Gastro

Question 1

What makes up the biliary tree?

Answer 1

hepatic duct, cystic duct makes up the common bile duct which combines with pancreatic duct to form hepatopancreatic ampulla leading into the duodenum

Question 2

What is liver cirrhosis and what are the common causes?
What examination signs could you find?

Answer 2

Liver cirrhosis is the result of chronic inflammation and damage to liver cells. The functional liver cells are replaced with scar tissue (fibrosis). Nodules of scar tissue form within the liver.

Fibrosis affects the structure and blood flow through the liver, increasing the resistance in the vessels leading into the liver. This increased resistance and pressure in the portal system is called portal hypertension.

The four most common causes of liver cirrhosis are:

Alcohol-related liver disease
Non-alcoholic fatty liver disease (NAFLD)
Hepatitis B
Hepatitis C

Examination findings:
Cachexia (wasting of the body and muscles)
Jaundice caused by raised bilirubin
Hepatomegaly (enlargement of the liver)
Small nodular liver as it becomes more cirrhotic
Splenomegaly due to portal hypertension
Spider naevi (telangiectasia with a central arteriole and small vessels radiating away)
Palmar erythema caused by elevated oestrogen levels
Gynaecomastia and testicular atrophy in males due to endocrine dysfunction
Bruising due to abnormal clotting
Excoriations (scratches on the skin due to itching)
Ascites (fluid in the peritoneal cavity)
Caput medusae (distended paraumbilical veins due to portal hypertension)
Leukonychia (white fingernails) associated with hypoalbuminaemia
Asterixis (“flapping tremor”) in decompensated liver disease

Question 3

What investigations would you do if suspecting liver cirrhosis?

Answer 3

Non-Invasive Liver Screen
Abnormal liver function tests without a clear cause require a non-invasive liver screen, which includes:

Ultrasound liver (used to diagnose fatty liver)
Hepatitis B and C serology
Autoantibodies (autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis)
Immunoglobulins (autoimmune hepatitis and primary biliary cirrhosis)
Caeruloplasmin (Wilsons disease)
Alpha-1 antitrypsin levels (alpha-1 antitrypsin deficiency)
Ferritin and transferrin saturation (hereditary haemochromatosis)

Autoantibodies relevant to liver disease include:

Antinuclear antibodies (ANA)
Smooth muscle antibodies (SMA)
Antimitochondrial antibodies (AMA)
Antibodies to liver kidney microsome type-1 (LKM-1)

Blood Tests
Liver function tests (LFTs) may be normal in cirrhosis. However, in decompensated cirrhosis, all the liver markers become deranged, with raised:

Bilirubin
Alanine transaminase (ALT)
Aspartate transferase (AST)
Alkaline phosphatase (ALP)

Other blood results include:

Low albumin due to reduced synthetic function of the liver
Increased prothrombin time due to reduced synthetic function of the liver (reduced production of clotting factors)
Thrombocytopenia (low platelets) is a common finding and indicates more advanced disease
Hyponatraemia (low sodium) occurs with fluid retention in severe liver disease
Urea and creatinine become deranged in hepatorenal syndrome
Alpha-fetoprotein is a tumour marker for hepatocellular carcinoma

Question 4

What is the management for liver cirrhosis?

Answer 4

There are four principles of management:

Treating the underlying cause
Monitoring for complications
Managing complications
Liver transplant

The underlying cause needs to be addressed. For example:

Stop drinking alcohol
Lifestyle changes for non-alcohol fatty liver disease
Antiviral drugs for hepatitis C
Immunosuppressants for autoimmune hepatitis

Monitoring for complications involves:

MELD score every 6 months
Ultrasound and alpha-fetoprotein every 6 months for hepatocellular carcinoma
Endoscopy every 3 years for oesophageal varices

Liver transplantation is generally considered when there are features of decompensated liver disease. The four key features can be remembered with the “AHOY” mnemonic:

A – Ascites
H – Hepatic encephalopathy
O – Oesophageal varices bleeding
Y – Yellow (jaundice)

Question 5

What are complications of liver cirrhosis?

Answer 5

There are several important complications of cirrhosis:

Malnutrition and muscle wasting
Portal hypertension, oesophageal varices and bleeding varices
Ascites and spontaneous bacterial peritonitis
Hepatorenal syndrome
Hepatic encephalopathy
Hepatocellular carcinoma

Malnutrition
Cirrhosis leads to malnutrition and muscle wasting. Patients often have a loss of appetite resulting in reduced intake. Cirrhosis affects protein metabolism in the liver and reduces the amount of protein the liver produces. It also disrupts the ability of the liver to store glucose as glycogen and release it when required. Overall, less protein is available for maintaining muscle tissue and muscle tissue is broken down for use as fuel.

Management involves nutritional support guided by a dietician, with:

Regular meals
High protein and calorie intake
Reduced sodium intake to minimise fluid retention
Avoiding alcohol

Portal Hypertension and Varices
The portal vein comes from the superior mesenteric and splenic veins and delivers blood to the liver. Liver cirrhosis increases the resistance to blood flow in the liver. As a result, there is increased back pressure on the portal system. This is called portal hypertension. The back pressure of blood results in splenomegaly.

Back pressure in the portal system causes swollen and tortuous vessels at sites where collaterals form between the portal and systemic venous systems. These collaterals can occur at several locations, notably the:

Distal oesophagus (oesophageal varices)
Anterior abdominal wall (caput medusae)

Varices are asymptomatic until they start bleeding. Due to the high blood flow, bleeding from varices can cause patients to exsanguinate (bleed out) very quickly.

