blood transfusion

Question 14

Cirrhosis - symptoms

Answer 14

• 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

Question 15

Cirrhosis - hand and nail signs

Answer 15

• 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)

Question 16

Cirrhosis - facial signs

Answer 16

• telangiectasia
• spider angiomata
• jaundiced sclera
• xanthelasma (yellow plaques on eyelids secondary to lipid deposition) in PBC
• red tongue in alcoholic liver disease

Question 17

Cirrhosis - abdominal signs

Answer 17

• 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

Question 18

Cirrhosis - complications

Answer 18

• ascites / peripheral oedema
• gastro-oesophageal varices
• HCC
• spontaneous bacterial peritonitis
• Hepatic encephalopathy
• hepatorenal syndrome
• hypogonadism
• hepatic osteodystrophy (osteoporosis and osteomalacia)

Question 19

Cirrhosis - investigations

Answer 19

• 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

Question 20

Cirrhosis - management

Answer 20

• 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

Question 21

Acute liver failure - features

Answer 21

• 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

Question 22

Wilson’s disease - main features

Answer 22

• 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)

Question 23

Autoimmune Hepatitis - features

Answer 23

• 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

Question 24

Haemochromatosis - features

Answer 24

• 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

Question 25

Liver cancer - main features

Answer 25

• 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

Question 26

Primary Biliary Cholangitis (or cirrhosis) - features

Answer 26

• 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

Question 27

Ischaemic Hepatitis

Answer 27

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.