Hepatitis A, B, C

Definition/Description

Hepatitis is defined as inflammation of the liver.  This inflammation may be caused by various diseases, toxins, or viral infections.[1]

Hepatitis A is a contagious liver infection cause by the hepatitis A virus. It causes inflammation that affects your livers ability to function.[2] It is the most common of the two hepatitis viruses enterically transmitted  in the US and one of the two that is vaccine preventable.[3]

Hepatitis B is another contagious liver infection that is caused by the Hepatitis B virus. The virus can cause an acute, short-term, infection that may last for several weeks or months.  The virus and infection may also lead to a chronic infection, leading to a long-term illness.[1]

Hepatitis C is an infection caused by a virus that attacks the liver and leads to inflammation. Most people who have the infection often do not know that they have the disease, and are often asymptomatic. It is considered to be among the most serious of the hepatitis viruses.[4] About 80% of people who have the virus develop chronic hepatitis, and many people also can develop cirrhosis or even liver cancer.[5]

Prevalence

About 3,600 cases of Hepatitis A are reported each year. However, since not all people are symptomatic, more people are infected than are diagnosed and reported.[6]

Estimates for the prevalence of the Hepatitis B virus claim that more than one third of the world's population has been infected with 5% of the population being chronic carriers.[7] Approximately 25% of all carriers will develop a serious liver diease, while there are over one million deaths due to the infection of the Hepatitis B virus.[7]  According to the CDC, there were an estimated 43,000 new Hepatitis B infections in the United States in 2007, with the number of actue infections significantly declining. [1] For chronic infections, estimates range from 800,000-1.4 million people in the United States.[1]

Every year around 3-4 million people are infected with the Hepatitis C virus. About 150 million people are chronically infected and at risk of developing liver cirrhosis and even liver cancer. More than 350,000 people die from hepatitis C-related liver disease every year.[8]

Characteristics/Clinical Presentation

Hepatitis A Hepatitis B Hepatitis C

Symptoms usually do not appear until 2-6 weeks after you have been exposed to the virus. They are usually mild, but can last up to several months (2-6 months), especially in adults

It is important to note that not everyone will develop signs and symptoms of the virus.[6]
A vaccination is recommended for children age 12-23 months and for adults who are at high risk for the infection.[3]

Acute infections may present with no symptoms, present with a gradual onset of symtpoms in a few days-weeks, or present with symptoms very quickly.[9] Adults and children older than 5 are most likely to show symptoms of an acute Hepatitis B infection typically within 90 days of the exposure, but may show between 6 weeks and 6 months of the exposure to the virus.[1][9] Acute symptoms may last several weeks or up to 6 months.[1]

Chonic Hepatitis B infection may result in ongoing symptoms or may be symptom free for as many as 30 years.[1]

Early on, Hepatitis C usually is asymptomatic. When signs and symptoms begin to set in, they are generally mild and flu-like. 

About 75-85% of recently infected people develop chronic disease and 60-70% of chronically infected people develop chronic liver disease. Also 5-20% develop cirrhosis and 1-5% die from cirrhosis or liver cancer.[8]

1. Dark urine
2. Fatigue
3. Itching
4. Loss of appetite
5. Low-grade fever
6. Nausea and vomiting
7. Pale or clay-colored stools
8. Jaundice
9. Abdominal pain
10. Headache
11. Diarrhea
12. Muscle Pain[2]

1. Fever

2. Fatigue

3. Loss of appetite

3. Nasuea and vomiting

4. Abdominal Pain

5. Dark urine

6. Clay-colored bowel movements

7. Muscle[9] and joint pain

8. Jaundice

9. Symptoms of liver damage for chronic infections

1. Fatigue
2. Fever
3. Nausea or poor appetite
4. Muscle and joint pains
5. Tenderness of your liver[4]
6. Abdominal pain
7. Dark urine
8. Grey-coloured feces
9. Jaundice[8]
10. Abdominal swelling
11. Itching[10]











Associated Co-morbidities

Some co-morbidities that may be associated with Hepatitis A, B, C include:

  • Diabetes
  • Obesity
  • HIV
  • ESRD
  • Maladaptive lifestyle habits
  • Poor quality of life[11]
  • Liver disease
  • Disorders of lipid metabolism
  • Non-traumatic joint disorders
  • GI disorders[12]
  • Alcoholism
  • Blood-clotting disorders
  • Hypertension[13]

Medications

There is no specific treatment for Hepatitis A. Rest is recommended when the symptoms are most severe. When in the acute stages, it is recommended that you avoid any toxic substances to the liver, including Tylenol.[6]


