Infection Control Today - 06/2004: Acute Viral Hepatitis

June 1, 2004

Acute Viral Hepatitis

Acute Viral Hepatitis
A PROBLEM PATHOGEN FOR HEALTHCARE PROFESSIONALS

BY CAROLYN L. TWOMEY, RN, BSN

Think back to the early days of yourmedical career. Hepatitis was the scourge we heard about the days ofhepatitis A, hepatitis B and non-A non-B. Today, viral hepatitis is still amajor player worldwide, outdistancing HIV in prevalence and risk. Current WorldHealth Organization (WHO) statistics show that, among the 35 million healthworkers worldwide, about 3 million receive percutaneous exposures to bloodbornepathogens each year; two million of those to HBV, 0.9 million to HCV and 170,000 to HIV. 1 Yet in the late 1980s, the threat of HIVmade the world take a new look at healthcare professionals risks. As aresult, universal precautions, and then standard precautions, became thebenchmark against which all practice was evaluated.

According to Fry, acute viral hepatitis results in ashort-lived, debilitating acute illness that infrequently causes death of apatient. However, certain hepatitis viruses result in chronic disease that lastsfor the life of the patient. 2 The impact of this chronic state is notwithout consequence for healthcare practitioners and perioperative practitionersin particular. We are also finding those who have developed the carrier state ofthe disease while not having a great deal of impact to that individual that host certainly remains infectious to others.

Today, increased numbers of patients are presenting withcirrhosis or hepatocellular carcinoma, two altogether increasingly commonsequelae of chronic hepatitis. According to experts, this augmented prevalenceof chronic hepatitis is a significant occupational hazard to any healthcarepractitioner who encounters blood or body fluid as a reality of their practice. It is no surprise to learn that occupationally acquiredhepatitis infection is on the rise.3

Today, seven specific viruses known as hepatotropic viruseshave been identified as being responsible for the disease we commonlycall hepatitis.4 There are other viruses that also cause liver infections, suchas Epstein-Barr, yellow fever and cytomegalovirus, but these infections are notclassified as acute viral hepatitis and are considered discrete syndromes.5 Ofthe seven acute viruses, hepatitis F has provisional designation from someexperts but remains unrecognized by such bodies as the WHO.6 Many expertsbelieve, however, that there are additional hepatitis virusesunidentified as of yet.7-8 It is important to understand the risk of each of theseviruses to the patient as well as the healthcare professional.

Hepatitis A

Hepatitis A (HAV) is a single-strand RNA virus or, morespecifically, a picornavirus. HAV is a non-enveloped virus that is excreted instable form from the infected liver to the bile and hence to thegastrointestinal (GI) tract. Investigationally, it has survived in contaminated freshwater, seawater, wastewater, soils, marine sediment, live oysters and creme-filled cookies.9This virus is quite resistant to degradation in theenvironment, which fosters its preservation and spread within populations.10

Sources place the U.S. prevalence rate at approximately 200,000 annually11-12 and worldwide at 1.4 million cases annually.13 Hepatitis A infections in children,as well as some adults, are often subclinical in nature, therefore theprevalence rate may indeed be quite a bit higher.

Those at risk for acquiring HAV include:

  • People in household/sexual contact with infected person

  • Medical and paramedical personnel

  • International travelers to endemic countries

  • Preschool children attending day-care centers, their parents and siblings

  • Day-care center employees

  • Residents and staff of closed institutions

  • Homosexually active men

  • Injecting drug users using unsterilized needles

  • Persons with clotting factor disorders

  • Persons with chronic liver disease

  • Food service establishments/food handlers

  • Persons who consume raw oysters or clams14

The viral antigen is found in serum, stool and liver duringacute infection.15 Transmission of the virus occurs principally through thefecal-oral route and rarely via parenteral introduction. In order for thetransmission to occur parenterally, a blood donor would have to be in theprodromal phase at the time of blood donation. The course of the disease can becharacterized in four stages:

The incubation phase, when high concentrations of the virusare shed carrying the greatest probability of transmission, occurs within two toeight weeks (or about 10-50 days) after exposure.16-17 During this time the patient remains asymptomatic.

