Liver Disease and Liver Failure Flashcards
Kupffer cells
The immune cells of the liver.
Bile plays an essential role in the absorption of what vitamins?
Vitamins D, E, A, K (fat soluble vitamins)
Wilson disease is the excess of what ion in the blood?
Copper
What can be the cause of a low platelet count?
- Liver disease means liver is not making thrombopoetin thus low platelet count.
Hepatic encephalopathy
Hepatic encephalopathy is a decline in brain function that occurs as a result of severe liver disease. In this condition, your liver can’t adequately remove toxins from your blood. This causes a buildup of toxins in your bloodstream, which can lead to brain damage.
Wilson disease
Wilson disease is an inherited disorder in which excessive amounts of copper accumulate in the body, particularly in the liver, brain, and eyes. The signs and symptoms of Wilson disease usually first appear between the ages of 6 and 45, but they most often begin during the teenage years.
Acute liver failure
The progression of jaundice to hepatic encephalopathy in the absence of previous chronic liver disease.
What is hyper acute liver failure?
The progression of jaundice to hepatic encephalopathy in less than 7 days.
<7days
What are the normal causes of hyperacute liver failure?
Trauma
Paracetamol overdose
Causes of acute liver failure:
- Infection – hepatitis A, B, E, HSV, VZV
- Drugs – paracetamol, Halothane, TB
- Poisoning – Amanita phalloides, paracetamol, herbal remedies
- Immune and Metabolic – Autoimmune hepatitis,
- Wilsons disease, acute fatty liver of pregnancy
- Other – Budd-Chiari, ischaemic hepatitis, trauma
Budd–Chiari syndrome
Budd–Chiari syndrome is a very rare condition, affecting one in a million adults. The condition is caused by occlusion of the hepatic veins that drain the liver. It presents with the classical triad of abdominal pain, ascites, and liver enlargement.
Paracetamol overdose criteria
High lactate and high phosphate are poor prognostic indicators.
Criteria that determines whether you need an emergency liver transplant:
What are the causes of death in ALF?
Raised intracranial pressure
Sepsis - (bacterial or fungal)
Acute renal failure
Multi-organ failure
Complications of chronic liver disease:
- Poor liver synthetic function (low albumin, deranged coagulation, raised bilirubin). - suggests problems with liver synthesis e.g clotting factors etc
- Ascites - fluid in abdomen
- Sepsis and Spontaneous bacterial peritonitis
- Recurrent hepatic encephalopathy - liver cannot metabolise toxins and so they pass to the brain.
- Variceal bleeding
- Hepatocellular cellular carcinoma
- Poor quality of life, intractable itching and fatigue
What condition is shown here?
Ascites
What condition is shown here?
Palmar erythema is a rare skin condition where the palms of both hands become reddish.
- can be due to pregnancy or liver cirrhosis.
Ascites summary
Why are submandibular excisions most common?
- what artery may be damaged during removal of the gland.
The high salivary viscosity of submandibular gland secretions favors stone formation.
The facial artery lies between the gland and mandible and is often ligated during excision of the gland.
What condition is shown here?
- clue this patient has liver cirrhosis!
Hepatic hydrothorax
What does hepatic hydrothorax refer to and in whom does it present?
Hepatic hydrothorax refers to the presence of a pleural effusion (usually >500 mL) in a patient with cirrhosis who does not have other reasons to have a pleural effusion (eg, cardiac, pulmonary, or pleural disease) [1,2]. Hepatic hydrothorax occurs in approximately 5 to 10 percent of patients with cirrhosis.
Varicies
Enlarged or swollen veins.
- Dad in the leg. Can occur in many places, esophagus, leg, stomach etc.
What can cause accute liver failure?
Diseases causing acute failure: Acute fatty liver, Wilson’s disease, Budd-Chiari syndrome.
Paracetamol overdose.
What can cause chronic liver failure?
Autoimmune, haemochromatosis, infections.
Haemochromatosis
Haemochromatosis is a medical condition that causes people to absorb too much iron from their diet. It accumulates around the body over time, damaging many organs, including the liver, and eventually causing disease.
What are the complications of chronic liver failure?
Portal hypertension, SBP, HCC.
SBP
Spontaneous bacterial peritonitis (SBP) is infection of ascitic fluid without an apparent source. Manifestations may include fever, malaise, and symptoms of ascites and worsening hepatic failure.
What is TIPS and what is it used for?
