Liver 2

Hepatitis

  1. Alcoholic Hepatitis 
  2. Autoimmune Hepatitis EBV 
  3. Epstein Barr Virus 
  4. Hepatitis A 
  5. Hepatitis B 
  6. Hepatitis C 
  7. Hepatitis D 
  8. Hepatitis E 
  9. Hepatitis G 
  10. Viral Hepatitis

 

Alcoholic Hepatitis 

In This Article

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Introduction

  • This is a very common cause of liver injury. It is caused by excessive alcohol intake.
  • Typically there will be steatosis of the liver. In this pathological change, fat globules begin to accumulate in the cytoplasm of liver cells. this can be pretty harmless, and as a result, is not very specific for predicting if the liver will develop cirrhosis.
  • Mallory’s hyalin is an aggregate of filament found in the hepatocytes that, if present, indicate a risk of irreversible changes in hepatocytes, that may ultimately lead to cirrhosis. Mallory’s hyalin is not specific for alcoholic liver disease.
  • When we talk about alcohol, we are actually referring to ethanol.
  • Ethanol is oxidised to acetaldehyde. Acetaldehyde is then converted to acetate by the mitochondria of liver cells. The liver does 90% of this metabolism. Acetate is then released into the bloodstream and taken up by peripheral tissues where it is metabolised to carbon dioxide, fatty acids and water.
  • Alcohol dehydrogenases are present in many tissues around the body, and some people believe that the gastric mucosa itself is responsible for a lot of alcohol metabolism.
  • Also, alcoholic drinks often contain a lot of sugar – for example a typical pint of beer contains 250 calories! For this reason a lot of alcoholics will not lose weight despite severe malnutrition.

 

Long-term effects of alcohol use are all due to ethanol. The short term effects of alcohol use can often be due to other alcohols present in the drink, such as isoamyl alcohol.These additional alcohols are known as cogeners. Brandy and bourbon contain the highest percentage of cogeners.

 

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Epidemiology

  • 10-30% of heavy drinkers will develop cirrhosis
  • 50% will have fatty liver.
  • Nutritional factors are controversial, although it is possible that malnutrition and obestiy both contribute to liver damage.
  • High alcohol consumption combined with hep C infection also greatly increases the risk of hepatitis.
  • In males with hepatitis, average alcohol consumption was about 16 units/day over a period of 8 years. However, this is highly variable. In females, the corresponding figure was 11 units/day.
  • Approximately 1/3 of alcoholics have a parent who is an alcoholic.

 

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Pathology

  • The first sign is fatty liver. This occurs in most heavy drinkers at some time, but it is completely reversible upon cessation of alcohol.
  • The hepatocytes have to divert resources away from metabolising fats to metabolising alcohol. As a result, fat metabolism is altered resulting in fat deposits inside the cells. There are more fats released into the blood stream (fatty acids) and within the hepatocytes, there is increased synthesis of triglycerides and fatty acids.
  • Acetaldehyde is a product of alcohol metabolism. It binds to liver cell proteins, and causes hepatocytes injury, leading to inflammation. This inflammation can be a causatory factor in cirrhosis. It is likely that this produces Mallory’s sign.
  • Alcohol stimulates collagen synthesis by fibroblasts as well as fibroblast proliferation.
  • Ultimately, the fibrosing process will end up linking hepatic veins to portal veins, and in these places, cell regeneration occurs, and nodules form – this is the start of the process of cirrhosis.

 

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Clinical signs

  • Malnutrition
    • Very thin arms and legs(due to muscle wasting)
    • Swollen abdomen
    • Red tongue (iron-deficiency anaemia)
    • Dry scaly cracked skin (due to zinc /fatty acid deficiency)
  • Endocrine
    • Gynaecomastia
    • Testicular atrophy
    • Loss of body hair
    • Signs of 'pseudo-Cushings’ (red face, hump, striae)
  • Face /skin
    • Parotid enlargement
    • Spider naevi
    • Easy bruising
    • Dupuytren’s contracture
  • Neuromuscular
    • Tremor
    • Memory loss / cognitive impairment
    • Peripheral myopathy- degradation of muscle
    • Epilepsy
    • Wernicke-Korskoff syndrome
  • Cardiovascular
  • Bone

 

Generally, patients with fatty liver have few symptoms, however they may notice nausea and malaise. LFT’s may be slightly unusual.

