Hepatitis C is liver inflammation and damage caused by viral infection. Hepatitis C can be classified into two major categories: Acute hepatitis C and chronic hepatitis C. HCV can take variant forms worldwide, these forms are known as “genotypes”. At least six major genotypes of HCV have been discovered globally and each one of these genotypes contains several subtypes.

Hepatitis C infection results from hepatitis C virus (HCV). Mostly, the virus distributed by blood’s contact from person to person. The risk of hepatitis C infection may increase in case of health care providers who have been exposed to infected blood, people with HIV, or receiving a tattoo or piercing by blood-infected equipment. The lack of a productive cell culture system has contributed to a partial understanding of HCV lifecycle. The mode of HCV entry remains unknown despite the fact that at the surface of target cells, various molecules have been implicated in the receptor complex. Failure in controlling the viral replication caused by weak CD4 and CD8 T-cell responses during acute infection will lead to persistent infection.

Most people diagnosed with hepatitis C are asymptomatic. Usually, chronic hepatitis C remains "silent" for many years, until a serious liver damage occurs to cause distinct signs and symptoms of liver disease. The followings are some of these signs and symptoms: Fatigue, jaundice, itchy skin, poor appetite, ascites, and spider-like blood vessels on the skin. HCV infection is diagnosed in two steps: The first step is done by using a serological test to screen anti-HCV antibodies to identify the infected individuals. The second step comprises of conducting of nucleic acid test for HCV ribonucleic acid (RNA) to confirm the presence of chronic infection.

Tests such as liver biopsy, magnetic resonance elastography (MRE), and transient elastography can be carried out by physicians to assess liver damage in chronic hepatitis. A combination of antiviral medicines can be regarded as the standard method of treatment for hepatitis C infection. Newer direct-acting antiviral medicines such as simeprevir (Olysio) and sofosbuvir (Sovaldi) could be prescribed by physicians as well as older hepatitis C medicines such as ribavirin and peginterferon alfa-2a .

Hepatitis C infection that persists over many years can cause significant complications, such as cirrhosis (scarring of the liver), liver cancer, or liver failure. A list published by WHO comprises limited primary interventions to prevent hepatitis C infection such as hand hygiene especially during performing medical procedures, and cautious disposal of sharps and waste.

A good sign for an effective treatment for hepatitis C infection can be spotted once no presence of the virus appeared in the blood of infected person 12 weeks or more after conducting the treatment. This is called "sustained virologic response (SVR)". According to WHO, an estimated 71 million people have chronic hepatitis C infection worldwide, 20% (14 million) knew that they are infected by the disease and approximately 399 000 people die each year from hepatitis C.

Hepatitis C is defined as a viral infection that can lead to liver inflammation and damage. Inflammation process triggers swelling when injury or infection hit the tissues of the human body. Contaminated blood with hepatitis C virus (HCV) is the main method of hepatitis C virus transmission. Hepatitis C virus (HCV) is an enveloped RNA virus with limited host range (humans and chimpanzees), descend from the Flaviviridae viruses family tree and first discovered in 1989.

Hepatitis C can be classified into two major categories:

• Acute hepatitis C: Usually the infected person will have no apparent symptoms and it is very rare for this type to cause any life-threatening consequences. About 15–45% of infected persons could be treated spontaneously within a period of 6 months after getting the disease without receiving any significant treatment.
• Chronic hepatitis C: Chronic hepatitis C is the type which can stay for too long. Chronic hepatitis C appear once the body is no longer able to resist the virus. The studies show that about 75 - 85 % of people diagnosed previously with acute hepatitis C will develop chronic hepatitis C at a certain stage.

HCV can take variant forms worldwide; these forms are known as “genotypes”. At least six major genotypes of HCV have been discovered globally and each one of these genotypes contains several subtypes. In the United States as in Europe, the most common genotypes of HCV are 1a and 1b subtypes.

Up to 73% of HCV cases in Japan are attributed to subtype 1b. Subtype 2c is found commonly in northern Italy and it is relatively expected to find subtypes 2a and 2b in Japan, North America, and Europe. It also expected to find HCV genotype 3a among intravenous drug abusers in both the US and in Europe.

In North Africa and the Middle East, HCV genotype 4  is reported to be the dominant genotype in the regions.Genotype 5 reported mostly in South Africa and genotype 6 reported in Hong Kong. It has been suggested by many researchers that genotypes 7 through 11 should be identified as a single genotype 6 or related variants to genotype 6.However, the prevalence of genotypes 7, 8, and 9 have been detected only among patients from Vietnam, and genotypes 10 and 11 were seen in infected Indonesian patients.

Hepatitis C infection results from hepatitis C virus (HCV). The virus distributed by blood’s contact from person to person. The less common modes of transmission are through sexual activities or from an infected mother to the baby. However, a baby cannot get hepatitis C from his mother by breastfeeding.

