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Hepatitis C


Introduction.
Definition of hepatitis.
History of HVC.
Etiology of HVC infection.
Epidemiology and routes of transmission of HVC.
Clinical features of HVC infection.
Diagnosis of HVC infection.
Treatment of HVC infection.
Prevention of HCV infection.
Conclusion.
References.


Introduction

Hepatitis C is one of the most common health problems. This essay will outline the etiology, epidemiology, clinical features, diagnosis, treatment and prevention of HCV.
 

Definition:

Hepatitis in general can be defined as an inflammation of the liver (1)
 


History:

Hepatitis C was first discovered in 1989 when a group of scientists (Choo & colleagues) succeeded to clone a viral genome from a chimpanzee after it had been experimentally infected with a contaminated human factor VIII concentrate.  Circulating antibodies to a recombinant epitope were then detected.  This experiment had proven that this virus was the etiological agent in most cases of post-transfusion non-A non-B hepatitis.  With the aid of the electron microscope, in mid 1995, the HCV was seen for the first time. (3)(9)

 


Etiology (virology):

The etiological agent for hepatitis C is a virus known as HCV.   HCV is a positive-strand RNA, 50 to 60 nm (30 to 60 nm, other reference) in size and contains 3011 amino acids and 903 nucleotides.  It  belongs to the family of Flaviviride.  Since the virus has no DNA intermediates in it's life cycle, it can not integrate into the host genome.  HCV has the ability to replicate in the liver due to the presence of a negative strand intermediates.  Moreover, the replication of the virus with a high rate of mutation leads to immunological distinct variants which in turn, enable the virus to persist for longer times.  It is believed that the high rate of mutation occurs in the HVR1 domain. (2)(3).


Epidemiology and routes of transmission:

Several studies were done in different parts of the world to estimate the  prevalence of HCV infection.  In the USA, for example, one study showed that 1.4 % of the  population are HCV positive, while 0.1 to 0.7% of healthy volunteer blood donors are HCV positive. (3).  A similar study done in Australia found out that 0.3 % of blood donors, 68 % of intravenous drug abusers and 39 % of prisoners are HCV positives. (5).   In Japan, 1.3 % of population are anti HCV.  In New York, 0.9 to 1.4 % of volunteer donors are HCV positive.  The prevalence for thalassaemics range between 10 to 50 %, while it is more than 50 % among haemophiliacs in the USA and about 90 % in UK. (11).  The prevalence in developing countries, such as, parts of Africa and Middle East ranged between 4 to 6%. (3).  The route of transmission of HCV is blood to blood contact.  This may occur by several ways:  Among drug abusers who share needles contaminated with  HCV positive blood dorplets.  Blood transfusion is another way of transmission HCV infection in which the patient receives HCV positive blood.  Sharing toothbrushes, razors or nail scissors with infected persons could be a way to get HCV infection because blood from infected individuals may stay on these instruments and get in contact with healthy individuals' blood.  In addition, sexual activities with an HCV positive partner have a great risk of getting HCV infection.  Moreover, an infected pregnant woman may transmit  the infection to her fetus. (3)(5)(9)(10)


Clinical features

The incubation period of the virus is 15 to 150 days (3), 20 to 90 days (4), and the average is 50 days.  Acute HCV infection  is usually asymptomatic.  15 to 20% of patients develop malaise, anorexia and weakness.  25% of patients with post transfusion hepatitis develop jaundice, but it is mild and self-limiting.  Fulminate liver failure is rare.  In addition, extra hepatic features, such as, arthritis, agranulocytosis, aplastic anaemia and diffuse neurological problems may occur (6).

Strong associations:


Suggested associations:


Weak association:


HCV infection  is self-limiting in 15% of cases.  70 to 80 % (3)(5) 60 to 70 % (4) of patients develop chronic hepatitis on an average of 10 years. Chronicity is due to the failure of the host immune system to clear up the virus (5).  Cirrhosis may develop in 25 % of patients with chronic hepatitis on an average duration of 21 years, while hepatocellular carcinoma occurs on an average duration of 29 years.  It has been found that hepatocellular carcinoma occurs largely among patients with HCV cirrhosis and not often among patients with chronic HCV infection who don’t have cirrhosis. (3)


Diagnosis:

Hepatitis C testing should be done for people with high suceptibility to HCV infection. Examples:  Patients with a history of blood transfusion before the year 1990; hepatitis C was first identified in 1990, and blood used for transfusion before this year was not tested for HCV. Patients with a history of chronic hemodialysis; this group of patients are exposed to blood transfusion more than other patients and the chance of receiving HCV positive blood is larger.  In addition, people with multiple sexual partners, drug abusers and people practicing tattoos are other HCV infection risk groups.  The diagnostic tests are based on detecting antibodies formed against HCV antigens.  The second and third generating enzyme linked immuno-sorbent assays [ELISA] are the initial test to be done. This test evolves c22 and c33 antigens.  For confirmation, polymerase chain reaction [PCR], to show HCV RNA in liver and serum, is done.  PCR is a very sensitive test.  However, it is not used as an initial test.  It is used as a confirmatory test and to monitor the response to anti viral therapy. It is worth mentioning that persistent elevation of aminotransferase enzyme levels indicates possiblity of chronic HCV, while positive results of ELISA or PCR with normal levels of ALT enzyme indicate healthy carrier individuals. (3)(5)(8)(11)