The prodromal phase, when symptoms like loss of appetite,fatigue, abdominal pain, nausea and vomiting, fever, diarrhea, dark urine andpale stools appear, followed by the icteric phase, during which jaundicedevelops. Clinically, none of the hepatitis viruses can bedifferentiated from other hepatitis viruses, and they require serology testingto determine a virus-specific diagnosis.18 It is at this stage that patientsoften seek medical help. The icteric phase generally begins within 10 days ofthe initial symptoms. Fever usually improves after the first few days.19 It mustbe noted that high viral shedding continues to occur until one to two weeksafter the onset of jaundice, the icteric phase and may be more prolonged in children and the immunocompromised patient.20

In rare circumstances, extensive necrosis of the liver occursduring the first six to eight weeks of the disease, resulting in fulminanthepatitis. The hallmark signs of fulminant hepatitis include high fever,marked abdominal pain, vomiting and the development of hepatic encephalopathyassociated with coma and seizures. The mortality rate of these patients is 70percent to 90 percent, with a high correlation to increased age. Survival isunusual over 50 years of age. In patients with chronic hepatitis B or C orunderlying liver disease, who are super-infected with HAV, the mortality rate increases dramatically.21

Finally, there is the convalescent phase, where resolution ofthe disease is slow, but patient recovery is uneventful and complete. Chronicsequelae with persistence of HAV infection for more than 12 months are notobserved.22 Because the liver sheds the virus into the bile, completeelimination of the virus from the host typically occurs within weeks to months.23

It has been established that during ingestion of contaminatedfood or water, the virus binds to the epithelium of the upper GI tract where itis absorbed into the circulation. HAV is more prevalent in areas where poorsanitation, insufficient water treatment, or inadequate (or non-existent)handwashing takes place.24 This is carried over in food-preparation situationswith either poor regulation of handwashing or contaminated produce as wassuspected in the recent Pennsylvania outbreak of HAV in October and November2003 related to green onion contamination.25 Experts estimate that as many as 50percent to 75 percent of adults in the United States are positive for antibodies to HAV.26

An effective HAV vaccine has been developed and is recommendedfor those who travel internationally. This vaccine is also recommended for thosewith chronic HBV or HCV, for whom the co-infection with HAV is severe andpotentially fatal. Because HAV does not have a chronic phase, there has beenlittle focus on occupational exposure. The frequency is low and the occupationalimpact on healthcare workers is negligible.27 Treatment is supportive care and antivirals are not indicated in this case.

Hepatitis B

The hepatitis B virus (HBV) is a double-stranded DNA virusmade up of a core surrounded by a lipoprotein coat, which contains the surfaceantigen HbsAg and gives rise to the term enveloped virus. 28 In the 1940sit was identified as a disease called serum hepatitis.29 Historically,clinicians found that not only were intravenous substance abusers particularlyvulnerable but also those who had received blood transfusions. It wasparticularly concerning that the donation of blood could take place when therewas no clinical manifestation of the disease. Because patients with HBV havevery high viral titers, as much as 108 to 1010 viral units per milliliter, apercutaneous exposure to even minute amounts of blood is a risk forseroconversion.30 HBV is 100 times more infectious than HIV.31 This fact alsoexplains the severity of infection of those who receivedHBV-contaminated blood prior to current strategies for screening of the bankedblood supply, which has been established in the last 25 years.32 It is notedthat the sensitivity of the screening tests have increased significantly in thelast 15 to 20 years and the risk of seroconversion in the U.S. today isnominal.33 In addition, those agents that are derived from plasma, such asclotting factors, are subjected to additional procedures, which result in littleor no transmission of HBV.

The prevalence of HBV is greatest in developing nations withinadequate medical care. In countries with higher standards of living such asthe U.S., Canada, the U.K., and other European nations, prevalence ismuch lower.34 In the U.S., infection is most common in young adults. Thereare four recognized modes of transmission:

  • From mother to child at birth

  • By contact with an infected individual

  • By sexual contact

  • By percutaneous exposure to bloodor other infected fluids

Because the enzymes within the GI tract inactivate thisvirus, feces are not a risk source. Although HbsAg has been found in all bodyfluids, only blood, vaginal and menstrual fluids, and semen have beendemonstrated to be infectious. It is important to note here that HBV can surviveat least seven days on environmental surfaces or in dried blood35 andinoculation can occur via such household items as: toothbrushes, baby bottles,toys, razors, eating utensils in contact with mucous membranes or openings in the skin.36

HBV risk groups include:

  • Infants born to infected mothers

  • Children in day care

  • Sexual and household contacts of infected individuals healthcare workers

  • Patients and employees in hemodialysis centers

  • Injecting drug users

  • People sharing unsterile medical or dental equipment

  • Those providing orreceiving acupuncture and/or tattooing with unsterile devices

