Written by Julie Bick, Ph.D.
Hepatitis is a general term used to refer to the swelling and inflammation of the liver that can be caused by different factors ranging from viral infections, alcohol consumption, and the use of some medications to a person’s genetics. Certain genetic profiles or immune disorders can also result in what is called autoimmune hepatitis, where the immune system mistakenly attacks the liver. Depending on the underlying cause, hepatitis can be acute with flare-ups that then go away, or chronic, which most frequently manifests with milder symptoms, but which comes with a higher risk of progressing to long-term liver damage and possible liver failure.
The liver functions as the body’s detoxification system, by processing nutrients and drugs, filtering the blood, and supporting immune system functions. Hepatitis impedes the function of the liver resulting in a range of physiological symptoms such as jaundice and fatigue to digestive issues and fever.
Most people don’t think about hepatitis as a growing health issue however infection rates are increasing in many population demographics. With the availability of high-quality clinical tests, vaccines for Hepatitis A and B, and a curative drug for Hepatitis C, the focus now is on supporting the successful implementation of surveillance programs, community outreach, and improved access to care to help reduce the rates of infection in the US and throughout the world.
In this blog we review the different types of hepatitis, the risk factors for contracting them, and how these are being approached clinically to address the global burden of hepatitis.
Like other autoimmune disorders, autoimmune hepatitis is most often diagnosed in people with other autoimmune diseases such as Thyroiditis and Grave’s disease, Type 1 diabetes, celiac disease and ulcerative colitis, and immune thrombocytopenia and hemolytic anemia. Women have almost a four-fold higher risk for autoimmune disorders compared with men, and although the underlying cause of this is not clear a range of factors including hormones, microchimerism, and the microbiome have been implicated (Kronzer et. al. 2021).
The symptoms associated with autoimmune hepatitis are wide-ranging from flu-like symptoms and fatigue to ascites buildup and vomiting and so diagnosis may involve a range of laboratory tests including liver function (liver enzyme activities and inflammatory markers), complete blood counts, coagulation and electrolyte panels, along with screening for autoimmune antibodies. In some instances, imaging diagnostics such as CT scans, MRIs or ultrasound may be employed, and a biopsy performed to confirm the diagnosis and stage the disease status of the liver. Rates of autoimmune hepatitis are increasing globally overall but at an increased rate in northern latitudes such as the UK where the incidence of autoimmune hepatitis has doubled over the last 10 years (Webb et. al. 2012).
Treatment options for autoimmune hepatitis include corticosteroids or immunosuppressive therapies to dampen the immune system and help stop the attack on the liver. However, autoimmune hepatitis should be considered a chronic condition, and regular screens of liver function are recommended (Muratori et. al. 2023)
Viral hepatitis refers to viral infections that affect the liver. There are five distinct classes of viral hepatitis, A, B, C, D, and E with different epidemiology.
Hepatitis A is a highly contagious acute liver infection, caused by the hepatitis A virus (HAV). The infection is most transmitted through a fecal-oral route, typically transmitted by an infected person who has not washed their hands properly after using the bathroom. However, there are other exposure routes of infection including sexual contact, the consumption of shellfish that has been harvested from contaminated water, or the drinking of water contaminated with raw sewage.
Although anyone can contract hepatitis A, there are groups at higher risk of infection and severity of symptoms if infected. Hepatitis A accounts for ~25% of hepatitis cases in developing countries, however, cases in the USA are increasing rapidly among individuals experiencing homelessness and drug users. The incubation period for the infection is anywhere from two to six weeks, during which time the infected individual is contagious and may or may not have any symptoms. About 80% of infected individuals recover within three to four months, and only in rare cases does the infection become chronic. Hepatitis A is typically diagnosed using a serology assay that detects the presence of anti-HAV antibodies (IgM and IgG) in blood, or alternatively using Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) test that directly detects the virus. Liver function should be monitored over the course of the infection since the increased activity of alanine aminotransferase (ALT) and aspartate aminotransferases (AST) enzymes are typical in patients.
Unlike most viruses, the Hepatitis A virus can live outside of the body for several months. Therefore, infected individuals should ensure that they disinfect all surfaces on which they prepare food and engage in enhanced handwashing procedures for extended periods until the infection has cleared.
