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This hepatitis virus is associated with acute infection and does not cause chronic disease or a carrier state. It is transmitted by close personal contact and oral-fecal contamination. The course of the disease last several months and symptoms and jaundice occur about 45 days after infection.


Screening travelers for hepatitis A antibodies: an observational cost-comparison study of vaccine use.

Lee KK, Beyer-Blodget J.

Department of Medicine, Kaiser Permanente Medical Center, 2025 Morse Ave, Sacramento, CA 95825-2115, USA.

West J Med 2000 Nov;173(5):325-9 Abstract quote

OBJECTIVES: To measure the seroprevalence of antibodies to hepatitis A virus (anti-HAV) in a health plan population of travelers and to determine whether prevaccination screening for anti-HAV can reduce unnecessary vaccination and thus promote the most effective, economic use of hepatitis A vaccine.

DESIGN: Observational, cost-comparison study.

SETTING: Central injection clinic of a health maintenance organization medical center.

SUBJECTS: Five hundred twenty-seven adults who denied having previous hepatitis A or vaccination.

MAIN OUTCOME MEASURES Subgroups with the greatest prevalence of anti-HAV seen between June 1995 and April 1996 for immunizations before traveling to nonindustrialized countries. Relative costs of their screening and immunization.

RESULTS: The presence of anti-HAV precluded the need for vaccination in 148 subjects (28.1%). The highest prevalence of anti-HAV (82.7%) was found in subjects born in nonindustrialized countries (62/75), in subjects who had previously traveled to areas of endemic hepatitis A (32.1% [135/420]), and in subjects born before 1945 (29.2% [92/315]). Costs of screening and vaccinating travelers were cheapest if prevaccination antibody sera testing was limited to subjects born in nonindustrialized countries and those born before 1945.

CONCLUSIONS: Prevaccination screening of travelers for hepatitis A can be done selectively on the basis of age and country of origin. This strategy could lead to a more economic use of the vaccine and clinic resources.



Worldwide epidemiology of hepatitis A virus infection.

Shapiro CN, Margolis HS.

Hepatitis Branch (WHO Collaborating Centre for Research and Reference in Viral Hepatitis, Centers for Disease Control and Prevention, Atlanta, GA 30333.

J Hepatol 1993;18 Suppl 2:S11-4 Abstract quote

Patterns of hepatitis A virus (HAV) infection and clinical disease differ worldwide, and correlate with socioeconomic conditions (and hygienic and sanitary conditions) of each geographic area.

In least developed countries with very poor sanitary and hygienic conditions, HAV spreads readily, and most persons are infected as young children. Because most persons become infected at an age when HAV infection is often asymptomatic, reported disease rates in these areas are low and outbreaks of disease are rare. In developing countries and some regions of developed countries, sanitary conditions are variable, and transmission can predominate in children, adolescents or adults, depending on the geographic region. Paradoxically, since HAV transmission occurs in these areas in older age groups compared with least developed countries where HAV transmission is highly endemic, reported rates of hepatitis A can be higher. In developed countries, sanitation and hygienic conditions are good, and infection rates in children are generally low. Communitywide epidemics can contribute significantly to the burden of disease, as can occasional day care center and common-source outbreaks. In some areas, disease tends to be among specific risk groups, such as travellers to hepatitis A endemic areas, and intravenous drug users among whom hygienic practices may be poor. As countries develop economically with improvement of sanitary conditions, overall endemicity of HAV infection decreases, and disease patterns may change.

As the endemicity of HAV transmission decreases, the reported rate of clinical hepatitis A can increase, due to the shift in the average age of infection to an age when clinical illness is more frequent.

Seroepidemiology of hepatitis A in the United States.

Koff RS.

Department of Medicine, University of Massachusetts Medical School, Framingham.

J Infect Dis 1995 Mar;171 Suppl 1:S19-23 Abstract quote

The seroepidemiology of hepatitis A depends on the biologic features of the agent.