Prophylaxis of bleeding in stable oesophageal varices involves:

Non-selective beta blockers (e.g., propranolol) first-line
Variceal band ligation (if beta blockers are contraindicated)

Variceal band ligation involves a rubber band wrapped around the base of the varices, cutting off the blood flow through the vessels.

Bleeding Oesophageal Varices
Bleeding oesophageal varices is a life-threatening emergency. Initial management involves:

Immediate senior help
Consider blood transfusion (activate the major haemorrhage protocol)
Treat any coagulopathy (e.g., with fresh frozen plasma)
Vasopressin analogues (e.g., terlipressin or somatostatin) cause vasoconstriction and slow bleeding
Prophylactic broad-spectrum antibiotics (shown to reduce mortality)
Urgent endoscopy with variceal band ligation
Consider intubation and intensive care

Other options to control the bleeding include:

Sengstaken-Blakemore tube (an inflatable tube inserted into the oesophagus to tamponade the bleeding varices)
Transjugular intrahepatic portosystemic shunt (TIPS)

Transjugular intrahepatic portosystemic shunt (TIPS) is a technique where an interventional radiologist inserts a wire under x-ray guidance into the jugular vein, down the vena cava and into the liver via the hepatic vein. A connection is made through the liver between the hepatic vein and portal vein, and a stent is inserted. This allows blood to flow directly from the portal vein to the hepatic vein, relieving the pressure in the portal system. The two main indications are:

Bleeding oesophageal varices
Refractory ascites

Ascites
Ascites refers to fluid in the peritoneal cavity. The increased pressure in the portal system causes fluid to leak out of the capillaries in the liver and other abdominal organs into the peritoneal cavity. The drop in circulating volume caused by fluid loss into the peritoneal cavity causes reduced blood pressure in the kidneys. The kidneys sense this lower pressure and release renin, which leads to increased aldosterone secretion via the renin-angiotensin-aldosterone system. Increased aldosterone causes the reabsorption of fluid and sodium in the kidneys, leading to fluid and sodium retention. Cirrhosis causes transudative (low protein content) ascites.

Management options include:

Low sodium diet
Aldosterone antagonists (e.g., spironolactone)
Paracentesis (ascitic tap or ascitic drain)
Prophylactic antibiotics (ciprofloxacin or norfloxacin) when there is <15 g/litre of protein in the ascitic fluid
Transjugular intrahepatic portosystemic shunt (TIPS) is considered in refractory ascites
Liver transplantation is considered in refractory ascites

Spontaneous Bacterial Peritonitis
Spontaneous bacterial peritonitis (SBP) occurs in 10-20% of patients with ascites. It has a mortality of 10-20%. It involves an infection developing in the ascitic fluid and peritoneal lining without a clear source of infection (e.g., an ascitic drain or bowel perforation).

Spontaneous bacterial peritonitis can be asymptomatic. Presenting features include:

Fever
Abdominal pain
Deranged bloods (raised WBC, CRP, creatinine or metabolic acidosis)
Ileus (reduced movement in the intestines)
Hypotension

The most common organisms are:

Escherichia coli
Klebsiella pneumoniae

Management involves:

Taking a sample of ascitic fluid for culture before giving antibiotics
Intravenous broad-spectrum antibiotics according to local policies (e.g., piperacillin with tazobactam)

Hepatorenal Syndrome
Hepatorenal syndrome involves impaired kidney function caused by changes in the blood flow to the kidneys relating to liver cirrhosis and portal hypertension.

The exact pathophysiology is still being debated. A simplified version is that portal hypertension causes the portal vessels to release vasodilators, which cause significant vasodilation in the splanchnic circulation (the vessels supplying the gastrointestinal organs). Vasodilation leads to reduced blood pressure. The kidneys respond to the reduced pressure by activating the renin-angiotensin-aldosterone system, which leads to vasoconstriction of the renal vessels. Renal vasoconstriction combined with low systemic pressure results in the kidneys being starved of blood and significantly reduced kidney function.

Hepatorenal syndrome has a poor prognosis unless the patient has a liver transplant.

Hepatic Encephalopathy
Hepatic encephalopathy is also known as portosystemic encephalopathy. It is thought to be caused by the build-up of neurotoxic substances that affect the brain.

One toxin particularly worth remembering is ammonia, produced by intestinal bacteria when they break down proteins. Ammonia is absorbed in the intestines. There are two reasons that ammonia builds up in the blood in patients with cirrhosis: Firstly, the liver cells’ functional impairment prevents them from metabolising the ammonia into harmless waste products. Secondly, collateral vessels between the portal and systemic circulation mean that the ammonia bypasses the liver and enters the systemic system directly.

Acutely, hepatic encephalopathy presents with reduced consciousness and confusion. It can present more chronically with changes to personality, memory and mood.

Factors that can trigger or worsen hepatic encephalopathy are:

Constipation
Dehydration
Electrolyte disturbance
Infection
Gastrointestinal bleeding
High protein diet
Medications (particularly sedative medications)

Management involves:

Lactulose (aiming for 2-3 soft stools daily)
Antibiotics (e.g., rifaximin) to reduce the number of intestinal bacteria producing ammonia
Nutritional support (nasogastric feeding may be required)

Question 6

What is non-alcoholic fatty liver disease?
What are its stages in order?
What are the risk factors?

Answer 6

Non-alcoholic fatty liver disease (NAFLD) is characterised by excessive fat in the liver cells, specifically triglycerides. These fat deposits interfere with the functioning of the liver cells. The early stages of NAFLD can be asymptomatic. However, it can progress to hepatitis and liver cirrhosis.