The risk of hepatitis C infection is increased in case of:

• Health care providers who have been exposed to infected blood, which accidentally occur if an infected needle penetrates the skin.
• Having HIV.
• Previous injection or inhaling illegal drugs.
• Receiving a tattoo or piercing by blood-infected equipment.
• Being a child of a woman with a hepatitis C infection.
• Receiving hemodialysis treatment for too long.
• Staying in prison for a period of time.
• The age group with the highest incidence of hepatitis C infection is between 1945 and 1965(the baby boomer generation). It is recommended for anyone who born from 1945 to 1965 to get a one-time test for hepatitis C.
• Receiving clotting factor compound prior to 1987 or organ transplant or blood transfusion prior to 1992.

The lack of a productive cell culture system has contributed to a partial understanding of HCV lifecycle. The mode of HCV entry remains unknown despite the fact that at the surface of target cells, various molecules have been implicated in the receptor complex according to various studies.

Failure in controlling the viral replication caused by weak CD4 and CD8 T-cell responses during acute infection will lead to persistent infection. HCV does not appear to be cytopathic once the chronic infection takes place. Local non-specific immune responses will result in liver lesions. Fibrogenesis will be triggered by local inflammation and hepatic stellate cells, which will play a major role in the process. External factors such as viral co-infections and chronic alcohol consumption can facilitate the progression of liver cirrhosis.

The tendency toward chronicity is a major feature of HCV infection and it has the ability to escape the immune response of the host due to its high genetic variability. The innate immune response is the first mechanism of host defense against HCV infection. Endogenous secretion of interferon and NK (natural killer) cells are the two actions involved in this mechanism. The mechanisms by which the action of interferon type one manifest are:

• Inducing cellular protein kinases to repress the regulation of protein synthesis of the infected cells;
• Expression of major histocompatibility (MHC) genes on the antigen presenting cells and target cells will be increased;
• Activating Mx proteins or 2’-5’ oligoadenylate synthetase to decrease viral replication rate;
• The regulation of natural killer (NK) cells, dendritic cells (DC) and CD8 lymphocytes activity will be enhanced and increased;
• Stimulating of the death of cells by activating molecules associated with apoptosis.

The second mechanism is the adaptive immune response, which determines the evolution of HCV infection. It has been proved that an early, strong, polyclonal and multispecific response from CD4 and CD8 T lymphocytes is correlated with viral clearance.

Humoral and cellular immune response are the two distinct tactics that used by this mechanism to fight against pathogens. Humoral immune response uses neutralizing and non-neutralizing antibodies (Non-nAbs) which can endorse antiviral activity. Cellular immune response uses virus-specific CTLs and CD4 T helper cells, which play key effector and regulatory roles respectively and also can stimulate antiviral immunity.

Most people diagnosed with hepatitis C are asymptomatic. People who diagnosed with an acute hepatitis C infection may have symptoms within 1 to 3 months after the virus entered the bloodstream.Usually, chronic hepatitis C remains "silent" for many years, until a serious liver damage occurs to cause distinct signs and symptoms of liver disease. The followings are some of these signs and symptoms:

• Fatigue
• Itchy skin and swelling ( mainly in the legs)
• Ascites or accumulation of fluid in the abdomen
• Mental confusion, drowsiness and slurred speech
• Vulnerability to get bleeding and bruises
• Poor appetite and weight loss
• Jaundice (yellow discoloration of the skin and eyes) and spider-like blood vessels on the skin
• Dark-colored urine

Few people are diagnosed during the acute phase of the disease because acute HCV infection usually appears without distinct symptoms. The infection is also undiagnosed in the people who tend to develop chronic HCV infection because the infection shows no symptoms until decades when symptoms develop secondary to critical liver damage.

HCV infection is diagnosed in two steps:

The first step: It is done by using a serological test to screen anti-HCV antibodies to identify the infected individuals.

The second step:  It is carried out after the result of the serological test determine the positivity of anti-HCV antibodies. Due to the fact that about 15–45 percent of people infected with HCV are able to get rid of the virus spontaneously by a strong immune response and still their test will show positivity for anti-HCV antibodies, a nucleic acid test for HCV ribonucleic acid (RNA) will be required to confirm the presence of chronic infection.

Assessment of the degree of liver damage (fibrosis and cirrhosis) have to be conducted after a patient diagnosed with chronic hepatitis C infection. A variety of tests can be carried out by physicians to assess liver damage in chronic hepatitis. Tests such as.

• Liver biopsy: The obtaining of the biopsy requires the inserting of a thin needle through the abdominal wall by using ultrasound guidance to remove a small piece of liver tissue for laboratory testing.
• Magnetic resonance elastography (MRE): It creates a visual map that can show gradients of stiffness throughout the liver by utilizing magnetic resonance imaging technology with sound waves. Presence of fibrosis can be related to stiffing or scarring of liver tissue that caused by chronic hepatitis C. The noninvasive character of magnetic resonance elastography makes it a proper alternative to liver biopsy.
• Transient elastography: This test estimates liver’s stiffness by measuring the dispersal speed of ultrasound transmitted vibrations through the liver and it is considered the noninvasive test.