Mild alcoholic hepatitis may be indistinguishable from fatty liver disease- often the two co-exist. The symptoms of mild alcoholic hepatitis tend to be more severe:

  • Anorexia
  • Nausea
  • Abdominal pain
  • Weight loss
  • Drugs

- See more at: http://almostadoctor.co.uk/content/systems/gastrointestinal-tract/liver/hepatitis/alcoholic-hepatitis#sthash.1hruEPau.dpuf

 

Autoimmune Hepatitis EBV 

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Introduction

Autoimmune hepatitis is a cause of chronic hepatitis. It is also sometimes referred to as chronic active hepatitis.  Any hepatitis that typically lasts >6 months is referred to as chronic

It is characterised by:

  • Increased IgG levels
  • Antibodies against:
    • Liver specific proteins
    • Non-live specific proteins
  • Mononuclear infiltrate within the liver
    • Monocytes, macrophages, lymphocytes, plasma cells, macrophages and mast cells

 

There are three types of AIH, which can be distinguished histologically:

  • AIH – 1 – shows the presence of anti-smooth muscle antibodies (ASMA’s), andsometimes anti-nucelar antibodies (ANA’s)
  • AIH – 2 – has liver-kidney microsomal type 1 antibodies (LKM-1) and sometimes anti-liver cytosol 1 antibodies (anti-LC1).
  • AIH – 3 – has antibodies to soluble liver proteins or liver-pancreas antigen.
    • Actin antibody is related to prognosis. Those with actin antibody presence are more likely to require transplant than those without.
    • HLA-DR3 and HLA-DR4 are associated with increased risk for AIH.
    • In HLA-DR3 patients the disease tends to occur earlier, and is more likely to require transplantation.
    • ANA’s – antinuclear antibodies are present in many autoimmune diseases: Rheumatoid arthritisSLE, scleroderma, polymyositis, dermatomyositis, as well as AIH. In many of these diseases the ANA blood test can help diagnosis.

 

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Epidemiology

  • Auto-immune hepatitis is rare. It Western Europe and the US  there are <1 case per 100 000
  • The M:F ratio is 1:3
  • Peaks of incidence: Age 10-20, and 45-70. The lower peak is more common and:
    • § Accounts for about half of cases
    • § Typically premenstrual girls
    • § 80% of AIH-2 patients are children
  • Other autoimmune disease in the patient, or first degree relatives:
    • 20% of patients have another autoimmune disease
    • 40% of patients have a first degree relative with an autoimmune disease

 

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Pathology

The disease is thought to occur in genetically pre-disposed individuals who come into contact with an environmental trigger. 

Many patients with autoimmune hepatitis have a low CD8 count. They also often have a genetically determined reduced level of CD4 T cells, which are associated with fighting viral infection. Thus it may be possible that a viral infection triggers off the production ofautoantibodies in susceptible individuals. For example, the hepatitis C virus has a close relation to LKM-1 antibody mentioned above.

Drugs and Environmental agents have also been cited as possible causes.

  • Very rarely, AIH may be the result of Hep AHep BEBV
  • More commonly AIH is caused by Hep C

 

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Presentation

  • May initially be acute presentation, but will always eventually become chronic.
  • Up to 50% of patients present as if an acute viral hepatitis.
  • In other cases, there is typically an insidious onset
  • Non-specific symptoms:
  • Liver-specific problems:

 

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Prognosis

  • Many patients will have severe cirrhosis by the time of diagnosis
  • About 25% of patients will have a liver transplant
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Epstein Barr Virus 

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Introduction

Epstein-Barr virus (EBV) is a type of human herpes virus. It is extremely widespread, and is contracted by close person to person contact. It can cause a wide range of clinical consequences, and the most common clinical manifestation is Infectious Mononucleosis.
 