  • Individualstraveling to or living in areas where HBV is endemic

  • Sexually active heterosexuals

  • Male homosexuals37

The manifestation of HBV infection varies considerablydepending on the patients age, immune status and the stage of diseaseprogression when the infection is identified. Some report that only 25 percentof infected patients present with a clinical syndrome. Seventy-five percentpresent with nonspecific viral symptoms or no clinical presentationmanifestation at all.38 The clinical phases of the infection are:

1. The incubation period varies between 45 and 120 days,depending on the level of the inoculum, mode of transmission, and host immunity.The average is 60 to 90 days. The onset of symptoms is insidious, initiatingwith tiredness, anorexia, abdominal discomfort, nausea and vomiting, mild feverif at all, and sometimes a rash. The larger the inoculum, the shorter theincubation period, with the largest inoculum occurring through bloodtransfusion.

2. The icteric phase usually occurs within 10 days of theonset of initial symptoms, beginning with dark urine and clay-colored stools.Initial jaundice appears in the mucous membranes, conjunctiva, sclera, and thenskin. It becomes clinically apparent when total bilirubin exceeds 20to 40 mg/l. This rise in bilirubin is accompanied by hepatomegaly andsplenomegaly.

3. The recovery phase follows in about four to 12 weeks, withthe resolution of jaundice and the development of protective antibodies innearly 95 percent of adults.39 As little as 1 percent may progress to fulminant hepatitis.40

4. The chronic phase of HBV occurs in 5 percent to 10 percentof those who acquire acute HBV as adults as the virus continues to survive inthe body. In children, this percentage can be considerably higher, but theyinstead become chronic carriers. Chronic hepatitis can result in seriousdestructive liver disease, including cirrhosis (in as much as 20 percent) andhepatocellular carcinoma. World-wide HBV is attributed with causing 60 percent to 80 percent of liver cancers.41HBV is a serious world-wide pathogen for which there is aneffective vaccine.

Many experts believe that global control of HBV is possiblethrough vaccination. According to the WHO, 85 percent to 90 percent ofHBV-associated deaths are vaccine-preventable.42 There are those who have beenvaccinated and report no subsequent titer. The recommended subsequent step is torepeat the series at double the dose.43 If one is a clinical practitioner, Frybelieves a prudent choice would be to leave a practice arena that has a risk forblood-borne pathogen exposure. Finally, treatment is focused primarily on management ofsymptoms.

Other treatment strategies may include:

  • Antivirals, which help support the patients immunesystem

  • Immune modulators, which help the patients immune system base a defense

  • Interferon , used in the case of chronic HBV, which results in asustained remission for about 35 percent of chronic HBV patients

Treatment ofthe sequelae of end-stage chronic hepatitis B, such as peritoneovenous shunts,sclerotherapy, resection of hepatocellular carcinoma and liver transplantationare among the surgical intervention options. These patients represent asignificant occupational risk for any perioperative practitioner.

A single hollow-needle percutaneous exposure has the riskof 30 percent probability of transmission insusceptible hosts. Occupationallyacquired HBV is common among surgeons; it has been identified as having occurredin 25 to 30 percent of operating surgeons who have been in the practice ofsurgery for more than 10 years. Lastly, it is estimated that 250 HCWs, primarilynurses and surgeons, die annually as a result of occupationally acquired HBV. The HBV vaccine can prevent occupationallyacquired HBV.44

One particularly thorny issue is that of whether a chronicallyinfected professional should continue to participate in surgery. Transmissionrates (practitioner to patient) of as much as 13 percent in surgical cases havebeen reported.45 An expert panel, which has been very recently convened, iscurrently studying this very issue.

Some sources consider hepatitis C (HCV) to be the virus ofgreatest significance in the U.S. 46-47 While this may be true, it isimportant to review some of the material contained within the NIH ConsensusStatement of Management of Hepatitis C: 2002. The state-of-the-scienceconference was convened to review current well-substantiated clinical data andto establish a consensus report (June 2002). The report states that theincidence of newly diagnosed HCV has declined in the US. Although the exactreasons are ambiguous, it is acknowledged that there has been a decrease incases among injecting drug users, as well as a decrease in cases directlyattributable to the implementation of blood donor screening.48 Current estimates place new HCV infections in the U.S. at 35,000 per year.49

