Introduction
As the body’s second largest organ, and the performer of dozens of metabolic tasks, the liver certainly lives up to its status as a vital organ. However, the liver is also a susceptible organ. Hepatitis is a blanket term defined as inflammation of the liver. It can be caused by any number of conditions; the focus here will be on viral hepatitis. Viral hepatitis itself is subdivided into several main categories, designated by letter, and those divisions are themselves subdivided into various genotypes- the result of natural genetic mutations. Depending on the type, the infection can be self limiting or a lifelong chronic condition, and the resultant damage to the liver can be fatal, including the development of cancer.
Our knowledge of viral hepatitis has come a long way since the disease was first identified. Blum (2016) notes that between 1963 and 1989, five different forms of viral hepatitis were identified. We now know of several subdivisions within those five, making treatment a challenge, because the forms behave differently. The various types of viral hepatitis have different pathways, specific to their genetic makeup and behavior. Tajiri and Shimizu (2016) identify hepatitis B as a DNA virus. Hepatitis C, by contrast, is an RNA virus containing 9600 nucleotides, per El-Guindi (2016). Hepatitis C was formally classified in 1989 after its isolation. El-Guindi (2016) points out that prior to being designated hepatitis C, the virus was simply referred to as non-A/non-B hepatitis. Lee, Yang, Yuan, L’Italien, and Chen (2014) indicate that there are six known subtypes of hepatitis C. El-Guindi (2016) also mentions that hepatitis C uses LDL (low density lipoprotein) receptors to gain entry to the liver. Hepatitis A has also been identified as an RNA virus (Hinkle and Cheever, 2014). Hepatitis E was first identified in the 1980’s; as stated by Dalton, Saunders, and Woolson (2015), hepatitis E was initially dismissed because it is similar to hepatitis A in that both are transmitted through the fecal oral route and both are seen as self limiting. We now know that hepatitis E can progress to a chronic condition, and chronic hepatitis E can occur in up to 60% of transplant recipients, according to Dalton, Saunders, and Woolson (2015). Chronic hepatitis E can progress to cirrhosis within two years, per Dalton, Saunders, and Woolson (2015), suggesting a progression even faster than hepatitis B or C. Hinkle and Cheever (2014) refer to yet another variant, hepatitis G, which appears in patients receiving blood transfusions.
Pathophysiology
One of the challenges of diagnosis is that many people infected with a form of viral hepatitis may be asymptomatic. Aebi-Popp, Duppenthaler, Rauch, De Gottardi, and Kahlert (2016) state that “it is very likely that more than half of HCV-infected newborns are not diagnosed as their mothers are not tested during pregnancy and their newborns are asymptomatic after delivery.” (p.52) El-Guindi (2016) states that “mild symptoms of fatigue and fever present in only 15% of children at the time of primary diagnosis.” (p.84) Paul et al., (2016) state that patients with hepatitis E show no signs of liver disease other than an elevated alanine aminotransferase (ALT) level. Even if a person is experiencing outward signs and symptoms, they may be like those of other illnesses.
Which of the major divisions of viral hepatitis, and even which subdivision, is also important to consider. For those infected with hepatitis C, for example, those with genotype 1B are three times more likely to develop liver cancer than those infected with other strains of hepatitis C virus, according to Lee, Yang, Yuan, L’Italien, and Chen, (2014). As for hepatitis E, per Dalton, Saunders, and Woolson (2015), genotypes 1 and 2 may be self limiting diseases, but can prove fatal in pregnant women. Dalton, Saunders, and Woolson (2015) indicate that hepatitis E genotype 3 poses little risk to pregnant women compared to genotype 1, although Paul et al., (2016) indicate that genotypes 3 and 4 can lead to liver failure and cirrhosis, especially in the immunocompromised.
Hepatitis B and C are both blood borne pathogens, although hepatitis B is present in all body fluids. Being present in blood, hepatitis B and C can be passed not only horizontally, but vertically during childbirth. Vertical transmission cannot be overlooked, as it is one of the most common methods of transmission globally. Aebi-Popp, Duppenthaler, Rauch, De Gottardi, and Kahlert (2016) point out that currently, there is no routine testing for pregnant women who may be infected with hepatitis C because there are inadequate methods to prevent vertical transmission. El-Guindi (2016) notes that children can gain hepatitis C antibodies passively in utero from their infected mothers, providing 12-15 months of protection.