Many infections (up to 50%) are subclinical and asymptomatic. In (the other) 50% of people, primary infection with the virus will cause clinical symptoms, usually in the form of infectious mononucleosis.
In both subclinical, and clinical primary infections, the host will carry the virus asymptomatically for the rest of their life, after the initial presentation has resolved.
 
Long-term, it has been associated with an increased risk of B cell lymphoma, T cell lymphoma, Hodgkin’s lymphoma, and nasopharyngeal carcinoma.

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Epidemiology

  • Up to 95% of individuals carry the virus
  • Approximately 50% of cases are symptomatic on primary infection, most commonly in the form of Infectious Mononucleosis
  • Can present at any age. May be more common in teenagers, and occasionally referred to as ‘kissing disease’

 

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Infectious Mononucleosis

Infectious mononucleosis (IM) also known as Glandular Fever is the most common clinical manifestation of EBV.

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Presentation and Diagnosis

Often described as ‘flu-like’ symptoms they can be difficult to differentiate from other viral and URTI causes. Any combination of the following may be present:

  • Headache
  • Fever
  • Tonsillitis / sore throat
  • Cervical lymph node enlargement and tenderness (usually symmetrical)
  • Malaise and severe fatigue
  • May have tonsillar exudate
  • Nausea / vomiting / GI symptoms. Up to 90% of patients also have a mild hepatitis
  • Splenomegaly occurs in 50% of patients
  • Jaundice and hepatomegaly are rare
  • Occasionally patients may present with hepatitis with none of the other features

 
It can be difficult to differentiate from other cause or URTI / sore throat. As in tonsillitis, there are four parameters that can help differentiate a viral from a bacterial cause. If all four are present, there is a 50% chance the cause is bacterial. Antibitoics should only be recommended if all four features are present (although in reality, they are often given when all features are not present)

  • Fever >38 degrees
  • Tender cervical lympadenopathy
  • Tonsillar Exudate
  • No cough

Often in a bacterial cause, there is asymmetrical cervical lymphadenopathy also.
 
It is particularly important to differentiate EBV from bacterial causes because giving amoxicillin or ampicillin in EBV infection is contraindicated and can cause a rash (which is unrelated to any penicillin hypersentivity).

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Treatment

  • Avoid antibiotics
  • Most cases resolve spontaneously within 1-2 weeks
  • Fatigue can persist for several weeks or months

 
Most individuals subsequently develop lifelong immunity to further acute infections.

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Other Infections

EBV can affect almost any organ, and is associated with a wide range of diseases. It is often screened for in wide ranging presentations where no cause can be found, and is also often part of a liver screen.  

- See more at: http://almostadoctor.co.uk/content/systems/gastrointestinal-tract/liver/hepatitis/ebv-epstein-barr-virus#sthash.AWmkGyiL.dpuf

 

 

Hepatitis A 

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Aetiology and Epidemiology

  • The most common hepatitis virus. It is often seen in epidemics (usually in children), and most commonly occurs in the autumn
  • Often found in communities with overcrowding
  • Commonly found in water – partiuclarly beware salads washed in contaminated water  - often patient may have had recent travel abroad
  • Very common, particularly in developing world. In some countries, 100% of the population has been infected by the age 10 – but the disease is often asymptomatic in children and so may go unnoticed
  • In the developed world, 5-40% of the population have had the infection
  • There are sometimes 'mini-epidemics' in children in nursey / day-care centres
  • Often found after flooding
  • Shellfish have also been implicated in transmission – possibly due to human sewage reaching their habitat
  • There isn’t a carrier state
  • The virus can be killed by boiling water for 10 minutes.
  • Vaccination provides immunity for 10 years

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Pathology

  • Incubation 2-6 weeks
  • Oro-faecal transmission. Viral shedding occurs in the faeces at about the time of the onset of symptoms
  • RNA virus

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Signs and Symptoms

  • Many patients are asymptomatic. They may never know they have had the disease
  • Very rarely it can be lifethreatening (mortality 0.3-2%)
  • Symptoms depend on age:
    • < 4 years - 90% anicteric
    • 15 years – 40 – 70% icteric
  • May be a prodromal phase
  • Jaundice, malaise, abdominal pain, nausea & fever – usually lasting around 2 weeks
    • Jaundice may occur 1-2 weeks after other symptoms. As the jaundice worsens, other symptoms may subside, but the urine may become dark and the stools pale, due to intrahepatic cholestasis (i.e. the intrahepatic bile ducts get blocked)
    • 10% of patients get splenomegaly resulting in a palpable spleen
  • Other non-specific symptoms – including distaste for cigarettes!