HCV is a RNA virus, which is bloodborne and is thereforecommunicable in much the same routes as HBV through contact with blood andbloody fluids. And much like HBV, some place those who demonstrate the clinicalsyndrome (once infected) at about 15 percent to 30 percent, while those who areinfected and not identified at as much as 70 percent to 85 percent. 50-52 Because of this lack of identification, expertsanticipate a fourfold increase in the number of adults diagnosed with chronic HCVfrom 1990-2015. 53 Experts now concede that the majority of HCVinfections become chronic and estimate that about 4 million Americans have beeninfected and 2.7 of them are chronically infected.54 The Consensus statement didpoint out that the National Health and Nutrition Examination Survey (NHANES) isa survey of households. It does not take into account those individuals who areincarcerated, homeless or institutionalized, all of which are acknowledgedhigh-risk groups.

HCV is not related to the other hepatitis viruses, as a memberof the flavivirus. It is instead related to viruses that cause yellow fever anddengue fever.55 Interestingly enough, there are now six major genotypes of HCV. While all six types occur throughout the world, the mostcommon genotype in the U.S. is genotype 1 (a and b) and it accounts for 70percent to 80 percent of what is seen in the US.

Experts believe that the many varieties of HCV play a role inthe survival of the virus. It makes creating a vaccine exceedingly difficultwith todays technology, and it contributes to the difficulty the hostsimmune system has in destroying the virus or creating antibodies. HCV can alsomutate its amino acid pattern in an infected individual over a period of time,contributing to the difficulty in making a successful vaccine.56-57 In addition,this ability to mutate explains why some patients respond to interferon andothers do not.

Those patients with HCV types 2 or 3 are more likely torespond to interferon while those with types 1 or 4 do not.58-59 Recent studieshave shown that combined therapy with interferon and ribavirin is moresuccessful than monotherapy alone and is becoming the treatment ofchoice.60-62

  • Those at risk for HCV include:

  • Intravenous drug users (accounts for 60 percent of new cases)

  • Recipients of blood transfusions before 1992

  • Transplant recipients of solid organ transplants

  • Those acquiring tattoos, ear piercingsor body piercings

  • Those who practice substance abuse, such as snorting ofcocaine63-66

The clinical phases of HCV are:

  • The incubation period, which may occur from 15-150 days

  • The icteric phase, when the acutely infected patient may exhibit fatigue andjaundice

  • The recovery phase

  • The chronic phase, where the majority of patients who are acutely infected progress

In those chronically infected,cirrhosis occurs in as much as 20 percent with hepatocellular carcinomaoccurring in as much as 2 percent to 4 percent per year during the first fiveyears after diagnosis.67-68 Although we tend to view HCV as a less severedisease, one study reports a cumulative rate of hepatocellular carcinoma at 75percent after 15 years in patients with cirrhosis.69

As to HCW risk, estimates place the risk of infection at arate of as much as 10 percent after percutaneous exposure with a contaminatedhollow needle. There have also been two reports of transmission through splashto the eyes. To date, there is no solid information of transmission via solidneedles although surgical acquisition of HCV has been documented.70 Expertsconsider this virus a significant occupational risk.

Diagnosis today has changed because of the availability ofRT-PCR studies. This study is positive within two to three weeks of infection,long before the antibody test is positive. Because of HCW concern regardingtransmission today, most proceed with the RT-PCR rather than the recombinantimmunoblot assay (RIBA). There is no vaccine and no studies show any benefit from using interferon as a post-exposure treatment.71 Theonly strategy for prevention is avoidance of exposure to blood and body fluids.

Hepatitis D

Hepatitis D, or delta, is an RNA virus, which is bloodborne.In and of itself, it cannot cause infection of the liver but it is synergisticwith HBV because it can only replicate in the presence of HBV. It is seenprimarily among injecting drug users. Diagnosis is suspected when the course ofHBV is remarkably severe, more than 50 percent of those cases resulting infulminant HBV being attributed to HDV coinfection. Infection is establishedusing the RT-PCR assay. There are reports of some benefit from interferon .However, many of these patients will progress to endstage liver disease and become candidates for transplantation.72-72

Prevalence rates are as yet unknown. It is considered ofminimal risk to HCWs as an occupational infection. It is important to rememberthat effective HBV vaccination thwarts the infection risk of HDV aswell.74-77

Hepatitis E

Hepatitis E is a RNA virus, which causes sporadic and epidemichepatitis. It is endemic in developing countries with poor sanitation.HEV is seen most commonly in ages 15 to 40. If it is present in children, theyare almost always asymptomatic and anicteric.