Due to the modes of transmission, viral hepatitis is often a comorbidity with one or more other infectious diseases. A concern for the treatment of viral hepatitis is that people may already suffer from a condition at the time of their infection. Wong and Gish (2016) point to the already high and increasing rates of obesity, both in the United States and worldwide, which would already compromise liver function through the development of fatty liver, so that a disease like hepatitis C would progress to fulminant hepatic failure more quickly. Alcoholism can also weaken the liver and make treatment of hepatitis more difficult. Hepatitis B can be transmitted sexually, and so an infected individual may also have another STI such as syphilis, chlamydia, gonorrhea, or HIV. HIV is also a common comorbidity of hepatitis C, due to the sharing of needles for illicit or even medical drug use. According to El-Guindi (2016), a public campaign to vaccinate against schistosomiasis in Egypt between the 1960’s and 1980’s involved the sharing of needles between family members; after disposable and sanitary needles were used, rates of transmission of hepatitis C dropped significantly, although today rural Egypt has the highest prevalence of hepatitis C in the world. (figure E) As pointed out by Lee, Yang, Yuan, L’Italien, and Chen (2014), iv drug use accounts for 60% of hepatitis C infection in the US, and 80% in Australia, while the use of unsanitary needles in health care settings accounts for the majority of hepatitis C infections in the developing world. Hepatitis A and E are both transmitted through the ingestion of contaminated food and water, and so can be transmitted with any other bacterial, fungal, or parasitic agent likewise transmitted.
Each of the major types of viral hepatitis has its own method or methods of transmission, though the clinical signs and symptoms are similar, if numerous, as outlined by Hinkle and Cheever (2014). These symptoms are primarily related to the gastroenterological system, and include nausea, vomiting, or diarrhea. Systemic symptoms include fever with its associated characteristics of elevated temperature, malaise, weakness, and sweating. However, given the many functions of the liver, impairment of this organ can lead to even more severe problems. As the liver synthesizes clotting factors, chronic or extensive hepatic damage can interfere with the body’s clotting capacity. The liver also has the function of conjugating bilirubin, a byproduct of the breakdown of dead erythrocytes. As levels rise, bilirubin is deposited in the skin and sclera of the eyes, giving them a yellowish color referred to as jaundice. The liver also produces bile, necessary for the breakdown of fats. Alteration of hepatic function can impair bile secretion, leading to difficulty in digesting fat, which then is passed in the feces, a condition referred to as steatorrhea. El-Guindi (2016) notes that feces may turn a light color and urine a dark color, also due to altered bilirubin metabolism. Plasma proteins such as albumin and globulin, instrumental in creating an osmotic gradient to pull blood from tissues and back into venous circulation, and for transporting hormones, are produced in the liver, and if their levels decrease, blood pressure and fluid balance can be compromised. Fluid volume is also disrupted through the symptom of ascites, which occurs when blood flow is backed up through the scarred liver, engorging the spleen and abdominal vessels so that fluid enters the peritoneal cavity, leading to a swollen abdomen that is characteristic of liver dysfunction. The liver detoxifies harmful substances in the body; if the liver is injured, these toxins can build up, stressing the kidneys and other organs. Ammonia, one of these toxins, can lead to irreversible brain damage in large amounts. Lastly, impaired lipid metabolism can lead to higher LDL levels, contributing to atherosclerosis and potentially heart attack and stroke. Wong and Gish (2016) point out the link between hepatitis C and cardiovascular diseases because of increased insulin resistance due to chronic infection with the virus.