Around 25% of adults are estimated to have non-alcoholic fatty liver disease.

he stages of non-alcoholic fatty liver disease are:

1. Non-alcoholic fatty liver disease
2. Non-alcoholic steatohepatitis (NASH)
3. Fibrosis
4. Cirrhosis

Non-alcoholic fatty liver disease shares the same risk factors as cardiovascular disease and diabetes:

• Middle age onwards
• Obesity
• Poor diet and low activity levels
• Type 2 diabetes
• High cholesterol
• High blood pressure
• Smoking

Question 7

What investigations would you do if you suspected Non-alcholic fatty liver disease?

What is the managment?

Answer 7

Raised alanine aminotransferase (ALT) on the liver function blood tests is often the first indication that a patient has NAFLD.

Liver ultrasound can confirm the diagnosis of hepatic steatosis (fatty liver), seen as increased echogenicity. Ultrasound does not indicate the severity, function of the liver or presence of fibrosis. It can be normal in NAFLD.

The enhanced liver fibrosis (ELF) blood test is the first-line investigation for assessing fibrosis in non-alcoholic fatty liver disease. It measures three markers (HA, PIIINP and TIMP-1) and uses an algorithm to provide a result that indicates whether they have advanced fibrosis of the liver:

10.51 or above – advanced fibrosis
Under 10.51 – unlikely advanced fibrosis (NICE recommend rechecking every 3 years in NAFLD)

NAFLD Fibrosis Score (NFS) is another option for assessing liver fibrosis in NAFLD. It is based on an algorithm of age, BMI, liver enzymes (AST and ALT), platelet count, albumin and diabetes.

Fibrosis 4 (FIB-4) score is another option for assessing liver fibrosis in NAFLD. It is based on an algorithm of age, liver enzymes (AST and ALT) and platelet count.

Transient elastography (“FibroScan”) can be used to assess the stiffness of the liver using high-frequency sound waves. It helps determine the degree of fibrosis (scarring) to test for liver cirrhosis. It is used where the enhanced liver fibrosis (ELF) test indicates advanced fibrosis.

Liver biopsy may be required to confirm the diagnosis and exclude other causes of liver disease.

TOM TIP: Both the NFS and FIB-4 scores use the AST:ALT ratio to assess the severity of liver fibrosis. The normal ratio is less than 1. A ratio greater than 0.8 in NAFLD suggests advanced fibrosis. An AST:ALT ratio greater than 1.5 (meaning a disproportionately high AST) indicates alcohol-related liver disease rather than NAFLD.

Diagnosis
The diagnosis requires the presence of ultrasound findings of a fatty liver, risk factors and excluding other causes of liver disease with a careful alcohol history and full non-invasive liver screen. Liver biopsy is the gold standard test.

Management involves:

• Weight loss
• Healthy diet (Mediterranean diet is recommended)
• Exercise
• Avoid/limit alcohol intake
• Stop smoking
• Control of diabetes, blood pressure and cholesterol
• Refer patients where scoring tests indicate liver fibrosis to a liver specialist
• Specialist management may include vitamin E, pioglitazone, bariatric surgery and liver transplantation

Question 8

What are the stages of alcohol-related liver disease?
What investigations would you do?

Answer 8

There is a stepwise progression of alcohol-related liver disease.

1. Alcoholic fatty liver (also called hepatic steatosis)

Drinking leads to a build-up of fat in the liver. This process is reversible with abstinence.

2. Alcoholic hepatitis

Drinking alcohol over a long period causes inflammation in the liver cells. Binge drinking is associated with the same effect. Mild alcoholic hepatitis is usually reversible with permanent abstinence.

3. Cirrhosis

Cirrhosis is where the functional liver tissue is replaced with scar tissue. It is irreversible. Stopping drinking can prevent further damage. Continued drinking has a very poor prognosis.

Blood test results suggesting alcohol-related liver disease include:

Raised mean cell volume (MCV)
Raised alanine transaminase (ALT) and aspartate transferase (AST)
AST:ALT ratio above 1.5 particularly suggests alcohol-related liver disease
Raised gamma-glutamyl transferase (gamma-GT) (particularly notable with alcohol-related liver disease)
Raised alkaline phosphatase (ALP) later in the disease
Raised bilirubin in cirrhosis
Low albumin due to reduced synthetic function of the liver
Increased prothrombin time due to reduced synthetic function of the liver (reduced production of clotting factors)
Deranged U&Es in hepatorenal syndrome

Liver ultrasound may show early fatty changes with “increased echogenicity”. Later, it can show changes related to cirrhosis. Ultrasound is used to screen for hepatocellular carcinoma in patients with cirrhosis.

Transient elastography (“FibroScan”) can be used to assess the elasticity of the liver using high-frequency sound waves. It helps determine the degree of fibrosis (scarring).

Endoscopy can be used to assess for and treat oesophageal varices when portal hypertension is suspected.

CT and MRI scans can be used to look for fatty infiltration of the liver, hepatocellular carcinoma, hepatosplenomegaly, abnormal blood vessel changes and ascites.

Liver biopsy can be used to confirm the diagnosis of alcohol-related hepatitis or cirrhosis, particularly in patients where steroid treatment is being considered for alcohol-related hepatitis.

Question 9

How do you manage alcohol related liver disease?
How do you manage alchol withdrawals?
What is Wernicke-Korsakoff Syndrome?

Answer 9

The general principles of managing alcohol-related liver disease are:

• Stop drinking alcohol permanently (drug and alcohol services are available for support)
• Psychological interventions (e.g., motivational interviewing or cognitive behavioural therapy)
• Consider a detoxication regime
• Nutritional support with vitamins (particularly thiamine – vitamin B1) and a high-protein diet
• Corticosteroids may be considered to reduce inflammation in severe alcoholic hepatitis to improve short-term outcomes (but not long-term outcomes)
• Treat complications of cirrhosis (e.g., portal hypertension, varices, ascites and hepatocellular carcinoma)
• Liver transplant in severe disease (generally 6 months of abstinence is required)

Managing Alcohol Withdrawal:

The CIWA-Ar (Clinical Institute Withdrawal Assessment for Alcohol, revised) tool can be used to score the patient on their withdrawal symptoms and guide treatment.