People who are at risk of contracting HEV include:

  • Persons residing in endemic areas International travelers to endemic areas

  • Refugees in temporary overcrowded camps following catastrophes78

The incubation period is from three to eight weeks with anaverage of 40 days. The clinical presentation is analogous to HAV although theseverity is generally greater than HAV. Typically HEV is self-limiting, althoughit can result in a fulminant form in rare circumstances. At present, there hasnot been any documentation of a carrier state or associated cirrhosis orhepatocellular carcinoma.79

Hepatitis G/GBV-C was identified in 1995-1996 when studyingthe frozen sera of a surgeon (with the initials GB) who had presented with non-Anon-B hepatitis more than 20 years previously.80 There were three viralserotypes identified, which were named GBV-A, GBV-B and GBV-C. GBV-C or HGV, aswell as the other two, are similar in sequencing to HCV and other flavivirusorganisms. This may indicate that HCV and HGV could be the first in a series ofrelated viruses that had previously escaped identification.81-82

HGV is a bloodborne pathogen with routes of transmissionsimilar to HBV and HCV. While the disease is still to be defined, to date theacute phase appears to be occult and the frequency of chronic infection isunresolved. There has been little documentation of progression to cirrhosis whenit is the only infecting pathogen. There is also substantiation that HGV issynergistic with HBV and HCV yielding a much more rapid course to cirrhosis inthese cases. RT-PCR is the only way to identify this virus. It is interesting tonote that in large numbers of banked blood units, HGV has been identified withat least the same prevalence of HCV as in the general population.83 To date,there is no screening test of blood products for HGV as the long-term sequelaeare yet defined. Although the risk of HGV hasnt been determined, rememberthat the original virus was isolated from a surgeon.84

Occupational Risk

The No. 1 indication for liver transplantation today arepatients with endstage renal disease and portal hypertension secondary to viralhepatitis.85 Because of this need and the occult nature of so many of thesehepatitis viruses, hepatitis, particularly B, C, and G, have become asignificant risk to HCWs. Occupational exposure to HCV via hollow needlestickand subsequent seroconversion is estimated at 1.8 percent and HBV at 30percent.86 For susceptible surgeons who have been in practice for morethan 10 years, 25 percent to 30 percent have occupationally-acquired HBV. Therehave been reports of transmission of HBV and HCV from splash to the eyes. Thereis no data available on solid needle transmission in the surgical environment. Experts warn that because there is no vaccine or immunoglobintherapy in the case of HCV or HGV, the only preventive measure is prudentselection of barrier protection.87

While all of the science and research is interesting, thefinal conclusions determined throughout the studies and papers are:

  • Get your Hepatitis B vaccine, no excuses.

  • Check your Hepatitis B titer and repeat vaccine at double the dose if titers are inadequate

  • If your HBV titer continues to reflectlack of vaccination, consider your risk of exposure in your chosen profession

  • Assure your best barrier protection. Optimally, in the perioperativeenvironment, this means eye protection, double gloving, perhaps double gowningor sleeving when cases demand it

  • Maintain a keen awareness of sharps in your working environment and consider employing changes in your practice, such as no-touch passing of instruments or the use of blunt needles

  • Use a surgical scrub with the best persistence you can achieve in order to give you your best barrier protection under yourglove88-91

One final note about your selection of barrier protection.Consider this question. The last time you removed your gloves after a case inthe OR and found blood on your hands, did you know you had a barrier breech?Would the benefit of knowing at the time of the barrier breech have been ofbenefit?

I would guess that most answered yes to this question. Ofcourse, we want to know, but how do we go about doing just that? There are twomethods on the market today either electronic monitoring devices or aproprietary color puncture indicator glove system.92 Electronic monitoringsystems, which include a pad for the practitioners to stand on and afreestanding monitor, are both equipment-intensive and costly. The coloredpuncture indication system, which includes a colored under-glove used with atranslucent outer glove, significantly increases the immediate awareness ofperforation in the presence of fluid.93-94 Think of it as a good, better, bestscenario: a high-quality single glove barrier is good; a double-gloving barrieris better; and a color puncture indicator glove system that tells youimmediately that there is a breach in your first line of defense is the best. Numerous experts and practitioners call it fundamental andvital... you call it visible protection.

Carolyn L. Twomey, RN, BSN, is a clinical nurse consultant forRegent Medical.