Hepatitis A, B, C

Original Editors -Emily Schmidt Allyson Simmonds  from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Top Contributors - Allyson Simmonds, Emily Schmidt, Vidya Acharya, Lucinda hampton, Kim Jackson, Admin, Elaine Lonnemann, Rujuta Naik, WikiSysop, Wendy Walker, Evan Thomas, Karen Wilson, Nupur Smit Shah and 127.0.0.1  

Introduction

Hepatitis is defined as inflammation of the liver.

• The condition can be self-limiting or can progress to fibrosis (scarring), cirrhosis or liver cancer.
• Hepatitis viruses are the most common cause of hepatitis in the world (infections, toxic substances, and autoimmune diseases can also cause hepatitis)

The most common types of viral hepatitis are Hepatitis A, Hepatitis B, and Hepatitis C. The other types of viral hepatitis are hepatitis D and E and are less frequently encountered. Based on the etiology of hepatitis, the severity can range from mild and self-limiting to severe illness requiring liver transplantation.

Hepatitis can be further classified

• Acute - inflammation of the liver lasts for less than 6 months; usually self-resolving but can cause fulminant liver failure depending on the etiology
• Chronic - inflammation/insult of the liver lasts longer than 6 months; can cause liver damage that includes liver fibrosis, cirrhosis, hepatocellular carcinoma, and features of portal hypertension leading to significant morbidity and mortality

Epidemiology

Viral Hepatitis is considered a major public health issue. Viral hepatitis infects millions of people annually causing significant morbidity and mortality.

• Chronic Hepatitis B and C infection can cause liver damage that includes liver fibrosis, cirrhosis, hepatocellular carcinoma, and features of portal hypertension.
• Viral hepatitis ends up causing 1.4 million deaths annually, and hepatitis B and C viruses are responsible for about 90% of those deaths.
• The World Health Organization (WHO) estimated that 1.3 million people have died due to hepatitis in 2015, and 1 in 3 people in the world have had infections with either hepatitis B or hepatitis C virus.
• Reportedly, infection rates show that 2 billion people infected with the hepatitis B virus, 185 million with the hepatitis C virus, and 20 million with the hepatitis E virus. 
• Hepatitis A virus affects 90% of children in high endemic regions. 
  

Characteristics/Clinical Presentation

Viral Hepatitis

Can be different in every individual depending on the type of virus causing the infection. Patients can be entirely asymptomatic or only mildly symptomatic at presentation. A small number of patients can present with rapid onset of fulminant hepatic failure.

Typically patients with viral hepatitis go through 4 phases.

• Phase 1 (viral replication phase) - Patients are usually asymptomatic in this phase, and laboratory studies are positive for markers of hepatitis.
• Phase 2 (prodromal phase) - Patients in this phase usually present with anorexia, nausea, vomiting, malaise, pruritus, urticaria, arthralgias, and fatigue. Many times these patients are misdiagnosed as having gastroenteritis or viral infection.
• Phase 3 (jaundice phase) - Patients in this phase present with dark-colored urine and pale-colored stool. Some patients develop jaundice and right upper quadrant pain with liver enlargement.
• Phase 4 (convalescent phase) - Patients typically start noticing the resolution of symptoms, and laboratory studies show liver enzymes returning to normal levels.

Hepatitis A - Usually present with symptoms similar to gastroenteritis or viral respiratory infection, including symptoms of fatigue, nausea, vomiting, fever, jaundice, anorexia, and dark urine. Symptoms usually start after the incubation period is over, and they resolve spontaneously in a majority of patients

Hepatitis B - Enter the prodromal phase after the incubation period and have symptoms of anorexia, malaise, and fatigue which are the most common initial clinical symptoms.  Some patients may experience right upper quadrant pain due to hepatic inflammation.  Once these patients progress to the jaundice phase, they develop jaundice and painful hepatomegaly.  dark-colored urine and pale-colored stools. After this phase, clinical course can be variable, some patients experience rapid improvement in the symptoms, and others can develop a prolonged illness with a slow resolution with periodic flareups.  A small number of patients can have rapid progression of the disease that can lead to fulminant hepatic failure over a few days to weeks.

Hepatitis C - Develop similar symptoms after the incubation period to those of hepatitis B virus infection during the acute infection phase with symptoms of anorexia, malaise, and fatigue.  However, 80% of patients remain asymptomatic and do not develop jaundice

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
• Liver disease
• Disorders of lipid metabolism
• Non-traumatic joint disorders
• GI disorders
• Alcoholism
• Blood-clotting disorders
• Hypertension

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.

Diagnostic Tests/Lab Tests/Lab Values

Depending on the cause and how advanced the disease is, hepatitis typically is diagnosed with some combination of blood tests, imaging tests, and liver biopsy.

1. Blood tests are run to

• Detect the presence of a specific hepatitis virus or for antibodies produced by the immune system to fight the virus
• May include- Liver Function Tests, Antibody Tests,Antibody Tests.
• Look for signs of liver damage .

2. Imaging tests - cannot detect a viral infection of the liver, but can reveal inflammation, changes in size, and tumors that can be consequences of chronic infection or liver disease caused by hepatitis.

3. Liver biopsy - a section of tissue taken from the liver and evaluated under a microscope to look for identifying features disease.The most common type of liver biopsy is a percutaneous biopsy,

Management

Medical Management

Hepatitis A

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. 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. It is most important to prevent contracting the disease. Sexual activities should be avoided 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 a person is infected or not. Refrain from preparing food for others while one is infected, as this way the disease is passed on. Also avoid unclean food or water, especially if travelling.