The treatment options for hepatitis C infection can include:

• Medications: A combination of antiviral medicines can be regarded as the standard method of treatment for hepatitis C infection. Since 2013, direct-acting antiviral medicines are the newer category which recommended in treating hepatitis C infection. Hepatitis C genotype, the presence of existing liver damage, other medical conditions and prior treatments will determine the proper choice of medicines. One or more of these newer, direct-acting antiviral medicines might be prescribed by the physician to treat hepatitis C infection:

• Simeprevir  (Olysio)
• Sofosbuvir  (Sovaldi)
• Daclatasvir  (Daklinza)
• Elbasvir/Grazoprevir  (Zepatier)
• Ledipasvir/Sofosbuvir  (Harvoni)
• Ombitasvir/Paritaprevir/Ritonavir  (Technivie)

The period which needed to treat hepatitis C infection by using medicines is from 12 to 24 weeks. Older hepatitis C medicines can be used with the newer medicines, older medicines such as:

• Ribavirin
• Peginterferon alfa-2a  (Pegasys) or peginterferon alfa-2b

The treatment of hepatitis C by using medication might involve various side effects such as:

• Nausea and vomiting
• Fatigue and fever
• Mental depression

• Liver transplantation: Liver transplantation remains as an option if the patient has developed critical complications from chronic hepatitis C infection. During this procedure, the surgeon replaces the damaged liver with a healthier liver. Deceased donors are the source of the transplanted livers. However, the infection is likely to return and requiring treatment with antiviral medication; therefore, liver transplant alone does not cure hepatitis C in most cases.

Hepatitis C infection that persists over many years can cause significant complications, such as:

• Cirrhosis (scarring of the liver): Cirrhosis may occur after 20 to 30 years of hepatitis C infection development. Liver cirrhosis can alter liver’s functions and can increase the possibility of having hepatocellular carcinoma disease (liver cancer).
• Liver cancer: Studies indicate that hepatitis C infection may lead to liver cancer only in a small number of people.
• Liver failure: Liver may stop functioning if cirrhosis reaches critical level without treatment.

Avoiding the contact with blood of infected persons is the only way to prevent hepatitis C infection. There is no vaccine for hepatitis C but there are vaccines for hepatitis A and hepatitis B only.  A list published by WHO comprises limited primary interventions which can be recommended to prevent hepatitis C infection, the interventions include:

• Hand hygiene, especially during performing medical procedures.
• The cautious disposal of sharps and waste.
• Presenting holistic harm-reduction services to people who inject drugs such as using of sterile injecting equipment.
• The careful use of health care injections.
• HIV, syphilis, hepatitis B, and hepatitis C testing when blood donation occurs.
• Focusing in correct use of condoms.
• Continuous training for healthcare personnel.

For people infected with the hepatitis C virus, WHO recommends:

• Getting proper education and counseling regarding treatment options for hepatitis C.
• Adopting proper medical management including antiviral therapy (if recommended by a physician).
• Regular checkup for early diagnosis of chronic liver disease.
• Preventing co-infection by immunization by taking hepatitis A and B vaccines.

In addition, decreasing or abstaining alcohol consumption should be advised to patients because alcohol can worsen the condition of liver cirrhosis.

Nearly 75% to 85% of people who hepatitis C positive are vulnerable to develop chronic hepatitis C. This condition can lead to liver cirrhosis, liver cancer, or even both. The genotype of hepatitis C determine the prognosis for hepatitis C. Type 1 genotype is more likely to be treated spontaneously but it can lead to more critical chronic infection.

A good sign for effective treatment can be spotted when no presence of the virus appeared in the blood of infected person 12 weeks or more after conducting the treatment. This is called "sustained virologic response (SVR)". More than 90% of people who show improving for some genotypes have this type of response.

• Several facts have been published by WHO concerning HCV, the following are some:

•  In 2015, there were 1.75 million new HCV infections (23.7 new HCV infections per 100 000 people).
• An estimated 71 million people have chronic hepatitis C infection worldwide and approximately 399 000 people die each year from hepatitis C.
• Of the 71 million persons living with HCV infection globally, 20% (14 million) knew that they are infected by the disease. 7.4% (1.1 million) of those diagnosed were started on treatment in 2015.

• According to a study published in the international journal of medical sciences, in Europe, the general prevalence of HCV is about 1% but varies among the different countries. In Central and South America, a recent community-based study conducted in San Juan, Peurto Rico, showed that estimated prevalence of HCV in 2001-2002 was 6.3%. The estimated prevalence in Australia has been reported as 2.3% with the virus affecting 210,000 people by 2001.Also, there have been fewer studies in Africa which investigated the condition, but lower rates have been reported – 1.6% among blood donors in Ethiopia and 0.9% in Kenya.
• Reports from the American centers for disease control and prevention (CDC) emphasizing that approximately 3.5 million Americans are currently living with hepatitis C and roughly half of them still do not know the condition of their disease.