Clinical Practice Guideline

for

VIRAL HEPATITIS

Developed for the

Aerospace Medical Association

by their constituent organization

American Society of Aerospace Medicine Specialists

 

Overview. Viral Hepatitis is a major cause of liver disease today.  We currently know of 6 possible hepatitis viruses.  These viruses are A, B, C, D, E, and G.  These viruses cause acute and chronic forms of hepatitis, with a clinical course ranging from sub-clinical to fatal. There are almost 5 million cases of chronic viral hepatitis in the United States, with an estimated 15,000 deaths per year from liver disease including cirrhosis and liver cancer.  All this contributes to make chronic liver disease the tenth leading cause of death in the United States.

 

Fecal-Oral Hepatitis: These forms of hepatitis are caused by the A and E viruses.  Hepatitis A has been known for sometime.  It is transmitted fecal-orally and has an incubation period of 15-45 days.  The case fatality rate ranges from 0.1% - 2.7%.  Chronic infection has not been reported.  IgG anti-HAV appears early and confers lifelong immunity.  A vaccine with 99% efficacy has also recently been developed.

 

Hepatitis E has just recently been identified.  The E virus is found primarily in the Third World.  The case fatality rate ranges from 0.5% - 4%, but pregnant women have been found to have 20% case fatality rates in their 2nd and 3rd trimester.  In general hepatitis E is a mild, self-limited disease, and chronic infection has not been reported.  There is no vaccine available against hepatitis E, but it does appear that the production of IgG antibodies does confer lifelong immunity.

 

Parenteral Hepatitis: The B, C, and D viruses cause these forms of hepatitis.  The first diagnostic test for hepatitis B virus was developed in 1964.  The virus is transmitted by blood or from sexual contact.  It has an incubation period of 45 – 180 days.  The acute infection varies from asymptomatic to cholestatic hepatitis with jaundice, and rarely liver failure is seen.  The case fatality rate is 0.5% - 1%.  Recovery from the acute infection can confer immunity from re-infection.  Only 2% - 10% of these infections progress to a chronic infection, but premature death is seen in 15% - 25% of these chronic cases.  Treatment of chronic HBV infection is largely supportive, with a select group able to be treated with interferon alfa-2b.  This treatment with interferon shows an overall response rate of 33% compared to 12% in untreated individuals.  The World Health Organization estimates there will be 400 million carriers of the virus by the year 2000.  There are approximately 1.25 million chronic cases in the United States, as indicated by HbsAg positivity. 

 

The hepatitis C virus was discovered in 1989.  Up until then it was commonly known as Non-A, Non-B hepatitis.  Just like the hepatitis B virus, blood and sexual contact transmit it.  The incubation period is 2 – 26 weeks long.  Generally the acute infection is asymptomatic or very mild, with 60% - 70% of patients having no symptoms.  After acute infection 75% - 85% will go on to have chronic infections.  In this population of chronically infected individuals there will be 30% - 40% who maintain normal ALT levels.  However this does not mean they do not have chronic hepatitis, which can only be confirmed by histology.  The course is usually insidious with few signs or symptoms for up to two decades.  Studies have shown that 10% - 20% of chronic patients will develop cirrhosis in 20 – 30 years, and 1% - 5% will develop hepatocellular carcinoma.  Factors predicting the severity of chronic hepatitis C are not well established, except for the case of HCV exacerbated by alcohol ingestion.  Treatment of chronic HCV infection is similar to the chronic HBV treatments.  The response rate to a six-month course of interferon treatment is from 40% - 60% of patients, but only half of these show any sustained response.  Improved results have been shown with increased dosages, duration, or the addition of ribavirin, but all of these options increase the already significant level of side effects.  According to the CDC, 4 million people (1.5% of the population) are chronically infected with hepatitis C.  It is common form of blood borne infection in the United States, with 8,000 – 10,000 deaths per year.

 

The third known cause of chronic viral hepatitis is type D (Delta) type hepatitis.  It was discovered in 1977.  Hepatitis D virus (HDV) is unique in that it is a defective RNA virus, which can only replicate in the presence of HBsAg.  Acute HDV occurs either as a co-infection or as a super-infection.  In both cases the addition of the delta virus is often associated with a severe infection.  Approximately 70% - 80% of hepatitis D infected individuals will go on to have chronic disease.  The mortality and morbidity are increased.  In the acute infection of HDV the mortality ranges from 2% - 20%. 

 

New Virus: Hepatitis G virus (HGV) is a newly discovered Flaviviridae virus related to HCV.  Its role as an etiologic agent of viral hepatitis is still unknown.  HGV is frequently found in recipients of blood products, and patients with hepatitis.  HGV RNA has been found in 3.9% of blood donors with elevated serum alanine aminotransferase (ALT), and in 0.8% of blood donors with normal ALT.  Several studies have found patients with a long-term viremia, but a British study found that recovery from viremia was a common phenomenon in hemophiliacs.  The process of elucidating the clinical course of HGV infection is complicated by frequent co-infection with HBV or HCV.  The ability to test for HGV is also complicated and expensive.  The aeromedical concerns with HGV are minimal, until further evidence and technology develop a clearer picture of the role of HGV in chronic hepatitis.

