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EPATITIS    

  
   

 

Definition:

Hepatitis C infection is a blood-borne disease, caused by the hepatitis C virus (HCV), a small, enveloped, single-stranded RNA (RiboNucleic Acid) virus, which is the only known member of the so-called hepacivirus genus in the family of Flaviviridae.  HCV is divided into six major genotypes, numerically named as ‘genotype 1’, ‘genotype 2’, etc., and is considered one of the most serious viruses affecting the liver.

Most people, who become infected with HCV, do not even notice that they are infected, because of the lack of symptoms; they often get diagnosed years later, when the liver damage that was caused by HCV becomes obvious during a routine medical exam, or secondary symptoms.  After many years, HCV can result in the development of liver failure, liver cirrhosis or liver cancer – all are potentially fatal disorders of the liver.

Furthermore, chronic HCV infection increases the risk of developing non-Hodgkin’s lymphomas by up to 30%, and other disease conditions.

            Transmission:

HCV is primarily transmitted via blood or blood products, especially prior to 1992, when improved blood screening tests for HCV became available.  The same is valid for organ transplant recipients and patients receiving hemodialysis for kidney failure.  Improperly sterilized medical or dental equipment could also be the cause of an HCV transmission.

In addition, HCV can spread by way of infected needles, especially if shared needles are used for injecting illicit drugs, not following strict hygiene standards in a health care facility, or from contaminated needles used in tattooing or body piercing procedures.  In the USA, it is estimate that 60% to 80% of all intravenous (IV) drug abusers are infected with HCV.

Newborn babies can acquire the virus during delivery in rare cases (less than 5%) when the mother is HCV positive, especially, if the mother is also infected with the human immunodeficiency virus (HIV).  Breast feeding has not been linked with an HCV transmission.

HCV can also be transmitted during sexual intercourse with a partner who harbors the virus, especially during anal sex, categorizing HCV into the group of potential sexually transmitted diseases (STDs).

Obviously, health care workers are at a higher risk than the overall population, due to their everyday exposure to potentially infected patients and their blood products.

And finally, sharing personal items such as toothbrushes, razors, cuticle and nail scissors, etc, can potentially transmit the virus from an HCV positive individual to the HCV negative family member or live-in partner.

Sporadic transmission of HCV – i.e. the case of an HCV infection without any known source of infection, occurs in about 10% of acute HCV infections, and in up to 30% of chronic HCV infections.

HCV can be transmitted by an infected person, even though the person does not exhibit any characteristic or obvious signs, thus making it often impossible to know whether your partner is or is not infected with HCV.

Acute hepatitis C – refers to the first six months following the primary infection with the hepatitis C virus.  During this phase, up to 60-70% of infected people do not exhibit any (identifiable) symptoms, while the remaining patients show mild and non-specific symptoms, making it very difficult to diagnose the infection in its early stages. 

Chronic hepatitis C – is defined as a hepatitis C viral infection that persists for more than six months.  Even this stage is often asymptomatic and usually only discovered accidentally.

HCV cannot be spread through casual contact such as hugging, kissing, or sharing eating or cooking utensils. 

            Historic Review:

The hepatitis C virus was clearly identified in 1987 by scientists of Chiron Corporation and the CDC (Center for Disease Control and Prevention), and confirmed in 1988.  The hepatitis C virus was first discovered in the mid 1970s by Dr. Harvey J. Alter at the NIH (National Institute of Health) and termed at that time the ‘non-A non-B hepatitis (NANBH) virus’, as it was primarily demonstrated in hepatitis cases following blood transfusions, which were neither caused by the hepatitis A virus, nor the hepatitis B virus. 

            Epidemiology:

Hepatitis C infects an estimated 170 million people worldwide.  Co-infection with HIV is fairly common and HCV prevalence rates among HIV positive people are considerably higher.  Furthermore, a concomitant HIV infection results in a more rapid progression towards chronic hepatitis C and subsequently irreversible liver damage, such as cirrhosis, liver failure or liver cancer.