Indications for HCV PCR (5)
 



Treatment:

Treatment of chronic HCV infection depends mostly on interferon alpha 2b.  The immunological rule of INF alpha is explained as follows:  INF alpha binds to specific receptors in the UNinfected cells, this leads to the activation of various genes and the  production of various enzymes that affect uncoating, cell entry and viral replication; resulting in infection resistant cells.  Moreover, INF alpha increases NK cells ( natural killer cells) activity.  It also enhances the maturation of cytotoxic T cells and increases surface expression of HLA class 1 antigens. (3)(10). It is important to know that interferon treatment may not only worsen autoimmune hepatitis, but it also leads to autoimmune disorders, such as, hypothyroidism or hyperthyroidism, idiopathic thrombocytopenic purpura. (3)  Contraindications for interferon treatment are:  pregnancy, depressive illnesses, cytopenia, alcohol drinking, hyperthyroidism, renal transplantation and autoimmune diseases. (5)  Anti viral agents and immunomodulatory agents can also play a role in the treatment of hepatitis C infection by altering viral replication and modifying the immune response of the host. (3).  Several trials were done to study the effect of herbal medication on HCV infection.  One medication prepared from thistle (plant) is believed to have hepatoprotective properties.  However, it is UNproven yet whether this treatment is useful in the case of chronic HCV infection or not.  Chinese herbal medication (CH100) has also been studied on patients with HCV infection.  Although treatment with the Chinese herbal medication for over 6 months has showed a reduction in ALT levels ,this reduction could be secondary to antiinflammatory activity of the preparation rather than due to direct effect on the virus. (5)  Till now, there is no vaccine available for HCV, this may be due to the high rate of mutation the virus undergoes. (10)(11)



Prevention:

Preventing the infection can be achieved by eliminating the risk factors; first of all,  blood should be screened before donation.  Moreover, try to use your own razors, toothbrushes, and nail scissors, so that you avoid being contaminated by HCV positive blood.  In addition, make sure that you clean any wound you may get and cover cuts with clean dressing.  In addition, avoid sharing needles or any injecting equipments.  An important point to be mentioned is that health care workers are a group in high risk of HCV infection, so, they should always be careful when dealing with patients.  A last point, safe sexual practices are of great value in the prevention of HCV infection. (2)(3)(5)(9)


Conclusion:

HCV  infection is a popular health problem, aquired through blood to blood contact. The etiological agent is an RNA virus.  It was recently discovered in 1989.  Most patients with HCV develop chronic hepatitis, which in turn may develop to liver cirrhosis. The current treatment is interferon alpha.  It protects the uninfected cells from being infected by the production of enzymes that prevent viral replication, uncoating and cell entry.  The prevention of HCV infection can be achieved by blood screening for HCV before donation, avoiding sharing needles or any injecting equipment and following  safe sexual practices.
Finally I want to thank Prof. Sharkawy, Prof. Lukic, Dr. Berg, Dr. Agarwal, Dr. Adeyemi and other staff members who have helped me in my task.


References:

(1) Roper, Nancy(ed) Pocket Medical Dictionary.14th ed  EDINBURGH, CHURCHILL LIVINGSTONE, 1987 P 127eom
(2) European Journal of Gastroenterology & Hepatology 1999, Vol, 11 No 1 by Tilman, Sauerbruch,  Wolfgang H. etal.  P 43
(3) http:// www.acponline.org/journals/15 oct96/hepatc.htm
(4) licture by Dr. Rashad  (acute liver disease)
(5) Australian Family Physician Vol. 27, No 9, september 1998 by Dakshesh Vaki,  Geoff McCaughan   P 780-784, 795-797
(6) Kumar, Parven. Clark, Michael Clinical Medicine. 3rd ed. Bailliere Tindall. UK 1994, p 256
(7) Rubin, Emanuel.  Farber, John Essential Pathology. 2nd ed. J.B LIPPINCOTT COMPANY, Philadelphia, 1992, PP 405-407
(8) DAVIDSON'S Principles and Practice of Medicine 7th ed CHURCHILL LIVINGSTONE. EDIMBURUGH 1998 PP 514-515
(9) http:// home.texoma.net/ ~moreland/what.html
(10) MIMS.  PLAYFAIR.  ROITT.  etal  Medical Microbiology   2nd ed Mosby  London PP 168, 282, 59, 116
(11) SHRLOCK.   DOODLEY.  Disease of the Liver and Biliary System  9th ed  Blackwell Scientific Publications  London 1993 PP 284-285