The alphabet rhyme we learned as children seldom is forgotten, but the specifics of hepatitis A, B, and C could be. “A clinical review of viral hepatitis,” by Loader and colleagues (page 15 of this issue), refreshes our basic knowledge, and anything infectious deserves a broad scope.
Multiple outbreaks of food-related hepatitis A have occurred in recent years. In 2013, patients from nine states contracted hepatitis A from frozen pomegranate seeds imported from Turkey. In 2016, contaminated frozen scallops from the Philippines served in Hawaiian restaurants resulted in 292 cases of hepatitis A. Also in 2016, contaminated frozen strawberries imported from Egypt and served in a US smoothie chain affected a nine-state area. In each instance, multiple patients were hospitalized.1-3
Patients who become infected with hepatitis A as a result of drug use or homelessness are even more vulnerable. Of the 1,521 cases reported in 2017 in California, Michigan, Kentucky, and Utah, more than half of the affected patients were homeless, used drugs or both; 71% were hospitalized and 3% died.4 Costs to contain the outbreak in San Diego County alone were close to $3 million and incorporated an aggressive public health approach. Handwashing stations and portable toilets were installed where the homeless congregated; city sidewalks were regularly washed with a bleach solution; and nurses, homeless outreach workers, and law enforcement officers led the effort to raise awareness about the importance of vaccinations. Free vaccines were offered at libraries and homeless encampments, firefighter paramedics could administer vaccines, and a media blitz got the word out every day.5
The most significant risk was person-to-person contact resulting from poor sanitation and hygiene rather than ingestion of contaminated food. This led to new recommendations this year from the Advisory Committee on Immunization Practices that incorporated homelessness as an indication for hepatitis A vaccine.4 The prevention efforts cited in the clinical review for traveling infants also apply to adults over age 40 years. We are a mobile society with more than 93 million US citizens traveling to foreign countries in 2018 alone.6,7 Few exceptions remain to administering or receiving this low-cost, readily accessible vaccine if indicated.
Immigrants from Southeast Asia and sub-Saharan Africa account for more than 60% of patients living with chronic hepatitis B in the United States.8 Caribbean immigrants of African descent also are disproportionately affected.9 The Hepatitis B Research Network further characterized these populations through data collection on 1,625 adults with untreated chronic hepatitis B.10 Of these, 72% were Asian, 15% black, and 82% foreign-born. Factors affecting seeking care and/or vaccination for hepatitis B included income, insurance, and education. With more than 100 dialects and even more linguistic nuances in Southeast Asian immigrants, appreciating the effect of cultural differences is challenging. Much like those infected with HIV, a large percentage of patients (estimates as high as 65%) do not know they have hepatitis B infection. Despite the odds, in 2013, the CDC launched a “Know Hepatitis B Campaign” to promote testing in Asian Americans and Pacific Islanders.11 Perceived barriers included lack of knowledge, fear, and costs associated with a diagnosis. The strongest component was developing and/or using culturally understandable materials. All forms of communication used (written, television, radio, community outreach, digital media) had to be ethnically appropriate and focused on Chinese, Korean, and Vietnamese dialects. Outcomes are not available but clinicians must be proactive with at-risk immigrant populations.
Patients coinfected with HIV and HBV pose additional concerns. The initial workup for anyone newly infected with HIV includes HBV serologies. Those lacking immunity should be vaccinated irrespective of CD4 counts even though development of immunity is more likely with CD4 counts greater than 350 cells/mcL. Coinfected patients who have not cleared the virus and remain positive for hepatitis B surface antigen with a hepatitis B viral load will need treatment. Two-drug therapy with a tenofovir and emtricitabine coformulation is the treatment of choice. Monotherapy is not an option. Many other agents are in the lengthy pipeline. With victory won for direct-acting antivirals for hepatitis C, time will tell which class, if any, wins the race for a cure for hepatitis B.
Spend as few as 30 minutes watching television and you will hear at least one commercial about a drug that cures hepatitis C. Advertisements also have found their place in magazines, leaving few untargeted. With estimates ranging from as low as $600,000 for a single magazine ad to $100 million for one drug in multimedia formats, this seems rather staggering. But hepatitis C complicated by cirrhosis, hepatocellular carcinoma and liver transplant also results in a heavy cost burden. Calculations based on quality of life years that include complications, drug costs, insurance reimbursements, and various discounts result in treatment complexities.12
Though the pharmaceutical company income exceeds the costs of advertising and costs to patients can be high even without development of complications, is there really a better way than media blitzes to reach a broad audience? The caveat is whether the patient meets the treatment criteria and how clinicians can be placed in difficult positions when criteria are not in concurrence with patient wishes. For patients with HIV/HCV coinfection who are more likely to experience complications (including development of cirrhosis 12 to 16 years earlier than those with mono-infection), delays in treatment deserve careful scrutiny. Reasons for delay include nonadherence to HIV treatment, active substance abuse that may interfere with treatment monitoring, and the potential to develop resistance to the direct-acting antivirals in patients with known issues of poor adherence. Drug-drug interactions include HIV medications and other commonly used drug classes such as statins, proton pump inhibitors, antimycobacterials, azole antifungals, anticonvulsants, and immunosuppressive agents. As complicated as treatment can be, data to date have shown that achieving a sustained viral response is just as achievable in this population as those with HCV mono-infection.
The troubling epidemiology related to each type of hepatitis should give us pause. As clinicians, we have to ask the potentially uncomfortable questions about drug use, living conditions, and sexual practices to really know our patients. In many instances, if we do not ask, they will not tell. If a patient's HIV status is not known, ask about potential risks in the initial examination and at follow-up visits if risks are identified. Patients can acquire HIV and hepatitis C concurrently, particularly if they abuse IV drugs or are men who have sex with men.13 We must recognize that food products, particularly imported ones, still pose health threats. As the immigrant population continues to increase, clinicians must learn to adapt to cultural differences.
One of the most satisfying aspects about medicine is the constant ability to glean new information from successes and failures. The learning curve for hepatitis began when icterus was first recognized in Greco-Roman times, extended to the mid-20th century when one of its causes was definitively recognized as viral, and continues today with respect to treatment and prevention.14 As Henry Ford stated, “Failure is simply the opportunity to begin again, this time, now intelligibly.”
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