- What is hepatitis
- Acute hepatitis
- Chronic hepatitis
- Hepatitis A
- Hepatitis B
- Hepatitis C
- Hepatitis D
- Hepatitis E
- Diagnosis of hepatitis
- Reactivation of hepatitis B
- Immune reconstitution inflammatory syndrome
- Skin signs of chronic liver failure
- Skin signs of acute hepatitis
- Skin signs of chronic hepatitis
Hepatitis is a nonspecific term for inflammation of the liver. There are acute and chronic forms of hepatitis, which may result in nausea, jaundice, fatigue and abnormal liver function blood tests.
Hepatitis may be caused by:
- Drug toxicity or allergy
- Gall bladder disease
- Autoimmune disease
- Metabolic disease e.g. fatty liver (non-alcoholic steatohepatitis)
- Infections by parasites, bacteria, fungi and viruses.
What is viral hepatitis?
The term “viral hepatitis” is often used to describe infection by a virus from the hepatotrophic family. These infections are called hepatitis A (HAV), hepatitis B (HBV), hepatitis C (HCV), hepatitis D (HDV) and hepatitis E (HEV).
Newly discovered pathogens (e.g. virus SEN-V) may account for additional cases of non-A/non-E hepatitis.
Many other virus infections can cause hepatitis including:
- Epstein-Barr virus (mononucleosis, glandular fever)
- Herpes simplex virus (cold sore virus).
After the initial infection, acute viral hepatitis may cause a self-limited illness or go unnoticed. Acute infections with HAV and HBV are usually symptomatic but acute infections with HCV are usually unnoticed.
Common symptoms of acute viral hepatitis include fever, loss of appetite, nausea, vomiting, diarrhoea and jaundice and dark urine.
The injured liver fails to break down bile properly resulting in high levels of circulating bilirubin, a greenish pigment. This stains the skin – jaundice. Liver function tests show high levels of aminotransferase (ALT).
Severe viral hepatitis due to HAV, HBV or HEV (in Asia) results in acute liver failure or fulminant hepatitis in up to 1% of cases. Clinical features of fulminant hepatitis include:
- Ascites or fluid in the abdomen is due to low levels of circulating albumin (blood protein).
- Unchecked bleeding because the liver stops making blood-clotting proteins. Coagulation tests show raised prothrombin time and INR (International Normalised Ratio).
- Raised blood sugar (diabetes) in severe hepatitis.
- Encephalopathy due to a build-up of toxins in the brain, which causes confusion, drowsiness and personality changes, and eventually loss of consciousness or coma.
- Overwhelming infection with other organisms e.g. Vibrio vulnificus and Escherichia coli.
Most cases of acute viral hepatitis resolve over days to weeks. Supportive care may be all that is necessary. Fulminant hepatitis may also resolve with supportive care but may require liver transplantation or result in death.
Acute viral hepatitis may evolve into chronic hepatitis; this is particularly common with HBV and HCV infections. HAV and HEV never progress to chronic hepatitis.
The majority of newborn babies infected with HBV develop chronic infection (90%) whereas a minority of adults with HBV develop chronic infection (5%).
HCV results in chronic infection in 70% of cases.
Many of these patients remain well, despite the infection. However, 20% develop liver cirrhosis – this may take decades to evolve but can eventually be life threatening. Chronic hepatitis can also affect joints, muscles, the nervous system, kidneys and skin.
HAV is an RNA virus that is transmitted mostly by faecal-oral route, for example by drinking untreated water or by eating contaminated food. It can be carried by houseflies.
It has an incubation period of approximately 4 weeks, though this is quite variable. It is excreted in the stool from the first week of infection. Adults with acute infection are in general more unwell than children and have a higher chance of dying from it.
HAV never causes chronic infection.
Who is at risk of hepatitis A?
HAV infection is common in the developing world, especially in the Middle East. Most people in these regions become infected as children but adult travellers are at risk of the disease.
- Hepatitis A vaccine can be used by adults and children over 1 year and is recommended for travellers to the developing world.
- Avoid exposure to contaminated water or untreated tap water – if in doubt, drink bottled drinks or boil water.
- Ensure meat and seafood has been thoroughly cooked – do not eat raw shellfish.
- Avoid cream products such as mayonnaise, cheese or yogurt.
- Practice good hygiene by washing hands frequently and drying with paper towel.
Treatment for hepatitis A
There is no specific treatment for HAV infection, which usually resolves spontaneously over several weeks.
People at high risk of disease within 2 weeks of exposure to infection may be prescribed the blood product intravenous immunoglobulin, which provides short-term immunity.
