Day: March 16, 2024

Overview Wilson’s disease is a rare condition characterised by abnormal copper deposition. Wilson’s is an inherited, multi-system, progressive disorder of copper metabolism. Named after British neurologist Dr Samuel Alexander Kinnier Wilson, it has an estimated incidence between 1 in 30,000 and 1 in 100,000. It often presents with liver involvement or neuropsychiatric symptoms, but it can present in a number of other ways including haemolysis. Though it can develop at any age, it most commonly occurs between the ages of 5 and 35. Aetiology Wilson’s disease is an autosomal recessive disorder. It is caused by mutations to the ATP7B gene on chromosome

Overview Primary sclerosing cholangitis is an immune-mediated disease characterised by cholestasis, bile duct strictures and hepatic fibrosis. Primary sclerosing cholangitis (PSC) is an immune-mediated chronic cholestatic liver disease. It causes progressive inflammation, fibrosis and destruction of both the intra- and extra-hepatic bile ducts. This leads to problems with poor bile flow (cholestasis), narrowing of bile ducts (stricturing) and ultimately chronic scarring (cirrhosis). PSC is one of many causes of bile duct damage and narrowing that are broadly termed ‘cholangiopathies’. Sclerosing cholangitis is a cholangiopathy that can be divided into primary and secondary: Primary: refers to PSC. Absence of another identifiable cause.

Overview Primary biliary cholangitis is an autoimmune cholestatic liver disease that can lead to cirrhosis. Primary biliary cholangitis (PBC) is an autoimmune liver disorder. It causes autoimmune destruction of the small, intrahepatic bile ducts that leads to poor bile flow (i.e. cholestasis), progressive fibrosis, and eventually cirrhosis. Epidemiology PBC is a rare disease that affects approximately 35/100,000 people in the UK. PBC is more commonly diagnosed in older women over the age of 50. The female to male ratio approaches 10:1. The median age at diagnosis is 65 years old. There is known to be genetic susceptibility (increased risk of a family member

Overview Paracetamol poisoning is the most common overdose seen in the UK. Paracetamol is a commonly used anti-pyretic and analgesic that can be purchased ‘over the counter’. It has an excellent safety profile and is used for a variety of conditions. However, in overdose, it can lead to drug-induced liver injury (DILI). Within the UK, paracetamol overdose is the most common cause of acute liver failure (ALF) requiring liver transplantation. Paracetamol overdose is frequently seen in the emergency department and most hospitals will have a local policy for its management. These policies will be based on advice from the national poisons information

Overview Non-alcoholic fatty liver disease (NAFLD) essentially refers to the presence of excess fat in the liver in the absence of excess alcohol consumption. Non-alcoholic fatty liver disease (NAFLD) is a rising problem worldwide. It is defined as excess fat with the liver, which is known as hepatic steatosis (i.e. fatty liver). A small amount of fat in the liver is normal, but when this is present in > 5% of hepatocytes we term it NAFLD. NALFD is strongly linked to obesity and the metabolic syndrome. NAFLD is a condition that actually encompasses a spectrum of pathological conditions including: Non-alcoholic fatty

Overview Hereditary haemochromatosis is an autosomal recessive disorder that results in iron overload. Hereditary haemochromatosis (HH) is one of the most common genetic disorders seen in Northern European populations. The disease is most commonly related to genetic variants (i.e. mutations) in the HFE gene that has an important role in iron regulation, although other genes have been identified. The disease is characterised by a state of iron overload that most commonly affects the liver, heart, joints, pancreas, and pituitary gland. Classically, it was termed ‘bronzed diabetes’ due to the typical skin pigmentation and development of diabetes mellitus from iron overload. The main manifestation

Overview Hepatocellular carcinoma is a primary liver cancer that occurs most commonly in patients with cirrhosis. Hepatocellular carcinoma (HCC) is one of the major complications of cirrhosis and chronic hepatitis B. It is a primary liver malignancy that is often diagnosed late with poor prognosis. Cancers affecting the liver may be primary or secondary: Primary: cancer initiated in the liver. Commonly due to HCC or cholangiocarcinoma. Secondary: cancer that started somewhere else but metastasised to the liver. Early recognition and treatment of HCC is crucial to improve survival. The five year survival with early disease is as high as 90%, but