Chronic Hepatitis B can be treated with antiviral therapy to prevent further liver damage.[14] Approved drugs for Hepatitis B include:[15][14][16]

Method Adverse Side Effects
Interferon Alpha

Injection

Multiple times per week for 6 months-1 year

flu-like symptoms, depression, headaches

Pegylated Interferon

used with high levels of the virus to simulate teh immune system

Injection

Once weekly for 6 months-1 year

flu-like symptoms, depression, various persistent unpleasant side effects

Nucleoside Analogs

prevent the virus from spreading by preventing the gentic code from being copied

Tenofovir

Oral

Once daily for at least 1 year

diarrhoea, naseau, skin rash, feeling of weakness, diziness
Entecavir naseau, insomnia, dizziness

Lamivudine

Adefovir Dipivoxil

Telbivudine

few side effects but not recommended as first line of treatment due to high rate of viral resistance


Since the Hepatitis C virus infects the blood and can lead to cirrhosis of the liver or liver cancer, the goal of medication is to prevent this from happening. Many patients with hepatitis C benefit from treatment with medications similar to Hepatitis B. The most common medication include antiviral medications including pegylated interferon alfa and ribavirin. Typically pegylated interferon alfa is receivied weekly through injections. Ribavirin is a capsule taken twice daily. Treatments are given from 24-48 weeks. Two newer drugs that may be available for use for patients with genotype 1 are Telaprevir and Boceprevir. These medications do have several side effects, and therefore, patients need to be watched closely. Some of the side effects of the medications can include depression and flu-like symptoms. If patients develop cirrhosis or liver cancer, the patient may be a candidate for a liver transplant.[10]

Diagnostic Tests/Lab Tests/Lab Values

A primary care physician will conduct a physical exam when looking for Hepatitis A Virus. During the physical exam, they may find that you have an enlarged and tender liver. Also, they will have you partake in blood tests. The blood tests will look at IgM and IgG antibody levels as well as liver enzymes. In both cases the antibody and enzyme levels will be raised.[6] 

Blood tests are done to check for the Hepatitis B virus. The blood tests available may include:[1]

Hepatitis B Surface Antigen HBsAG Positive test means the person has an acute or chronic infection and can transmit the virus to others.
Hepatitis B Surface Antiobody anti-HBs Positive test means a person is immune from getting the virus.
Total Hepatitis B Core Antibody anti-HBc Positive test means a person is currently or previously has been infected.
IgM Antibody to Hepatitis B Core Antigen IgM anti-HBc Positive test means a person has been infected within the past 6 months.
Hepatitis B "e" Antigen HBeAg Positive test means a person has high levels of the virus in the blood and can spread the virus to others easily.
Hepatitis B e Antibody HBeAb or anti-HBe Positive test means a person has a chronic infection but have low levels of the virus in their blood.
Hepatitis B Viral DNA Positive test means the virus is mutiplying and is highly contagious or the person has a chronic infection with an increased risk for liver damage.


Blood tests are also done to check for the Hepatitis C Virus. They specifically look at EIA assay to detect the hepatitis C antibody and the hepatitis C RNA assay to measure virus levels. Genetic testing can be done to check for the hepatitis C genotype. Six different genotypes exist. Most people have genotype 1 infection, which is the hardest to treat. Genotypes 2 and 3 are also common, but typically respond better to treatment. Tests can also be done to monitor the amount of liver damage: albumin levels, liver function tests, and prothrombin time. A liver biopsy can also be done to assess liver damage.[10]

Etiology/Causes


Hepatitis A Hepatitis B Hepatitis C
Cause Hepatitis A virus Hepatitis B virus Hepatitis C virus

Method of transmission

Mostly found in stools and blood of infection person and is therefore spread primarily via person-to-person contact.

Hepatitis A can spread when a person unknowingly ingests the virus from objects, food, or drinks contaminated by small, undetected amounts of stool from an infected person. (CDC)

Hepatitis A can also spread from close personal contact with an infected person such as through sex or caring for someone who is ill.

