A former hepatitis virus researcher reminisces on the progress made and challenges remaining in the fight to eradicate chronic viral hepatitis.
July 28, 2014. “Hepatitis: Think Again.” That is the motto for this year’s World Hepatitis Day, a program championed by the World Hepatitis Alliance to raise awareness, encourage prevention, and improve access to treatment for viral hepatitis. The World Health Organization (WHO) endorsed the global recognition of this event in 2010. Chronic viral hepatitis has been called a “silent killer” since often no symptoms are apparent until a life-threatening condition develops.
Hepatitis refers to liver inflammation, which is frequently caused by infection with a number of unrelated liver viruses termed hepatitis viruses A-E. The hepatitis viruses A (HAV) and E (HEV) are generally self-limiting causes of food poisoning, while infection with the blood-borne hepatitis B (HBV) or C viruses (HCV) can lead to chronic hepatitis, which may cause long-term cirrhotic damage, end-stage liver disease, and hepatocellular carcinoma (HCC). Hepatitis D (HDV) exacerbates HBV infections. It is only observed in HBV-infected individuals, and not in isolation, since it requires the HBV coat protein to replicate.
About a third of the people on the planet have been infected with HBV at one time or another and there are an estimated 360 million people chronically infected with hepatitis B (WHO Weekly epidemiological record). This highly-infectious DNA virus is easily spread from blood, blood products or sexual intercourse, but not from causal contact, like hugging or kissing. Routine serological testing has screened it out of blood since the late 60s. In highly endemic regions, such as China, the virus is predominantly spread perinatally, whereas in the developed world, anti-HBV immunoglobulin (HBIG) treatment is routinely used to block that transmission, followed by vaccination of the newborns. Most of the new hepatitis B cases seen in the US and in other developed nations can be traced to preexisting infections in immigrants from Asia, the Pacific Islands, and from several other low-moderate income countries (CDC Viral Hepatitis Facts).
A blood-derived HBV vaccine was being used by the late 70s; while the recombinant DNA-based version of this vaccine widely-used today was introduced in the 80s. This vaccine is amongst the most widely-used, efficacious, and safest products that biotechnology has created. HBV infection is the major cause of HCC development, so this vaccine is also considered the first anti-cancer vaccine. Approximately one third of newborns worldwide are being vaccinated against HBV today and this appears to generate life-long immunity against the virus (WHO Weekly epidemiological record). Numerous long-term clinical studies have found no evidence of any serious adverse event or disease association linked to the use of this vaccine (WHO Weekly epidemiological record).
Nucleosides are the mainstay of HBV therapy and the latest versions of these molecules are generally well-tolerated and quite effective at completely suppressing the virus. Yes, rare exceptions due to viral mutations and other underlying comorbid and psychosociological conditions do complicate this. And, in addition, the hardy nature of the HBV covalently-closed circular (cccDNA) genome necessitates long-term use of these drugs to keep the virus suppressed, but HBV antivirals generally work well.
Virtually all of the non-A, non-B post-transfusion hepatitis described years ago in textbooks were found to be attributable to HCV after its RNA genome was cloned in the late 80s. It is estimated that there are 180 million people chronically-infected with HCV. Detection is routine and the virus is therefore largely screened out of the world’s blood supply. But individuals who have received blood or blood products before this time may have inadvertently contracted HCV. HCV is less transmissible than HBV and usually involves direct injection of blood or blood-products into the bloodstream and monogamous heterosexual couples have a low risk of contracting it from an infected mate (CDC Hepatitis C Information for Health Professionals). Most of the HCV transmission today in the developed world is among intravenous drug users, while those who experimented even only once with injectable drugs are at risk of being infected (CDC Viral Hepatitis Statistics & Surveillance).
There is no vaccine for HCV and there is no expectation that an effective vaccine will be available anytime soon.
While HCV has caused a lot of hurt and suffering in the world, it turns out that the virus itself is a wimp. In fact, HCV infection is the only chronic viral infection that can be cured using antiviral agents. Every few years a new generation of HCV antivirals emerges with better cure rates— but at a greater expense. The latest treatment regimens using Direct Acting Antivirals claim 90% cure rates— and a near $100,000 treatment pricetag ($1,000 per pill). The WHO guidelines and recommendations for healthcare providers in low- to middle-income countries regarding hepatitis C released this year addresses the challenges faced in the management of this disease with limited economic resources.
Tremendous strides have been made in the past generation to identify, prevent and cure chronic viral hepatitis, but with over half a billion people infected with HBV and HCV worldwide, it remains a major public health issue—the biggest problem continues to be that most people don’t know that they are infected. The motto for this year’s World Hepatitis Day reemphasizes how critical it is for anyone with a risk factor for HBV or HCV infection to be tested because the battle against viral hepatitis is being won, but the war is not over.
Victor E. Buckwold, Ph.D. received his Ph.D. in Microbiology from the University of Southern California where he studied HBV. He then worked 17 more years on hepatitis virus drug discovery and development in industry. Currently he works and resides in the Philadelphia area.