Symptoms:

In general, a hepatitis C infection produces no obvious signs or symptoms during its early stage of infection.  If symptoms appear, they usually consist of mild and non-specific, often flu-like symptoms such as:

  • Fatigue;
  • Muscle and joint pain;
  • Nausea and/or poor appetite;
  • Tenderness in the right upper abdomen – the area of the liver (‘liver pain’).

Later stage symptoms of a chronic hepatitis C infection may still be non-specific, and include in addition to the above listed symptoms (even decades after primary infection):

  • Persistent and/or recurring yellowing of the skin and eyes (jaundice);
  • Low-grade fever;
  • Increased nausea and vomiting, accompanied by diarrhea and/or abdominal pain;
  • Skin rash and increased loss of appetite;
  • Increased fatigue;
  • Palmar erythema (focal reddening of the palm of the hand) and/or vascular spiders (spider-shaped vascular markings, especially on the abdomen).

Hepatitis C can cause more or less severe liver damage, even in the context of no obvious or diagnostic symptoms.

Chronic hepatitis C can result in a fatal outcome – the cirrhosis of the liver.  Once a patient develops cirrhosis, the accompanying signs and symptoms become more obvious and easier to recognize. In addition to the above listed symptoms, complaints and physical findings associated with cirrhosis may include:

  • Fluid retention and swelling of the abdomen (ascites), as well as swelling of the feet/legs;
  • Dark urine;
  • A clearly enlarged liver (hepatomegaly), often associated with an enlarged spleen (hepatosplenomegaly);
  • Muscle wasting;
  • Scratches or abrasions of the skin (excoriations).

Additional extrahepatic symptoms and manifestations may include:

  • Kidney disease;
  • Severe joint and muscle aches;
  • Neuropathy (‘hepatic encephalopathy’);
  • The appearance of cryoglobulins, rheumatoid factors and so-called low-complement levels in blood serum;
  • Glomerulonephritis;
  • Porphyria cutanea tarda (PCT) – severe blistering of the skin, and some rare complications such as:
    • Non-Hodgkin’s type, (high-grade) B-cell lymphoma;
    • Seronegative arthritis;
    • Lichen planus (papular inflammatory disease of skin and oral mucosa);
    • Fibromyalgia (widespread pain and tenderness to touch).

Furthermore, cirrhosis of the liver has a high tendency to progress into fatal liver (hepatic) cancer, a condition that can only be treated (if at all) by performing a liver transplant.

 
Diagnosis:

Hepatitis C is most readily diagnosed when serum aminotransferases are elevated and anti-HCV is present in serum. The diagnosis is confirmed by the finding of HCV RNA in serum.

Acute hepatitis - the hepatitis C virus is usually detectable in the blood within one to three weeks after infection, and antibodies to the virus are usually detectable within three to 12 weeks. Approximately 15-40% of persons infected with HCV clear the virus from their body during the acute phase.   

The remaining 60-85% of patients infected with HCV, will develop a chronic hepatitis C infection.

Liver function tests (LFTs) show variable (often also non-specific) elevation of the enzymes ALT (alanine aminotransferase), AST (aspartate aminotransferase) and GGTP (gamma glutamyl transpeptidase).  

A liver biopsy is the best diagnostic test to determine the amount of scarring and inflammation, subsequent to the chronic hepatic inflammatory process. Radiographic studies such as ultrasound or CT scan show the liver injury only late in the course, when the disease is already fairly advanced.  Thus, secondary diseases such as thyroiditis (inflammation of the thyroid gland) with hyper- or hypothyroiditis (over- or underproduction of thyroidal hormones) symptoms and other disease processes associated with the above listed symptoms often lead to the first diagnosis of a hepatitis C infection.