 

Aeromedical Concerns: The spectrum of acute hepatitis can range from asymptomatic to GI symptoms, fatigue, and malaise, to mortality.  In general acute hepatitis is only aeromedical of concern during the short period of symptoms.  These symptoms can distract the pilot from the job of safely flying the aircraft.  The typical course of acute hepatitis is usually complete resolution after several weeks.  The only major concern is the type of hepatitis and whether it will progress to chronic hepatitis.

 

Chronic hepatitis is a more significant aeromedical problem.  The chronic diseases can cause similar symptoms of fatigue and malaise, therefore affecting safety of flight, but for an indefinite amount of time.  Chronic hepatitis also has the ability to progress to chronic liver disease, cirrhosis, or hepatocellular carcinoma.  Treatment is also problematic.  The side effects of interferon and ribavirin therapies are very common and serious.  Interferon side effects include flu-like symptoms that normally occur 6 to 8 hours after injections.  These include malaise, fever, tachycardia, headache, and chills, and should abate after a couple of weeks of treatment.  Later common side effects include fatigue, malaise, apathy, and cognitive & behavioral changes.  10% - 15% of patients discontinue treatment due to the long-term side effects.  Alcohol use in the patient with chronic hepatitis adversely affects the course of the disease.  The NIH consensus on Hepatitis C recommended no alcohol use by patients with the virus.

 

Treatment and Aeromedical Disposition: Patients with hepatitis A or E should only need to demonstrate recovery from the acute disease.  This can easily be demonstrated by normal LFT’s.  Patients with hepatitis B, C, or D will require more documentation.  Patient information should include a complete history, including the type and severity of symptoms, etiologic agent, chronology of antibody test and liver function test, liver biopsy results (if done), and any treatments.  Anti-HBs should be considered to demonstrate immunity and recovery from the hepatitis B infection, and does not require further documentation.  Any patient with hepatitis C should also have a HCV RNA PCR to help determine chronicity.  If no HCV RNA is found on a repeat test then the patient can be considered as not chronically infected.  Hepatitis D patients should require follow-up as long as they are flying.  Any history of alcohol use and current abstinence should be documented.  Aircrew who are currently undergoing treatment with interferon or ribavirin should not be fit to fly.  Otherwise the level of chronic disease should determine whether the aircrew is fit to fly.  A patient with hepatitis G should be written up in the aerospace literature. 

 

Experience: In the US military, hepatitis A is grounding until liver enzymes return to normal.  Acute hepatitis B is grounding until liver enzymes return to normal.  Chronic hepatitis B is disqualifying and requires a waiver.  Any chronic hepatitis B infection that produces a symptomatic relapse is disqualifying and will not be waivered.  There is no defined policy at this time that discusses policy in aircrew with hepatitis D, E, or G infections.  Current military policy instruct flight surgeons to refer hepatitis C cases to the appropriate aeromedical referral center.

 

In civil aviation treatment with any form of Interferon alpha is disqualifying.  This is due to its side effect profile.  Chronic hepatitis B may be qualifying, if it is stable.  Hepatitis C is generally acceptable providing the airman has no systemic symptoms or evidence of cirrhosis.  Once the airman is placed on treatment he/she is disqualified.   The treatment of Hepatitis C is unacceptable for medical certification as mentioned above. 

 

In the FAA as of January 1, 2001 there were approximately 469 first-, 428 second-, and 1,027 third-class airmen granted medical certification for one of the forms of hepatitis. 

 

References:

 

Dawson GJ, Schlauder GG, Pilot-Matias TJ, et al. Prevalence studies of GB virus-C infection using reverse transcriptase-polymerase chain reaction. J Med Virol 1996;50:97-103.

 

CDC Recommendations for Prevention and Control of Hepatitis C Virus (HCV) Infection and HCV-Related Chronic Disease. MMWR, 1998; 47(No. RR-19).

 

Hepatitis C Supplement 1. Hepatology. 1997; 26(3): 1S – 155S.

 

Hoofnagle JH, DiBisceglie, Adrian M, Drug Therapy: The Treatment of Chronic Viral Hepatitis, The New England Journal of Medicine, 1997; 336(5): 347-356.

 

Hoofnagle, JH.  Type D (Delta) Hepatitis, JAMA, 1989; 261(9): 1321- 1325.

 

Lee, WM.  Medical Progress: Hepatitis B Virus Infection, The New England Journal of Medicine, 1997; 337(24): 1733-1745.

 

Purdy MA, Krawczynski K.  Hepatitis E. Gastroenterology Clinics of North America. 1994; 23(3): 537-546.

 

Yamada-Osaki M, Sumazaki R, Kajiwara Y, Miyakawa T, Shirahata A, Matsui A, Natural Course of HGV infection in haemophiliacs, British Journal of Haematology, 102(2): 616-21, 1998 July.

 

 

August 2, 2006