HBV is a partially double-stranded DNA genome virus of the hepadnavirus family. There are eight different genotypes (A-H). It is usually transmitted by blood or blood products or by sexual contact.
Initial infection is usually not symptomatic but 1-2% of people will develop liver failure early after their initial infection. A similar number will develop chronic infection, which can lead to cirrhosis or liver cancer (25-40%). HBV may also result in kidney disease (glomerulonephritis). Infected newborns are more likely than adults to progress to chronic hepatitis B.
Who is at risk of hepatitis B?
HBV is found in blood, saliva, semen and vaginal secretions. An infected mother may transmit HBV to her baby at the time of birth – this is called vertical transmission.
Prevention of hepatitis B
- Vaccination offers good protection against infection.
- Prevent or reduce exposure by using latex condoms and not sharing drug or tattoo needles.
- Health workers should be careful to avoid needle stick injury.
- HBV immune globulin and vaccine should be given within 12 hours of birth to infants of HBV positive mothers.
Treatment for hepatitis B
Most people with acute HBV infection recover completely without treatment. If the infection is severe, lamivudine or another antiviral medication may be prescribed.
Carriers may be offered treatment to reduce the chance of cirrhosis and liver cancer. Alpha interferon and pegylated interferon slow the replication of the virus and stimulate immune clearance of the virus. Other effective drugs include lamivudine, adefovir dipivoxil, entecavir, and telbivudin.
HCV virus is an RNA virus and is a major cause of acute and chronic hepatitis. There are at least six major genotypes. It is transmitted by injected blood.
Most patients with acute hepatitis C infection are asymptomatic but 70% develop chronic infection. This can lead to progressive liver disease, cirrhosis, and liver cancer (hepatocellular carcinoma) in approximately 20% of those infected.
Who is at risk of hepatitis C?
Hepatitis is usually acquired by blood transfusions (in the absence of screening for HCV), through unsafe sex and IV drug use – horizontal transmission. Hepatitis C affects all races and both sexes equally. It is disproportionately associated with poverty. The peak age for infection is 30-50 years; it is rarely seen in children.
Prevention for hepatitis C
- There is no available vaccine for HCV.
- Avoid risky behaviour such as sharing needles or personal items such as toothbrushes and razors.
Treatment of hepatitis C
If acute hepatitis C does not resolve on its own within 2 to 3 months, it should be managed with drug therapy.
Various treatments are available to treat chronic HCV infection. They include:
- Pegylated interferon and ribavirin
- Ledipasvir with sofosbuvir
- Paritaprevir with ritonavir and ombitasvir
- Dasabuvir and ribavirin
HDV is spread through infected blood at the same time as infection with HBV or in people who are already infected with HBV. The same preventative measures are important.
Chronic hepatitis D is usually treated with pegylated interferon.
HEV is transmitted by faecal-oral spread i.e., via food or water contaminated by faeces from an infected person.
People at most risk are international travellers visiting developing countries, and those who have unprotected sex with an infected person.
There is no vaccine for HEV. As for HAV, avoid drinking contaminated water and practicing good hygiene and sanitation.
Hepatitis E usually resolves on its own over several weeks to months.
Blood tests may include:
- Liver function, particular transaminase levels (AST, ALT) and bilirubin.
- Coagulation (blood clotting) tests to evaluate prothrombin time
- Renal (kidney) function
Urine is tested for bilirubin.
Liver biopsy may be recommended for the initial assessment of disease severity in patients with chronic HBV or HCV.
Serological tests for hepatitis
- IgM antibodies appear early in acute infection.
- IgG appears later.
- Anti-HBs becomes detectable in late convalescence. It indicates immunity following infection and remains detectable for life. It is not seen in chronic carriers.
- HBsAG (Hepatitis B surface antigen) can be present in acute and chronic HBV infection. Its presence for greater than 6 months is suggestive of chronic infections.
- HBe is a secreted protein of unknown function. Its expression is high when the virus is rapidly replicating. Anti-HBe becomes detectable as viral replication falls. It indicates low infectivity in a carrier.
- Anti-HCV indicates prior exposure or infection. The third generation assays for anti-HCV are sensitive and specific and can detect antibodies within 4 to 10 weeks of infection.
- PCR for HCV particles is the most specific test. PCR can be helpful to diagnose acute HCV infection before antibodies develop.