Chlordiazepoxide (Librium) is a benzodiazepine used to combat the effects of alcohol withdrawal. Diazepam is a less commonly used alternative. It is given orally as a reducing regime titrated to the required dose based on the local alcohol withdrawal protocol (e.g., 10 – 40 mg every 1 – 4 hours). The dose is reduced over 5-7 days.

High-dose B vitamins (Pabrinex) is given intramuscularly or intravenously, followed by long-term oral thiamine. This is used to prevent Wernicke-Korsakoff syndrome.

Wernicke-Korsakoff Syndrome:

Alcohol excess leads to thiamine (vitamin B1) deficiency. Thiamine is poorly absorbed in the presence of alcohol. Alcoholics often have poor diets and get many of their calories from alcohol. Thiamine deficiency leads to Wernicke’s encephalopathy and Korsakoff syndrome.

Features of Wernicke’s encephalopathy include:

Confusion
Oculomotor disturbances (disturbances of eye movements)
Ataxia (difficulties with coordinated movements)

Features of Korsakoff syndrome include:

Memory impairment (retrograde and anterograde)
Behavioural changes

Question 10

How do you manage hepatitis B?

Answer 10

Management of hepatitis B involves:

A low threshold for screening patients at risk of hepatitis B
Screen for other viral infections (e.g., HIV, hepatitis A, C and D)
Referral to gastroenterology, hepatology or infectious diseases for specialist management
Avoid alcohol
Education about reducing transmission
Contact tracing and informing potential at-risk contacts
Testing for complications (e.g., FibroScan for cirrhosis and ultrasound for hepatocellular carcinoma)
Antiviral medication can be used to slow the progression of the disease and reduce infectivity
Liver transplantation for liver failure (fulminant hepatitis)

Question 11

What ivestigations would you do if suspected autoimmune hepatitus?
What is the management?

Answer 11

Investigations will show high transaminases (ALT and AST) and minimal change in ALP levels (a “hepatitic” picture). Raised immunoglobulin G (IgG) levels are an important finding.

Management:
Treatment is with high-dose steroids (e.g., prednisolone). Other immunosuppressants are also used, particularly azathioprine. Immunosuppressant treatment is usually successful at inducing remission (controlling the disease).

Liver transplant may be required in end-stage liver disease. Autoimmune hepatitis can reoccur in the new liver.

Question 12

What is haemochromatosis and what is its key presentation?

Answer 12

Haemochromatosis is an autosomal recessive genetic condition resulting in iron overload. There is excessive total body iron and deposition of iron in tissues. It is an iron storage disorder.

Key presentation:
bronze skin

Question 13

What is Wilsons disease and what is its key presentation?

Answer 13

Wilson’s disease is an autosomal recessive genetic condition resulting in the excessive accumulation of copper in the body tissues, particularly in the liver.

It is caused by mutations in the Wilson disease protein gene on chromosome 13 (also called the ATP7B copper-binding protein). This copper-transporting protein is important in helping remove excess copper from the body via the liver. Copper is excreted in the bile.

Key presentation:
Kayser-Fleischer rings

Question 14

What is primary biliary cholangitis?

Answer 14

Primary biliary cholangitis is an autoimmune condition where the immune system attacks the small bile ducts in the liver, resulting in obstructive jaundice and liver disease. It was previously known as primary biliary cirrhosis.

Pathophysiology
Primary biliary cholangitis affects the small bile ducts inside the liver (the intrahepatic ducts). There is inflammation and damage to the epithelial cells of the bile ducts (the cholangiocytes). Over time, this can lead to obstruction of bile flow through these ducts. Reduced flow of bile is called cholestasis. The back-pressure of bile and the overall disease process ultimately lead to liver fibrosis, cirrhosis and failure.

Bile acids, bilirubin and cholesterol are excreted through the bile ducts into the intestines. When obstruction to the outflow of these chemicals means they are not being excreted, they build up in the blood. Raised bile acids cause itching, and raised bilirubin causes jaundice.

Raised cholesterol causes cholesterol deposits in the skin called xanthelasma. Xanthomas are larger nodular deposits of cholesterol in the skin or tendons. Raised cholesterol increases the risk of atherosclerosis and cardiovascular disease.

Bile acids help with the digestion of fats. Reduced or absent bile acids in the gastrointestinal tract cause abdominal symptoms, malabsorption of fat and greasy stools.

Bilirubin is responsible for the darker colour of stools. A lack of bilirubin results in pale stools. Excretion of bilirubin via the urine causes dark urine.

Question 15

How does primary biliary cholangitis present?
What are the main investigations?
What is the main treatment?

Answer 15

The typical patient is a white woman aged 40-60 years. Often patients are asymptomatic at diagnosis, with the problem picked up on abnormal liver function tests. However, they may present with:

• Fatigue
• Pruritus (itching)
• Gastrointestinal symptoms and abdominal pain
• Jaundice
• Pale, greasy stools
• Dark urine

Liver function tests show:

Raise alkaline phosphatase (the most notable liver enzyme as with most “obstructive” pathology)

Autoantibodies relevant to primary biliary cholangitis are:

Anti-mitochondrial antibodies (AMA) are the most specific to PBC and form part of the diagnostic criteria

Treatment:
Ursodeoxycholic acid is the most essential treatment to remember in primary biliary cholangitis. It is a non-toxic, hydrophilic bile acid that protects the cholangiocytes from inflammation and damage. It makes the bile less harmful to the epithelial cells of the bile ducts. It slows the disease progression and improves outcomes

Question 16

What is primary sclerosing cholangitis?