Data and Statistics
Viral hepatitis is among the most prevalent illnesses in the world. It is reported that between three and seven million people in the United States are infected with hepatitis C (Wong and Gish, 2016). Paul et al., (2016) report that hepatitis E virus (HEV) is a leading global cause of acute viral hepatitis, with 20 million estimated infections and 70,000 deaths per year. The story is far more grim for hepatitis B. Minuk, Bautista, and Klein (2016) point out that hepatitis B is most prevalent in Southeast Asia and Sub-Saharan Africa, and the worldwide incidence tops several hundred million. (see figure D) Bereket-Yucel (2007), states that hepatitis B is “more likely than HIV to be transmitted because it is present in higher concentrations in the blood and more stable in the environment.” Hepatitis D is unique in that, according to Hinkle and Cheever (2014), the virus essentially piggybacks hepatitis B, and uses hepatitis B surface antigen for its own replication, so that infection with hepatitis D is rare since it obligates a preexisting infection with hepatitis B. As much of the world lives in areas with poor sanitation and inadequate clean water supply, hepatitis A is a frequent occurrence. This is important because as people from developed countries travel to these areas, they are at risk for contracting the virus. Hepatitis E is also transmitted through consumption of contaminated products, especially pork, although fruit or shellfish can also be reservoirs, according to Dalton, Saunders, and Woolson (2015). As per Aebi-Popp, Duppenthaler, Rauch, De Gottardi, and Kahlert (2016), “the worldwide prevalence of HCV in pregnant women varies: 8.6% in Egypt, 3.6% in Benin, 1.5% in Nigeria and 1.5% In France. The estimated number of people in Europe who are HCV antibody positive varies by country from 0.4% to 5.2%.” (p.52)
Age, gender, any other present comorbidities, and the level of the host’s immune response all play major roles in limiting or eliminating the threat posed by viral hepatitis. As viral hepatitis progresses, inflammation of liver cells leads to constriction of portal vessels, followed by the death of damaged cells and their replacement with scar tissue. El-Guindi (2016) looks at a study of Italian children with hepatitis C, in which the infected children developed portal hypertension, with resultant ascites and esophageal varices. As Wu and Chang (2015) show, there is clearly a relationship between gender and progression among those with hepatitis B after puberty, as males are far more likely to progress into more severe manifestations and final stages than females, due to the tendency of testosterone to increase hepatitis B transcription and estradiol to inhibit it. As stated by Tajiri and Shimizu (2016), while the majority of those infected with hepatitis B can move into an asymptomatic carrier state through immune surveillance and medical treatment, those who do not- ten to fifteen percent of all cases- continue on a progressive course leading to cirrhosis, fulminant hepatic failure, or liver cancer. Dalton, Saunders, and Woolson (2015) point out that acute hepatitis E infection occurs more often in males, and commonly at an older average age, 63.5 years. Hepatitis A, in contrast, does not lead to a chronic or carrier state and typically does not progress to a state where liver function is severely hampered, according to Hinkle and Cheever (2014).
Increased immigration from the developing world is leading to higher incidences of viral hepatitis in developed countries, placing strain on medical and financial resources. Ng, Myers, Manuel, and Sanmartin, (2016) refer to a demographic study that showed that while the overall prevalence of hepatitis B in Canada was 0.5%, there was a 3% prevalence among immigrants. Ng, Myers, Manuel, and Sanmartin, (2016) state that although liver cancer accounts for only about 1% of all cancer cases in Canada, its incidence has risen sharply in recent decades due to a high number of immigrants from countries where hepatitis B and C are more common. Hepatitis C is the leading cause of liver cancer and the single most likely reason for a liver transplant, despite the fact that transplantation does not cure the virus (Wong and Gish, 2016). According to Ng, Myers, Manuel, and Sanmartin, (2016), 80% of all cases of liver cancer worldwide can be attributed to infection with hepatitis B or hepatitis C. Minuk, Bautista, and Klein (2016) raise the question of whether viral hepatitis infects healthy hepatocytes and causes cancerous mutations, or if hepatitis infects infects cancerous stem cells which attack the liver once activated and matured. This is very significant data considering that worldwide, according to Minuk, Bautista, and Klein, (2016), liver cancer is the third most fatal and fifth most common cancer overall.