Spread through contact with body fluids such as semen, vaginal fluids, saliva, and blood.[1][9] Spread when come into contact with contaminated blood.
Contracted when exposed to:

1. Food or drink that has been contaminated by stools containing the Hepatitis A virus

2. Contact with stool or blood of a person infected

3. A person with the disease does not wash his/her hands properly after using the restroom and touches other objects or foods

4. Participating in sexual practices involving oral-anal contact with an infected individual[6]

1. Childbirth- passed from mother to child

2. Sexual contact from unprotected intercourse

3. Shared needles- injection drug use or those given contaminated with syringes an needle-stick injuries in healthcare settings

4. Sharing personal items such as razors or toothbrushes with an indivdual infected

5. Direct contact with blood or an open sore of an individual infected[1]

6. Any blood or bodily fluid touches skin, eyes, or mouth[9]

1. Blood transfusions and organ transplants  before 1992.

2. Shared needles- injection drug use or those given with contaminated syringes and needle-stick injuries in health-care settings

3. Childbirth- passed from mother to child

4. Sexual contact from unprotected intercourse

5. Long-term kidney dialysis

6. Regular contact with blood work

7. Sharing personal items such as razors or toothbrushes with an individual infected[10]

Risk Factors

1. Traveling

2. Native people of America

3. Restaurant workers and food handlers

4. Chidlren living in communities that have high rates of the disease

5. Children and workers in day care facilities

6. Individuals engaging in anal/oral sex with STDs or HIV

7. People with chronic liver disease

8. If you eat raw shellfish frequently

9. Laboratory workers who handle live Hepatitis[3] 

1. Unprotected sexual intercourse with an infected partner

2. Blood transfusions (uncommon in the United States)

3. Contact with blood at work

4. Long-term kidney dialysis

5. Recieving a tattoo or acupuncture with an unclean needle

6. Sharing needles during drug use

7. Sharing personal items with an infected individual

8. Were born to a Hepatitis B infected mother[1][9]

9. Traveling to countries with high rates of the virus

10. Men who have sexual contact with other men

11. Living with a person infected with chronic Heptatitis B[1]


Systemic Involvement

Variable systemic involvement can occur with Hepatitis due to the nature of the virus causing a widespread infection in the body.  Most predominantly the infection involves the liver and lymphatic system.  Other systemic areas of involvement include progression into renal, endocrine, dermatological, cardiovascular, rheumatologic, and central nervous system diseases.[17]

Medical Management (current best evidence)

There is no specific treatment for Hepatitis A. Rest is recommended when the symptoms are most severe. Individuals with acute hepatitis should avoid alcohol and any substances that are toxic to the liver, such as Tylenol. Fatty foods that can cause vomiting should also be avoided during the acute phase.[6] It is important to maintain comfort and an adequate nutritional balance as recovery can take several weeks up to a month. It is also important to constantly replace fluids that you may be losing.[18]
It is most important to focus on preventing yourself from contracting the disease, if you do not have it, or preventing others from contracting the disease. In order to do this you should avoid sexual activities if you have the disease, and avoid sexual activities with an individual who has Hepatitis A, as a condom does not offer adequate protection. Also, wash your hands thoroughly after using the toilet, whether you are infected or not. Refrain from preparing food for others while you are infected, as this is a way to pass the disease on.[2] Also avoid unclean food or water, especially if traveling.[6]

There is no available treatment for acute Hepatitis B infections. Patient with an acute infection are recommended to rest and get an adequate nutritionally intake of food and fluids.

Individuals with chronic Hepatitis B medical management will involve medical monitoring, abstinence from alcohol, and antiviral therapy in order to suppress the infection and end active liver disease.  These individuals should avoid consumption of alcohol completely becuase it will make the liver disease worse. Antiviral therapy is appropriate for patients with a chronic Hepatitis B infection who have tested positive for hepatitis B surface antigen for at least six months, have abnormal blood levels of liver enzymes, actively dividing virus in the blood, and a liver biospy showing moderate disease activity.  Alpha interferon, an injection, and lamivudine, an oral treatment, are two drug therapies appropriate for those with a chronic infection.[19]

Hepatitis C does not always require treatment. There are 6 genotypes of Hepatitis C and they all respond differently to treatment. A good screening is required before starting the treatment to determine the most appropriate approach. Combination of antiviral therapy with interferon and ribavirin has been the most common form of treatment for Hepatitis C. Interferon is not widely available globally and is not well tolerated depending on the genotype the patient presents with. Therefore, not all patients finish their interferon treatment. Although hepatitis C is considered to be curable, it is not always the case. Two new drugs have been developed that may be better tolerated and they are: telaprevir and boceprevir. However, more testing needs to be done to ensure that these new drugs lead to greater access and treatment globally.[8]

If your liver has been severly damaged, a liver transplant may be an option. It is important to realize that a liver transplant is not the cure and the use of antiviral medications continues after the liver transplant takes place.[4] It is also recommended that people be careful not to take vitamins, nutritional supplements, or new over-the-counter medications without first discussing it with their primary care physician. It is important to avoid any substances that are toxic to the liver such as alcohol, as it can speed up the progression of the disease.