Hepatitis A virus (HAV) is shed in the stool, and infectivity titers are significantly higher for stool than for other body materials. As a consequence, the predominant mode of spread is through fecal-oral routes. Common-source vectors include contaminated foods, water, and bivalve mollusks. Risk factors include contact with a person with hepatitis A, attendance or employment at a day care center, recent international travel, exposure to infected food or water during an outbreak, homosexual activity, and injecting drug use. No known risk factors are identified in many cases.

Almost 40% of individuals in the United States are seropositive for prior HAV infection, and rates increase with age, perhaps reflecting an aging cohort of persons infected in earlier times when the infection was more common. Not unexpectedly, this decrease in current infection rates has increased the number of susceptible persons.

Prolonged fecal excretion of hepatitis A virus in adult patients with hepatitis A as determined by polymerase chain reaction.

Yotsuyanagi H, Koike K, Yasuda K, Moriya K, Shintani Y, Fujie H, Kurokawa K, Iino S.

First Department of Internal Medicine, University of Tokyo, Japan.

Hepatology 1996 Jul;24(1):10-3 Abstract quote

In hepatitis A virus (HAV) infection, fecal excretion of the virus has been reported to cease shortly after symptoms occur. Although there have been several reports on detection of HAV in feces using polymerase chain reaction (PCR), the duration of fecal HAV shedding in human adult hepatitis A has not been well described.

In the present study, we applied the reverse-transcription (RT)-PCR system to the detection of fecal HAV RNA in 10 patients with sporadic hepatitis A.

The viral genomic RNA was detected in the stools from five patients after the onset of clinical symptoms. All stool samples collected within 10 days of onset of illness were HAV-RNA-positive, and the duration of positivity lasted from a few days to as long as 3 months. In four patients, HAV RNA was detected in the stool even after the serum alanine transaminase (ALT) levels had peaked, and in one patient well after ALT levels fell to normal.

These results show that fecal shedding of HAV can last for months after resolution of symptoms and such patients could be a source of further spreading of the virus in the community.



Prevalence of hepatitis A virus antibodies in patients with chronic liver diseases.

Lopez Serrano A, Anton Conejero MD, Alcaraz Soriano MJ, Garcia del Castillo G, Gomez Pajares F, Moreno-Osset E.

Digestive System Medicine Service, Hospital Universitario Dr. Peset, Valencia, Spain.

Rev Esp Enferm Dig 2000 Aug;92(8):508-17 Abstract quote

OBJECTIVE: The age of persons with hepatitis A virus (HAV) infection in the general population has risen; these persons are at increased risk of clinically severe disease, especially patients with chronic liver disease. The aim of the present study was to analyze the prevalence of total antibodies against HAV in patients with chronic liver disease.

METHODS: In a prospective study carried out between September 1998 and June 1999, 180 patients seen in the chronic liver disease outpatient department were studied. The prevalence of total anti-HAV antibodies was determined by age group, etiology and degree of histological damage, and according to the antecedents of risk for parenteral infection. A nonconditional logistic regression model was fitted with anti-HAV positivity as the dependent variable.

RESULTS: Mean age was 44.1 years, with an anti-HAV prevalence of 77.2% (varying from 42.9% in the 21-25-year-old group to more than 83% in patients > 56-years old). Differences across groups regarding other categories (histological damage, etiology and history of parenteral or drug use) were not statistically significant, but the probability of anti-HAV positivity increased with age and a history of drug addiction.

CONCLUSIONS: The prevalence of total anti-HAV antibodies is high among patients with chronic liver disease. We therefore recommend this test before vaccination against HAV, until current recommendations on universal childhood vaccination are implemented, in order to prevent hepatitis A epidemics in the general population.



Laboratory Markers  

Sensitive assays for hepatitis A antibodies.

Miller WJ, Clark W, Hurni W, Kuter B, Schofield T, Nalin D.

Department of Cellular and Molecular Biology, Merck Research Laboratories, West Point, PA 19486.

J Med Virol 1993 Nov;41(3):201-4 Abstract quote

Two commercial assay kits for detecting antibody to hepatitis A virus (anti-HAV) have been modified in order to increase their sensitivity. These modifications are made by less dilution of the test serum, in the case of Abbott HAVAB-M assay, or by an increase in the volumetric ratio of the test serum to the labeled anti-HAV in the case of the Abbott HAVAB assay. These modifications result in 5- to 20-fold increases in test sensitivity and enable the detection of anti-HAV at 2-3 weeks following vaccination.

