Gastroenterology Flashcards
Liver cirrhosis definition
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.
Causes of liver cirrhosis
The four most common causes of liver cirrhosis are:
Alcohol-related liver disease
Non-alcoholic fatty liver disease (NAFLD)
Hepatitis B
Hepatitis C
Cirrhosis also has many rarer causes:
Autoimmune hepatitis
Primary biliary cirrhosis
Haemochromatosis
Wilsons disease
Alpha-1 antitrypsin deficiency
Cystic fibrosis
Drugs (e.g., amiodarone, methotrexate and sodium valproate)
Liver cirrhosis 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
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
Antinuclear antibodies (ANA)
Smooth muscle antibodies (SMA)
Antimitochondrial antibodies (AMA)
Antibodies to liver kidney microsome type-1 (LKM-1)
Blood tests for liver disease
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
The enhanced liver fibrosis (ELF) blood test is the first-line investigation for assessing fibrosis in non-alcoholic fatty liver disease. It is not used in patients with other causes of 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)
Ultrasound is used to diagnose non-alcoholic fatty liver disease
Ultrasound is used to diagnose non-alcoholic fatty liver disease (once other causes are excluded). Fatty changes appear as increased echogenicity.
In liver cirrhosis, an ultrasound may show:
Nodularity of the surface of the liver
A “corkscrew” appearance to the hepatic arteries with increased flow as they compensate for reduced portal flow
Enlarged portal vein with reduced flow
Ascites
Splenomegaly
Ultrasound is used as a screening tool for hepatocellular carcinoma (alongside alpha-fetoprotein).
Transient Elastography
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 in patients at risk of cirrhosis:
Alcohol-related liver disease
Heavy alcohol drinkers (men drinking more than 50 units or women drinking more than 35 units per week)
Non-alcoholic fatty liver disease and advanced liver fibrosis (score 10.51 or more on the ELF blood test)
Hepatitis C
Chronic hepatitis B
Other investigations for liver disease
Endoscopy can be used to assess for and treat oesophageal varices when portal hypertension is suspected.
CT and MRI can be used to look for hepatocellular carcinoma, hepatosplenomegaly, abnormal blood vessel changes and ascites.
Liver biopsy can be used to confirm the diagnosis of cirrhosis.
MELD Score
NICE recommend using the MELD (Model for End-Stage Liver Disease) score every 6 months in patients with compensated cirrhosis. The formula considers the bilirubin, creatinine, INR and sodium and whether they require dialysis, giving an estimated 3-month mortality as a percentage.
Child-Pugh Score
The Child-Pugh scores uses 5 factors to assess the severity of cirrhosis and the prognosis. Each factor is considered and scored 1, 2 or 3. The minimum overall score is 5 (scoring 1 for each factor), and the maximum is 15 (scoring 3 for each factor). You can remember the features with the “ABCDE” mnemonic:
A – Albumin
B – Bilirubin
C – Clotting (INR)
D – Dilation (ascites)
E – Encephalopathy
Management of liver cirrhosis
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)
Complications and prognosis of liver cirrhosis
The course of the disease is variable. Overall, 5-year survival is about 50% once cirrhosis has developed. The MELD score or Child-Pugh score can be used as prognostic tools.
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
Liver cirrhosis and 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)
Lactulose works in several ways to reduce ammonia:
Speeds up transit time and reduces constipation (the laxative effect clearing the ammonia before it is absorbed)
Promotes bacterial uptake of ammonia to be used for protein synthesis
Changes the pH of the contents of the intestine to become more acidic, killing ammonia-producing bacteria
Rifaximin is the usual choice of antibiotic as it is poorly absorbed and stays in the gastrointestinal tract. Neomycin and metronidazole are alternatives.
Stages of alcohol-related liver disease
- Alcoholic fatty liver (also called hepatic steatosis)
Drinking leads to a build-up of fat in the liver. This process is reversible with abstinence.
- 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.