Treatment and Future Developments
Currently, the trend in treating viral hepatitis is to move away from the use of interferons and antivirals. Hepatitis B exhibits a similar behavior to HIV in that the virus can move into a latent or dormant phase, maintaining a reserve stock to reemerge at an opportunistic time, so that while “current HBV antiviral drugs are highly effective in suppressing viral replication, they cannot cure.” (Ebert and Pellegrini, 2016, p.1) Ebert and Pellegrini (2016) point out that hepatitis B integrates its own genetic material into that of the host, making complete eradication difficult; hepatitis C does not. Because of this integration into the host DNA, even if the initial immune response is able to curtail viral replication and alleviate symptoms, hepatitis B DNA will still be present in the host, as stated by Tajiri and Shimizu (2016). Per Tajiri and Shimizu (2016), the rate of viral replication can be held in check by CD8 T cells specific for hepatitis B, although the levels of circulating T cells was the same in those with low levels of hepatitis B and those with high levels of viral activity. Behrooz, Khodadoostan, Pouria, and Adibi, (2016) state that “the goals of treatments are consistent suppression of the virus replication and prevention of progression of the disease to cirrhosis, liver failure, and hepatocellular carcinoma,” (p.167) and show the results of one study where after treatment with tenofovir, nine of seventeen patients had undetectable levels of hepatitis B DNA, and fifteen of seventeen tested negative for hepatitis B antigen. Tajiri and Shimizu (2016) state that up to 90% of persons with hepatitis B enter this latent phase. With this in mind, one of the strategies in treating hepatitis B is to develop medications that will trigger the release of latent virus, and effect a cure by eliminating the reserve pool. (Ebert and Pellegrini, 2016) Another possible pathway, according to Wu and Chang (2015), is interferon- ɤ, which inhibits the production of furin, a protein in the endoplasmic reticulum used by hepatitis B in replication. Since hepatitis A and E are considered self limiting, treatment often is rest and fluid replacement, with an antipyretic or antidiarrheal if needed.
Hepatitis C remains a difficult virus to eliminate. The virus’ rapid mutation rate, similar to HIV, makes finding a permanent curative medication unlikely, and aids in the virus’ own defense against the host’s immune system, as stated by El- Guindi (2016). One of the other challenges of hepatitis C management is that the virus colonizes other organs besides the liver, such as lymphatic tissue, and about 3% of the viral load is outside the liver, according to El-Guindi (2016). Aebi-Popp, Duppenthaler, Rauch, De Gottardi, and Kahlert, (2016) point out that using newer DAA (direct action antiviral) drugs may safely eliminate hepatitis C in pregnant women and prevent vertical transmission. These newer drugs are encouraged not only for their therapeutic value, but also because of the lower incidence of adverse effects. The impact of side and adverse effects on a patient cannot be underestimated, as they may lead to noncompliance. Rosenthal and Graham (2016) discuss the shortcoming of interferon-alfa in treating viral hepatitis due to toxicity. El-Guindi (2016) points to problems with the use of Ribavirin in the treatment of children with chronic hepatitis C, which included thyroid dysfunction, fever, hemolysis, and slowed growth by as much as 1.6 cm less than average. There is also a push to improve education about modes of transmission and ways to improve sanitation and hygiene. A study of wrestlers in Iran by Kordi, Neal, Pourfathollah, Mansournia, and Wallace (2011) found that among the participants, 12% shared razors and 2% shared syringes for drugs, even though these items are relatively cheap and easily accessible. El-Guindi (2016) mentions simple measures that can go a long way towards prevention, such as hand washing, wearing gloves when coming into contact with body fluids, proper use of needles, and screening of blood products. A hindrance to successful treatment of viral hepatitis, as with any disease, is cost and availability of resources. Rosenthal and Graham (2016) state that when the Medicare Modernization Act was passed, the US government lost its ability to negotiate prices for drugs, at a current loss of $15–16 billion annually; using sofosbuvir as their example, they show that while the regimental cost in the US is $84,000, it is $54,000 in the UK, and $25,000 in Spain.