Answer 16

Primary sclerosing cholangitis is a condition where the intrahepatic and extrahepatic bile ducts become inflamed and damaged, developing strictures that obstruct the flow of bile out of the liver and into the intestines. Sclerosis refers to the stiffening and hardening of the bile ducts, and cholangitis is inflammation of the bile ducts. Chronic bile obstruction eventually leads to liver inflammation (hepatitis), fibrosis and cirrhosis.

The cause is unclear and thought to be combined genetic and environmental factors. There is a strong association with ulcerative colitis, with around 70% of cases occurring alongside pre-existing ulcerative colitis. Less commonly, it can be associated with Crohn’s disease.

The key risk factors for primary sclerosing cholangitis are:

Male
Aged 30-40
Ulcerative colitis
Family history

Question 17

What are the investigation for primary sclerosing cholangitis?

What is the management?

Answer 17

Liver function tests show:

Raise alkaline phosphatase (the most notable liver enzyme as with most “obstructive” pathology)

Magnetic resonance cholangiopancreatography (MRCP) is the diagnostic imaging investigation. It involves an MRI scan that gives a detailed view of the bile ducts, showing bile duct strictures in primary sclerosing cholangitis.

Management:
Endoscopic retrograde cholangio-pancreatography (ERCP) may be used to treat dominant strictures. This involves inserting an endoscope down the oesophagus, past the stomach, to the duodenum and the opening of the common bile duct (the sphincter of Oddi). This gives the operator access to the biliary system. Strictures can be dilated. Stents can be inserted to keep the ducts open. Antibiotics are given alongside ERCP to reduce the risk of infection (bacterial cholangitis).

Question 18

What are the rsik factors for hepatocellular carcinoma (HCC)?

How does HCC present?

Answer 18

The main risk factor for hepatocellular carcinoma (HCC) is liver cirrhosis due to:

• Alcohol-related liver disease
• Non-alcoholic fatty liver disease (NAFLD)
• Hepatitis B
• Hepatitis C
• Rarer causes (e.g., primary sclerosing cholangitis)

There are non-specific presenting features associated with liver cancer:

• Weight loss
• Abdominal pain
• Anorexia
• Nausea and vomiting
• Jaundice
• Pruritus
• Upper abdominal mass on palpation

Question 19

What are the investigations for hepatocellular carcinoma?

What is the management for hepatocellular carcinoma?

Answer 19

Relevant investigations in assessing liver cancer are:

Alpha-fetoprotein (tumour marker for hepatocellular carcinoma)
Liver ultrasound is the first-line imaging investigation
CT and MRI scans are used for further assessment and staging of the cancer
Biopsy is used for histology

Hepatocellular carcinoma has a very poor prognosis unless diagnosed early.

Surgery may be possible in early disease. Resection can be used when the tumour is isolated in a removable liver area. A liver transplant is an option when the tumour is isolated to the liver and the patient meets specific criteria.

Other options for treating liver cancer include:

Radiofrequency ablation (destroying the tumour cells with heat)
Microwave ablation (destroying the tumour cells with heat)
Transarterial chemoembolisation (TACE)
Radiotherapy
Targeted drugs (e.g., kinase inhibitors and monoclonal antibodies)

Question 20

What conditions does painless jaundice suggest?

Answer 20

Painless jaundice should make you think of cholangiocarcinoma or cancer of the head of the pancreas. Pancreatic cancer is more common, so this is likely the answer in your exams.

Cholangiocarcinoma is a type of cancer that originates in the bile ducts. The majority are adenocarcinomas. It may affect the bile ducts inside the liver (intrahepatic ducts) or outside the liver (extrahepatic ducts). The most common site is in the perihilar region, where the right and left hepatic ducts have joined to become the common hepatic duct just after leaving the liver.

Cholangiocarcinoma is associated with primary sclerosing cholangitis. However, only 10% of patients with cholangiocarcinoma have primary sclerosing cholangitis. Cholangiocarcinoma usually presents in patients over 50 years old unless related to primary sclerosing cholangitis.

Obstructive jaundice is the key presenting feature to remember. Obstructive jaundice is associated with:

Pale stools
Dark urine
Generalised itching

Question 21

What is gastro-oesophageal reflux disease (GORD)?
What are the causes and triggers?
How does it present?

Answer 21

Gastro-oesophageal reflux disease (GORD) is where acid from the stomach flows through the lower oesophageal sphincter and into the oesophagus, where it irritates the lining and causes symptoms.

The oesophagus has a squamous epithelial lining that makes it more sensitive to the effects of stomach acid. The stomach has a columnar epithelial lining that is more protected against stomach acid.

Certain factors can exacerbate or worsen the symptoms of GORD:

• Greasy and spicy foods
• Coffee and tea
• Alcohol
• Non-steroidal anti-inflammatory drugs
• Stress
• Smoking
• Obesity
• Hiatus hernia

Dyspepsia is a non-specific term used to describe indigestion. It covers the symptoms of GORD:

• Heartburn
• Acid regurgitation
• Retrosternal or epigastric pain
• Bloating
• Nocturnal cough
• Hoarse voice

Question 22

What are the investigation and management?

Answer 22

The usual medical strategy when someone presents for the first time is to exclude red flags like dysphagia, address potential triggers, offer a 1 month trial of a proton pump inhibitor and consider H. pylori testing.

Question 23

What is Helicobacter Pylori + what are its investigations and treatments?

