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EPATITIS    

 
   

 

Definition:

Hepatitis – infection of the liver – can be caused by a number of different viruses.  Hepatitis B (HBV) is caused by a mostly double-stranded DNA (desoxyribonucleic acid) virus of the Hepadnaviridae family, and is the most common serious liver infection worldwide.  The current prevalence (current infection rate) of HBV infection is estimated to be between 3% and 6% of all people worldwide, with more than 350 million people being considered chronic carriers of HBV, resulting in more than 250,000 HBV-related deaths each year.

The HBV genome (‘chromosomal make-up’) has four genes: pol, env, pre-core and X, which encode the viral DNA-polymerase, envelope protein, pre-core protein (becomes the viral capsid) and protein X, respectively. While the function of protein X is not yet clear, it may be involved in the development of cancer of the liver.

 The HB virus can be transmitted from person to person via contact with infected blood or blood products, then called a blood-borne virus or ‘serum hepatitis’; or via semen (sexually transmitted disease – via genital organs, oral or anal sex) or other body fluids (e.g. saliva).  An infected expecting mother can transmit the virus to the unborn baby.

The incubation period (the time span between infection and outbreak of disease symptoms) can range from six (6) weeks to six (6) months.  An HBV infection has two distinct phases – an acute and a chronic phase:

Acute, short-term, hepatitis B develops shortly after exposure to the HB virus.  This infection can develop into a very severe, life-threatening acute hepatitis, called ‘fulminant’ hepatitis.

Chronic, long-term, hepatitis B, by definition, lasts longer than six months, and may never resolve completely.  About 5% to 10% of adults who become infected with HBV will progress into chronic infections and carriers of the virus (‘chronic HBV carriers’).  Amazingly, up to two-thirds of those chronic carriers do not get sick or die of the virus, yet they can transmit the virus to other people by way of bodily secretions (sexual intercourse, and rarely, untested blood transfusions).  Chronic hepatitis can result in granulomatous scar-like changes of the liver tissue, called cirrhosis.  Cirrhosis is a non-reversible process of dying liver tissue, ultimately resulting in chronic liver failure.  Furthermore, cirrhosis and chronic hepatitis B can also lead to the development of liver cancer, the so-called hepatocellular carcinoma, a condition that will end in death unless a liver transplantation can be performed in time.  Up to 25% of patients with a chronic HBV infection die as a result of the liver disease.

             Transmission:

HBV is found in highest concentrations in a patient’s blood and blood products (serum, plasma).  While less concentrated, HBV can also be transmitted via other bodily fluids, such as semen, vaginal secretions, saliva (kissing!) wound exudates, etc.

People who are considered high risk patients for becoming potentially infected with HBV include:

  • Promiscuous men and women (with multiple sex partners), especially during unprotected intercourse, i.e. without using (male/female) condoms;
  • People with other sexually transmitted diseases (high risk profile);
  • Men or women who have sex with a person who is (acutely or chronically) infected with HBV;
  • People who inject drugs by sharing needles;
  • People who receive (improperly tested) blood transfusions or other blood products;
  • Patients who undergo dialysis for kidney disease;
  • Homosexual men;
  • Health care workers who accidentally stick themselves with needles or other sharp surgical instruments, which are contaminated with HBV infected blood;
  • Infants, born to HBV infected mothers;
  • In some cases – the course of transmission cannot be identified.

Age is an important determinant as to the development of chronic HBV infection – thus, the younger the person at the time of infection, the more likely he/she will develop a chronic HBV infection:

  • Newborn infants, infected at birth – 90% will develop into chronic HBV carriers;
  • Children, first infected prior to age 5 – will result in chronic HBV carriers in 30% of cases;
  • Children and young adults, older than 5 years of age can still become chronic HBV patients in 6% of cases;
  • Adults will become chronic carriers in 5% to 10% of all HBV cases.

The hepatitis B virus cannot be transmitted by way of casual contacts such as:

  • Handshaking;
  • Being sneezed or coughed at;
  • Breastfeeding;
  • Hugging;
  • Eating food or drinking liquids;
  • Casual contact settings such as at the office or during social settings.

Since HBV is a DNA virus, it replicates within the liver cells (hepatocytes) themselves.  During an active HBV infection, the body’s immune system, especially so-called virus-specific ‘cytotoxic T-lymphocytes’ (CTLs) attack the virus inside the liver cells.  Now, the CTLs destroy infected cells and produce an antiviral cytokine, which is a protein that communicates with other immune cells and recruits them to further fight the invading pathogen – the virus.  However, during this entire process, the CTLs and corresponding immune response not only destroy the virus itself, they also destroy the liver cells that host the virus, and thus contribute to most of the liver cell damage and tissue injury associated with the HBV infection.  