The earlier detection of anti-HAV is important to vaccine development in assuring the presence of antibody levels in travelers sooner after vaccination.

Analysis of immunoassays to detect antibodies to hepatitis A virus (anti-HAV) and anti-HAV immunoglobulin M.

Hess G, Faatz E, Melchior W, Bayer H.

Boehringer Mannheim GmbH, Germany.

J Virol Methods 1995 Feb;51(2-3):221-8 Abstract quote

Two newly developed anti-HAV tests were assessed, using a total of 1835 sera. These two tests are being distributed under the trademarks Enzymun-Test anti-HAV and Enzymun-Test IgM anti-HAV. The anti-HAV test was compared to anti-HAV tests from other manufacturers and featured a high sensitivity combined with a high level of reproducibility and specificity. In terms of sensitivity, reproducibility and specificity, the IgM test proved to be comparable to other IgM anti-HAV tests used for the diagnosis of acute type A hepatitis.

Combining both tests was shown to be useful to recognize an acute or past hepatitis A virus infection. In addition, the high sensitivity of the anti-HAV test makes this test extremely useful to assess the immunoresponse to the hepatitis A vaccine.

Host immune response to hepatitis A virus.

Stapleton JT.

Department of Internal Medicine, University of Iowa, Iowa City 52242.

J Infect Dis 1995 Mar;171 Suppl 1:S9-14 Abstract quote

Hepatitis A virus (HAV) is transmitted by the fecal-oral route. The virus crosses through the gastrointestinal tract by an uncharacterized mechanism and travels to the liver, where it replicates in hepatocytes. It is released into the bloodstream and is simultaneously present in the bile and shed in the feces.

Fecal shedding and viremia are maximal at the onset of liver function abnormalities and terminate about the time humoral immunity is detected, approximately 28 days after exposure. IgM, IgA, and IgG anti-HAV antibodies are usually present at onset of symptoms. Although the IgM response becomes undetectable usually within 6 months, IgG responses frequently persist for life, providing protection against reinfection. Pre- and postexposure immunization with pooled human serum immunoglobulin (ISG) is approximately 90% effective in preventing hepatitis A.

Recipients of ISG have very low levels of detectable anti-HAV antibodies, and vaccines that elicit anti-HAV levels comparable with those produced by ISG should confer similar protection.

Detection of hepatitis A viral RNA in sera of patients with acute hepatitisA.

Kwon OS, Byun KS, Yeon JE, Park SH, Kim JS, Kim JH, Bak YT, Kim JH, Lee CH

Department of Internal Medicine, Korea University College of Medicine, Seoul.

J Gastroenterol Hepatol 2000 Sep;15(9):1043-7 Abstract quote

BACKGROUND AND AIMS: The Detection of hepatitis A virus (HAV) is important for diagnosis and epidemiological studies of hepatitis A. The polymerase chain reaction (PCR) technique is a sensitive test to detect HAV-RNA in specimens. The aims of the present study were to clarify the detection rate of serum HAV-RNA by PCR and the natural history of HAV viraemia, and to determine the correlation between viraemia and the clinical characteristics in patients with acute hepatitis A.

METHODS: Hepatitis A virus RNA was tested in 74 serum samples which were serially collected from 27 patients with acute hepatitis A. A nested reverse transcription (RT)-PCR for HAV-RNA was performed with primer sets located at the VP1 region of the HAV genome and the PCR products were electrophoresed on a 1.5% agarose gel.

RESULTS: Hepatitis A virus RNA was found in 18 of 27 (67%) patients with hepatitis A. There were no significant differences between groups positive and negative for HAV-RNA in clinical and laboratory data, except the time interval between clinical onset and initial serum sampling for RT-PCR (10 +/- 6 vs 19 +/- 14 days) and the alanine aminotransferase (ALT) level at initial serum sampling for RT-PCR (1436 +/- 1416 vs 518 +/- 432 IU/L). The mean duration of HAV viraemia was 30 +/- 19 days (range, 5-59 days). The duration of HAV viraemia and duration of abnormal ALT levels from clinical onset were positively correlated (r = 0.685, P = 0.007).