With all three of the diseases preventing contraction of the virus, and therefore the infection, is key. Prevention can help avoid passing on the disease or contracting the illness. The risk of infection can be reduced by:

  • Recieving Hepatitis A and B vaccines
  • Avoiding unnesscessary and unsafe injections
  • Avoiding unsafe blood products
  • Avoiding unsafe sharps and waste collection and disposal
  • Avoding the use of illicit drugs and sharing injection equipment
  • Avoiding unprotected sex with infected individuals
  • Avoiding the sharing of sharp personal items that may be contaminated with infected blood
  • Avoiding tattoos, piercings, and acupuncture performed with contaminated equipment[8][1]


Vaccines

If you have been exposed to the Hepatitis A infection and have not had it before or have not received the vaccine, ask your doctor or nurse about receiving either immune globulin or the Hepatitis A vaccine. Vaccines that protect against the virus are available and begin to protect you for weeks after receiving the initial dose. The 6-12 month booster is required for long-term protection.[6] It is especially important that children age 12-23 months or adults at a high risk for contracting the virus get a vaccine. Also it is important for anyone one year of age and older traveling to or working in countries with high or intermediate prevalence of Hepatitis A (central or south America, Mexico, Asia), children and adolescents 2-18 who live in states or communities where routine vaccination has been implanted because of high disease prevalence, men who have sex with men, people who use street drugs, people with chronic liver disease, people who are treated with clotting factors, and people who work in HAV laboratories to get vaccinated for safety reasons.[20][10]

Hepatitis B can be prevented in 95% of recipients with the proper vaccine.[7] Individuals who believe they may have contracted the Hepatitis B virus can recieve the Hepatitis B vaccine, the Hepatitis B immune globulin, within 24 hours to potentially prevent infection.[1] A surface antigen of the Hepaitis B virus is what makes up the vaccine.  These vaccines are produced by two methods: plasma derived or recombinant DNA.[7]

All individuals suffering from chronic liver disease, such as Hepatitis B and C, should recieve Heptatits A immunization as well as the Hepatitis B immunization.[19]

Physical Therapy Management (current best evidence)

A multifaceted approach is needed in the treatment of Hepatitis A, B, and C. No specific physical therapy intervention are appropriate for the specific infection of Hepatitis, but Hepatitis may likely be a comorbidity of a patient seen in physical therapy.With any other medical condition, it is important to educate patients on their disease and risk factors to promote awareness and improvement in their health lifestyle.  In physical therapy, an emphasis of proper musculoskeletal health will be an important foundation for the patient's overall health. Stretching to improve flexiblity could help alleviate symptoms of muscle pain. It is also important for the patient to remain physically active in order to maintain the healthiest lifestyle possible and prevent the patient from developing secondary co-morbidities due to inactivity. General strengtheing and aerobic activity might be appropriate for a deconditioned patient. Individualizing a physical therapy program focusing on the impairments of the patient is of utmost importance for any patient.

During physical activity it is important to monitor the patient for signs and symptoms of fatigue. For Hepatitis A bed rest is the recommended form of treatment and being aware of the acuteness of the Hepatitis infection is important when screening for physical therapy. Supportive therapy and patient education is used to ensure the patient is comfortable and has an adequate nutritional balance for all three infections. It is also important to remind the patient to refrain from the use of alcohol or intake of fatty substances.[18]


Differential Diagnosis

Differential diagnosis for acute Hepatitis includes:[21]

  • Epstein-Barr Virus: leads to infectous mononucleosis with presenting syptoms of fever, sore throat, swollen lymph glands, swollen liver or spleen, jaundice, right upper quandrant pain[22][23]
  • Cytomegaolovirus: usually affecting infants where the symptoms of the infection vary[24]
  • Alcoholic Hepatitis: jaundice, scleral icterus, muscle wasting, ascities, edema, spider angiomata, asterixis,
  • Drug-Induced Liver Injury
  • Mushroom Ingestion: stomachaches, drowsiness, confusion, gastrointestional issues, heart, liver or kidney damage[25]
  • "Shock Liver:" low cardiac output leading to hepatic ischemia presenting with low blood pressure to cause weakness and lightheadedness and liver damage[26]

Differential diagnosis for chronic Hepatitis includes:[21]