In spite of the body’s fight against the HBV, some people will continue to harbor HBV DNA following the primary infection.  If these people have an impaired immunity later in life, e.g. because of another serious illness such as HIV/AIDS or cancer, reactivation of the hepatitis B virus can occur, resulting in another serious infection.

              Pregnancy and HBV:

All pregnant women should be tested for hepatitis B as part of their prenatal care and screening procedures, especially if they fall into any of the high risk groups as listed above.  While a hepatitis infection should not cause major problems during the pregnancy, the newborn baby needs to be treated immediately in the delivery room with two injections – a hepatitis B vaccine and one dose of hepatitis B immune globulin (HBIg).  If this procedure is performed within the first 12 hours of the baby’s life, the newborn has a 90% chance of being protected against a lifelong hepatitis B infection, provided it receives a second and third ‘booster’ injection at age one-month and six-months, respectively – if this procedure is not followed properly, the newborn has a 95% chance of developing chronic hepatitis B! 

The mother can and should breastfeed her newborn in any case, as the benefits outweigh any possible risks; especially, if the baby has received its HBV vaccine, any potential risks are further reduced. 


Symptoms:

Hepatitis B can often be difficult to suspect, as about 50% of all infected people do not present with any typical symptoms.  Furthermore, any symptoms develop only within 30 to 180 days of primary exposure to the virus; since they are often mild, they are contributed to an outbreak of influenza or a similar non-specific illness. 

Symptoms include:

  • Loss of appetite;
  • Increased feeling of tiredness (’fatigue’);
  • Nausea and vomiting;
  • Itching – locally, or all over the body;
  • Pain over the liver – on the right side of the abdomen (belly), just under the rib cage;
  • Jaundice – a yellow discoloration of the skin and the sclera (white) of the eyes;
  • Urine turns dark yellow (like tea);
  • Stool (feces) turns clay colored or gray in color.

The jaundice, itching and change in color of both urine and stool are the result of the liver’s inability to process bilirubin (from an unconjugated to a conjugated status) within the liver tissue.  Conjugated bilirubin is necessary to digest (especially) fatty foods, and is the cause of the brown color of stool.  However, in liver diseases, such as hepatitis B, the unconjugated (unprocessed) form of bilirubin will increase and subsequently accumulate within the skin and mucous membranes (yellow coloring and itching); finally, it will be excreted via urine (dark colored urine).

Also, symptoms of acute hepatitis B can be very similar to the symptoms of hepatitis A and/or hepatitis C.

Prolonged nausea and vomiting (see above) can result in (severe) dehydration with subsequent intense feeling of weakness, confusion, difficulty to concentrate, anuria (no urinary output), and increased irritability.

‘Fulminant hepatitis’, while unusual, is a very severe and life-threatening illness, unless treatment is started at the earliest possible point in time.  In addition to jaundice and abdominal swelling, extreme sleepiness, lethargy, as well as mental disturbances, such as confusion and hallucinations (hepatic encephalopathy) can develop very suddenly.

As the disease progresses, normal liver functions begin to cease more and more, until overt liver failure becomes evident by symptoms such as:

  • Fluid retention, leading to swelling of the abdomen/belly (ascites), followed by swelling of the legs;
  • Persistent jaundice;
  • Severe loss of appetite, with subsequent weight loss and signs of wasting;
  • Blood tinged vomiting;
  • Bleeding incidents from the mouth and nose, as well as from the rectum and blood in stool (melena = ‘black stool’ due to active bleeding into the intestinal tract/stool);
  • Progressive development of hepatic encephalopathy, ending in hepatic coma.

Chronic hepatitis B viral infection may be completely asymptomatic (no obvious symptoms at all), or it may be associated with a slowly progressing chronic inflammation of the liver tissue, resulting in cirrhosis (severe granulomatous/fibrous changes of liver tissue) over a period of many years.  Cirrhosis is an unstoppable process of tissue destruction with subsequent failure of the liver tissue to perform any and all of its intended tasks – be it to detoxify certain substances or be it to process or produce certain substances that the body requires for functioning in a proper and healthy manner. Chronic hepatitis and the development of cirrhosis also dramatically increase the risk of developing fatal hepatocellular carcinoma (cancer of the liver).  Furthermore, chronic HBV infection is also linked to the development of certain severe renal diseases, such as ‘membranous glomerulonephritis’ of the kidneys.


Diagnosis:

As mentioned above (see Symptoms), many patients do not exhibit any symptoms, although they are infected with the virus and the disease is slowly progressing within their body.