CONCLUSION: In conclusion, HAV-RNA RT-PCR is a useful tool to detect HAV viraemia and to study the molecular epidemiology of HAV infection.



Fulminant hepatitis associated with hepatitis A virus superinfection in patients with chronic hepatitis C.

Vento S.

Department of Infectious Diseases, University of Verona, Verona, Italy.

J Viral Hepat 2000 May;7 Suppl 1:7-8 Abstract quote

There have been conflicting reports of the clinical outcome of acute hepatitis A virus (HAV) infection in patients with chronic hepatitis C virus (HCV) infection. A prospective study evaluated 432 patients with chronic hepatitis C (183 with cirrhosis) over a 7-year period.

Of the 17 patients with concurrent HAV infection, seven developed fulminant hepatitis and six died. None of these patients had cirrhosis; however, the HLA phenotype (A1; B8:DR3) appeared to be a significant factor in the development of fulminant hepatitis. Patients with this phenotype had high titres of antinuclear antibodies, antismooth muscle antibodies and antiasialoglycoprotein-receptor antibodies, possibly reflecting the induction of autoimmune hepatitis in this group. The high frequency of fulminant hepatitis in patients with HAV/HCV coinfection contrasts with other surveys, although a large Centers for Disease Control and Prevention (CDC) survey demonstrated that HAV infection in patients with pre-existing chronic liver disease (CLD) is associated with increased mortality.

It is likely that CLD has some importance as an underlying factor in the development of fulminant hepatitis following HAV infection. Further prospective studies are needed to clarify this issue.

Fulminant hepatitis A in patients with chronic liver disease.

Lefilliatre P, Villeneuve JP.

Division of Hepatology, Centre Hospitalier Universitaire de Montreal, Quebec. .

Can J Public Health 2000 May-Jun;91(3):168-70 Abstract quote

Fulminant hepatitis is a rare complication of acute hepatitis A virus (HAV) infection. We report three cases of fulminant hepatic failure with death due to HAV infection in patients with pre-existing chronic liver disease. Data from the literature also indicate a high case fatality rate during HAV superinfection in patients with chronic hepatitis B, particularly those with cirrhosis, and in patients with alcoholic cirrhosis. In patients with chronic hepatitis C, results are conflicting with some reports indicating a high fatality rate of HAV superinfection and others not, irrespective of the presence or absence of cirrhosis.

Based on our observations and this review of the literature, we suggest that patients with chronic liver disease should be vaccinated against hepatitis A.

Acute hepatitis A: combination of the relapsing and the cholestatic forms, two rare variants.

Rachima CM, Cohen E, Garty M.

Recanati Center for Medicine and Research, Rabin Medical Center, Petach-Tikva, Israel.

Am J Med Sci 2000 Jun;319(6):417-9 Abstract quote

Here we present an unusual case of a 23-year-old, otherwise healthy man who had a biphasic form of viral hepatitis A with a combination of two variants, the relapsing and cholestatic forms. One month after resolution of the first phase of acute hepatitis A, he was readmitted with jaundice and intense pruritus. During hospitalization, his serum bilirubin level increased to 50.2 mg/dL, with a slight increase in the other levels of liver enzymes. He was treated with ursodeoxycholic acid and later with corticosteroid therapy, resulting in resolution of symptoms and improvement of his liver function tests after 2 weeks. Medication therapy seems to be justified in markedly symptomatic patients with relapsing hepatitis.



The pathology of hepatitis A in man.

Teixeira MR Jr, Weller IV, Murray A, Bamber M, Thomas HC, Sherlock S, Scheuer PJ.

Liver 1982 Mar;2(1):53-60 Abstract quote

Liver biopsies from 17 patients with serologically established hepatitis A were examined by light microscopy. Biopsies were taken from 2 to 27 weeks after onset of symptoms.

All showed acute hepatitis, usually with centrilobular lesions but also commonly with a striking portal and periportal inflammatory reaction, resembling that seen in chronic active hepatitis. The infiltrate was rich in plasma cells. Centrilobular cholestasis was common and occasionally severe. Neither cholestasis nor the periportal lesion appeared to be related to patient age or to the timing of liver biopsy. All patients made a full recovery and none developed chronic liver disease.