- 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.
Recommended alcohol consumption
The UK recommendations (Department of Health updated 2021) are not regularly to drink more than 14 units per week. This should be spread evenly over 3 or more days and not more than 5 units in a single day. Binge drinking is defined as 6 or more units for women and 8 or more for men in a single session.
Complications of alcohol in early pregnancy
Pregnant women should avoid alcohol completely. Alcohol in early pregnancy can lead to:
Miscarriage
Small for dates
Preterm delivery
Fetal alcohol syndrome
Complications of Alcohol
Alcohol-related liver disease
Cirrhosis and its complications (e.g., hepatocellular carcinoma)
Alcohol dependence and withdrawal
Wernicke-Korsakoff syndrome (WKS)
Pancreatitis
Alcoholic cardiomyopathy
Alcoholic myopathy, with proximal muscle wasting and weakness
Increased risk of cardiovascular disease (e.g., stroke or myocardial infarction)
Increased risk of cancer, particularly breast, mouth and throat cancer
Examination Findings with Excess Alcohol
Signs suggestive of excessive alcohol consumption include:
Smelling of alcohol
Slurred speech
Bloodshot eyes
Dilated capillaries on the face (telangiectasia)
Tremor
Investigating alcohol-related liver disease
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.
Managing alcohol-related liver disease
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)
CAGE questions
The CAGE questions can be used to quickly screen for harmful alcohol use:
C – CUT DOWN? Do you ever think you should cut down?
A – ANNOYED? Do you get annoyed at others commenting on your drinking?
G – GUILTY? Do you ever feel guilty about drinking?
E – EYE OPENER? Do you ever drink in the morning to help your hangover or nerves?
AUDIT questionnaire
The Alcohol Use Disorders Identification Test (AUDIT) was developed by the World Health Organisation to screen people for harmful alcohol use. It involves 10 questions with multiple-choice answers and gives a score. A score of 8 or more indicates harmful use.
Alcohol Withdrawal
Alcohol dependence involves a risk of withdrawal symptoms. These range from mild and uncomfortable to delirium tremens. Symptoms occur at different times after alcohol consumption ceases:
6-12 hours: tremor, sweating, headache, craving and anxiety
12-24 hours: hallucinations
24-48 hours: seizures
24-72 hours: delirium tremens
Delirium Tremens
Delirium tremens is a medical emergency associated with alcohol withdrawal. There is a 35% mortality rate if left untreated.
Alcohol is a depressant substance. It stimulates GABA receptors in the brain. GABA receptors have a relaxing effect on the rest of the brain. Alcohol also inhibits glutamate receptors (also known as NMDA receptors), causing a further relaxing effect on the electrical activity of the brain (glutamate is an “excitatory” neurotransmitter).
Chronic alcohol use results in the GABA system becoming down-regulated and the glutamate system becoming up-regulated to balance the effects of alcohol. When alcohol is removed, the GABA system under-functions and the glutamate system over-functions, causing extreme excitability of the brain and excessive adrenergic (adrenalin-related) activity. This presents with:
Acute confusion
Severe agitation
Delusions and hallucinations
Tremor
Tachycardia
Hypertension
Hyperthermia
Ataxia (difficulties with coordinated movements)
Arrhythmias
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
Wernicke’s encephalopathy is a medical emergency with a high mortality rate. Korsakoff syndrome is often irreversible and results in patients requiring full-time institutional care. Prevention and treatment involve thiamine supplementation and abstaining from alcohol.
Non-alcoholic fatty liver disease
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.
Stages of non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease
Non-alcoholic steatohepatitis (NASH)
Fibrosis
Cirrhosis
Risk factors for non-alcoholic fatty liver disease
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
It is associated with metabolic syndrome, which is a combination of hypertension, obesity and diabetes. Metabolic syndrome is common and dramatically increases the risk of cardiovascular disease and other health problems.
Investigating non-alcoholic fatty liver disease
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.