There is a vaccine for hepatitis A, and it is recommended for all children aged 12 months to 18 years of age, as well as adults at higher risk of infection. The vaccine can also be administered following exposure or potential exposure and has been shown to prevent the development of hepatitis A if given within 2 weeks.
Hepatitis B is the most prevalent serious liver infection globally, with about 350 million patients worldwide living with chronic Hepatitis B, and of this, 1.25 million are in the United States. The hepatitis B virus is considered highly infectious and is transmitted through infected blood-to-blood contact, sexual activity, and illicit drug use. Around one in three infected individuals do not even know they have the virus, which is one reason why infection rates are so high globally.
There are two forms of infection, acute and chronic. Acute infection is resolved within a few months by most patients, however, for about 5-10% of adults, 30-50% of children, and 90% of infants the infection persists to a chronic state resulting in liver failure, cirrhosis, or liver cancer. Each year around 5000 Americans die of Hepatitis B- related liver complications. Infection rates are much higher in other populations such as those of Asian descent with around one in ten individuals infected with the virus.
Currently, there are no medications to treat recently acquired Hepatitis B infection, but there is a vaccine that is approved for all ages. Antivirals have been used to manage chronic Hepatitis B infection, with various degrees of success (Wu et. al. 2019). Since children and infants are most at risk of developing a chronic infection, all pregnant mothers should get tested for Hepatitis B during each pregnancy. Infants born to infected mothers should receive hepatitis B immunoglobulin and the vaccine within 12 hours of birth.
Testing for Hepatitis B typically involves ELISA-based screening. The presence of the hepatitis B surface antigen (HBsAg) is indicative of active infection, and if a patient tests positive for HBsAg for longer than six months, then that is a sign of chronic Hepatitis B. Imaging is used to assess the scarring or ‘fibrosis’ of the liver and liver biopsies are used to stage chronic hepatitis B and detect liver cancer.
Unlike for Hepatitis A and B, there are no vaccines to protect against hepatitis C infection. The HCV virus is transmitted through blood and bodily fluids, although it is rarely spread through sexual activity but rather through the sharing of needles, and unscreened blood products. An estimated 58 million people live with chronic hepatitis C infection globally, with approx. 1.5 million new infections annually. In the US it is estimated that 17,000 new infections occur each year, adding to the estimated 3.2 million Americans with chronic hepatitis C. The reason for these high infection rates is due largely to the fact that most individuals don’t know they are infected until they show signs of liver damage. This can be decades after initial infection, by which time they may have put others at risk of infection. A small percentage of infected individuals do recover rapidly (within six months), however for most people (75-85%) go on to develop chronic hepatitis C. Infection rates are highest in so-called baby boomers born between 1945 and 1965, who are more likely to have been exposed to unsafe medical procedures such as blood transfusions with unscreened donor blood before screening for HCV was introduced in 1992. As a result, hepatitis C testing is recommended for this population, as well as those who have received long-term hemodialysis, illicit drug users, and those who may have been exposed to the virus through tattoos and piercings. In the US rates of acute hepatitis C are highest among American Indian and Alaska Native populations, who have lower access to health care and were most impacted by the opioid epidemic.
The good news is that there are effective treatments for hepatitis C with up to 90% of patients cleared of the virus within eight to twelve weeks of initial treatment. The selection of the treatment is driven by several factors including the genotype strain and viral load of HCV and the cirrhosis state of the liver. Significantly, clearing of the virus lowers the patient’s risk of cirrhosis and liver cancer. Sadly, there are still obstacles to accessing treatment for hepatitis C. Medicare coverage is not sufficient to cover the costs of these expensive curative drugs and health insurance companies are known to impose liver-fibrosis score restrictions as well as sobriety requirements before coverage is provided, which most impacts indigenous persons.
Many people outside of the healthcare sector have not even heard of hepatitis D, but it is a growing concern, particularly in indigenous and Asian populations. The hepatitis D virus (HDV) requires the hepatitis B virus for its replication, hence HDV infection occurs when an individual is infected with HDV and HBV simultaneously -this is referred to as co-infection, or they contract hepatitis D after first contracting hepatitis B- this is referred to as superinfection. Superinfection is associated with the rapid progression of hepatitis and hepatocellular carcinoma. Globally, around 5% of patients with chronic hepatitis B are also infected with HDV. Vaccination with the hepatitis B vaccine can help reduce the impact of HDV infection (Rizzetto et al. 2021), and there have been significant reductions in HDV cases through vaccination of babies, and the prophylaxis use of antivirals for those in high-risk groups such as intravenous drug users.