The histological changes differed from those reported in children and in chimpanzees in the presence of centrilobular lesions, but resembled them in that the latter two groups also had periportal lesions. These lesions may lead to a false impression of impending chronicity if the aetiology of the hepatitis is not known at the time of liver biopsy.




Pathology of acute hepatitis A in humans. Comparison with acute hepatitis B.

Okuno T, Sano A, Deguchi T, Katsuma Y, Ogasawara T, Okanoue T, Takino T.

Am J Clin Pathol 1984 Feb;81(2):162-9 Abstract quote

Little is known about the pathologic characteristics of viral hepatitis A in humans. The authors compared the histologic features in liver biopsy specimens taken within 30 days of the onset of illness from 15 patients with hepatitis A and 14 patients with acute hepatitis B.

In both hepatitis A and B, liver cell damage and necrosis were diffusely located, with accentuation in the centrilobular and midzonal areas in which ballooning degeneration and variation in cytoplasmic staining quality were observed frequently. One case of epidemic hepatitis A showed prominent periportal liver cell necrosis with inconspicuous centrilobular liver cell alterations. Kupffer cell mobilization was mild in hepatitis A, but more striking in hepatitis B. The portal inflammation was more pronounced and rich in plasma cells in hepatitis A than in hepatitis B.

In summary, there were no major differences in the pathologic features of acute hepatitis A and B as sampled within 30 days of the onset of illness.


Prognostic Factors  

Clinical course and consequences of hepatitis A infection.

Ciocca M.

Paediatric Hepatologist, Children's Hospital Juan P. Garrahan, Combate de los Pozos 1881 (CP 1245), Capital Federal, Buenos Aires, Argentina.

Vaccine 2000 Feb 18;18 Suppl 1:S71-4 Abstract quote

Hepatitis A virus (HAV) is a small, non-enveloped RNA virus belonging to the Picornaviridae, for which only one serotype has been identified. Transmission is usually through the faecal-oral route by person-to-person contact. The most common risk factors are household or sexual contact with a sufferer, attendance or working at a day-care centre, international travel, and association with food or waterborne outbreaks; 55% of cases have no identifiable risk factors. HAV infection may be symptomatic or asymptomatic, and shows three phases. Virus is shed during the incubation phase, anti-HAV IgM appears during the symptomatic phase and can be used for diagnosis, and anti-HAV IgG appears at the same time but persists lifelong.

Unusual clinical manifestations of hepatitis A include cholestatic, relapsing and fulminant hepatitis. Hepatitis A accounts for 93% of cases of acute hepatitis in Argentina, including 7% of atypical clinical cases. Hepatitis A is the major cause of fulminant hepatitis, and has been reported to account for 10% of liver transplants in children in France and 20% in Argentina. One-year survival after liver transplantation is 64%.

Prevention must be considered as the main means of averting this severe illness.


Long-term persistence of anti-HAV antibodies following active immunization with hepatitis A vaccine.

Maiwald H, Jilg W, Bock HL, Loscher T, Sonnenburg F.

Department of Infectious Diseases and Tropical Medicine, University of Munich, Germany.

Vaccine 1997 Mar;15(4):346-8 Abstract quote

Seventy-one anti-hepatitis A virus (HAV) negative volunteers were immunized against hepatitis A.

An inactivated hepatitis A vaccine (HAVRIX, SmithKline Beecham), derived from tissue cell cultures, at single doses of 720 ELISA units was used following a schedule of vaccinations at month 0.1 and 6. The vaccines were tested for the presence of HAV antibodies 1 month after each vaccination and then after 2, 3, 4 and 5 years. The annual decrease of anti-HAV titres was 25%. Five years after vaccination a protective antibody titre, varying between 20 and 5200 mIU ml-1, could be demonstrated in all 47 retested volunteers with a geometric mean titre (GMT) of 442 mIU ml-1. Levels of anti-HAV-antibodies following active immunization were significantly higher in female volunteers. This could be consistently demonstrated throughout the observation period.