Hepatitis B

There is no available treatment for acute Hepatitis B infections. Patients with 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 the active liver disease.  These individuals should avoid consumption of alcohol completely because it makes 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 biopsy showing moderate disease activity. Antiviral therapy helps in preventing further liver damage. Approved drugs for Hepatitis B include:

	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 stimulate the 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 genetic code from being copied
Tenofovir	Oral Once-daily for at least 1 year	diarrhoea, nausea, skin rash, feeling of weakness, dizziness
Entecavir	Oral Once-daily for at least 1 year	nausea, insomnia, dizziness
Lamivudine Adefovir Dipivoxil Telbivudine	few side effects but not recommended as first line of treatment due to high rate of viral resistance

Hepatitis C

Hepatitis C does not always require treatment. There are 6 genotypes of Hepatitis C and they all respond differently to a 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. 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. 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 received 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 the liver has been severely 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.  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.

Prevention

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:

• Receiving Hepatitis A and B vaccines
• Avoiding unnecessary and unsafe injections
• Avoiding unsafe blood products
• Avoiding unsafe sharps and waste collection and disposal
• Avoiding 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

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. It is especially important that children age 12-23 months or adults at 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.

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

All individuals suffering from chronic liver diseases, such as Hepatitis B and C, should receive Hepatitis A immunization as well as the Hepatitis B immunization.

Physical Therapy Management

A multifaceted approach is needed in the treatment of Hepatitis A, B, and C. No specific physical therapy intervention is 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 healthy lifestyle.  In physical therapy, an emphasis on proper musculoskeletal health will be an important foundation for the patient's overall health. Stretching to improve flexibility 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 strengthening 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 are 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.

Differential Diagnosis

Differential diagnosis for acute Hepatitis includes:

• Epstein-Barr Virus (EBV): leads to infectious mononucleosis with presenting symptoms of fever, sore throat, swollen lymph glands, swollen liver or spleen, jaundice, right upper quadrant pain
• EBV Hepatitis is an uncommon diagnosis and causes a self‐limiting hepatitis. It predominantly affects older people, with almost 30 per cent of patients being over the age of 60. The diagnosis of EBV hepatitis is usually made in patients with unexplained hepatitis regardless of age
• Cytomegalovirus: usually affecting infants where the symptoms of the infection vary
• Alcoholic Hepatitis: jaundice, scleral icterus, muscle wasting, ascites, oedema, spider angiomata, asterixis,
• Drug-Induced Liver Injury

• Mushroom Ingestion: stomachaches, drowsiness, confusion, gastrointestinal issues, heart, liver or kidney damage
• "Shock Liver:" low cardiac output leading to hepatic ischemia presenting with low blood pressure to cause weakness and lightheadedness and liver damage

Differential diagnosis for chronic Hepatitis includes:

• 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
• 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
• Primary Biliary Cirrhosis: inflamed and damaged bile ducts presenting with fatigue, pruritus, dry eyes/mouth, jaundice
• Primary Sclerosing Cholangitis: swelling and scarring of bile ducts presenting with fatigue, itching, jaundice, enlarged liver or spleen, weight loss, repeat cholangitis
• Hereditary Hemochromatosis: genetically inherited iron overload disease presenting with joint pain, fatigue, abdominal pain, loss of sex drive, cardiovascular issues
• Wilson's Disease: genetically inherited disease of copper overload presenting with swelling of the liver or spleen, jaundice, fluid buildup in the legs/abdomen, easily bruised, fatigue, physical coordination, tremors, muscle stiffness, behavioral changes, anemia, low platelet count, low WBC count, slower clotting time
• Alpha-1-antitrypsin deficiency: genetically inherited disease that presents as lung disease but can be associated with liver disease and cirrhosis of the liver
• Celiac Disease: condition that damages the lining of the small intestine to prevent absorption of parts of food that presents with abdominal pain, constipation, decreased appetite, lactose intolerance, diarrhoea, nausea and vomiting, unexplained weight loss, stools that float or are foul-smelling, bruising 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
• Primary liver cancer
• Metastatic cancer
• Herpes Simplex Virus: visceral involvement in infants and pregnant women specifically the oesophagus, lungs, and liver with HSV viremia
• Varicella-Zoster Virus: generalized rash is typical but can also present with encephalitis, pneumonitis, myocarditis, and hepatitis
• Human Parvovirus: can present with haematological disorders that may present similar to hepatitis

Alternate diagnosis for Hepatitis A

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 non-thrombotic obstruction to hepatic venous outflow. Hepatomegaly, ascites, and abdominal pain are characteristics of the disorder
• Cytomegalovirus: resulting in fever of unknown origin, pneumonia, hepatitis, encephalitis, myelitis, colitis, uveitis, retinitis, and neuropathy
• Other Hepatitis Virus

Differential diagnosis for Hepatitis B include:

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

Differential diagnosis for Hepatitis C are:

• Alcohol Liver Disease: Complications such as oesophageal or gastric variceal bleeding, ascites, coagulopathy, hepatic encephalopathy, and liver cancer are associated with the disease.
• Hepatic Steatosis: Non-alcoholic hepatic steatosis, or non-alcoholic fatty liver disease, is the most common cause of chronic liver disease.
• 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
• Other Chronic Liver Dieases
• Autoimmune Hepatitis: Autoimmune hepatitis is a chronic disease of unknown cause, characterized by continuing hepatocellular inflammation and necrosis and tending to progress to cirrhosis.
• Cholangitis: an infection of the biliary tract with the potential to cause significant morbidity and mortality.
• Viral Hepatitis
  

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