This article was originally featured in the June 2020 Issue of OTR and is reprinted with permission of ON THE RISK, Journal of the Academy of Life Underwriting.
Before we can properly assess the risk of hepatitis, we need to ensure we have the proper educational foundation. What exactly is hepatitis? Who is most at risk? What do the lab results really mean?
What Is Hepatitis?
Hepatitis is an inflammation of the liver that can progress to fibrosis (scarring), cirrhosis or liver cancer. Although hepatitis viruses are the most common cause of hepatitis, other causes such as toxic substances (alcohol and certain drugs) and autoimmune diseases are to blame, too. The hepatitis B virus is about 100 times more infectious than HIV.
Scientists have identified six hepatitis viruses, which are referred to as types A, B, C, D, E and G. Types A, B and C are the cause of about 90% of acute hepatitis cases in Canada. People infected with hepatitis can experience symptoms ranging from nil to mild to serious liver damage. Many people recover completely from an infection; however, others, depending on the type of hepatitis, may become carriers of the disease and can unknowingly spread it to others.1 It is estimated that 3.5 million people in the US have hepatitis C, and 850,000 have hepatitis B. More than half of these people do not know they have the virus. Since 2012, more deaths have occurred due to hepatitis C in the US than all 60 of the other reportable infectious diseases combined.2,3,4
The various types of hepatitis provide a spectrum of concern because of the range of illness and risk of death they may cause, as well as the potential for outbreaks and epidemic spread. Hepatitis B and C can lead to chronic disease in hundreds of millions of people, and combined, they are the most common cause of liver cirrhosis and cancer.
Understanding Hepatitis – A Focus on Hepatitis B
For the above reasons, we as underwriters must be aware of the convoluted particulars surrounding hepatitis to assess mortality and morbidity risk accurately. As hepatitis B tends to be the more commonly seen in underwriting, we will focus on this virus.
For starters, we need to know about the virus and how it may be transmitted. Hepatitis B virus (HBV) is a viral infection that attacks the liver and can cause acute and chronic disease. Although it mainly infects the liver, it has been found in other tissues and organs, notably the kidneys or pancreas.
According to the World Health Organization (WHO), in 2015 hepatitis B resulted in 887,000 deaths, mostly from complications including cirrhosis and hepatocellular carcinoma. HBV is transmitted through exposure to infected body fluids (blood, blood products, semen, etc.), from infected mothers to infants at time of birth, during medical procedures or through injection drug use. A safe and effective vaccine to prevent HBV has been available since 1982 and is 95% effective.5
Did you know HBV can survive outside of the body for at least 7 days? During this time, the virus can still cause infection if it enters the body of someone unprotected by the vaccine. HBV has an incubation period between 30 and 180 days, with an average of 75 days. The virus may be detected within 30-60 days after infection, and it can persist and develop into chronic HBV.6,7
The likelihood of an HBV infection becoming chronic depends upon the age at which a person becomes infected. Eighty to ninety percent of infants infected during the first year of life develop chronic infections. Thirty to fifty percent of children infected before the age of 6 develop chronic infections. In adults who are otherwise healthy, less than 5% of those infected will develop chronic infection. Twenty to thirty percent of adults who are chronically infected will develop cirrhosis and/or liver cancer. Although an estimated 2 billion people worldwide are infected with HBV, according to the WHO, less than 1% of North America’s population is infected with either acute or chronic HBV.1,5
In symptomatic clinical acute hepatitis, the following symptoms may occur: fever, anorexia, nausea, abdominal pain or jaundice. These symptoms occur 1-3 months following an HBV infection. In approximately 1% of people, fulminant hepatic failure or death may occur. Most cases of acute viral hepatitis resolve spontaneously, but some do progress to chronic hepatitis.
Chronic hepatitis lasts longer than 6 months. Common causes include hepatitis B and C, autoimmune liver disease (autoimmune hepatitis) and steatohepatitis (non-alcoholic steatohepatitis or alcoholic steatohepatitis).
Many individuals have no history of acute hepatitis, and the first indication is the discovery of asymptomatic aminotransferase elevations. Signs and symptoms of chronic hepatitis vary significantly from person to person. Continued exacerbations and remissions of liver inflammation (reactivation hepatitis), a continued active hepatitis of varying degree and severity, a trivial inflammation, or a presence of cirrhosis or its complications (i.e., portal hypertension) may indicate the presence of chronic hepatitis.
