Tuesday [16/8/2022]

Question 1

What is faecal calprotectin and how effective is it? [2]

Answer 1

Faecal calprotectin is a test for intestinal inflammation that has been recommended by NICE as a screening tool for inflammatory bowel disease (IBD). It can also be used to monitor the response to treatment in IBD patients.

In adults, it has a sensitivity of 93% and specificity of 96% for IBD. In children, the specificity falls to around 75%

Question 2

What can cause raised faecal calprotectin? [5]

Answer 2

In addition to IBD, other causes of a raised faecal calprotectin include:
bowel malignancy
coeliac disease
infectious colitis
use of NSAIDs

Question 3

Barium enema UC [3]

Answer 3

loss of haustrations
superficial ulceration, ‘pseudopolyps’
long standing disease: colon is narrow and short -‘drainpipe colon’

Question 4

Clinical features UC vs DC [4]

Answer 4

CD

Diarrhoea usually non-bloody
Weight loss more prominent
Upper gastrointestinal symptoms, mouth ulcers, perianal disease
Abdominal mass palpable in the right iliac fossa

UC

Bloody diarrhoea more common
Abdominal pain in the left lower quadrant
Tenesmus

Question 5

extra-intestinal features UC [2]

Answer 5

Gallstones are more common secondary to reduced bile acid reabsorption

Oxalate renal stones* Primary sclerosing cholangitis more common

Question 6

Cx UC to CD [2]

Answer 6

Obstruction, fistula, colorectal cancer Risk of colorectal cancer high in UC than CD

Question 7

Histology UC to CD [2]

Answer 7

Inflammation in all layers from mucosa to serosa
increased goblet cells
granulomas
No inflammation beyond submucosa (unless fulminant disease) - inflammatory cell infiltrate in lamina propria
neutrophils migrate through the walls of glands to form crypt abscesses
depletion of goblet cells and mucin from gland epithelium
granulomas are infrequent

Question 8

Radiology CD [4]

Answer 8

Small bowel enema
high sensitivity and specificity for examination of the terminal ileum
strictures: 'Kantor's string sign'
proximal bowel dilation
'rose thorn' ulcers
fistulae

Question 9

Severity of UC [3]

Answer 9

The severity of UC is usually classified as being mild, moderate or severe:

mild: < 4 stools/day, only a small amount of blood
moderate: 4-6 stools/day, varying amounts of blood, no systemic upset
severe: >6 bloody stools per day + features of systemic upset (pyrexia, tachycardia, anaemia, raised inflammatory markers)

Question 10

Inducing remission for UC [4]

Answer 10

Treating mild-to-moderate ulcerative colitis
proctitis
topical (rectal) aminosalicylate: for distal colitis rectal mesalazine has been shown to be superior to rectal steroids and oral aminosalicylates
if remission is not achieved within 4 weeks, add an oral aminosalicylate
if remission still not achieved add topical or oral corticosteroid
proctosigmoiditis and left-sided ulcerative colitis
topical (rectal) aminosalicylate
if remission is not achieved within 4 weeks, add a high-dose oral aminosalicylate OR switch to a high-dose oral aminosalicylate and a topical corticosteroid
if remission still not achieved stop topical treatments and offer an oral aminosalicylate and an oral corticosteroid
extensive disease
topical (rectal) aminosalicylate and a high-dose oral aminosalicylate:
if remission is not achieved within 4 weeks, stop topical treatments and offer a high-dose oral aminosalicylate and an oral corticosteroid

Severe colitis
should be treated in hospital
intravenous steroids are usually given first-line
intravenous ciclosporin may be used if steroid are contraindicated
if after 72 hours there has been no improvement, consider adding intravenous ciclosporin to intravenous corticosteroids or consider surgery

Question 11

Maintaining remission UC [3]

Answer 11

Following a mild-to-moderate ulcerative colitis flare
proctitis and proctosigmoiditis
topical (rectal) aminosalicylate alone (daily or intermittent) or
an oral aminosalicylate plus a topical (rectal) aminosalicylate (daily or intermittent) or
an oral aminosalicylate by itself: this may not be effective as the other two options
left-sided and extensive ulcerative colitis
low maintenance dose of an oral aminosalicylate