Overview Hepatitis E is a small, non-enveloped RNA virus that can lead to acute and chronic hepatitis. Hepatitis E virus (HEV) was originally considered a disease of travellers returning from endemic areas where it can cause large outbreaks. However, it is now recognised as the most common cause of acute viral hepatitis in many countries. HEV is spread via the faeco-oral route, leading to locally-acquired infections or epidemic outbreaks. The spectrum of HEV is wide and depends on the underlying genotype (see chapter on hepatitis E virus), patient co-morbidities (e.g. immunosuppressed or immunocompetent) and pregnancy status. It can cause: Asymptomatic infections Acute viral hepatitis Chronic viral hepatitis Extra-hepatic manifestations

Overview Hepatitis D is caused by the defective hepatitis D RNA virus that needs hepatitis B for replication. Hepatitis D virus (HDV) is a unique RNA virus that can only establish infection in the human liver with the help of Hepatitis B virus (HBV). HDV has an outer envelope that contains the HBV surface antigen (HBsAg). Therefore, it can only establish infection in HBsAg-positive patients. There are two key terms to recognise with HDV infection: Coinfection: acute hepatitis D infection acquired at the same time of hepatitis B infection. Typically indistinguishable from acute hepatitis B alone. Superinfection: development of acute hepatitis D infection in

Overview Hepatitis C is caused by the hepatitis C virus (HCV), which is a major cause of chronic liver disease worldwide. Traditionally, hepatitis C virus (HCV) infection occurred followed blood transfusions or in association with intravenous drug use. It was an unknown pathogen causing a non-A, non-B hepatitis leading to chronic liver disease and hepatocellular carcinoma (HCC). This is now known as hepatitis C, which is caused by the small RNA virus hepatitis C. HCV leads to chronic infection in 75-80% of individuals and accounts for significant morbidity and mortality from cirrhosis and HCC. HCV is now a curable condition with a range of

Introduction Hepatitis B is caused by the hepatitis B virus (HBV) and can lead to both acute and chronic liver disease. Worldwide, hepatitis B is a major health problem. An estimated 240 million people have chronic hepatitis B, however, in the UK the prevalence is low (0.3%). It is caused by the hepatitis B virus (HBV), which may lead to both acute and chronic infection. Chronic hepatitis B (CHB) can lead to cirrhosis and hepatocellular carcinoma (HCC). Hepatitis B may cause an acute or chronic infection. Acute: can occur at any age. Majority of patients have a subclinical or anicteric (no

Overview The Hepatitis A virus is a non-enveloped single-stranded RNA virus. Spread via the faeco-oral route, hepatitis A belongs to the Hepatovirus genus of the Picornaviridae family. Hand washing and good hand hygiene are key to reducing transmission. It causes a viral hepatitis, and is frequently seen in travellers to endemic areas and those engaging in higher-risk sexual activities. The majority of adults infected experience symptoms (approx 70-95%). Commonly a mild self-limiting illness manifesting with flu like symptoms, abdominal discomfort and nausea. Children under the age of 5 are frequently asymptomatic. Hepatitis A under a electron microscope Image courtesy of Wikipedia Commons Risk factors Though uncommon in the UK, there

Overview Hepatitis refers to inflammation of the liver. Hepatitis is a general term that refers to inflammation of the liver parenchyma. It may be caused a variety of insults to the liver and characteristically causes a rise in the liver transaminases (e.g. ALT/AST). Worldwide, the most common cause is viral hepatitis (e.g. hepatitis B/C). Aetiology & pathophysiology There are several infectious and non-infectious causes of hepatitis. Hepatitis may be caused by both infectious and non-infectious aetiologies, which include: Hepatitis A Hepatitis B Hepatitis C Hepatitis D Hepatitis E Other viruses (e.g. cytomegalovirus, Epstein-Barr virus) Autoimmune hepatitis Alcoholic hepatitis Ischaemic hepatitis Non-alcoholic steatohepatitis Drug-induced hepatitis (often

Overview Gilbert syndrome is an autosomal recessive disorder that causes abnormal bilirubin processing in the liver. Gilbert syndrome is a benign, inherited cause of abnormal processing of bilirubin within the liver. This leads to recurrent episodes of unconjugated hyperbilirubinaemia. Epidemiology Gilbert syndrome is the most common cause of inherited jaundice. Gilbert syndrome is seen in all populations and usually presents around the time of puberty. This is thought to be because sex hormones affect bilirubin processing in the liver. Gilbert is seen more commonly in males. Bilirubin metabolism Bilirubin is a breakdown product of heme metabolism. Bilirubin is a breakdown product of haemoglobin, which