Thus, it is important for the physician or health care provider to collect a thorough and detailed medical history in addition to an equally thorough physical examination.  General blood tests and specific blood chemistry tests may show abnormalities that should alert the health care professional to an abnormality involving the liver.

Once the concrete suspicion of a liver-involving disease process has been determined, there are a host of specific laboratory tests that can confirm the early suspicion and provide more detailed information as to the stage and extent of the disease process.

The blood tests, called assays, detect the hepatitis B virus in serum or whole blood samples – either the virus’s antigens (proteins that are produced by the virus), or antibodies produced by the host to fight the virus:

HBcAg – hepatitis B core antigen – consists of 180 or 240 copies of viral core protein, representing the ‘inner core particle’ of the infectious virion containing the viral genome.

Hepatitis B surface antigen – HBsAg – is the antigen most frequently used to screen a potentially present infection.  However, HBsAg may not be detectable in the early phase of the infection, and it may become undetectable in later stages of the infection as the virus has been cleared by the body’s own defense system.

During the so-called ‘window phase’, in which the host remains a potentially infectious source, while successfully clearing the virus, IgM (Immunoglbulin M) antibodies, which are the major part of the early answer of the body’s immune system against newly developing and active infections, may be the only serological (blood-borne) evidence of the disease – called anti-HBc IgM.

Shortly following the appearance of the above mentioned HBsAg, a second antigen, called hepatitis B e antigen – HbeAg – will surface.  HBeAg is associated with an accelerated rate of viral replication, and thus increased infectivity.  Unfortunately, not all variants of Hepatitis B virus do produce this ‘e’ antigen, making this test unreliable, if it comes back negative.  During the normal course of a hepatitis B infection, HBeAg will slowly be cleared, while antibodies to the ‘e’ antigen will rise – the anti-HBe antibodies; this rise is an indication of a dramatic decline in viral replication, and thus the first sign of recuperation.    

In the later stages of recuperation, HBsAg will become undetectable, followed by an increase of IgG (Immunoglobulin G) antibodies to the hepatitis B surface antigen and core antigen (anti-HBs and HBc IgG, respectively).  A patient with a negative HBsAg result, but who is positive for anti-HBs will either have cleared an infection, or has been vaccinated previously.

Patients, who remain HBsAg positive for six months or longer, are considered to be chronic HBV carriers.  Chronic carriers also show increased blood serum levels of alanine aminotransferase (ALT – formerly SGPT, serum glutamic pyruvic transaminase) and signs of liver inflammation, which can be demonstrated by way of a liver biopsy.
    
Adult carriers who finally seroconvert to an HBeAg negative status, usually express very little viral replication, and thus may have a fairly small risk potential for long-term complications, or for transmitting the viral infection to other people.

Other, more sophisticated tests available, include PCR (polymerase chain reaction), a highly sensitive (and fairly expensive) test which can detect and measure the amount of viral nucleic acid (viral load) in a clinical specimen.  Determining a patient’s viral load is used to assess the status of infection and to monitor the effectiveness of any treatment schedule.


Treatment:

In otherwise healthy adult patients, acute hepatitis B usually does not need medical treatment. However, if the HBV infection becomes severe, symptoms such as vomiting and persistent diarrhea may lead to dehydration, and then the patient requires supportive therapy by restoring the lost fluids and electrolytes.  At this point in time, there is no specific treatment that can prevent acute infection from progressing into a chronic HBV infection.

For a chronic hepatitis B infection, antiviral treatment is required in order to stop the replication of the virus, and to prevent subsequent liver damage such as liver cirrhosis and liver cancer.  Patients who show a persistently elevated ALT (SGPT) blood level, a marker of the extent of liver damage, and concomitantly high HBV DNA levels, are prime candidates for therapy.  However, antiviral therapy is not indicated for every patient with chronic HBV infection – it has to be based on the evaluation of the disease status, via the diagnostic tests as described above, and the individual risk of progressing to chronic HBV.  Thus, there may be one, two, or more years between the first diagnosis of an HBV infection, and the need to start an antiviral therapy for chronic HBV.