Answer 23

Helicobacter pylori (H. pylori) is a gram-negative aerobic bacteria that can live in the stomach. It causes damage to the epithelial lining, resulting in gastritis, ulcers and an increased risk of stomach cancer. It avoids the acidic environment by forcing its way into the gastric mucosa, using flagella to propel itself. It creates gaps in the mucosa, exposing the epithelial cells underneath to damage from stomach acid.

H. pylori produces ammonium hydroxide, which neutralises the acid surrounding the bacteria. It also produces several toxins. The ammonia and toxins lead to gastric mucosal damage.

We offer a test for H. pylori to anyone with dyspepsia. They need 2 weeks without using a PPI before testing for H. pylori for an accurate result.

Investigations for H. Pylori are:

Stool antigen test
Urea breath test using radiolabelled carbon 13
H. pylori antibody test (blood)
Rapid urease test performed during endoscopy (also known as the CLO test)

A rapid urease test involves taking a small biopsy of the stomach mucosa. This is added to a liquid medium containing urea. H. pylori produce urease enzymes that convert urea to ammonia. Ammonia makes the solution more alkaline. A pH indicator (e.g., phenol red) changes colour if the pH rises, giving a positive result.

The H. pylori eradication regime involves triple therapy with a proton pump inhibitor (e.g., omeprazole) plus two antibiotics (e.g., amoxicillin and clarithromycin) for 7 days. Routine re-testing is not necessary after treatment.

Question 24

What is Barrett’s Oesophagus and what is the treatment?

What is Zollinger–Ellison Syndrome?

Answer 24

Barrett’s oesophagus refers to when the lower oesophageal epithelium changes from squamous to columnar epithelium. This process is called metaplasia. It is caused by chronic acid reflux into the oesophagus. Patients may notice improved reflux symptoms after they develop Barrett’s oesophagus.

Barrett’s oesophagus is a premalignant condition and a significant risk factor for developing oesophageal adenocarcinoma (cancer of the epithelial cells). There can be a stepwise progression from no dysplasia to low-grade dysplasia, high-grade dysphasia, and adenocarcinoma.

Treatment of Barrett’s oesophagus is with:

Endoscopic monitoring for progression to adenocarcinoma
Proton pump inhibitors
Endoscopic ablation (e.g., radiofrequency ablation)

Ablation can be used to destroy abnormal columnar epithelial cells, which are then replaced with normal squamous epithelial cells. Ablation has a role in treating low and high-grade dysplasia to reduce cancer risk.

TOM TIP: The histology of Barrett’s oesophagus is a common exam topic. Remember the term metaplasia, which means a change in the type of cell. This is different from dysplasia, which refers to the presence of abnormal cells. Remember that the normal epithelium is squamous, and in Barrett’s it changes to columnar.

Zollinger-Ellison syndrome is a rare condition where a duodenal or pancreatic tumour secretes excessive quantities of gastrin. Gastrin is a hormone that stimulates acid secretion in the stomach. Therefore, there is excess production of stomach acid, resulting in severe dyspepsia, diarrhoea and peptic ulcers.

Gastrin-secreting tumours (gastrinomas) may be associated with multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant genetic condition, which can also cause hormone-secreting tumours of the parathyroid and pituitary glands.

Question 25

What are peptic ulcers and what are the risk factors?

Answer 25

Peptic ulcers involve ulceration of the mucosa of the stomach (gastric ulcer) or the proximal duodenum (duodenal ulcer). Duodenal ulcers are more common.

Pathophysiology
The mucosa, also known as the mucous membrane, is the inner lining of the stomach and duodenum. It secretes mucus that coats the surface and forms a barrier that protects it from the stomach’s contents, particularly stomach acid and digestive enzymes. It secretes bicarbonate into this mucus coating to neutralise the stomach acid.

Factors that disrupt the mucus barrier or increase stomach acid increase the risk of mucosal ulceration.

Risk Factors
The risk key factors that disrupt the mucus barrier are:

Helicobacter pylori
Non-steroidal anti-inflammatory drugs (NSAIDs)

The risk key factors that increase stomach acid are:

Stress
Alcohol
Caffeine
Smoking
Spicy foods

Question 26

How do peptic ulcers present?
What are the signs of upper gastrointestinal bleeding?
How do ypu diagnose and what is the management?

Answer 26

Peptic ulcers present with non-specific symptoms of:

Epigastric discomfort or pain
Nausea and vomiting
Dyspepsia

The signs of upper gastrointestinal bleeding are:

Haematemesis (vomiting blood)
Coffee ground vomiting
Melaena (black, tarry stools)
Fall in haemoglobin on a full blood count

Chronic microscopic bleeding can lead to iron deficiency anaemia, with low haemoglobin, low mean cell volume (MCV) and low ferritin.

TOM TIP: Eating typically worsens the pain of gastric ulcers. The pain of duodenal ulcers tends to improve immediately after eating, followed by pain 2-3 hours later. Patients with gastric ulcers tend to lose weight due to the fear of pain on eating, whereas with duodenal ulcers, the weight is stable or increases. This helps you differentiate them in your MCQ exams.

Diagnosis:
Peptic ulcers can be diagnosed on endoscopy. During endoscopy, a rapid urease test (CLO test) can be performed to check for H. pylori. A biopsy is considered during endoscopy to exclude malignancy.

The core aspects of treating peptic ulcers are:

Stopping NSAIDs
Treating H. pylori infections
Proton pump inhibitors (e.g., lansoprazole or omeprazole)

Repeat endoscopy (at 4-8 weeks) may be performed to ensure the ulcer heals.

Question 27

What are the causes of an upper GI?
How can it present?