Relevance and Concluding Remarks
Much attention is given to transmission through sexual contact, poor sanitation, or healthcare acquisition; viral hepatitis is shed through body fluids. But one other realm goes largely unnoticed. Contact sports, by definition, involve sustained interaction and contact with an opponent, and often includes contact with one or more fluids, such as sweat, blood, or saliva. The threat of rampant hepatitis infection in sports is not novel. According to Bereket-Yucel (2007), there was a hepatitis B outbreak in the 1960’s in Swedish athletes that numbered hundreds of cases, a 1980 outbreak of hepatitis B among high school Japanese sumo wrestlers, and it was found that 20% of the American football team at Okayama University tested positive for hepatitis B, while the campus wide rate was under 2%. For any lifelong fan of professional wrestling, Abdullah the Butcher needs no introduction, nor does his use of weapons during his matches. This provides entertainment for fans, but also danger to his opponents- some of whom Abdullah infected with hepatitis C. Egan (2014) reported on the ensuing trial that brought to light some of the very real risks taken in what is considered a fake sport, and states that the most compelling piece of evidence in the trial was that the plaintiff, Devon Nicholson, who previously tested negative for hepatitis C, was found to be infected with the same strain of the virus as Abdullah (Lawrence Shreve), a strain found in only 10% of all hepatitis C cases. Gray (2013) conducted an interview with another popular wrestler, Nigel McGuiness (Steven Haworth), who was forced to retire after being infected with hepatitis B in 2012, stating:
I will never know for sure. 30% of people that test positive for hepatitis-B never know, because it’s so contagious. It’s a hundred times more contagious than HIV, so I will never know. All I do know is how I didn’t get it. I never used needles, I never had unprotected sex, which is how a lot of people get hepatitis-B. However, I was around a lot of blood. So you know as much as I know. There were dangers that were inherent being around blood. Whether I got it from them or whether I didn’t, the danger was certainly there. It was certainly there after the fact that I did have it, because if I had bled around anybody, they could have got it from me.
According to Bereket-Yucel (2007), as late as 2007, the International Federation of Associated Wrestling Styles and the International Boxing Federation did not require hepatitis B testing, even though such testing was required for HIV, while neither the International Federation of Sports Medicine nor the World Health Organization recommended hepatitis B vaccination for athletes. Despite the emphasis on blood in the above cases, Bereket-Yucel (2007) points to a study of 70 wrestlers of the Turkish national team to assess the possibility of transmission through sweat, finding that 9 of the 70 tested positive for hepatitis B- among those 9, 8 had detectable hepatitis B in a 200 microgram sample of sweat. Just something to consider the next time someone casually refers to professional wrestling, or sports in general, as childish nonsense.
Figure A:
http://2.bp.blogspot.com/-lttm1_s5Ldc/UaGSYOoiTiI/AAAAAAAADDA/wzZXw0eg-VU/s1600/hepatitis.jpg
Figure B: Jaundice
http://www.hispanichepatitisday.org/wp-content/uploads/2012/04/hepatitis-s2-person-with-jaundice.jpg
Figure C: Ascites
http://clinicalgate.com/wp-content/uploads/2015/03/B9781437713671000975_f097-001-97814377136712.jpg
Figure D: Prevalence of Hepatitis B
Figure E:
http://www.info.gov.hk/hepatitis/images/hep_c_eng_l.gif
Abdullah the Butcher
Figure F: Figure G:
Figure H:
https://i.ytimg.com/vi/elPoBEmm_RY/maxresdefault.jpg
References
Aebi-Popp, K., Duppenthaler, A., Rauch, A., De Gottardi, A., & Kahlert, C., (2016, Jan).
Vertical transmission of hepatitis C: towards universal antenatal screening in the
era of new direct acting antivirals (DAAs)? Short review and analysis of the situation in Switzerland. Journal of virus eradication, 2(1): 52–54. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4946698/
Behrooz, A., Khodadoostan, M., Pouria, B., and Adibi, P. (2016, Jul-Sep). Tenofovir in
treatment of Iranian patients with chronic hepatitis B virus infection: An open-
label case series. Journal of research in pharmacy practice, 5(3)166–170.
Bereket-Yucel, S., (2007, May). Risk of hepatitis B infections in Olympic wrestling.