Following a severe relapse or >=2 exacerbations in the past year
oral azathioprine or oral mercaptopurine

Other points
methotrexate is not recommended for the management of UC (in contrast to Crohn’s disease)
there is some evidence that probiotics may prevent relapse in patients with mild to moderate disease

Question 12

Cx with Inducing remission in CD

Answer 12

Colorectal cancer

Overview
risk of colorectal cancer is significantly higher than that of the general population although studies report widely varying rates
the increased risk is mainly related to chronic inflammation
worse prognosis than patients without ulcerative colitis (partly due to delayed diagnosis)
lesions may be multifocal

Factors increasing risk of cancer
disease duration > 10 years
patients with pancolitis
onset before 15 years old
unremitting disease
poor compliance to treatment

Colonoscopy surveillance in inflammatory bowel disease patients should be decided following risk stratification.

Question 13

I

Answer 13

Inducing remission
glucocorticoids (oral, topical or intravenous) are generally used to induce remission. Budesonide is an alternative in a subgroup of patients
enteral feeding with an elemental diet may be used in addition to or instead of other measures to induce remission, particularly if there is concern regarding the side-effects of steroids (for example in young children)
5-ASA drugs (e.g. mesalazine) are used second-line to glucocorticoids but are not as effective
azathioprine or mercaptopurine* may be used as an add-on medication to induce remission but is not used as monotherapy. Methotrexate is an alternative to azathioprine
infliximab is useful in refractory disease and fistulating Crohn’s. Patients typically continue on azathioprine or methotrexate
metronidazole is often used for isolated peri-anal disease

Question 14

Maintaining remission CD [4]

Answer 14

Maintaining remission
as above, stopping smoking is a priority (remember: smoking makes Crohn’s worse, but may help ulcerative colitis)
azathioprine or mercaptopurine is used first-line to maintain remission
methotrexate is used second-line
5-ASA drugs (e.g. mesalazine) should be considered if a patient has had previous surgery

Question 15

Cx associated with CD

Answer 15

As well as the well-documented complications described above, patients are also at risk of:
small bowel cancer (standard incidence ratio = 40)
colorectal cancer (standard incidence ration = 2, i.e. less than the risk associated with ulcerative colitis)
osteoporosis

Question 16

What is alcoholic fatty liver disease? [3]

Answer 16

Triglycerides accumulate amongst liver tissue as a result from two processes which are enhanced in alcohol over-consumption:
Reduction in fat export due to a decrease in liver fatty acid oxidation and lipoprotein reduction
Increased input of lipids to hepatic tissue due to increased peripheral lipolysis and triglyceride synthesis
This process can be enhanced if a person is also overweight/obese, leading to compounding non-alcoholic related fatty deposition in the liver
At this stage of ALD, it is potentially reversible if managed effectively

Question 17

What is alcoholic hepatitis [2]

Answer 17

This is a stage where there is combined liver steatosis and inflammation, with focal regions of liver necrosis

Question 18

What is alcoholic cirrhosis? [3]

Answer 18

A progressive process of hepatic tissue inflammation, degeneration and regeneration leads to excessive fibrogenesis and scarring of the liver
Existing liver tissue is replaced by excess extra-cellular matrix and collagen
This reduces the functional capacity of the liver, as well as distorting the normal architecture, leading to micronodules in the liver (and rarely, macronodules)

Question 19

Clinical features of alcoholic liver disease

Answer 19

Fatigue
Malaise
Abdominal pain
Anorexia
Weakness
Nausea and/or vomiting

As alcoholic liver disease is a spectrum, the signs and symptoms can differ depending on the severity of disease. Alcoholic hepatitis occurs in 30% of patients with excessive alcohol consumption, with symptoms including:
Jaundice (common)
Right upper quadrant pain (common)
Hepatomegaly (common, present in 70% of patients with ALD)
Generally an enlarged and smooth edge, but rarely tender to palpation
Palmar erythema
Peripheral oedema
Clubbing
Dupuytren’s contracture (present in 30% of patients with alcoholic liver disease)
Pruritis
If there is cholestasis leading to bile salt deposition in skin
Xanthomas
Spider angiomas
Multiple spider angiomas are characteristic of chronic liver disease, while solitary angiomas are seen in other systemic disease
Presence of spider angiomas correspond with a higher risk of ALD related mortality
The reported prevalence of spider angiomas in patients with liver cirrhosis is 31%