Immunosuppressive medications may reactivate HBV or HCV. For example:
- Chemotherapy for cancer
- Biologic therapy for psoriasis, Crohn disease and rheumatoid arthritis
- Long term systemic steroids
Patients are often tested for chronic hepatitis prior to starting these medications. Hepatitis treatment such as lamivudine may be prescribed one to two weeks prior to the immunosuppressive and continued long term. Antiviral therapy should be started immediately after a HBV flare is recognised as antiviral therapy take time to work, and may not prevent progression to liver failure to if delayed.
Patients with underlying liver disease may also be at increased risk of hepatotoxicity with these drugs.
Immune reconstitution inflammatory syndrome occurs in patients with human immunodeficiency virus (HIV) infection treated with active antiretroviral therapy (HAART). As the HIV infection lessens, the immune system begins to recover and over-reacts to pre-existing infection. This can result in a severe inflammatory reaction including severe hepatitis.
The pre-existing infection may have been previously diagnosed and treated or may have remained subclinical. Infections most commonly associated with IRIS include cytomegalovirus, herpes zoster, Mycobacterium avium complex (MAC), Pneumocystis pneumonia, and Mycobacterium tuberculosis (TB).
- Acute urticaria is commonly observed in patients with viral infections, including HAV, HBV and HCV.
- Urticaria associated with fever, headache and painful joints is known as serum sickness-like reaction, and affects 20% to 30% of patients with acute hepatitis B.
- HAV has been reported to cause an exanthem similar to scarlet fever (scarlatiniform eruption).
- Erythema multiforme – target-shaped lesions on hands and feet.
- Erythema nodosum – red lumps on shins.
Chronic liver failure from cirrhosis or hepatocellular carcinoma often results in changes to the skin.
- Jaundice – yellow skin and eyes
- Melanosis cutis – brown patches
- Guttate hypomelanosis-like lesions – white patches
- Bleeding into skin or mucosa – red or purple haemorrhages, petechiae, purpura or ecchymoses (bruises)
- Spider angiomas – also called spider nevus or spider telangiectasis
- Arteriovenous haemangioma –dome-shaped reddish facial papule
- Paper money skin – thread-like blood vessels (telangiectasia) and thin skin (atrophy)
- Palmar erythema – red palms
- Caput medusa – distended veins radiating from the umbilicus
- Scratch marks and nodular prurigo due to severe itch
- Dry skin
- Nail changes – clubbing, flat and brittle nails, opaque white nails (Terry nails), parallel white lines (Muehrcke lines)
- Loss of armpit and pubic hair – due to hormonal changes
- Regional variations in peripheral circulation, e.g., forearm warmer than calf
At least 20% of patients with chronic hepatitis due to HBV or HCV develop a skin disorder. It can be due to direct viral infection of skin cells. However, few of these are diagnostic of viral hepatitis and several are classified as autoimmune in origin.
Skin condition associated with both HBV and HCV
- Mixed cryoglobulinaemia (type 2) – circulating immunoglobulins that precipitate when cold, resulting in palpable purpura and cutaneous vasculitis because of immune complex deposition. About 85% are due to HCV infection, but HBV can also cause cryoglobulinaemia.
- Cutaneous and systemic vasculitis including leucocytoclastic vasculitis (palpable purpura affecting lower legs), livedoid vasculitis (livedo, atrophie blanche and small ulcers of the lower legs), urticarial vasculitis (persistent urticarial plaques), polyarteritis nodosum (tender nodules, livedo reticularis and ulceration) and capillaritis.
- Lichen planus – the most common type presents with firm odd-shape purplish-brown papules and plaques and whitish streaks inside the mouth.
- Porphyria cutanea tarda – liver injury triggers this metabolic disorder in genetically predisposed individuals, causing blisters in sun-exposed sites. It is provoked by HCV in up to 70% of cases.
- Increased susceptibility to skin tumours including skin cancer.
Skin conditions more often associated with HBV
- Dermatomyositis – weak muscles and a rash, often characterised by Gottron papules and heliotrope (purplish) swelling of the eyelids.
- Infantile papular acrodermatitis (Gianotti-Crosti syndrome) – a bumpy rash on the limbs of young children that lasts 2 to 3 months.
Skin condition more often associated with HCV
- Acral necrolytic erythema – scaly or blistered ring-shaped red or purple plaques on back of the hands, ankles and feet.
- Sialoadenitis, also called Sjögren disease or sicca syndrome – dry eye and mouth due to loss of salivary glands.
- Mooren corneal ulceration – resulting in pain, tearing and loss of sight.
- Antiphospholipid syndrome – due to immunoglobulins binding to platelets, blood vessel wall and clotting factors. It results in vascular destruction or bleeding.
Many other skin disorders have been described in patients with viral hepatitis but the relationship with the infection is unknown.