There are no standardized diagnostics for HDV, but high levels of anti-HDV IgG and IgM levels are typically used for primary screens, followed by a confirmatory test for HDV RNA in serum. Testing for HDV is recommended for all patients with seropositive for HBsAg, however, the rollout of this additional testing has been slow (Palom et al. 2022). These tests may be used for monitoring viral loads during treatment, which generally involve pegylated interferon alpha for a minimum of 48 weeks. Unfortunately, this treatment is very often poorly tolerated and not all patients are suitable candidates for its use.
Although not common in the US, an estimated 20 million people contract HEV globally every year, and this results in an estimated 3.3 million cases of hepatitis E, and more than 44,000 deaths per year. East and South Asia are the epicenters of the infection, and although not available outside of the country, China has developed a vaccine to address this health crisis. There are 4 different genotypes of HEV but genotypes 1 and 2 most commonly infect humans. The incubation period ranges from 2 to 10 weeks, and infected individuals can shed the virus through their feces during this time. Although children are the most common age group infected, they often experience mild to no symptoms. Adults with HEV often display jaundice, skin rash, and pain, all of which are common among liver illnesses. Pregnant women with HEV are at increased risk of acute liver failure and loss of the fetus, and this risk is much higher within the third trimester.
Diagnostic tests screen for anti-HEV IgM antibodies in blood, or reverse transcriptase polymerase chain reaction (RT-PCR) to detect the HEV RNA in blood or stool samples (Zhou, 2023). Although there are no drugs for HEV, immunosuppressed patients may benefit from the antiviral drug ribavirin or interferon.
Diagnostic tests and surveillance programs for hepatitis are playing a crucial role in addressing hepatitis by providing early detection that allows for more timely intervention and treatment, for better patient outcomes and an overall reduction of the burden of the disease on public health (visit the Hepatitis B Foundation website for an example of community outreach www.HepB.org). These diagnostics are also being implemented for patient monitoring during therapy- assessing viral loads, immune responses, and liver function during clinical drug development and helping to identify cases of drug resistance. The Hepatitis B Foundation is adopting HBV testing as a tool for pre-and early- liver cancer screening, a novel but valuable approach, which ultimately will save lives.
Hepatitis surveillance programs are invaluable in identifying the prevalence, incidence, and distribution of hepatitis viruses in different populations and geographical areas. This information helps researchers and policymakers understand the impact of hepatitis, identify high-risk populations, and develop targeted prevention and control strategies. Diagnostic tests also aid in evaluating the effectiveness of vaccination programs and monitoring changes in viral strains over time.
Here are some general guidelines for hepatitis screening:
In most cases, screening is not necessary unless you have specific risk factors or symptoms. Vaccination against hepatitis A is recommended for certain populations, such as travelers to endemic regions, men who have sex with men, illicit drug users, and individuals with chronic liver disease.
Screening for Hepatitis B is Recommended in Various Scenarios, Including:
Pregnant women: All pregnant women should be screened for hepatitis B surface antigen (HBsAg) during their first prenatal visit to prevent mother-to-child transmission.
High-risk individuals: Individuals at increased risk for hepatitis B infection, such as healthcare workers, people living with someone with chronic hepatitis B, individuals born in regions with high hepatitis B prevalence, and men who have sex with men, should consider regular screening.
Individuals with specific medical conditions: Screening may also be recommended for individuals undergoing immunosuppressive therapy, receiving hemodialysis, or with chronic liver disease or elevated liver enzymes.
In the past, one-time screening for hepatitis C was recommended for individuals born between 1945 and 1965 (Baby Boomers) due to the high prevalence of the infection in this population. However, current guidelines suggest that all adults should be screened for hepatitis C at least once, regardless of their birth cohort, as the infection can occur in individuals outside the Baby Boomer generation.
High-risk individuals: Current or past injection drug users, recipients of blood transfusions or organ transplants before 1992, individuals with HIV infection, and individuals with elevated liver enzymes or chronic liver disease, should consider regular screening.
It is best to consult with your healthcare provider for personalized advice on hepatitis screening, considering your risk factors and medical history.
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