Question 20

Oestrogen features of ALD

Answer 20

Gynaecomastia and testicular atrophy (in males)
Loss of body hair
Amenorrhoea (in females)
Loss of libido

Question 21

Portal hypertension in ALD

Answer 21

As inflammation and scarring occurs, alcoholic cirrhosis progresses and can lead to portal hypertension resulting in its own variety of features including:
Ascites (within 10 years of the diagnosis of cirrhosis, >50% of patients will develop this)
Dilated veins (e.g. caput medusae)
Variceal bleeding and haemorrhage
Splenomegaly

Question 22

Ix for ALD

Answer 22

Commonly, alcoholic liver disease is first identified following routine or screening liver function tests. ALD diagnosis is difficult, as there is no single diagnostic test which will distinguish that the liver damage was caused by alcohol itself.

Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST)
ALT
Raised in hepatocellular pattern of liver injury, including ALD
Occasionally also raised in skeletal muscle injury
AST
Raised in hepatocellular pattern of liver injury, including ALD
May also be raised in acute cardiac or skeletal muscle injury

The ratio of AST:ALT is of benefit in acute alcoholic hepatitis.
AST: typically 100-200IU/L
ALT: May be normal or only mildly raised, even in severe cases.
Ratio of AST:ALT is normally >2, a ratio of >3 is strongly suggestive of acute alcoholic hepatitis

Serum gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP)
GGT
Raised in association with chronic heavy alcohol consumption (>70% of individuals)
Not specific to ALD as it may also be raised in other pathologies such as obesity, non-alcoholic fatty liver disease, biliary obstruction, and hepatocellular carcinoma
ALP
Raised in cholestatic pattern of liver injury
May be normal, or if raised, may indicate cholestasis related to ALD

It is possible in ALD for all four markers (AST, ALT, ALP, GGT) to be raised. However it is important to consider the rise relative to their respective upper limit of normal.
In ALD, the AST and/or ALT levels will be raised much more compared to the ALP and/or GGT levels.
For example, if the AST is 160IU/mL (normal <40IU/mL), and the ALP is 150IU/mL (normal <130IU/mL), this would represent a hepatocellular injury, as the AST is 4x the upper normal limit, while the ALP is only slightly raised.
In alcoholic fatty liver disease (AFLD), normally there is a solitary mild increase in AST and ALT.

Serum bilirubin
May be elevated in liver disease, whether caused by ALD or otherwise.
Not useful to categorise a case as hepatocellular, cholestatic or infiltrative
Conjugated and unconjugated bilirubin fraction is useful to distinguish rise in bilirubin caused by liver disease versus haemolysis or Gilbert’s syndrome
Liver disease (many types, including ALD) will have elevated conjugated bilirubin
Haemolysis or Gilbert’s syndrome will have elevated non-conjugated bilirubin, more than 90% of total bilirubin will be unconjugated

Serum albumin
Reduced serum albumin
Liver synthesises albumin, therefore low levels indicates diminished synthetic function

Serum prothrombin time, INR
Elevated prothrombin time/INR
Indicates diminished synthetic function of liver

Liver ultrasound
May be used to differentiate abnormal liver function tests caused by other pathologies e.g. hepatocellular carcinoma, cholestasis, liver mass/abscess
If known ALD and cirrhosis, is useful to screen for hepatocellular carcinoma development

Liver biopsy
Not usually necessary for ALD due to invasiveness of procedure
If performed, may be percutaneous or transjugular
Histological findings vary depending on stage of ALD
Stage Histological findings
Steatosis (early ALD) Fat droplets, mostly in peri-venular areas
Alcoholic hepatitis Mallory-Denk bodies, neutrophil-rich inflammation with necrosis, hepatocyte ballooning
Steatofibrosis (cirrhosis) Peri-venular and peri-cellular fibrosis, fibrous septa, micronodular fibrosis (Laennec’s cirrhosis)