Diagnosing NAFLD
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.
Managing NAFLD
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
Types of viral hepatitis
Type of Virus
Transmission
Vaccine
Treatment
Hepatitis A
RNA
Faecal-oral route
Yes
Supportive
Hepatitis B
DNA
Blood/bodily fluids
Yes
Supportive/antivirals
Hepatitis C
RNA
Blood
No
Direct-acting antivirals
Hepatitis D
RNA
Always with hepatitis B
No
Pegylated interferon alpha
Hepatitis E
RNA
Faecal-oral route
No
Supportive
All viral hepatitis infections are notifiable diseases. The UK Health Security Agency need to be notified of all cases.
Other causes of hepatitis
Alcoholic hepatitis
Non-alcoholic steatohepatitis (NASH)
Autoimmune hepatitis
Drug induced hepatitis (e.g. paracetamol overdose)
Presentation of viral hepatitis
Viral hepatitis may be asymptomatic or present with non-specific symptoms of:
Abdominal pain
Fatigue
Flu-like illness
Pruritus (itching)
Muscle and joint aches
Nausea and vomiting
Jaundice
Liver function tests
A “hepatitic picture” on liver function tests refers to high transaminases (AST and ALT) with proportionally less of a rise in ALP. Transaminases are liver enzymes released into the blood due to inflammation of the liver cells.
Bilirubin can also rise as a result of inflammation of the liver cells. High bilirubin causes jaundice.
Hepatitis A
Hepatitis A is the most common viral hepatitis worldwide but relatively rare in the UK. It is an RNA virus transmitted via the faecal-oral route, usually in contaminated water or food. Vaccination is available to reduce the chance of developing the infection. It can cause cholestasis (slowing of bile flow through the biliary system), with pruritus, significant jaundice, dark urine and pale stools.
Diagnosis is based on IgM antibodies to hepatitis A. It usually resolves without treatment. Rarely it can lead to acute liver failure (fulminant hepatitis). Management is supportive, with basic analgesia.
Hepatitis B
Hepatitis B is a double-stranded DNA virus. It is transmitted by direct contact with blood or bodily fluids, such as during sexual intercourse or sharing needles (e.g., IV drug users or tattoos). It can also be passed through sharing toothbrushes, razors or contact with open cuts. It can be passed from mother to child during pregnancy and delivery (known as vertical transmission).
Most people fully recover from the infection within 1-3 months. However, 5-15% become chronic hepatitis B carriers. In carriers, the virus DNA has integrated into the cell nucleus. They continue to produce viral proteins.
Antibodies are produced by the immune system against pathogen proteins. Antigens are proteins that are targeted by the antibodies. Antibodies are part of the immune system. Antigens are part of the virus.
There are key viral markers to remember with hepatitis B:
Surface antigen (HBsAg) – active infection
E antigen (HBeAg) – a marker of viral replication and implies high infectivity
Core antibodies (HBcAb) – implies past or current infection
Surface antibody (HBsAb) – implies vaccination or past or current infection
Hepatitis B virus DNA (HBV DNA) – a direct count of the viral load
Screening for hepatitis B involves testing for HBcAb (for previous infection) and HBsAg (for active infection). When these are positive, further testing is performed for HBeAg and viral load (HBV DNA).
HBsAb demonstrates an immune response to HBsAg. The HBsAg is given in the vaccine, so having a positive HBsAb may indicate they have been vaccinated and created an immune response. The HBsAb may also be present in response to an infection. The other viral markers are necessary to distinguish between the presence of HBsAb due to previous vaccination and infection.
HBcAb can help distinguish acute, chronic and past infections. We can measure IgM and IgG versions of the HBcAb. IgM implies an active infection and will give a high titre with an acute infection and a low titre with a chronic infection. IgG indicates a past infection where the HBsAg is negative.