Overview Chronic liver disease is caused by repeated insults to the liver, which can result in inflammation, fibrosis and ultimately cirrhosis. Chronic liver disease (CLD) is the result of repeated damage to the liver by a variety of aetiological factors including alcohol, toxins, viruses and many others. CLD is generally defined as progressive liver dysfunction for six months or longer. The end result of chronic liver disease is cirrhosis, which describes irreversible liver remodelling. The liver is involved in numerous functions that are essential to maintain the bodies homeostasis. To appreciate the sequelae of CLD we must understand the normal role of

Overview Budd-Chiari syndrome is a vascular liver disorder due to obstruction of hepatic venous outflow. Budd-Chiari syndrome (BCS) describes a classic triad of hepatomegaly, abdominal pain and ascites due to hepatic venous obstruction. It is a vascular liver disease due to a variety of underlying disorders that each result in obstruction anywhere from the small hepatic venules in the liver to the entrance of the inferior vena cava (IVC) at the right atrium. Budd-Chiari syndrome with thrombus in all three hepatic veins Epidemiology In the general population, BCS occurs at 1 in 100,000 people. The epidemiology of BCS varies depending on geographical location. In non-Asian countries, the

Overview Autoimmune hepatitis is a chronic inflammatory liver disorder that can lead to cirrhosis, liver failure and death. Autoimmune hepatitis (AIH) is one of the major inflammatory disorders of the liver. It classically causes a chronic relapsing hepatitis that, if untreated, can lead to cirrhosis, liver failure and death. There is a wide spectrum of clinical presentation and the condition may overlap with other liver diseases including primary biliary cholangitis and primary sclerosing cholangitis. Epidemiology AIH may occur at any age and predominantly affects woman. The prevalence of AIH varies depending on geographical region. In Europe, it ranges from 10-17 per 100,000 population. The

Overview Alpha-1 antitrypsin deficiency is a rare autosomal recessive disorder that causes liver and pulmonary disease. Alpha-1 antitrypsin (AAT) is an abundant enzyme found within the body. It is produced in the liver and acts as a protease inhibitor. It is important in the inhibition of neutrophil elastase. Neutrophil elastase acts by damaging bacteria, but unchecked, it can lead to lung damage. Alpha-1 antitrypsin deficiency (AATD) refers to a lack of circulating AAT due to mutations that prevent it from being released from hepatocytes. This has knock-on effects in the liver and lungs. Liver: build up in hepatocytes. This can cause chronic damage

Overview Alcoholic hepatitis is a clinical syndrome due to progressive alcohol-mediated liver inflammation and injury. Alcoholic hepatitis generally refers to the acute onset of symptomatic hepatitis due to heavy alcohol consumption. It can occur at any age, but is more likely in middle-aged patients (e.g. 40-50 years) who have drank excess amounts of alcohol for many years. It is part of a wider spectrum of conditions known as alcohol-related liver disease (discussed below). Severe alcoholic hepatitis requiring hospital admission is associated with poor short-term survival. However, the true prevalence of alcoholic hepatitis is difficult to ascertain because many mild cases can be asymptomatic.

Overview Acute liver failure is a syndrome of acute liver dysfunction without underlying chronic liver disease. ALF is an uncommon condition associated with a high mortality. It is due to acute liver dysfunction in the absence of underlying chronic liver disease. ALF is characterised by coagulopathy (derangement in clotting) of hepatic origin and altered levels of consciousness due to hepatic encephalopathy (HE). The cause of ALF is numerous, but drug-induced liver injury (DILI) is the most common reason in Europe. This may be divided into paracetamol or non-paracetamol DILI. The true burden of ALF is difficult to quantify, but it is the primary indication for liver

Overview Haemolysis refers to the destruction of red blood cells (RBCs), which is broadly defined as a reduction in the life span below 100 days (normal 110-120 days). Haemolytic anaemia is defined as anaemia secondary to reduced survival of RBCs. They have a varied aetiology, as is the clinical presentation; together they represent approximately 5% of all anaemias. Regardless of the underlying cause, if erythropoiesis within the bone marrow cannot keep pace with the destruction of RBCs anaemia will ensue. Mild haemolysis may be completely asymptomatic whereas severe, acute haemolysis will lead to cardiopulmonary decompensation. Classification Haemolytic anaemia can be classified as inherited or aquired.