Other investigations to consider
Normally, investigations may be used in order to distinguish between causes of liver damage, as often the signs/symptoms are non-specific
Viral hepatitis serology
Serum ceruloplasmin
May be normal or raised in ALD
Low in Wilson's disease
Serum iron, transferrin and ferritin
To rule out haemochromatosis
Anti-mitochondrial antibody
To rule out primary biliary cirrhosis
Alpha-1 antitrypsin levels
To rule out alpha-1 antitrypsin deficienc

Question 23

Mx with ALD

Answer 23

Ideally, the aim of treatment in ALD is to prevent and/or slow the progression of liver damage, which can be fatal.

General measures
Alcohol abstinence
Likely the most important part of management is the complete cessation of alcohol consumption
This not only slows the progression of disease, but improves the long-term survival for patients, even in the late stages of disease where there is existing cirrhosis with de-compensation
Weight loss
This is particularly important in overweight or obese patients, where a component of liver disease may be caused by non-alcoholic fatty liver
Vaccinations
In the absence of past or current infection, hepatitis A and B immunisations should be provided to reduce likelihood of infection and compounding liver damage
Nutrition
A high protein dit should be instituted, particularly in those with alcoholic hepatitis (1-1.5g of protein/kg for adequate recovery)
Consider feeding tube for enteral feeding if anorexia or altered mental status

Alcohol withdrawal
The standard for treating acute alcohol withdrawal is benzodiazepines (e.g. diazepam)
Quick-acting benzodiazepine (e.g. lorazepam) for alcohol withdrawal seizures
Oral lorazepam is the first-line treatment for delirium tremens in alcohol withdrawal

Acute alcoholic hepatitis
While there is no single approved therapy for ALD, glucocorticoids (e.g. prednisolone) are considered the standard of care for acute alcoholic hepatitis and are often used
May improve short-term survival, but are unlikely to show a long-term benefit
The NICE guidelines suggest the use of Maddrey’s discriminant function (DF) to identify patients with severe acute alcoholic hepatitis
DF of >32 predicts a high mortality within 90 days, and means a liver biopsy should be considered, with corticosteroid treatment initiation
Pentoxifylline can be used as an alternative to glucocorticoids if they are contraindicated (e.g. hepatitis B viral infection, tuberculosis, other serious infection)

End-stage ALD
In patients with end-stage ALD (cirrhosis with decompensation), liver transplantation can be considered
Usually must be alcohol free for >6 months

Question 24

Cx of ALD

Answer 24

Hepatic encephalopathy
In severe cases, hepatic encephalopathy can occur as a result of significant toxin build-up (ammonia), characterised by symptoms and signs including:
Confusion
Drowsiness
Hyperventilation
Asterixis
Fetor hepaticus
This should be managed with supportive care plus lactulose until laxative effect is achieved.

Portal hypertension
This complication occurs once liver cirrhosis is established.
If the blood vessels in the liver are blocked due to severe liver fibrosis, a high pressure develops in the portal venous system.
This leads to large varices within the venous system in the esophagus, stomach, rectum and umbilicus.
This results in secondary complications such as variceal haemorrhage which can be life-threatening, ascites and splenomegaly.
Ascites can be complicated by spontaneous bacterial peritonitis (suspect in patients with abdominal distention, pain +/- fever)
This can be managed with a transjugular intrahepatic portal-systemic shunt (TIPSS) if there is acute bleeding, particularly if gastric varices are present

Hepato-renal syndrome
As a result of portal hypertension, there is widespread splanchnic vasodilation
This leads to a reduction in the effective circulating volume, which can reduce the blood flow to the kidneys, compromising the renal system and potentially leading to a life-threatening acute kidney failure

Hepatocellular carcinoma
Once liver cirrhosis is established, there is a significantly increased risk in development of hepatocellular carcinoma
Hepatic ultrasound should be undertaken serially approximately every 6 months to yearly to screen for liver cancer development