A biopsy is necessary to confirm the diagnosis, grade and stage of the disease. Treatment is directed toward complications and the underlying condition, for instance, corticosteroids for autoimmune hepatitis or antiviral therapy for viral hepatitis. A liver transplant is often indicated for decompensated cirrhosis.
You may think your body would produce serious symptoms if your liver started to fail, but that isn’t always the case. Liver damage isn’t always apparent. In fact, its signs can be very subtle.
Underwriting Hepatitis B
Since HBV is a complex disease, in some cases a discussion with your medical director may be helpful. When possible, get serial liver tests, all liver biopsy reports and ultrasound results. When the aspartate aminotransferase (AST) levels exceed the alanine aminotransferase (ALT) levels, cirrhosis should be excluded. Know the stages of hepatitis B to make an informed decision.
Stages of HBV
- Stage 1 – Immune tolerance stage: In healthy adults, stage 1 lasts between 2-4 weeks, which is the incubation period. For those people infected at birth, this stage can last for decades.
- Stage 2 – Immune active stage of acute infection: This usually lasts up to 4 weeks, and HBeAg can be detected.
- Stage 3 – Inactive carrier: HBV DNA levels are low or undetectable. Transaminase levels are usually within normal limits.
In areas where the endemic level is high, up to 90% of the population has evidence of past or present infection. A high incidence of chronic liver disease and hepatocellular carcinoma (HCC) can be seen in adults.
Serology to Note
HBsAg (hepatitis B surface antigen): If HBsAg is present, the person is infectious. HBsAg presence is the hallmark indicator of infection.
Anti-HBs: This is the antibody to HBsAg. If present, it usually indicates a recovery process and immunity from HBV.
HBeAg (hepatitis B e-antigen) is a product of the HBV gene found in both acute and chronic infection. Its presence indicates active viral replication and high levels of the virus in the infected person. HBeAg present beyond 10 weeks indicates it has advanced to chronic hepatitis and probably to chronic liver disease.
HBeAb or anti-HBe (hepatitis B e-antibody) is produced temporarily during an acute infection or consistently during or after a burst in viral replication. Spontaneous conversion from e-antigen to e-antibody is predictive of a long-term clearance of the infection in those receiving antiviral therapy.
Total hepatitis B core antibody (anti-HBc) is present at onset of symptoms in acute hepatitis B and persists throughout life. The core antigen (HBcAg) cannot be detected, but its antibody usually appears along with or shortly after, HBsAg.
IgM anti-HBc indicates infection with HBV within the last 6 months. This infection is present in the “window period” when HBsAg is undetectable and before anti-HBs appear.
Anti-HBc IgG (IgG antibody to hepatitis B core antigen) is a lifelong marker of past or chronic infection. It is not induced by vaccination.
Once you have received the blood profile and hepatitis screens, it can be challenging to make sense of what you see. To comprehend the results, consider a few of the following scenarios.
- Scenario 1: HBsAg, anti-HBc and the Anti-HBs are all negative, indicating the proposed insured is susceptible to the hepatitis B virus.
- Scenario 2: HBsAg is negative, anti-HBs and the anti-HBc are both positive, indicating the person is immune due to natural infection.
- Scenario 3: HBsAg and the anti-HBc are both negative, and the anti-HBs is positive, indicating immunity due to hepatitis B vaccination.
- Scenario 4: HBsAg, anti-HBc and IgM anti-HBc are all positive, while anti-HBs is negative, indicating the individual is acutely infected.
- Scenario 5: HBsAg and anti-HBc are both positive, but the IgM anti-HBc and anti-HBs are both negative, indicating the individual is chronically infected.
- Scenario 6: HBsAg and the anti-HBs are negative, but the anti-HBc is positive. The interpretation of this result is unclear. There are four possibilities: (1) a resolved infection, which is most common; (2) a false positive anti-HBc, thus susceptible; (3) low level chronic infection; or (4) a resolving acute infection.
Other Important Test Results
Liver function tests can also be used to assess the level of liver damage. Acute hepatitis B results in high levels of ALT and AST (with ALT usually being higher). In chronic inactive disease, liver function tests are usually normal, but occasional fluctuations up to five times the upper limit of normal can occur. In reactivation phases, unusually high levels of ALT are possible. If the AST is higher than the ALT, cirrhosis must be excluded, typically by a liver biopsy.