Based on these data the antibody persistence was calculated over time. GMTs at protective levels higher than 20 mIU ml-1 can be expected to persist for at least 15 years.

Immunogenicity of hepatitis A vaccination in decompensated cirrhotic patients.

Arguedas MR, Johnson A, Eloubeidi MA, Fallon MB.

UAB Liver Center, Division of Gastroenterology and Hepatology, Department of Medicine, University of Alabama at Birmingham, 35294-0007, USA.

Hepatology 2001 Jul;34(1):28-31 Abstract quote

Hepatitis A virus (HAV) vaccination is recommended in chronic liver disease because of an increased morbidity and mortality associated with HAV superinfection. However, data regarding the efficacy of HAV vaccination in patients with advanced chronic liver disease is limited.

We assessed the efficacy of a standard HAV vaccination schedule in decompensated chronic liver disease in comparison with compensated disease and defined clinical predictors associated with seroconversion. Eighty-four anti-HAV antibody-negative patients, 49 with compensated liver disease, and 35 with decompensated disease were enrolled. Seroconversion was measured by qualitative and quantitative anti-HAV antibody measurements 1 month after each vaccine dose, and univariate/multivariate analysis was performed to define clinical predictors associated with seroconversion. One month after the primary dose, 71.4% of patients with compensated liver disease had detectable anti-HAV antibody compared with 37.1% with decompensated liver disease (P <.05). One month after the booster dose, 98% of compensated patients seroconverted compared with 65.7% with decompensated disease (P <.05). The median serum antibody concentration in compensated liver disease was 76.4 mIU/mL at month 1 and 327.91 mIU/mL at month 7 compared with 20.0 mIU/mL and 102.57 mIU/mL, respectively, in decompensated disease. On multivariate analysis, Child-Pugh class was the only factor predicting response to vaccination. Seroconversion after HAV vaccination was significantly less common in decompensated liver disease and the presence of advanced disease (Child-Pugh class B/C) predicted a lower response rate.

These findings indicate that the response to HAV vaccination in chronic liver disease is optimal when targeted to patients before the development of hepatic decompensation.

Safety and efficacy of hepatitis A vaccination in liver transplantation recipients.

Arslan M, Wiesner RH, Poterucha JJ, Zein NN.

Division of Gastroenterology and Hepatology and Internal Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA.

Transplantation 2001 Jul 27;72(2):272-6 Abstract quote

OBJECTIVE: Vaccination against hepatitis A (HAV) has been shown to be safe and effective in healthy subjects and in patients with chronic liver disease (CLD). The safety and efficacy of HAV vaccines in liver transplant (OLT) recipients have not been established. The objective of this study is to assess the safety and efficacy of inactivated hepatitis A vaccine in OLT recipients.

METHODS: Thirty-seven HAV seronegative OLT recipients were enrolled. Patients received two doses of vaccine 6 months apart. Postvaccination IgG anti-HAV were determined at 1, 6, and 7 months after the first vaccine dose. Side effects were monitored for 3 days after each vaccination shot. An unvaccinated control group (45 patients) was followed for evidence of seroconversion. Seroconversion rate was also compared with those reported in healthy patients and in patients with chronic liver disease.

RESULTS: Testing was available for all the cases at 1 month, and for 26 and 23 patients at 6 and 7 months, respectively. Only 3 of 37 patients (8%) had seroconversion at 1 month. At 6- and 7-month time points, 5 of 26 (19%) and 6 of the 23 (26%) patients had seroconversion, respectively. Vaccine responders had higher total white blood cell count and lymphocyte count and were further out from transplant compared with nonresponders. None of the unvaccinated patients had seroconversion over the follow-up time. Seroconversion rates in OLT recipients were significantly lower than that reported in healthy individuals (P=0.001) or in pre-OLT patients with CLD (P=0.001). All patients tolerated the vaccine well. C

ONCLUSIONS: HAV vaccination is safe in OLT recipient. Efficacy of HAV vaccination in OLT recipients, as measured by a commercially available enzyme immunoassay, is low and alternative strategies should be developed to improve response rate.

Robbins Pathologic Basis of Disease. Sixth Edition. WB Saunders 1999.

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