 

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Investigations

  • Only one antigen has been found – HAV. However, it is not tested for as levels vary during the course of an infection. Instead we test for anit-HAV – the levels of which are more predictable.
    • You can see IgM in the blood for the first 6 weeks, then IgG after that.
  • Diagnosis – abnormal LFTs / +ve IgM anti-HAV
    • ALT > AST
    • AST may be > 1000
  • IgM HAV antibody may be positive for up to 6 months after clinical feautres subside
  • IgG antibody positive indicates past exposure
  • Prognosis - can be determined by INR

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Treatment

  • Usually self limiting. Does not usually require hospital admission in uncomplicated cases.
  • Rest and dietary modification seem to have little effect – basically, you just have to sit it out!
  • In most people, the severity of the virus peaks 4 weeks after infection, and symptoms will be virtually gone 2 weeks later.

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 Complications

  • Acute fulminant liver failure is rare – 0.1 to 0.4%
  • Not associated with chronic liver disease
  • The mortality rate is low – around 0.3%, increasing to 2% with age and other co-morbities.
  • Extra-hepatic complications are very rare, but include arthritis, myocarditis and renal failure.
  • 10% of patient’s will have a relapse before recovery.
  • Some patients may ‘feel ill’ for months after the disease – this is known as post hepatitis syndrome and it is a functional disease that is treated by reassurance

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Prophylaxis

Hepatitis A vaccine is recommended for travellers before they visit:

  • Indian subcontinent
  • Africa
  • Central & South America
  • The Far East
  • Eastern Europe

Hepatitis A vaccine schedule:

  • Initial dose 4-6 weeks before travel
  • Booster at 6-12 months later
  • Provides immunity for 10 years

- See more at: http://almostadoctor.co.uk/content/systems/gastrointestinal-tract/liver/hepatitis/hepatitis#sthash.QlXCIg9J.dpuf

 

Hepatitis B 

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Epidemiology and Aetiology

  • Major health problem – 300 million carriers
  • Incubation 1 - 4 mths
  • Parenteral transmission – sexual, IV, perinatal
  • 0.5% of UK population are carriers, but this is as much as 10-15% in some countries in the developing world. in some far eastern countries, 1/3 of people are carriers. E.g. in Yemen ¼ of the population have hep B

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Presentation

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Acute Hepatitis B

  • Incubation period 6 weeks - 6 months
  • 1% of patients will develop liver failure
  • 90% will recover
  • 10% will go on to develop chronic hepatitis B infection
  • Jaundice, malaise, abdominal pain, nausea & fever - 1 to 3 months
  • 70% anicteric (not jaundiced)

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Maternal transmission is different

  • 90% of newborns born to infected mothers will have chronic hepatitis B infection
  • Up to 25% will have chronic complications. Including:
    • Cirrhosis
    • Hepatocellular carcinoma

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Diagnosis

  • Derranged LFTs
  • Positive HBsAg
  • Carrier status is indicated by presence of e antigen. ‘e-antigen positive carrier’

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Understanding Hepatitis B testing

There are several antigens and antibodies that are present during, and following Hepatitis B infection. Understanding which of these is present and when can help you identify if a persen has a current or past infection, and their immunity status.
Description: http://almostadoctor.co.uk/sites/default/files/uploadedwysiwygimages/Notes%20Images/xHepatitis_B.png.pagespeed.ic.XuF9ZIm60E.png