HBV DNA viral load testing is crucial to monitoring and managing chronic hepatitis B patients. The HBV DNA level is a predictor of cirrhosis and HCC development. According to the Canadian Journal of Gastroenterology, HBV DNA measurements are usually repeated every 3–6 months to monitor the disease. These levels will also need to be monitored frequently during treatment to test the patient’s response to treatment, to measure his or her compliance (or non-compliance), and to assess for the development of treatment resistance.
Screening for HCC may include alpha-fetoprotein (AFP) testing. AFP is a tumor marker and, if present, can be indicative of HCC. Keep in mind the AFP only has a sensitivity of approximately 60%. If the AFP is elevated, an ultrasound and/or biopsy will likely be recommended to confirm a diagnosis of HCC.
Due to the risk of complications from biopsies, Fibroscans are now being used more frequently in place of the biopsy to determine the likelihood of fibrosis and cirrhosis. The Fibroscan measures the stiffness of the liver and correlates this stiffness with the amount of fibrosis and possible cirrhosis present. The liver biopsy is still the gold standard.
There is no curative treatment available for acute hepatitis B. There are treatment recommendations for chronic HBV, yet opinions differ on the stage at which this treatment should begin. Most agree that treatment should start when HBV DNA levels are at or above 2,000 IU/mL vs. 20,000 IU/mL, as well as when the ALT has been elevated for at least 3 months. The aim of treatment is to reduce the inflammation and infectivity, but it is not always effective. Treatment is usually with interferon-alpha or nucleoside analogues (lamuvidine or entecavir). The main mortality risks associated with chronic hepatitis B infection are the development of cirrhosis or hepatocellular carcinoma.
Now that you have your blood profile, your hepatitis screens completed, and you know what the results mean, here are a few tips you can use to help assess the risk for the different lines of business. Remember to review your company’s specific guidelines.
1. Life Insurance
Acute hepatitis B: Best-case scenario is if the proposed insured has fully recovered, with normal liver enzymes, AFP levels within normal limits, no co-infection (HCV or HIV) and no lifestyle concerns (injected drugs, alcohol, etc.). Acute hepatitis B should resolve within 6 months. As always, keep in mind the cause or route of transmission.
Note: Details of HBeAg, anti-HBeAg and HBV DNA levels are essential for accurate assessment of chronic hepatitis B cases. A negative e-antigen means the virus is not replicating, and that’s a good thing.
Chronic hepatitis B: See above for the best-case scenario and take note of the cause or route of transmission. Keep in mind that those who seroconvert to HBeAg negative, either spontaneously or following treatment, have a better prognosis. Nevertheless, viral reactivation and the development of HBeAg negative hepatitis remain a risk.
Note: When underwriting mortality and/or morbidity risks, it is helpful to keep in mind the complications that arise from chronic hepatitis B infections. These include liver fibrosis or cirrhosis (scarring of the liver), liver failure and liver cancer, as well as treatment. Treatment can cause some significant side effects.
2. Critical Illness Insurance
Ensure you have clear family history information. According to the Hepatitis B Foundation (www. hepb.org), people with hepatitis B or hepatitis C, who also have a family history of liver cancer, are at the highest risk of developing liver cancer, especially at a young age.
When considering an application for critical illness insurance (CI), take into account the following factors: age, family history, cause of infection, acute or chronic infection, and if the individual is experiencing any symptoms. Additional factors to consider include: any previous treatment, current serology and other investigations completed. All of these factors, in addition to your company’s guidelines, will determine the eligibility of critical illness insurance. Consider the entire picture.
3. Disability Insurance
Depending on your company’s philosophy, in the best cases (asymptomatic, full recovery, normal or stable liver enzymes, and no fibrosis), you may wish to consider waiting periods and/or exclusions.
As underwriters, we need to ensure we have a solid foundation of knowledge and a thorough understanding of the complexities and progression of the HBV disease to underwrite the risk and make the best decisions possible. Utilize the medical directors available to you. Their vast expertise could give you further insight into your case. Hopefully this article furthers your knowledge of underwriting HBV.
3. Centers for Disease Control and Prevention (nd), Viral Hepatitis.
4. CATIE (2016), Hepatitis B.
5. Ontario Association of Optometrists (2017), Hepatitis and the eyes.
6. Action Hepatitis Canada (nd), Hepatitis B: Meeting our Elimination Targets.
7. World Health Organization, (September 2019), What is hepatitis?