The five most common blood tests for diagnosing HCV are:

  • Anti-HCV test – detects the presence of (protein) antibodies in blood to the virus, indicating a positive exposure to HCV.  While the test can only tell whether somebody has been exposed to HCV at some point in time, it does not confirm an active HCV infection.
  • HCV-RNA test – since the HC virus is a RNA virus, this test can indicate whether the patient has an active HCV infection. 
  • HCV RIBA test – is an additional test, confirming the presence of antibodies to the HC virus. The RIBA (Recombinant Immuno-Blot Assay) test cannot distinguish whether the patient is currently infected or has previously been exposed to the virus. A positive test confirms the patient’s exposure to the virus, not an active disease process.
  • Viral Load or Quantitative HCV tests – measure the number of viral HCV RNA particles in the patient’s blood.  These tests are usually used prior to or during the course of treatment, in order to determine the response rate to the therapy.  A successful therapy should decrease the viral load by at least 99% as early as four to 12 weeks after the initiation of the treatment.  
  • Viral genotyping – is intended to determine the genotype of the virus. There are six major types of HCV known at this point in time – the most common genotype, genotype 1 is less likely to respond to current treatment schedules than genotypes 2 or 3, and also requires a much longer period of therapy (48 weeks vs. 24 weeks for genotypes 2 and 3). 

The best approach to confirm a diagnosis of HCV includes a test for HCV RNA by using either a sensitive assay test such as the polymerase chain reaction (PCR) or the transcription-mediated amplification method (TMA).  However, these tests are rather difficult (sensitive) and expensive to perform and thus are limited to well equipped and staffed laboratories.

The so-called ‘Recombinant Immunoblot Assay’, also called ‘Western Blot test’ can be used to confirm anti-HCV reactivity. If this test is positive, the patient has most likely recovered from a hepatitis C infection and developed persistent antibodies. 

Chronic Hepatitis C - is diagnosed by confirming the presence of anti-HCV antibodies with concurrently elevated blood serum levels of aminotransferase levels (ALT and AST) for more than six months. Testing for HCV RNA (by PCR) confirms the diagnosis and documents that viremia (virus present in the blood) is present.

            Differential Diagnosis:

There are a number of major disease processes that can clinically be confused with a chronic hepatitis C infection such as:

  • Chronic hepatitis B and/or D;
  • Alcoholic hepatitis;
  • Non-alcoholic steatohepatitis (fatty liver);
  • Autoimmune hepatitis;
  • Wilson disease (copper accumulation in tissues);
  • Sclerosing cholangitis (inflammatory disease of the intra- and extrahepatic bile ducts);
  • Alpha-1-antitrypsin deficiency related hepatic disease (genetic disease, often resulting in cirrhosis);
  • Drug-induced liver disease.

In summary, the diagnosis of ‘hepatitis C’ is rarely made during the acute phase of the disease, because the majority of people who are infected, experience no or no specific symptoms during this phase of the disease.

Chronic hepatitis C may be suspected during a thorough physical examination, based on the patient’s past medical history, especially if it includes a history of IV drug abuse or inhaled substance usage such as cocaine, a history of piercings or tattoos, some unexplained symptoms, or abnormal liver enzymes or liver function tests, identified during routine blood testing.

 
Treatment:

The diagnosis of HCV does not necessarily mean that the disease needs to be treated.

Thus, acute hepatitis C does not require treatment if the liver abnormalities are rather minimal, and the long-term risk of developing a serious chronic disease appears slight, while the side effects of the treatment can be severe.

However, treatment is strongly recommended if:

  • A positive test result such as the presence of anti-HCV antibodies or HCV RNA indicate that the hepatitis C virus is circulating in the patient’s bloodstream;
  • Levels of the liver enzyme ALT are significantly elevated;
  • A liver biopsy indicates significant liver damage.

Drug treatment includes pegylated interferon alpha, also called peginterferon, in combination with ribavirin, a broad-spectrum antiviral agent.  Currently, there are two forms of pegylated interferon available – peginterferon alpha-2a and peginterferon alpha-2b.