Clinical Status

Serological Markers

Immunity following previous natural exposure

Anti-HBc (may be negative if infection was a long time ago)
Anti-HBs

Previously Vaccinated

Anti-HBs

Acute Infection

HBs-Antigen
Anti-HBc
HBV-DNA
HBe-Antigen (may be negative depending on timing)

Chronic Infection

HBs-Antigen
Anti-HBc
HBV-DNA
(all above still positive 6 months after diagnosis)

  

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Pathology

In chronic disease, viral DNA may become incorporated into host DNA. HbsAg is present on the surface of infected hepatocytes, and this causes T cells to induce apoptosis in these cells. The pathogenesis is different to that of HAV (Hepatitis A Virus) , where the apoptosis is not induced by the immune system, but by the infected cell itself – thus HAV does not have the ability to cause chronic disease.

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Complications

  • Acute liver failure rare – 0.1 to 0.5%
  • Chronic Hepatitis B is specified as viraemia at 6 months after initial diagnosis/sympotms
  • Chronic infection depends on age of infection:
    • 90% of people who get the disease in vertical transmission (i.e. from their mum) will develop chronic disease
    • 5-10% of adults will develop chronic disease
  • 30% of people with chronic infection will get cirrhosis
  • In chronic HBV 40% men and 15% women die from liver failure

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Management

  • Antiviral therapy for selected patients with chronic infection
    • Lamivudine
    • Entecavir
    • Tenofovir (adefovir)
  • The aim of treatment is to reduce the risk of complications. Therefore patients who already have cirrhosis are likely not to benefit. Other factors when deciding who to treat include:
    • HBe-antigen status
    • Elevated Transaminase
    • HBV DNA levels
    • Not cirrhotic
  • Prevented by vaccination

- See more at: http://almostadoctor.co.uk/content/systems/gastrointestinal-tract/liver/hepatitis/hepatitis-b#sthash.CNsHty1P.dpuf

 

 

Hepatitis C 

  • This is unusual as hepatitis viruses go, as it very rarely causes acute infection. People will only become aware of infection when they develop serious liver disease later in life.
  • 80% of those exposed to the virus will develop chronic infection. Spontaneous late clearance of the disease is very rare.
  • Blood transfusion and blood products are a major means of transmission. It is also though that it can be sexually transmitted, but this is not particularly common.
  • Prevalence in the UK is about 0.02%. In Africa it is about 6%, and in Egypt is as high as 19%.
  • About 80% of those in the UK with haemophilia have hepatitis C.
  • Major health problem – 150 million infected. Incubation 6 - 12 wks – however this figure is fairly meaningless, due the fact that acute disease is so rare.
  • 85% anicteric. 10-15% of patients will have jaundice and perhaps other general symptoms suggestive of hepatitis.
  • Jaundice, malaise, abdominal pain, nausea & fever - mild
  • Diagnosis – abnormal LFTs / +ve anti-HCV
  • Acute liver failure rare – < 0.1%
  • Chronic infection very common – 85% & 1 – 4 % ® HCC
  • Antiviral therapy for chronic infection
  • No vaccine available
  • 30% of chronic HCV develop cirrhosis within 20 – 30 years
  • Worldwide it is the leading cause of liver disease.
  • 95% of new cases in UK are due to IV drug use. Sexual transmission is also possible but less common.
  • Male patients are more likely to develop fibrosis with chronic infection.
  • Interferon is the most common treatment for chronic infection.
  • Progression from chronic hepatitis to cirrhosis takes 20-40 years. This happens more quickly in male patients, immunosupressed patients, and those who drink a lot of alcohol.
  • About 20% of Hep C patients will develop cirrhosis within 20 years.
    • 5 year survival once cirrhosis has set in is 95%. 10-year is 81%
    • ¼ of patients will develop complications, such as ascites. Once these have developed, 5-year survival drops to 50%
    • 2-5% of cirrotic patients will develop hepatocarcinoma.
  • - See more at: http://almostadoctor.co.uk/content/systems/gastrointestinal-tract/liver/hepatitis/hepatitis-c#sthash.8nF7tTrA.dpuf

 

Hepatitis D 

 