Answer 27

The key sources of bleeding are:

Peptic ulcers (the most common cause)
Mallory-Weiss tear (a tear of the oesophageal mucosa)
Oesophageal varices (secondary to portal hypertension in liver cirrhosis)
Stomach cancers

The presenting features of an upper gastrointestinal bleed are:

Haematemesis (vomiting blood)
Coffee ground vomit (caused by vomiting digested blood with the appearance of coffee grounds)
Melaena (tar-like, black, greasy and offensive stools caused by digested blood)

Question 28

What is IBD and what are its features?

Answer 28

Inflammatory bowel disease involves recurrent episodes of inflammation in the gastrointestinal tract. The two main types are ulcerative colitis and Crohn’s disease. They are associated with periods of exacerbation and remission.

Inflammatory bowel disease is thought to be caused by a combination of factors related to genetics, environment and the gut microbiome. The typical patient presents in their 20s.

The general presenting features of inflammatory bowel disease are:

• Diarrhoea
• Abdominal pain
• Rectal bleeding
• Fatigue
• Weight loss

Question 29

What are the differentiating features of Cronhs and ulcerative collitus?

Answer 29

Differentiating features of Crohn’s can be remembered with the “crows” NESTS mnemonic:

N – No blood or mucus (PR bleeding is less common)
E – Entire gastrointestinal tract affected (from mouth to anus)
S – “Skip lesions” on endoscopy
T – Terminal ileum most affected and Transmural (full thickness) inflammation
S – Smoking is a risk factor (don’t set the nest on fire)

Crohn’s is also associated with strictures and fistulas.

Differentiating features of ulcerative colitis can be remembered with the “you see (UC)” CLOSEUP mnemonic:

C – Continuous inflammation
L – Limited to the colon and rectum
O – Only superficial mucosa affected
S – Smoking may be protective (ulcerative colitis is less common in smokers)
E – Excrete blood and mucus
U – Use aminosalicylates
P – Primary sclerosing cholangitis

Question 30

What investigations would you do if suspected IBD?

Answer 30

Blood tests include:

Full blood count for haemoglobin (low in anaemia) and platelet count (raised with inflammation)
C-reactive protein (CRP) indicates inflammation
Urea and electrolytes (U&Es) indicate electrolyte imbalances and kidney function
Liver function tests (LFTs) can show low albumin in severe disease (protein is lost in the bowel)
Thyroid function tests for hyperthyroidism as a cause of diarrhoea
Anti-tissue transglutaminase antibodies (anti-TTG) for coeliac disease as a differential diagnosis

Stool microscopy and culture can be used to exclude infection as a differential diagnosis (e.g., Salmonella).

Faecal calprotectin is around 90% sensitive and specific for inflammatory bowel disease in adults. It is used as an initial test before moving on to endoscopy.

Colonoscopy with multiple intestinal biopsies is the investigation of choice for establishing the diagnosis.

Imaging investigations (e.g., ultrasound, CT and MRI) can be used to look for complications such as fistulas, abscesses and strictures.

Question 31

How would you manage crohns and ulcerative collitus?

Answer 31

Ulcerative Colitis Management
Mild to moderate acute ulcerative colitis is treated with:

Aminosalicylate (e.g., oral or rectal mesalazine) first-line
Corticosteroids (e.g., oral or rectal prednisolone) second-line

Severe acute ulcerative colitis is treated with:

Intravenous steroids (e.g., IV hydrocortisone) first-line

Other options for severe acute ulcerative colitis include:

Intravenous ciclosporin
Infliximab
Surgery

Options for maintaining remission in ulcerative colitis are:

Aminosalicylate (e.g., oral or rectal mesalazine) first-line
Azathioprine
Mercaptopurine

Ulcerative colitis typically only affects the large bowel and rectum. Therefore, removing the entire large bowel and rectum (panproctocolectomy) will remove the disease. The patient has either a permanent ileostomy or an ileo-anal anastomosis (J-pouch).

An ileostomy is where the end portion of the small bowel (ileum) is brought onto the skin with a spout that drains stools directly into a tightly fitting stoma bag.

A J-pouch is where the ileum (small bowel) is folded back on itself and fashioned into a larger pouch, which is attached to the anus and functions like a rectum, collecting stools before the person opens their bowels.

Inducing remission in an exacerbation of Crohn’s disease is with:

Steroids (e.g., oral prednisolone or IV hydrocortisone) first-line
Enteral nutrition as an alternative, particularly where there are concerns about steroids affecting growth

Enteral nutrition involves a specially formulated liquid diet given orally or by NG feed that replaces the patient’s diet. This induces remission by:

Treating nutritional deficiencies
Improving the gut microbiome
Removing inflammatory foods

Where steroids alone are inadequate, adding other medications may be considered:

Azathioprine
Mercaptopurine
Methotrexate
Infliximab
Adalimumab

Maintaining remission in Crohn’s disease is tailored to the individual, based on risks, side effects, nature of the disease and patient wishes. This might involve no medications.

First-line for maintaining remission in Crohn’s is with either:

Azathioprine
Mercaptopurine

Methotrexate is an alternative for maintaining remission where first-line options are unsuitable.

Surgical options for Crohn’s include:

Resecting the distal ileum when the disease is isolated to this area
Treating strictures
Treating fistulas

Question 32

What are the symptoms of IBS?
What can make the symptoms worse?
What are some red flags conditions that are important to exclude?

Answer 32

Irritable bowel syndrome (IBS) is caused by a disturbance of the gut-brain interaction, resulting in troublesome abdominal and intestinal symptoms. Symptoms can significantly impact the patient’s life.

Irritable bowel syndrome is a functional disorder. This means there is no identifiable bowel disease underlying the symptoms, and the symptoms result from the abnormal functioning of an otherwise normal bowel.