Transjugular intrahepatic portosystemic shunt (TIPS) is a procedure that may be used to reduce portal hypertension and its complications, especially variceal bleeding. A TIPS procedure may be done by a radiologist, who places a small wire-mesh coil (stent) into a liver vein.
Hepato-renal syndrome
Hepatorenal syndrome (often abbreviated HRS) is a life-threatening medical condition that consists of rapid deterioration in kidney function in individuals with cirrhosis or fulminant liver failure.
How does liver disease lead to SBP (spontaneous bacterial peritonitis)?
- There is increased bacterial overgrowth.
- Increased intestinal permeability.
- Impaired local immunity and dysfunction in hepatic immunity.
- Infection can transmit from gut to liver.
*
The important manifestation of liver disease are:
Portal hypertension
Ascites
Hepatocellular carcinoma
Varicies
Spontaneous bacterial peritonitis
Hepatic encephalopathy
Explain the difference between unconjugated and conjugated bilirubin.
Unconjugated bilirubin is turned into conjugated bilirubin in the liver.
Unconjugated bilirubin is lipid soluble.
Conjugated bilirubin is water soluble and is excreted in urine. Presence of bilirubin in urine is indicative of conjugated bilirubinemia.
What does a AST:ALT ratio of 2:1 indicate?
Alcoholic liver disease
Summary of the stepwiseof alcoholic liver disease:
Alcoholic related fatty liver disease
Alcoholic hepatitis
Cirrhosis
How are liver function tests affected in alcoholic liver disease?
LFTs – elevated ALT and AST (transaminases) and particularly raised gamma-GT. ALP will be elevated later in the disease. Low albumin due to reduced “synthetic function” of the liver. Elevated bilirubin in cirrhosis.
Clotting – elevated prothrombin time due to reduced “synthetic function” of the liver
U+Es may be deranged in hepatorenal syndrome.
What is the general management of alcoholic liver disease?
- Stop drinking alcohol permanently
- Consider a detoxication regime
- Nutritional support with vitamins (particularly thiamine) and a high protein diet
- Steroids improve short term outcomes (over 1 month) in severe alcoholic hepatitis but infection and GI bleeding need to be treated first and do not improve outcomes over the long term
- Treat complications of cirrhosis (portal hypertension, varices, ascites and hepatic encephalopathy)
- Referral for liver transplant in severe disease however they must abstain from alcohol for 3 months prior to referral
Alcohol withdrawal (read summary)
6-12 hours: tremor, sweating, headache, craving and anxiety
12-24 hours: hallucinations
24-48 hours: seizures
24-72 hours: “delerium tremens”
What causes Wernicke’s encephalopathy?
Alcohol excess leads to thiamine (vitamin B1) deficiency. Thiamine is poorly absorbed in the presence of alcohol and alcoholics tend to have poor diets and rely on the alcohol for their calories. Wernicke’s encephalopathy comes before Korsakoffs syndrome. These result from thiamine deficiency.
Features of Wernicke’s
Confusion
Oculomotor disturbances (disturbances of eye movements)
Ataxia (difficulties with coordinated movements)
Features of Korsakoffs
Memory impairment (retrograde and anterograde)
Behavioural changes
^ often irreversible
What is liver cirrhosis?
Liver cirrhosis is the result of chronic inflammation and damage to liver cells. When the liver cells are damaged they are replaced with scar tissue (fibrosis) and nodules of scar tissue form within the liver.
What are the most common causes of liver cirrhosis?
Alcoholic liver disease
Non Alcoholic Fatty Liver Disease
Hepatitis B
Hepatitis C
Rare causes of liver cirrhosis:
Autoimmune hepatitis
Primary biliary cirrhosis
Haemochromatosis
Wilsons Disease
Alpha-1 antitrypsin deficiency
Cystic fibrosis
Drugs (e.g. amiodarone, methotrexate, sodium valproate)
What conditions can cause an extended APTT (activated partial thromboplastin time)?
Note: APTT works in the intrinsic pathway
Haemophilia A (VIII – X-linked recessive)
Haemophilia B (IX – X-linked recessive)
Haemophilia C (XI – autosomal recessive)
von Willebrands disease (as vWF pairs up with factor VIII)
What conditions can cause a prolonged PT?
Liver disease, disseminated intravascular coagulation (DIC), vitamin K deficiency and warfarin levels.
What do albumin and PT reflect in liver disease?
Albumin and prothrombin time are useful markers of the “synthetic function” of the liver. The albumin level drops and the prothrombin time increases as the synthetic function becomes worse.
Hyponatraemia in liver disease indicates what?
becomes worse.
Hyponatraemia indicates fluid retention in severe liver disease.
What is the Child-Pugh Score used for?Tchil
Indicates the severity of the cirrhosis and the prognosis.
What is the management plan for patients with liver cirrhosis?
Ultrasound and alpha-fetoprotein every 6 months for hepatocellular carcinoma
Endoscopy every 3 years in patients without known varices
High protein, low sodium diet
MELD score every 6 months
Consideration of a liver transplant
Managing complications
Complications of Liver cirrhosis
Malnutrition
Portal Hypertension, Varices and Variceal Bleeding
Ascites and Spontaneous Bacterial Peritonitis (SBP)
Hepato-renal Syndrome
Hepatic Encephalopathy
Hepatocellular Carcinoma
Treatment of stable varicies:
Propranolol reduces portal hypertension by acting as a non-selective beta blocker
Elastic band ligation of varices
Injection of sclerosant (less effective than band ligation)
Transjugular Intra-hepatic Portosystemic Shunt (TIPS
Transjugular Intra-hepatic Portosystemic Shunt (TIPS
Stenting to reduce pressure in the portal system and varicies.
Management of oesophageal varicies bleed
Resuscitation
- Vasopressin analogues (i.e. terlipressin) cause vasoconstriction and slow bleeding in varices
- Correct any coagulopathy with vitamin K and fresh frozen plasma (which is full of clotting factors)
- Giving prophylactic broad spectrum antibiotics has been shown to reduce mortality
- Consider intubation and intensive care as they can bleed very quickly and become life threateningly unwell
- Urgent endoscopy
- Injection of sclerosant into the varices can be used to cause “inflammatory obliteration” of the vessel
- Elastic band ligation of varices
Sengstaken-Blakemore Tube is an inflatable tube inserted into the oesophagus to tamponade the bleeding varices. This is used when endoscopy fails.
Cirrhosis causes what type of ascites regarding protein content?
Transudate asictes therefore low protein.
SAAG greater than 1.1g/dL
SAAG + results interpretation
SAAG = (serum albumin) – (ascitic fluid albumin)
A high SAAG (>1.1g/dL) suggests the ascitic fluid is a transudate.
A low SAAG (<1.1g/dL) suggests the ascitic fluid is an exudate.
Management of ascites:
Low sodium diet
Anti-aldosterone diuretics (spironolactone)
Paracentesis (ascitic tap or ascitic drain)
Prophylactic antibiotics against spontaneous bacterial peritonitis (ciprofloxacin or norfloxacin) in patients with less than 15g/litre of protein in the ascitic fluid
Consider TIPS procedure in refractory ascites
Consider transplantation in refractory ascites
SBP
- How does this occur?
Spontaneous Bacterial Peritonitis
This occurs in around 10% of patients with ascites secondary to cirrhosis and can have a mortality of 10-20%. It involves an infection developing in the ascitic fluid and peritoneal lining without any clear cause (e.g. not secondary to an ascitic drain or bowel perforation).
Summary of Hepatorenal syndrome
Hepatorenal syndrome occurs in liver cirrhosis. Hypertension in the portal system leads to dilation of the portal blood vessels, stretched by large amounts of blood pooling there. This leads to a loss of blood volume in other areas of the circulation, including the kidneys. This leads hypotension in the kidney and activation of the renin-angiotensin system. This causes renal vasoconstriction, which combined with low circulation volume leads to starvation of blood to the kidney. This leads to rapid deteriorating kidney function. Hepatorenal syndrome is fatal within a week or so unless liver transplant is performed.
Summary of hepatic encephalopathy
This is also known as portosystemic encephalopathy. It is thought to be caused by the build up of toxins that affect the brain. One toxin that is particularly worth remembering is ammonia, which is produced by intestinal bacteria when they break down proteins and is absorbed in the gut. There are two reasons that ammonia builds up in the blood in patients with cirrhosis: Firstly, the functional impairment of the liver cells prevents them metabolising the ammonia into harmless waste products. Secondly, collateral vessels between the portal and systemic circulation mean that the ammonia bypasses liver altogether and enters the systemic system directly.
Treatment of hepatic encephalopathy
By giving laxatives we help clear the ammonia from the gut before it is absorbed and by giving antibiotics we reduce the number of bacteria in the gut producing ammonia.
Laxatives (i.e. lactulose) promote the excretion of ammonia. The aim is 2-3 soft motions daily. They may require enemas initially.
Antibiotics (i.e. rifaximin) reduces the number of intestinal bacteria producing ammonia. Rifaximin is useful as it is poorly absorbed and so stays in the GI tract.
Nutritional support. They may need nasogastric feeding.
Stages of NAFLD
Non-alcoholic Fatty Liver Disease
Non-Alcoholic Steatohepatitis (NASH)
Fibrosis
Cirrhosis
Autoantibodies for what conditions are assessed in a liver screen?
Autoantibodies (autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis).
Management of NAFLD
- Weight loss
- Exercise
- Stop smoking
- Control of diabetes, blood pressure and cholesterol
- Avoid alcohol
- Refer patients with liver fibrosis to a liver specialist where they may treat with vitamin E or pioglitazone.
High protein in ascites can indicate what?
Infection - TB / SBP
Malignancy
Pancreatitis
Causes of a high SAAG in Ascites
A high SAAG (i.e. transudate) suggests the presence of portal hypertension, which may be caused by:
Cirrhosis
Hepatic failure
Venous occlusion (e.g. Budd Chiari syndrome)
Fulminant hepatic failure
Alcoholic hepatitis
Kwashiorkor malnutrition
Causes of a low SAAG (exudate) in ascites
Malignancy
Infection
Pancreatitis
Nephrotic syndrome
What are the two main types of primary liver cancer?
Hepatocellular carcinoma (80%) and cholangiocarcinoma (20%).
Liver metastasis
There is a poor prognosis of any cancer with liver metastasis. The first stage is to search for the primary (e.g. full body CT scan and thorough history and examination of the skin and breasts). It is not uncommon to have liver metastases of unknown primary.
What are the risk factors for HCC?
The main risk factor for hepatocellular carcinoma (HCC) is liver cirrhosis due to:
Viral hepatitis (B and C)
Alcohol
Non alcoholic fatty liver disease
Other chronic liver disease
Patients with chronic liver disease are screened for HCC.
Cholangiocarcinoma has what association?
Cholangiocarcinoma is associated with primary sclerosing cholangitis. However, only 10% of patients with cholangiocarcinoma had primary sclerosing cholangitis. Cholangiocarcinoma usually presents in patients > 50 years old unless related to primary sclerosing cholangitis.
What is the prognosis of liver cancer and why?
Liver cancer often remains asymptomatic for a long time and then presents late making prognosis poor.
Symptoms of liver cancer:
Weight loss
Abdominal pain
Anorexia
Nausea and vomiting
Jaundice
Pruritus
Cholangiocarcinoma often presents with painless jaundice in a similar way to pancreatic cancer.
What are the investigations carried out for liver cancer?
Alpha-fetoprotein is a tumour marker for hepatocellular carcinoma.
CA19-9 is a tumour marker for cholangiocarcinoma.
Liver ultrasound can identify tumours.
CT and MRI scans are used for diagnosis and staging of the cancer.
ERCP can be used to take biopsies or brushings to diagnose cholangiocarcinoma.
Summarise the treatment of hepatocellular carcinoma:
HCC has a very poor prognosis unless diagnosed early. Resection of early disease in a resectable area of the liver can be curative. Liver transplant when the HCC is isolated to the liver can be curative.
There are several kinase inhibitors that are licensed as medical treatment for HCC. They work by inhibiting the proliferation of cancer cells. Some examples of these are sorafenib, regorafenib and lenvatinib. They can potentially extend life by months.
HCC is generally considered resistant to chemo and radiotherapy. In certain circumstances they are used as part of palliative treatment or clinical trials.
Summarise the treatment for cholangiocarcinoma:
Cholangiocarcinomas have a very poor prognosis unless diagnosed very early. Early disease can potentially be cured with surgical resection.
ERCP can be used to place a stent in the bile duct where the cholangiocarcinoma is compressing the duct. This allows for drainage of bile and usually improves symptoms.
Cholangiocarcinoma is also generally considered resistant to chemo and radiotherapy.
What is a haemangioma?
Haemangiomas are common benign tumours of the liver. They are often found incidentally. They cause no symptoms and have no potential to become cancerous. No treatment or monitoring is required.
Focal nodular hyperplasia:
- what is it?
- who is it most common in?
Focal nodular hyperplasia is a benign liver tumour made of fibrotic tissue. This is often found incidentally. It is usually asymptomatic and has no malignant potential. It is often related to oestrogen and is therefore more common in women and those on the oral contraceptive pill. No treatment of monitoring is required.