Antiviral drugs used in the treatment of chronic HBV infections include:

  • Interferon alpha-2b – also called Intron A, is a protein modulator of the body’s own immune system, administered via subcutaneous injections; it slows the viral replication while concurrently boosting the body’s own immune system; it is often the drug of first choice.
  • Adefovir – a so-called ‘nucleotide analog reverse transcriptase inhibitor (ntRTI)’, slows viral replication; is a drug to be taken orally (by mouth); it prevents viral cells from multiplying;
  • Entecavir – given orally; a guanine analogue that inhibits reverse transcriptase, as well as viral DNA replication and transcription, and thus slows replication of the HB virus;
  • Lamivudine – a so-called ‘DNA-polymerase inhibitor, and thus slows the replication of HBV; it is a powerful antiretroviral drug which was originally developed to fight HIV; side effects include lactic acidosis and even an exacerbation of the hepatic damage, as well as an increased risk of the virus developing drug resistance;
  • Tenofovir – another nucleotide reverse transcriptase inhibitor (ntRTI) drug, that has been approved for HIV-treatment in combination with other drugs, but also for the HBV therapy; side effects include lactic acidosis and serious liver damage.

There is no surgical treatment option available, with the exception of performing a liver transplant in patients with severe liver damage/failure subsequent to the HBV infection. 

              Self-Care at Home

The goals of self-care are to relieve disease associated symptoms and to try preventing further progress of the disease.  Self-care suggestions are not curative, but can maintain a patient’s well-being and delay the disease progress:

  • Drink lots of fluids – water or juices, in order to prevent dehydration;
  • Avoid potentially liver damaging medicines;
  • Do not drink alcohol;
  • Check with your physicians regarding any other drugs, herbs or medicines you may be taking, because they may be altered in their effect by an inefficiently functioning liver;   
  • Adjust your nutrition to a well balanced diet that appeals to you;
  • Avoid excessive physical stress, be it hard labor or vigorous exercise, until symptoms begin to improve;
  • Avoid any activity that may spread the disease to others (e.g. unprotected sex).


Prevention:

Hepatitis B infection can be prevented by receiving a three-course vaccination – the first injection on day one, followed by one after one month, and a second booster injection after six months.  Today’s available vaccines are made using recombinant DNA technology, although convention, plasma-derived vaccines are still used; both vaccines are equally effective.

A ‘recombinant’ vaccine utilizes bacteria and/or yeast to produce large amounts of one specific viral or bacterial protein, which is purified and given to the patient by injection.  The patient’s own immune system will then produce antibodies to this protein, thus protecting the patient from this disease.

Older plasma-derived vaccines were using one of the viral envelop proteins (HBsAg, see above), which were harvested from patients with long-standing HBV infection.

Vaccination for hepatitis B should be routinely given to the following group of people:

  • All medical and health care personnel, as well as public safety workers who may become exposed to blood;
  • Promiscuous men and women – people who have multiple sex partners or have had sexually transmitted diseases in the past;
  • People who have hemopilia (a bleeding disorder) or other blood clotting disorders and thus require or receive blood transfusions of human blood clotting factors;
  • Patients with kidney disease who require hemodialysis;
  • Patients with other liver diseases, especially hepatitis C;
  • Drug addicts who most likely share needles and other drug paraphernalia;
  • Ideally, all children younger than 18 years of age, including newborns.

Prevention of perinatal (period before and after birth – from 5 months prior to giving birth to one month post delivery) infection can be achieved by routine screening of all pregnant women for HBsAg, followed by (routine) vaccination of the newborn in HBsAg-positive women or women with unknown HBsAg status.

If an unvaccinated person has been exposed to hepatitis B, he/she can be given a hepatitis B immune globulin, along with the regular hepatitis B vaccine – this combination treatment can still prevent transmission of the disease in 80% to 90% of cases.

Potential health risks can also occur when a person decides to get a tattoo or body piercing – if the tattoo artist or piercer does not sterilize needles and other equipment appropriately, uses disposable gloves, or washes hands properly, the chance of contracting hepatitis B can be increased considerably.  

And finally, since HBV is also part of the group of sexually transmitted diseases (STDs), all preventive measurements for STDs are equally valid and important to observe in order to prevent hepatitis B.  The use of latex male or female condoms is obligatory in almost any case, but especially, if you know that you or your partner is an HBV carrier.  

 

                                                   

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DISCLAIMER: The above article is only intended to provide general information regarding this topic. It is not intended and does NOT replace the need to consult a medical or other professional person, if you have or believe to have this disease/disorder. While the article was researched, written and reviewed by medical professionals, and Medicine for Africa, its staff and publisher made every effort to assure accuracy and correctness, it does not claim to be complete, correct or to reflect the very latest stand of medical/scientific knowledge in the disease’s/syndrome’s pathology, diagnostic and/or therapeutic development. Medicine for Africa, its founder, management, staff, writers, reviewers or publishers may NOT be made responsible or legally bound to any information provided above, and cannot be held liable to any conclusions or decisions the reader may draw after reading this article. The reader is explicitly advised to consult a licensed physician and to present his/her specific situation before making any health related decisions.

  
         

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