It occurs in up to 20% of the population. It affects women more than men and is more common in younger adults.

Symptoms
The three key features can be remembered with the IBS mnemonic:

I – Intestinal discomfort (abdominal pain relating to the bowels)
B – Bowel habit abnormalities
S – Stool abnormalities (watery, loose, hard or associated with mucus)

The specific symptoms vary with individuals. Common symptoms include:

• Abdominal pain
• Diarrhoea
• Constipation
• Fluctuating bowel habit
• Bloating
• Worse after eating
• Improved by opening bowels
• Passing mucus

Symptoms can be triggered or worsened by:

• Anxiety
• Depression
• Stress
• Sleep disturbance
• Illness
• Medications
• Certain foods
• Caffeine
• Alcohol

Differential Diagnosis
It is important to exclude serious underlying pathology. The top differentials to keep in mind are:

• Bowel cancer
• Inflammatory bowel disease
• Coeliac disease
• Ovarian cancer (often presents with vague symptoms, particularly bloating in women over 50 years)
• Pancreatic cancer

Question 33

How do you diagnose IBS?

What is the management?

Answer 33

A thorough history and examination are required to identify the typical features of IBS and exclude red flags for other underlying pathology.

Investigations can be used to assess for underlying differentials (normal in IBS):

Full blood count for anaemia
Inflammatory markers (e.g., ESR and CRP)
Coeliac serology (e.g., anti-TTG antibodies)
Faecal calprotectin for inflammatory bowel disease
CA125 for ovarian cancer

The NICE clinical knowledge summaries (updated 2022) suggest before a diagnosis, differentials need to be excluded, and the patient should have at least 6 months of abdominal pain or discomfort with at least one of:

• Pain or discomfort relieved by opening the bowels
• Bowel habit abnormalities (more or less frequent)
• Stool abnormalities (e.g., watery, loose or hard)

For a diagnosis, patients also require at least two of:

• Straining, an urgent need to open bowels or incomplete emptying
• Bloating
• Worse after eating
• Passing mucus

Management:
The first step is making a positive diagnosis, explaining the condition and reassuring the patient that evidence of other pathology has been excluded.

Lifestyle advice includes:

Drinking enough fluids
Regular small meals
Adjusting fibre intake according to symptoms (more fibre if predominantly constipated, less with diarrhoea/bloating)
Limit caffeine, alcohol and fatty foods
Low FODMAP diet, guided by a dietician
Probiotic supplements may be considered over-the-counter (discontinuing after 12 weeks if there is no benefit)
Reduce stress where possible
Regular exercise

First-line medications depend on the symptoms:

Loperamide for diarrhoea
Bulk-forming laxatives (e.g., ispaghula husk) for constipation (lactulose can cause bloating and is avoided)
Antispasmodics for cramps (e.g., mebeverine, alverine, hyoscine butylbromide or peppermint oil)

Question 34

What is Coeliac disease?

Answer 34

Coeliac disease is an autoimmune condition triggered by eating gluten. It can develop at any age and is thought to be caused by genetic and environmental factors. There is a link with other autoimmune conditions, particularly type 1 diabetes and thyroid disease.

TOM TIP: Remember for your exams that we test all new cases of type 1 diabetes and autoimmune thyroid disease for coeliac disease, even if they do not have symptoms.

Pathophysiology
In patients with coeliac disease, autoantibodies are created in response to exposure to gluten. These autoantibodies target the epithelial cells of the small intestine, leading to inflammation. These antibodies relate to disease activity and will rise with more active disease and may disappear with effective management. There are three antibodies related to coeliacs (particularly worth remembering the first two):

Anti-tissue transglutaminase antibodies (anti-TTG)
Anti-endomysial antibodies (anti-EMA)
Anti-deamidated gliadin peptide antibodies (anti-DGP)

Inflammation affects the small bowel, particularly the jejunum. The surface of the small intestine is covered in projections called villi, which increase the surface area and help with nutrient absorption. Coeliac disease causes atrophy of the intestinal villi, resulting in malabsorption.

Question 35

How do you diagnose Coeliac?
What is the management?
What are the complications?

Answer 35

Diagnosis
The patient must continue eating gluten while being investigated. Antibodies and histology may be normal if the patient is gluten-free.

The first-line blood tests are:

Total immunoglobulin A levels (to exclude IgA deficiency)
Anti-tissue transglutaminase antibodies (anti-TTG)

Anti-endomysial antibodies (anti-EMA) are a second-line option where there is doubt (e.g., a borderline result).

TOM TIP: Initial anti-TTG and anti-EMA antibody tests are IgA. Some patients have an IgA deficiency. When you test for these antibodies, it is important to test for total immunoglobulin A levels because if the total IgA level is low, the antibody test will be negative, even in a patient with coeliac disease. In this circumstance, you can test for the IgG version of anti-TTG or anti-EMA antibodies.

Patients with a positive antibody test are referred to a gastroenterologist to confirm the diagnosis by endoscopy and jejunal biopsy. Typical biopsy findings are:

Crypt hyperplasia
Villous atrophy

Management
A lifelong gluten-free diet should completely resolve the symptoms. Dietician input may be helpful. Relapse will occur upon consuming gluten. Coeliac antibodies may help monitor the disease.

Complications
If someone with coeliac disease continues eating gluten, even in tiny amounts, it can lead to:

Nutritional deficiencies
Anaemia
Osteoporosis
Hyposplenism (with immunodeficiency, particularly to encapsulated bacteria such as Streptococcus pneumoniae)
Ulcerative jejunitis
Enteropathy-associated T-cell lymphoma (EATL)
Non-Hodgkin lymphoma
Small bowel adenocarcinoma