The goal of the drug therapy is to eliminate the virus from the bloodstream. The combined treatment with one of the pegylated interferons and ribavirin can clear the HCV infection in 40% to 80% of cases. The success rate depends on the viral genotype that causes the infection – genotype 1 (the most common type in the USA) can be cleared in about 50% of cases, while genotype 2 and genotype 3 viral infections have a success rate of up to 80%.

A relatively high-dose drug treatment needs to be continued for 48 weeks with genotype 1 HCV, while genotype 2 or 3 HCV infections require a lower dose course of treatment for only 24 weeks. 

Side effects of these medications include:

  • Interferon:
    • Flu-like symptoms such as low-grade fever, headaches, muscle aches, etc.;
    • Irritability;
    • Concentration and memory problems;
    • Depression;
    • Fatigue and insomnia;
    • Nausea and vomiting;
    • Hair loss (reversible);
    • Weight loss, mild bone marrow depression;
    • Skin irritation.
  • Ribavirin:
    • Anemia (low red blood cell count);
    • Itching and skin irritation;
    • Nasal congestion;
    • Fatigue;
    • Birth defects.
  • Combination therapy may cause:
    • Psychosis and
    • Suicidal behavior.

Surgical treatment consists of a liver transplant – the best therapy for end-stage liver disease.  However, the need for a transplant exceeds by far the supply of donated organs – and a well trained medical staff is required to perform this transplantation.  Also, a liver transplant does not cure the HCV infection – it merely replaces the severely damaged liver with an undamaged liver. Furthermore, transplant patients with HCV are at an increased risk of developing fatal liver cirrhosis within five years after transplantation.

Alternative medicine therapy with the so-called milk thistle (Silybium marianum), a herb that has been used for centuries to treat jaundice and other liver disorders in Europe and elsewhere, has been confirmed in scientific studies to aid in the healing and rebuilding process of the liver.

Silymarin appears to stimulate the body’s production of antioxidant enzymes which help the liver to neutralize toxins, and thus also decrease the inflammation in the liver. However, milk thistle does not cure the hepatitis, nor does it protect from contracting HCV.

Lifestyle adjustment for patients with HCV should include:

  • Elimination of alcohol consumption (alcohol can speed the progression of the liver disease);
  • Avoidance of liver damaging medications, such as, for example, acetaminophen (Tylenol®, etc.);
  • Maintaining a healthy lifestyle – with regular exercise, plenty of rest and a healthy diet rich in fruits, vegetables and whole grain;
  • Preventing other people from coming into contact with the patient’s blood – do not share razors or toothbrushes; do cover open wounds; do not donate blood, body organs or semen; advise all health care workers and medical personnel of the HCV infection.

During pregnancy treatment for the mother with HCV is contraindicated. There is chance of about 4% that the infant will become infected with HCV at the time of birth. There is no treatment that can prevent this from happening. In mothers who are also HIV positive, the chance of HCV transmission to the newborn increases to up to 19%.

 
Prevention:

There is no vaccine available for protection against hepatitis C, although there is considerable research engaged in trying to develop a vaccine.

Thus, to-date, the only way of preventing a hepatitis C infection consists of protecting oneself from becoming infected, by taking proper precautions such as avoiding:

  • The usage of illegal drugs – sharing needles or other drug paraphernalia is the cause for more than 50% of all new hepatitis C infections;
  • Tattoos and body piercing – because the instruments that are being used for those procedures are often not properly sterilized, and thus can easily transmit hepatitis C and other blood borne infections;
  • Risky sexual behavior and promiscuity – unprotected sexual intercourse with a partner whose health status is not known, or with multiple partners, cannot only result in a hepatitis C infection, but also in the transmission of  HIV, as well as in one or more of other sexually transmitted diseases.  Only the proper usage of latex condoms can prevent these infections!
  • To share personal items such as razors, toothbrushes or nail clippers with a person who is a known hepatitis C carrier.

In summary, the only effective way of preventing new cases of hepatitis C infections consists of screening all blood supply and, for healthcare personnel, to take careful precautions when handling blood and body fluids or treating infected patients.

 

 

                                                   

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