HBeAg correlates with infectivity. Where the HBeAg is present, it implies the patient is in the acute phase of infection, where the virus is actively replicating. When the HBeAg is high, they are highly infectious to others. When the HBeAg is negative, but the HBeAb is positive, this implies they have been through a phase where the virus was replicating but has now stopped replicating and are less infectious.
Vaccination is available and involves injecting the hepatitis B surface antigen (HBsAg). Vaccinated patients are tested for HBsAb to confirm their response to the vaccine. The vaccine requires 3 doses at different intervals. Vaccination for hepatitis B is included as part of the UK routine vaccination schedule (as part of the 6-in-1 vaccine).
Managing Hepatitis B
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)
Hepatitis C
Hepatitis C is an RNA virus. It is spread by blood and body fluids (e.g., semen). No vaccine is available. Hepatitis C is now curable with direct-acting antiviral medications (e.g., sofosbuvir and daclatasvir).
Without treatment:
1 in 4 fight off the virus and make a full recovery
3 in 4 develop chronic hepatitis C
Complications of hepatitis C include:
Liver cirrhosis and associated complications of cirrhosis
Hepatocellular carcinoma
Testing involves:
Hepatitis C antibody is the screening test
Hepatitis C RNA testing is used to confirm the diagnosis of hepatitis C, calculate the viral load and identify the genotype
Management involves the same general principles as hepatitis B (described above).
Antiviral treatment with direct-acting antivirals (DAAs) is tailored to the specific viral genotype. They successfully cure the infection in over 90% of patients. The duration of treatment is typically 8 to 12 weeks.
Hepatitis D
Hepatitis D is an RNA virus. It can only survive in patients who also have a hepatitis B infection. It attaches itself to the HBsAg and cannot survive without this protein. There are very low rates in the UK. Hepatitis D increases the complications and disease severity of hepatitis B.
Hepatitis D can be treated with pegylated interferon alpha over at least 48 weeks. This treatment is not very effective and has significant side effects.
Hepatitis E
Hepatitis E is an RNA virus transmitted by the faecal-oral route. It is very rare in the UK. It usually produces only a mild illness, the virus is cleared within a month, and no treatment is required. Rarely it can progress to chronic hepatitis and liver failure, usually in immunocompromised patients. There is no vaccination.
Types of autoimmune hepatitis
There are two types of autoimmune hepatitis, with different age distributions and autoantibodies.
Type 1 typically affects women in their late forties or fifties. It presents around or after menopause with fatigue and features of liver disease on examination. It takes a less acute course than type 2.
Type 2 usually affects children or young people, more commonly girls. It presents with acute hepatitis with high transaminases and jaundice.
Investigating autoimmune hepatitis
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.
Autoantibodies in type 1 autoimmune hepatitis are:
Anti-nuclear antibodies (ANA)
Anti-smooth muscle antibodies (anti-actin)
Anti-soluble liver antigen (anti-SLA/LP)
Autoantibodies in type 2 autoimmune hepatitis are:
Anti-liver kidney microsomes-1 (anti-LKM1)
Anti-liver cytosol antigen type 1 (anti-LC1)
Liver biopsy forms part of the diagnosis. Key histology findings are interface hepatitis and plasma cell infiltration.
Managing autoimmune hepatitis
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.
Haemochromatosis
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.
The human haemochromatosis protein (HFE) gene is located on chromosome 6. The majority of cases of haemochromatosis relate to C282Y mutations in this gene. Mutations are required in both copies of the gene (homozygous) since it is an autosomal recessive condition. This gene is important in regulating iron metabolism.
Presentation of haemochromatosis
Haemochromatosis usually presents after age 40 when the iron overload becomes symptomatic. It presents later in females due to menstruation acting to eliminate iron from the body regularly. It presents with:
Chronic tiredness
Joint pain
Pigmentation (bronze skin)
Testicular atrophy
Erectile dysfunction
Amenorrhoea (absence of periods in women)
Cognitive symptoms (memory and mood disturbance)
Hepatomegaly