  • Non-alcoholic steatohepatitis: diagnosed by excluding other causes and the presence of a fatty liver because there are few symptoms of the disease that could possibly include fatigue, weight loss, weakness, cirrhosis in late stages[27]
  • Chronic Alcoholic Hepatitis: pain and swelling in abdomen, decreased appetite and weight loss, nausea and vomiting, fatigue, dry mouth, increased thirst, bleeding of the esophagus, jaundice, spider-like veins, dry or pale skin, redness of feet/hands, itching, cognitive issues, fainting, numbness in legs and feet[28]
  • Primary Biliary Cirrhosis: inflamed and damaged bile ducts presenting with fatigue, pruritus, dry eyes/mouth, jaundice[29]
  • Primary Sclerosing Cholangitis: swelling and scarring of bile ducts presenting with fatigue, itching, jaundice, englarged liver or spleen, weight loss, repeat cholangitis[30]
  • Hereditrary Hemochromatosis: genetically inheritied iron overload disease presenting with joint pain, fatigue, abdominal pain, loss of sex drive, cardiovascular issues[31]
  • Wilson's Disease: genetically inherithed disease of copper overload presenting with swelling of the liver or spleen, jaundice, fluid buildup in the legs/abdmonen, easily bruised, fatigue, physical coordination, tremors, muscle stiffness, behavioral changes, anemia, low platelet count, low WBC count, slower clotting time[32]
  • Alpha-1-antitrypsin deficiency: genetically inherited disease that presents as lung disease but can be associated with liver disease and cirrhosis of the liver[33]
  • Celiac Disease: condition that damages the lining of the small intestine to prevent absportion of parts of food that presents with abdominal pain, constipation, decreased appetite, lactose intolerance, diarrhea, nausea and vomiting, unexplained wieght loss, stools that float or are foul smelling, brusing easily, depression, fatigue, delay of growth, hair loss, itchy skin, missed menstrual periods, mouth ulcers, muscle cramps, joint pain, nosebleeds, seizures, tingling/numbness in hands/feet[34]
  • Primary liver cancer
  • Metastatic cancer
  • Herpes Simplex Virus: visceral involvment in infants and pregnant women specifically the esophagus, lungs, and liver with HSV viremia[23]
  • Varicella-Zoster Virus: generalized rash is typical but can also present with ecephalitis, penumonitis, myocarditis, and hepatitis[23]
  • Human Parvovirus: can present with hematologcial disorders that may present similiar to hepatitis[23]


Some alternate diagnoses for Hepatitis A that could be made based on the presenting signs and symptoms could be:

  • Budd-Chiari Syndrome: uncommon condition induced by thrombotic or nonthrombotic obstruction to hepatic venous outflow. Hepatomegaly, ascites, and abdominal pain are characteristics of the disorder[35]
  • Cytomegalovirus: resulting in fever of unknown origin, pneumonia, hepatitis, encephalitis, myelitis, colitis, uveitis, retinitis, and neuropathy[36]
  • Other Hepatitis Virus[37]

Other differenetial diagnoses for Hepatitis B include:[38]

  • Alcoholic liver disease
  • Non-alcoholic fatty liver disease
  • Autoimmune hepatitis
  • Metabolic and genetic disorders
  • Drug-induced liver disease
  • Granulomatous disorders

Some differential diagnoses that may be associated with Hepatitis C are:

  • Alcohol Liver Disease: Complications such as esophageal or gastric variceal bleeding, ascites, coagulopathy, hepatic encephalopathy, and liver cancer are associated with the disease.[39]
  • Hepatic Steatosis: Non-alcoholic hepatic steatosis, or non-alcoholic fatty liver disease, is the most common cause of chronic liver disease.[40]
  • Hemochromatosis: An autosomal-recessive disorder of inappropriately increased dietary iron absorption and increased iron release from erythrophagocytosis; Presenting features include fatigue, arthralgias, and diabetes mellitus[41]
  • Other Chronic Liver Dieases[42]
  • Autoimmune Hepatitis: Autoimmune hepatitis is a chronic disease of unknown cause, characterized by continuing hepatocellular inflammation and necrosis and tending to progress to cirrhosis.[43]
  • Cholangitis: an infection of the biliary tract with the potential to cause significant morbidity and mortality.[44]
  • Viral Hepitis[45]

Case Reports/ Case Studies

Hepatitis C Case Study

Resources

Chronic Liver Disease Foundation

Hepatitis Central

Hepatitis A Vaccine Information Sheet

Hepatitis B Foundation Resources and Links

Hepatitis B Advocate

Hepatitis C Virus Advocate

Recent Related Research (from Pubmed)

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