British Journal of sports medicine, 41(5): 306–310. doi: 10.1136/bjsm.2006.032847
Blum, H. (2016, May). History and Global Burden of Viral Hepatitis. Digestive Diseases,
34 (4) DOI: 10.1159/000444466
Dalton, H., Saunders, M., & Woolson, K., (2015, Jan.) Hepatitis E virus in developed
countries: one of the most successful zoonotic viral diseases in human history? Journal of virus eradication, 1(1): 23–29. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4946667/
Ebert, G. & Pellegrini, M. (2016). Hepatitis B virus and inhibitor of apoptosis proteins –
a vulnerable liaison. Cell Death Discovery, 2: 16014 doi: 10.1038/cddiscovery.2016.14
Egan, K., (2014, June 2). Judge delivers piledriver, awards bloody wrestler $2M decision.
The Ottawa Citizen. Retrieved from http://ottawacitizen.com/news/local-
news/judge-delivers-piledriver-awards-bloody-wrestler-2m-decision
El-Guindi, M. (2016, Jun) Hepatitis C Viral Infection in Children: Updated Review.
Pediatric gastroenterology, hepatology, and nutrition, 19(2) 83–95. doi: 10.5223/pghn.2016.19.2.83
Gray, R., (2013, May 22). Nigel McGuinness on losing his push in TNA, chances of an
in-ring return, ROH’s top guy. Wrestling News World.com Retrieved from
http://www.wrestlingnewsworld.com/nigel-mcguiness-on-being-buried-released-from-tna-chances-of-an-in-ring-return-rohs-top-guy
Hinkle, J., and Cheever, K. (2014). Brunner and Suddarth’s textbook of medical-surgical
nursing. 13th edition. Philadelphia: Wolters Kluwer Health Lippincott Williams
& Wilkins.
Kordi, R., Neal, K., Pourfathollah, A., Mansournia, M., & Wallace, W., (2011 Jul-Aug).
Risk of Hepatitis B and C Infections in Tehranian Wrestlers. Journal of athletic
training, 46(4): 445–450. Retrieved from
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419158/
Kudo, M. (2016 Jul) Risk of Hepatocellular Carcinoma in Patients with Hepatitis C Virus
Who Achieved Sustained Virological Response. Liver Cancer, 5(3): 155–161. doi: 10.1159/000443563
Lee, M., Yang, H., Yuan, Y., L’Italien, G., & Chen, C., (2014 Jul 28). Epidemiology and
natural history of hepatitis C virus infection. World Journal of Gastroenterology,
20(28): 9270–9280. doi: 10.3748/wjg.v20.i28.9270
Minuk, G., Bautista, W., and Klein, J. (2016, Mar. 29). Evidence of Hepatitis B Virus
Infection in Cancer and Noncancer Stem Cells Associated with Human
Hepatocellular Carcinoma. Canadian journal of infectious diseases and medical
microbiology, v2016; 2016 doi: 10.1155/2016/8931591
Ng, E., Myers, R., Manuel, D., & Sanmartin, C. (2016, Apr-Jun). Hospital stays for
hepatitis B or C virus infection or primary liver cancer among immigrants: a
census-linked population-based cohort study. Canadian Medical Association
Journal Open, 4(2): E162–E168. doi: 10.9778/cmajo.20150117
Paul, S., Pisanic, N., Heaney, C., Forman, M., Valsamakis, A., Jackson, A., …
Karnsakul, W. (2016, Jan.). Hepatitis E Virus Infection Among Solid Organ
Transplant Recipients at a North American Transplant Center. Open forum infectious diseases, 3(1) doi: 10.1093/ofid/ofw006
Rosenthal, E., & Graham, C., (2016). Price and affordability of direct-acting antiviral
regimens for hepatitis C virus in the United States. Infectious agents and cancer,
11: 24 doi: 10.1186/s13027-016-0071-z
Tajiri, K., and Shimizu, Y. (2016, July 28). New horizon for radical cure of chronic
hepatitis B virus infection. World journal of hepatology, 8(21): 863–873.
Wong, R., & Gish, R. (2016, May). Metabolic Manifestations and Complications
Associated With Chronic Hepatitis C Virus Infection. Gastroenterology and
Hepatology,12(5), 293-299. Retrieved from
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4973560/
Wu, J., & Chang, M., (2015). Natural history of chronic hepatitis B virus infection from
infancy to adult life -the mechanism of inflammation triggering and long-term
impacts. Journal of Biomedical Science, 22, 92. doi: 10.1186/s12929-015-0199-y