  • You can only contract this is you are also currently suffering from hepatitis B.
  • You can get two types of infection:
    • Normal co-existant infection – 90% of cases – this actually reduces the severity of the hep B infection! This is because infection with hepatitis D can reduce the replication rate of the hepatitis B virus. These people will usually make a full recovery from an unremarkable acute hepatitis
    • Superinfection – 10% of cases – this greatly worsens prognosis. It is due to chronic infection with both viruses. It is not really known what causes this. It can be detected by very high levels of anti-HDV in the blood.
  • With both types of co-infection there is an increased risk of fulminant liver disease.
  • Common mode of transmission is IV drug use (in the UK). In other parts of the world it is transmitted by close personal contact.
  • It is common in some parts of the Mediterranean, as well as Africa and South America.
  • There is only one identified antigen – HDV. The test for infection with hep D is anti-HDV.
  • To prevent hep D, basically, you need to prevent hep B infection!
  • - See more at: http://almostadoctor.co.uk/content/systems/gastrointestinal-tract/liver/hepatitis/hepatitis-d#sthash.CfIPYdyf.dpuf
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Hepatitis E 

 

  • You can only contract this is you are also currently suffering from hepatitis B.
  • You can get two types of infection:
    • Normal co-existant infection – 90% of cases – this actually reduces the severity of the hep B infection! This is because infection with hepatitis D can reduce the replication rate of the hepatitis B virus. These people will usually make a full recovery from an unremarkable acute hepatitis
    • Superinfection – 10% of cases – this greatly worsens prognosis. It is due to chronic infection with both viruses. It is not really known what causes this. It can be detected by very high levels of anti-HDV in the blood.
  • With both types of co-infection there is an increased risk of fulminant liver disease.
  • Common mode of transmission is IV drug use (in the UK). In other parts of the world it is transmitted by close personal contact.
  • It is common in some parts of the Mediterranean, as well as Africa and South America.
  • There is only one identified antigen – HDV. The test for infection with hep D is anti-HDV.
  • To prevent hep D, basically, you need to prevent hep B infection!
  • - See more at: http://almostadoctor.co.uk/content/systems/gastrointestinal-tract/liver/hepatitis/hepatitis-d#sthash.jHaL96nD.dpuf
  •  

 

Hepatitis G 

  • It behaves a bit like hep C.
  • Up to 2% of blood donors in US have this – but it is not considered pathogenic.

Viral Hepatitis

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Hepatitis is liver disease characterised by the presence of immune cells within the liver.

Viral Hepatitis

Many viruses are able to infect the liver, some of these will only affect the liver, whilst others may be systemic.

Hepatitis viruses A-E +G will primarily affect the liver.

Systemic viruses that will affect the liver include:

  • Herpes viruses
  • Epstein – Barr Virus (EBV)
  • Cytomegalovirus (CMV)
  • Varicella virus
  • Adenovirus
  • Yellow fever
  • Haemorrhagic viruses

 

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General effects after infection with a hepatitis virus

The most commonly recognised sign is an acute attack with icteric effects. Most people will make a complete recovery. Symptoms may last a few days to a couple of weeks, and include:

  • Fever
  • Malaise
  • Upper abdominal discomfort
  • Jaundice – often lasts a few days to a few weeks and then subsides. It is also one of the last symptoms to develop – it may not develop until 2 weeks after other symptoms, or indeed may not develop at all (anicteric hepatitis).
  • Symptoms usually last 3-6 weeks and then subside.
  • Development of ascites and oedema is very uncommon, but can still occur in the most serious cases.
  • The disease may have several ‘waves’ where the patient has several episodes of worsening symptoms before they make a full recovery
  • With some viruses (B, C &D) there is a chance of developing chronic disease.
  • Very few people die from acute viral hepatitis.
    • Fulminant liver failure can very rarely occur. The term ‘fulminant’ means the failure occurs very suddenly and is severe, but it is reversible. Technically, fulminant liver disease is where there is severe encephalopathy that develops within 2 weeks of the onset of jaundice.

 

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Clinical examination

Some or all of the following features may be present: