Fiore AE.
Hepatitis A transmitted by food.
Clin Infect Dis. 2004 Mar 1;38(5):705-15. doi: 10.1086/381671. Epub 2004 Feb 11.
Abstract/Text
Hepatitis A is caused by hepatitis A virus (HAV). Transmission occurs by the fecal-oral route, either by direct contact with an HAV-infected person or by ingestion of HAV-contaminated food or water. Foodborne or waterborne hepatitis A outbreaks are relatively uncommon in the United States. However, food handlers with hepatitis A are frequently identified, and evaluation of the need for immunoprophylaxis and implementation of control measures are a considerable burden on public health resources. In addition, HAV-contaminated food may be the source of hepatitis A for an unknown proportion of persons whose source of infection is not identified.
日野和彦：散発性A型肝炎の季節発生とその要因についての検討. 肝臓 1987; 28(7)/ 書誌.
Lemon SM, Ott JJ, Van Damme P, Shouval D.
Type A viral hepatitis: A summary and update on the molecular virology, epidemiology, pathogenesis and prevention.
J Hepatol. 2017 Sep 5;. doi: 10.1016/j.jhep.2017.08.034. Epub 2017 Sep 5.
Abstract/Text
Although epidemic jaundice was well known to physicians of antiquity, it is only in recent years that medical science has begun to unravel the origins of hepatitis A virus (HAV) and the unique pathobiology underlying acute hepatitis A in humans. Improvements in sanitation and the successful development of highly efficacious vaccines have markedly reduced the worldwide prevalence and incidence of this enterically-transmitted infection over the past quarter century, yet the virus persists in vulnerable populations and remains a common cause of food-borne disease outbreaks in economically-advantaged societies. Reductions in the prevalence of HAV have led to increases in the median age at which infection occurs, often resulting in more severe disease in affected persons and paradoxical increases in disease burden in some developing nations. Here, we summarize recent advances in the molecular virology of HAV, an atypical member of the Picornaviridae family, survey what is known of the pathogenesis of hepatitis A in humans and the host-pathogen interactions that typify the infection, and review medical and public health aspects of immunisation and disease prevention.
Copyright © 2017. Published by Elsevier B.V.
Kanda T, Sasaki-Tanaka R, Ishii K, Suzuki R, Inoue J, Tsuchiya A, Nakamoto S, Abe R, Fujiwara K, Yokosuka O, Li TC, Kunita S, Yotsuyanagi H, Okamoto H; AMED HAV and HEV Study Group.
Recent advances in hepatitis A virus research and clinical practice guidelines for hepatitis A virus infection in Japan.
Hepatol Res. 2024 Jan;54(1):4-23. doi: 10.1111/hepr.13983. Epub 2023 Nov 15.
Abstract/Text
In 2018, there was a hepatitis A outbreak in Japan, and hepatitis A virus (HAV) infection is considered a sexually transmitted disease. In general, patients with hepatitis A should be given attention, and this disease should be prevented more than ever. The Japan Agency for Medical Research and Development (AMED) Hepatitis A and E viruses (HAV and HEV) Study Group has worked on the project to create "Recent Advances in Hepatitis A Virus (HAV) Research and Clinical Practice Guidelines for HAV Infection in Japan". The group consists of expert hepatologists and virologists who gathered at virtual meeting on August 5, 2023. Data about the pathogenesis, infection routes, diagnosis, complications, several factors for the severities, vaccination, and current and future treatments for hepatitis A were discussed and debated for a draft version. The participants assessed the quality of cited studies. The finalized recommendations are presented in this review. The recent advances in HAV research and clinical practice for HAV infection in Japan, have been reviewed by the AMED HAV and HEV Study Group.
© 2023 Japan Society of Hepatology.
Hepatitis A Surveillance in the United States for 2019 | CDC.
Jeong HW, Kim MK, Yi HJ, Kim DM, Jeon SJ, Lee HK, Oh YH, Hwang YO.
Hepatitis A virus strains identified in jogaejeot associated with outbreaks in Seoul, South Korea.
Lett Appl Microbiol. 2021 Jul;73(1):107-112. doi: 10.1111/lam.13482. Epub 2021 May 5.
Abstract/Text
Jogaejeot, seasoned Venerupis philippinarum, is a traditional Korean fermented food, and hepatitis A virus (HAV) can be transmitted through contaminated food, especially bivalve shellfish, causing acute gastroenteritis worldwide. Here, we carried out a phylogenetic analysis to identify and characterize HAV strains in jogaejeot samples associated with hepatitis A (HA) outbreaks in Seoul, South Korea, in 2019. The HAV strains were identified using blast and molecular analysis of the amplified HAV VP1-P2B genome region. The HAV strains identified in the five jogaejeot samples shared at least 99% sequence identity, were all classified as genotype IA and were most closely related to strains that are widespread in East Asia. These results support a link between the consumption of jogaejeot and the HA outbreaks observed in 2019 in Seoul. In addition, they indicate a need for more stringent enforcement of food safety regulations for the shellfish industry, especially against HAV, and the value of widespread vaccination.
© 2021 The Society for Applied Microbiology.
NIID Infectious Diseases Weekly Report Japan [IDWR], 感染症発生動向調査週報 (IDWR) (niid.go.jp), accessed on 6/2/2024.
Hyun JJ, Seo YS, An H, Yim SY, Seo MH, Kim HS, Kim CH, Kim JH, Keum B, Kim YS, Yim HJ, Lee HS, Um SH, Kim CD, Ryu HS.
Optimal time for repeating the IgM anti-hepatitis A virus antibody test in acute hepatitis A patients with a negative initial test.
Korean J Hepatol. 2012 Mar;18(1):56-62. doi: 10.3350/kjhep.2012.18.1.56. Epub 2012 Mar 22.
Abstract/Text
BACKGROUND/AIMS: The nonspecific clinical presentation of acute hepatitis A (AHA) mandates the detection of anti-hepatitis A virus IgM antibodies (IgM anti-HAV) in the serum for obtaining a definitive diagnosis. However, IgM anti-HAV might not be present during the early phase of the disease. The aim of this study was to determine the optimal time for repeating the IgM anti-HAV test (HAV test) in AHA patients with a negative initial test.
METHODS: In total, 261 patients hospitalized with AHA were enrolled for this retrospective study. AHA was diagnosed when the test for IgM anti-HAV was positive and the serum alanine aminotransferase (ALT) level was ≥400 IU/L. Repeat HAV test was conducted after 1-2 weeks if the initial HAV test was negative but AHA was still clinically suspected.
RESULTS: The results of the initial HAV test were negative in 28 (10.7%) patients. The intervals from symptom onset to the initial-HAV-test day and from the peak-ALT day to the initial-HAV-test day were significantly shorter in the negative-initial-HAV-test group, but on multivariate analysis only the latter was significantly associated with negative results for the initial HAV test (β=-0.978; odds ratio [95% confidence interval]=0.376 [0.189-0.747]; P=0.005). The HAV test was positive in all patients when it was performed at least 2 days after the peak-ALT day.
CONCLUSIONS: The results of HAV tests were significantly associated with the interval from the peak-ALT day to the HAV-test day. The optimal time for repeating the HAV test in clinically suspicious AHA patients with a negative initial HAV test appears to be at least 2 days after the peak-ALT day.
四柳 宏：HAV-RNA検出法. 日本臨牀 2004；62(S8)：468.
Jung YJ, Kim W, Jeong JB, Kim BG, Lee KL, Oh KH, Yoon JH, Lee HS, Kim YJ.
Clinical features of acute renal failure associated with hepatitis A virus infection.
J Viral Hepat. 2010 Sep;17(9):611-7. doi: 10.1111/j.1365-2893.2009.01216.x. Epub 2009 Oct 11.
Abstract/Text
Acute hepatitis A (AHA) is one of the most common infectious diseases; it is usually a self-limiting disease affecting the liver. Although extrahepatic manifestations are not common, some cases have been reported associated with acute renal failure. We reviewed the clinical features of patients with AHA complicated by acute renal failure (ARF group) and compared them with patients with noncomplicated AHA (non-ARF group). The medical records of 208 consecutive patients with AHA who were diagnosed between January 2003 and October 2008 were reviewed. We identified 15 patients (7.2%) with ARF associated with AHA. There were no differences between the ARF and non-ARF group with regard to gender and age. The peak value of alanine aminotransferase (ALT) (median: 6060 IU/L vs 1792 IU/L, P < 0.001), prothrombin time (PT) (International normalized ratio, median 1.72 vs 1.10, P < 0.001), and total bilirubin level (median: 9.6 mg/dL vs 6.3 mg/dL, P = 0.04) were significantly higher in the ARF than in the non-ARF group. Twelve patients (80%) recovered completely with haemodialysis (seven patients, 46.7%) or only conservative management (five patients, 33.3%), while one patient underwent liver transplantation because of fulminant hepatic failure, and two patients died because of fulminant hepatic failure. There were no deaths among patients with noncomplicated AHA in the non-ARF group. Five patients underwent kidney biopsy; two patients were diagnosed with acute tubular necrosis, two patients with acute interstitial nephritis with IgA nephropathy and one patient with acute tubulointerstitial nephritis. All patients in the ARF group had microscopic haematuria and proteinuria (100%vs 31.1%, P < 0.001). Urine sodium levels were more than 10 mEq/L in 10 patients. The findings of high urinary sodium concentrations, microscopic haematuria and proteinuria did not support the diagnosis of hepatorenal syndrome (HRS). Patients with AHA with ARF had higher ALT levels, more prolonged PTs, and higher total bilirubin levels. The prognosis for these patients was poorer than for those without ARF. However, the patients with ARF and nonfulminant AHA had recovered with proper treatment and should not be confused with patients that have HRS.
Montgomery CD, Hall EJ, Pellegrino R, Yakes EA, Green JR.
Acquired Thrombotic Thrombocytopenic Purpura Associated with Acute Hepatitis A Infection.
Am J Med. 2021 Jun;134(6):e396-e397. doi: 10.1016/j.amjmed.2020.10.045. Epub 2020 Dec 11.
Abstract/Text
Al Jandale O, Jumah H, Jamil H.
Hepatitis A virus infection is complicated by both pancytopenia and autoimmune hemolytic anemia (AIHA).
Ann Med Surg (Lond). 2022 Jun;78:103765. doi: 10.1016/j.amsu.2022.103765. Epub 2022 May 11.
Abstract/Text
INTRODUCTION: Hepatitis A infection affects liver tissue primarily and might have some extrahepatic manifestations. Hematologically, the extrahepatic manifestations include aplastic anemia, red cell aplasia, and thrombocytopenia. There were reports about pancytopenia among patients with Hepatitis A infections, however, its association with autoimmune hemolytic anemia is rare as in our case.
CASE PRESENTATION: A 30-year-old male visited the emergency room with tiredness, unmeasured fever, and jaundice. He also mentioned that recently he had anorexia and weight loss without night sweating. Initial laboratory findings showed pancytopenia and marked elevation of AST and ALT. Direct Coombs and IgM anti-Hepatitis A virus were positive. Consequently, he was diagnosed with HAV complicated by both pancytopenia and AIHA and treated with prednisone (1 mg/kg) leading to significant improvement in his anemia.
DISCUSSION: This report describes a case of acute viral hepatitis A complicated with severe autoimmune hemolytic anemia and pancytopenia, which was successfully treated by high dose (1 mg/kg/day) prednisolone therapy.
CONCLUSION: This case represents a rare case in the literature review that can increase the awareness of the wide range of complications of HAV and its association with pancytopenia and AIHA.
© 2022 The Authors.
Onaga M, Hayashi K, Nishimagi T, Nagata K, Uto H, Kubuki Y, Hirono S, Tsubouchi H.
A case of acute hepatitis A with marked hemophagocytosis in bone marrow.
Hepatol Res. 2000 Jun;17(3):205-211. doi: 10.1016/s1386-6346(99)00076-5.
Abstract/Text
A previously well 18-year-old female was referred to our hospital because of abnormalities of blood biochemistry and slight jaundice. Because serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were elevated more than 6000 IU/L, the patient was suspected to have acute viral hepatitis. The platelet count on admission was 9.7x10(4)/µl, which was decreased from the initial value of 21x10(4)/µl for 3 days. The coagulation tests revealed marked elevation of D-dimmer, fibrinogen degradation products and thrombin-antithrombin III complex suggesting increase in fibrinolysis. Serum levels of high density lipoprotein cholesterol and ferritin were markedly decreased and increased, respectively. The bone marrow smears revealed proliferation of mature histiocytes ingesting platelets and erythrocytes, these pathological findings were consistent with those of hemophagocytic syndrome (HPS). In addition, anti-hepatitis A IgM antibody in the serum and hepatitis A virus (HAV) RNA in the stool were positive. Therefore, the patient was diagnosed as having acute hepatitis A with probable HPS. Since a fulminant clinical course was suspected, glucocorticoid pulse therapy was started immediately 7 days after onset and a favorable clinical outcome resulted.
Ide T, Sata M, Nouno R, Yamashita F, Nakano H, Tanikawa K.
Clinical evaluation of four cases of acute viral hepatitis complicated by pure red cell aplasia.
Am J Gastroenterol. 1994 Feb;89(2):257-62.
Abstract/Text
Four patients with acute viral hepatitis complicated by pure red cell aplasia were clinically evaluated. Two patients with hepatitis type A, one with hepatitis type B, and one with posttransfusion non-A non-B hepatitis had pure red cell aplasia. Only the patient with posttransfusion hepatitis was female, and the mean age of the four patients was 37.8 yr (31-51 yr.) The mean interval from the onset of hepatitis to the appearance of pure red cell aplasia was 30.5 days (27-37 days), and the development of hematopoietic disorders coincided with decreases in transaminase levels. Laboratory findings included peak serum glutamate pyruvate transaminase levels of 1305-3160 KU and decreases in the prothrombin time to about 50% in the two patients with hepatitis type A. Pure red cell aplasia was successfully treated by prednisolone or transfusion in all patients.
Hao Y, Wang W, Jacobs BC, Qiao B, Chen M, Liu D, Feng X, Wang Y.
Antecedent infections in Guillain-Barré syndrome: a single-center, prospective study.
Ann Clin Transl Neurol. 2019 Dec;6(12):2510-2517. doi: 10.1002/acn3.50946. Epub 2019 Nov 12.
Abstract/Text
OBJECTIVE: To investigate the spectrum of antecedent infections in Chinese patients with Guillain-Barré syndrome (GBS) and analyze the infections-related clinical phenotypes locally.
METHODS: A prospective case-control study of 150 patients diagnosed with GBS and age- and sex-matched neurological and healthy controls was performed to investigate recent infections of 14 pathogens serologically and collect the clinical data during a follow-up of 12 months.
RESULTS: In total, 53% of patients with GBS had a positive serology for recent infection, including Campylobacter jejuni (27%), influenza A (17%) and B (16%), hepatitis A virus (5%), dengue virus (3%), cytomegalovirus (3%), Epstein-Barr virus (3%), Mycoplasma pneumoniae (2%), herpes simplex virus (2%), varicella-zoster virus (1%), and rubella virus (1%). Serology for infections of hepatitis E virus, Haemophilus influenzae, and Zika virus was negative. There was a higher frequency of C. jejuni, influenza A, influenza B, and hepatitis A virus infections in GBS patients than both the neurological and healthy controls. C. jejuni infection was more frequent in younger GBS patients and was associated with antibodies against GM1, GalNAc-GD1a, and GM1:galactocerebroside complex. Influenza B infection was associated with a pure motor form of GBS.
INTERPRETATION: C. jejuni, influenza A, influenza B, and hepatitis A virus serve as the most common cause of antecedent infections in GBS locally. Influenza B-related GBS may represent a pure motor phenotype. Differences in the infectious spectrum worldwide may contribute to the geographical clinical heterogeneity of GBS.
© 2019 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals, Inc on behalf of American Neurological Association.
Stübgen JP.
Neuromuscular complications of hepatitis A virus infection and vaccines.
J Neurol Sci. 2011 Jan 15;300(1-2):2-8. doi: 10.1016/j.jns.2010.09.015.
Abstract/Text
The hepatitis A virus (HAV) infects millions of people worldwide every year. Case histories report on various acute neuropathy syndromes in the context of acute HAV infection, but any causal link has not been established. Epidemiological data also cast doubt on the importance of HAV as a trigger for Guillain-Barré syndrome. The virtual absence of a chronic HAV-infected state likely explains the rare occurrence of extrahepatic immune-mediated diseases, including an absence of chronic autoimmune neuromuscular disorders. Several vaccines against HAV provide effective protection against natural infection. Isolated case histories report on an unconvincing association between HAV vaccination and neuropathy. Medical and epidemiological data show insufficient evidence to support a causal relationship between HAV vaccines and neuropathy syndromes. Aluminum hydroxide, a HAV vaccine adjuvant, is considered a trigger of the macrophagic myofasciitis syndrome. This review concludes that it seems unnecessary to routinely consider HAV infection or vaccination as triggers of neuromuscular diseases.
Copyright © 2010 Elsevier B.V. All rights reserved.
Nakao M, Nakayama N, Uchida Y, Tomiya T, Oketani M, Ido A, Tsubouchi H, Takikawa H, Mochida S.
Deteriorated outcome of recent patients with acute liver failure and late-onset hepatic failure caused by infection with hepatitis A virus: A subanalysis of patients seen between 1998 and 2015 and enrolled in nationwide surveys in Japan.
Hepatol Res. 2019 Aug;49(8):844-852. doi: 10.1111/hepr.13345. Epub 2019 May 29.
Abstract/Text
AIM: A nationwide survey of acute liver failure (ALF) and late-onset hepatic failure (LOHF) has revealed that the outcomes of recent patients whose diseases were caused by infection with hepatitis A virus (HAV) have worsened, compared with those of previously reported patients. The factors associated with this deterioration were evaluated.
METHODS: A total of 83 patients with HAV infection seen between 1998 and 2015 were enrolled. All the patients had a prothrombin time-international normalized ratio of 1.5 or more and hepatic encephalopathy of grade 2 or more severe. The demographic and clinical features of 45 patients seen prior to 2003 (cohort 1) and 38 patients seen during 2004 and thereafter (cohort 2) were compared.
RESULTS: Three and four patients in cohort 1 and cohort 2, respectively, received liver transplantations; the survival rates among the remaining patients were 56% for cohort 2 and 79% for cohort 1 (P < 0.05). The mean age (±standard deviation) of the patients was higher in cohort 2 than in cohort 1 (58 ± 11 vs. 48 ± 13 years; P < 0.01). The percentages of patients with underlying metabolic diseases were 22% in cohort 1 and 61% in cohort 2 (P < 0.01). Diabetic mellitus was more common among deceased patients than among rescued patients (29% vs. 8%; P < 0.05) among patients who did not receive liver transplantations, and a multivariate analysis revealed that patient age and disease type were significantly and independently associated with the outcome.
CONCLUSION: The outcomes of recent patients with ALF or LOHF caused by HAV infection have recently worsened mainly because of an increase in underlying metabolic diseases as a consequence of aging.
© 2019 The Japan Society of Hepatology.
Sainokami S, Abe K, Ishikawa K, Suzuki K.
Influence of load of hepatitis A virus on disease severity and its relationship with clinical manifestations in patients with hepatitis A.
J Gastroenterol Hepatol. 2005 Aug;20(8):1165-75. doi: 10.1111/j.1440-1746.2005.03908.x.
Abstract/Text
BACKGROUND AND AIM: The purpose of the present study was to investigate the influence of viral load on disease severity and analyze the possible relationship of the load of hepatitis A virus (HAV) with disease severity and laboratory findings.
METHODS: Fifty-eight patients diagnosed with acute hepatitis A were used in the current study, of whom 12 patients progressed to severe acute hepatitis (s-AH) defined on the basis of a prothrombin time (PT) of <40% and 46 patients were diagnosed as having mild acute hepatitis (m-AH). The load of HAV was measured with real-time polymerase chain reaction.
RESULTS: Peak viral load showed a significant correlation with alanine aminotransferase (ALT) (r = 0.363, P = 0.0048) and PT levels (r = -0.330, P = 0.0110). In terms of disease severity, there was a significant correlation with ALT (r = 0.462, P = 0.0012) and PT levels (r = 0.400, P = 0.0059) in the m-AH group, but not in the s-AH group. A significant positive correlation of peak viral load with the C-reactive protein level (r = 0.270, P = 0.0400) and a significant negative correlation of peak viral load with the platelet count (r = -0.313, P = 0.0015) was also found.
CONCLUSIONS: The load of HAV was closely correlated with liver damage and disease severity in m-AH, but not in s-AH. The load of HAV was also closely associated with the increase in C-reactive protein level and enhancement of thrombocytopenia.
Hussain Z, Husain SA, Almajhdi FN, Kar P.
Immunological and molecular epidemiological characteristics of acute and fulminant viral hepatitis A.
Virol J. 2011 May 23;8:254. doi: 10.1186/1743-422X-8-254. Epub 2011 May 23.
Abstract/Text
BACKGROUND: Hepatitis A virus is an infection of liver; it is hyperendemic in vast areas of the world including India. In most cases it causes an acute self limited illness but rarely fulminant. There is growing concern about change in pattern from asymptomatic childhood infection to an increased incidence of symptomatic disease in the adult population.
OBJECTIVE: In-depth analysis of immunological, viral quantification and genotype of acute and fulminant hepatitis A virus.
METHODS: Serum samples obtained from 1009 cases of suspected acute viral hepatitis was employed for different biochemical and serological examination. RNA was extracted from blood serum, reverse transcribed into cDNA and amplified using nested PCR for viral quantification, sequencing and genotyping. Immunological cell count from freshly collected whole blood was carried out by fluorescence activated cell sorter.
RESULTS: Fulminant hepatitis A was mostly detected with other hepatic viruses. CD8+ T cells count increases in fulminant hepatitis to a significantly high level (P = 0.005) compared to normal healthy control. The immunological helper/suppressor (CD4+/CD8+) ratio of fulminant hepatitis was significantly lower compared to acute cases. The serologically positive patients were confirmed by RT-PCR and total of 72 (69.2%) were quantified and sequenced. The average quantitative viral load of fulminant cases was significantly higher (P < 0.05). There was similar genotypic distribution in both acute and fulminant category, with predominance of genotype IIIA (70%) compared to IA (30%).
CONCLUSIONS: Immunological factors in combination with viral load defines the severity of the fulminant hepatitis A. Phylogenetic analysis of acute and fulminant hepatitis A confirmed genotypes IIIA as predominant against IA with no preference of disease severity.
Yoshida Y, Okada Y, Suzuki A, Kakisaka K, Miyamoto Y, Miyasaka A, Takikawa Y, Nishizawa T, Okamoto H.
Fatal acute hepatic failure in a family infected with the hepatitis A virus subgenotype IB: A case report.
Medicine (Baltimore). 2017 Sep;96(35):e7847. doi: 10.1097/MD.0000000000007847.
Abstract/Text
RATIONALE: Hepatitis A viral infection is a well-known cause of subclinical or acute self-limited hepatitis. Few cases of hepatitis A virus (HAV)-associated acute liver failure (ALF) have been reported in low HAV endemic countries annually.
PATIENTS CONCERNS: To investigate the possible factors that affected the severity of HAV infection, a family cluster infected with the HAV subgenotype IB strain, which is not common in Japan, was described.
DIAGNOSES: This family consisted of five members who all were infected with HAV.
INTERVENTIONS: Four of the five patients hospitalized except for an asymptomatic patient.
OUTCOMES: Two of the five patients, men in their 50s and 60s, developed ALF, and one patient died. Various host factors, including sex (male), age, and a high bilirubin level, may affect the outcomes. Based on viral factors, HAV RNA was higher in the fatal case compared with others, and it decreased within a short period of time. The similarity of the nucleotide sequences was 99.9% among the HAV isolates based on an entire genomic sequence. Deletions and/or insertions on the HAV protein-coding sequences that caused a frameshift were found in surviving cases but not in the fatal case.
LESSONS: The rapid clearance of increased HAV and the absence of defective HAV might be closely associated with the onset of liver failure.
Fujiwara K, Kojima H, Yonemitsu Y, Yasui S, Imazeki F, Miki M, Suzuki K, Sakaida I, Okita K, Tanaka E, Omata M, Yokosuka O.
Phylogenetic analysis of hepatitis A virus in sera from patients with hepatitis A of various severities.
Liver Int. 2009 Jul;29(6):838-45. doi: 10.1111/j.1478-3231.2008.01919.x. Epub 2008 Nov 25.
Abstract/Text
BACKGROUND: We analysed the association of the 5' nontranslated region (5'NTR), nonstructural proteins 2B and 2C of the hepatitis A virus (HAV) genome, whose mutations have previously been shown to be important for enhanced replication in cell culture systems, in order to align all our data and examine whether genomic differences in HAV are responsible for the range of clinical severities.
METHODS: Our accumulated HAV strains of 5'NTR [nucleotide(nt) 200 and 500], entire 2B and 2C from 25 Japanese patients with sporadic hepatitis A, consisting of seven patients with fulminant hepatitis (FH), five with severe acute hepatitis (AHs) and 13 with self-limited acute hepatitis (AH), in whom the sequences of all three regions were available, were subjected to phylogenetic analysis.
RESULTS: Fulminant hepatitis patients had fewer nucleotide substitutions in 5'NTR, had a tendency to have more amino acid (aa) substitutions in 2B and had fewer aa substitutions in 2C than AH patients. Four FH and two AHs with a higher viral replication were located in the near parts of the phylogenetic trees, indicating the association between the severity of hepatitis A and genomic variations in 5'NTR, 2B and 2C of HAV.
CONCLUSIONS: Our study suggests that genetic variations in HAV not in one specific region but in 5'NTR, 2B and 2C might cooperatively influence replication of the virus, and thereby affect virulence. Viral factors should be considered and examined when discussing the mechanisms responsible for the severity of hepatitis A.
Spada E, Genovese D, Tosti ME, Mariano A, Cuccuini M, Proietti L, Giuli CD, Lavagna A, Crapa GE, Morace G, Taffon S, Mele A, Rezza G, Rapicetta M.
An outbreak of hepatitis A virus infection with a high case-fatality rate among injecting drug users.
J Hepatol. 2005 Dec;43(6):958-64. doi: 10.1016/j.jhep.2005.06.012. Epub 2005 Jul 11.
Abstract/Text
BACKGROUND/AIMS: In 2002, the first reported outbreak of hepatitis A virus (HAV) infection involving mostly intravenous drug users (IDU) occurred in Italy. We attempted a thorough evaluation of the outbreak, including epidemiological, clinical and virological analyses.
METHODS: We conducted an epidemiological investigation, including a case-control study, to identify the source and the modes of HAV transmission. Hepatitis B and C (HCV) viruses and human immunodeficiency virus (HIV) coinfections were clinically analysed. Sequence analysis of the VP1/2A junction of the HAV isolates was also performed.
RESULTS: Of the 47 symptomatic cases, 35 were IDUs. The only associated risk factor was contact (not related to injecting practices) with a jaundiced person (odds ratio: 5.8; 95% confidence interval: 1.3-29.9). Of the cases, 58% were anti-HCV positive and 4.7% anti-HIV positive. Three individuals died of acute liver failure: 2 were HCV-coinfected alcohol abusers, with underlying liver cirrhosis; 1 was HCV/HIV-coinfected. HAV-RNA was found in 15 of the 24 tested patients: genotype IB (8 cases) and IIIA (7 cases) were detected.
CONCLUSIONS: HAV was probably transmitted through the fecal-oral route, although parenteral transmission cannot be excluded. The high fatality rate was probably due to severe underlying liver damage. The occurrence of this outbreak highlights the need for routine HAV vaccination for IDUs.
Pramoolsinsap C.
Acute hepatitis A and acquired immunity to hepatitis A virus in hepatitis B virus (HBV) carriers and in HBV- or hepatitis C virus-related chronic liver diseases in Thailand.
J Viral Hepat. 2000 May;7 Suppl 1:11-2. doi: 10.1046/j.1365-2893.2000.00017.x.
Abstract/Text
A number of studies have suggested that the clinical course of hepatitis A virus (HAV) infection is more severe in patients with chronic liver disease (CLD). A study was undertaken to determine the impact of acute HAV in asymptomatic hepatitis B surface antigen (HBsAg) carriers (n = 20) and patients with hepatitis B virus (HBV)-(n = 8) or hepatitis C virus (HCV)-related (n = 4) CLD. Disease progression was compared with that in 100 patients with isolated HAV infection. No patient with HAV infection alone developed complications, and all recovered fully. Fulminant or submassive hepatitis occurred in 55% of HBsAg carriers and 33% of patients with HBV- or HCV-related CLD. The mortality rate in HBsAg carriers (25%) was not significantly different from that in the patients with CLD (33%). The seroprevalence of anti-HAV immunoglobulin G in 820 individuals was also determined. Approximately 50% of the individuals had acquired HAV infection between the ages of 21 and 30 years. It was demonstrated that HAV infection may have a more severe clinical course in patients with underlying CLD, particularly among older individuals. Vaccination for such patients should be considered.
Keeffe EB.
Is hepatitis A more severe in patients with chronic hepatitis B and other chronic liver diseases?
Am J Gastroenterol. 1995 Feb;90(2):201-5.
Abstract/Text
There are several published case series of acute hepatitis A, with coverage ranging from epidemics to case reports, that provide information regarding the clinical course and outcome of hepatitis A in patients with underlying chronic hepatitis B virus (HBV) infection (1-12). Only a few reports have addressed the outcome of hepatitis A in patients with other chronic liver diseases (2, 13). Some, but not all, of these reports suggest that hepatitis A superimposed on chronic hepatitis B or other chronic liver diseases is associated with higher peak laboratory abnormalities, more severe disease, including fulminant hepatic failure, and a higher case fatality rate. In addition, analysis of HBsAg titer and serum markers of HBV replication, including HBeAg, HBV DNA, and DNA polymerase, reveals suppression of HBV replication. With the availability of hepatitis A virus (HAV) vaccine in many countries and its imminent approval for use in the United States, the issue of whether or not patients with chronic liver diseases, including chronic HBV infection, should be a target group for vaccination to prevent hepatitis A warrants consideration. The purpose of this review is to analyze the published literature addressing the clinical course and outcome of acute hepatitis A in patients with chronic HBV infection and other chronic liver diseases to determine if hepatitis A is more severe in these patients.
Fujiwara K, Yasui S, Yonemitsu Y, Mikata R, Arai M, Kanda T, Imazeki F, Oda S, Yokosuka O.
Efficacy of high-dose corticosteroid in the early stage of viral acute liver failure.
Hepatol Res. 2014 May;44(5):491-501. doi: 10.1111/hepr.12148. Epub 2013 May 22.
Abstract/Text
AIM: Acute liver failure (ALF) is a worldwide problem despite its rare incidence because of its extremely high mortality. There are no beneficial therapies except for emergency liver transplantation for ALF. However, in Japan where the problem of a shortage of donor livers still remains, therapies other than transplantation must be further investigated for patients with ALF. Our aim was to elucidate the efficacy of high-dose corticosteroid (CS) in decreasing liver enzyme levels in the early stage of ALF.
METHODS: Thirty-one consecutive Japanese patients with viral ALF in the early stage were prospectively examined for their clinical and biochemical features and treatment responses during 2 weeks after the start of treatment. Nineteen were treated with high-dose methylprednisolone, and 12 having clinical and biochemical backgrounds with no significant difference were treated without CS.
RESULTS: The aspartate aminotransferase : alanine aminotransferase ratio became lower in patients treated with CS than in controls (P < 0.05). Fifteen of 19 patients in the CS group and eight of 12 in the control group recovered (P = 0.36). Hepatitis B viral infection and advanced liver damage at the start of treatment were associated with poor prognosis (P < 0.05). Complications during the therapy were not greater in the CS group than control (P = 0.64).
CONCLUSION: The introduction of high-dose CS in the early stage of ALF was effective in suppressing the destruction of hepatocytes. CS-treated patients showed slightly higher survival rates and slightly more improved liver regeneration than controls, although the differences were not statistically significant.
© 2013 The Japan Society of Hepatology.
Fujiwara K, Abe R, Yasui S, Yokosuka O, Kato N, Oda S.
High recovery rate of consciousness by high-volume filtrate hemodiafiltration for fulminant hepatitis.
Hepatol Res. 2019 Feb;49(2):224-231. doi: 10.1111/hepr.13255. Epub 2018 Nov 9.
Abstract/Text
AIM: An artificial liver support (ALS) system sustaining patients with acute liver failure (ALF) in good condition until recovery of the native liver or performance of liver transplantation (LT), is essential for the improvement of the poor prognosis of ALF despite the lack of survival benefit. We aimed to investigate the efficacy of various ALS systems for fulminant hepatitis (FH) carried out in our liver unit so far, focusing on the restoration of consciousness from hepatic encephalopathy.
METHODS: One hundred and ten consecutive adult Japanese patients with FH admitted to Chiba University Hospital (Chiba, Japan) between 1988 and 2016 who received ALS were analyzed.
RESULTS: Recovery rate of consciousness improved with the increased dialysate flow rate and filtrate rate: 37.5% by plasma exchange (PE), 51.9% by PE + continuous hemodiafiltration (CHDF), 57.7% by slow PE (sPE) + high-flow CHDF (HFCHDF) (QD = 300 mL/min), 88.6% by HFCHDF (QD = 500 mL/min) (+ sPE), and 92.9% by on-line HDF (OLHDF) (+ sPE). All patients except one, who could not be fully treated because of circulatory failure, recovered consciousness by OLHDF, including those whose liver function were completely abolished. Superiority of HFCHDF (QD = 500 mL/min) and OLHDF was also shown in patients who died without LT or received LT.
CONCLUSIONS: More effective ALS should be recognized considering the extremely high recovery rate of consciousness. In particular, OLHDF with predilution reduces the cost of substitution fluid by supplying an unlimited amount of dialysate as substitution fluid prepared using an on-line system, and simplifies the procedure for the management.
© 2018 The Japan Society of Hepatology.
Nakada TA, Oda S, Abe R, Hattori N.
Changes in acute blood purification therapy in critical care: republication of the article published in the Japanese Journal of Artificial Organs.
J Artif Organs. 2020 Mar;23(1):14-18. doi: 10.1007/s10047-019-01113-7. Epub 2019 Jun 24.
Abstract/Text
Acute blood purification therapy is an essential artificial organ in critical care. In the review article, looking back on the history, we describe our present knowledge and techniques of acute blood purification therapy in critical care. The topics include continuous hemodiafiltration (CHDF), online HDF as an artificial liver support, blood purification therapy aiming to remove pathogenic substances of sepsis, a procedure for connecting a CRRT device into an extra-corporeal membrane oxygenation circuit, and replacement fluid for CHDF. We also raise remaining issues and clarify the future direction of acute blood purification therapy in critical care. This review was created based on a translation of the Japanese review written in the Japanese Journal of Artificial Organs in 2017 (Vol. 46, No. 1, pp. 67-70), with adding some references.
Uemoto S, Inomata Y, Sakurai T, Egawa H, Fujita S, Kiuchi T, Hayashi M, Yasutomi M, Yamabe H, Tanaka K.
Living donor liver transplantation for fulminant hepatic failure.
Transplantation. 2000 Jul 15;70(1):152-7.
Abstract/Text
BACKGROUND: Living donor liver transplantation (LDLT) was originally indicated only for elective cases of pediatric patients with end-stage liver disease. In Japan, however, where liver transplantation from brain-dead donor is performed very rarely, this indication has been expanded to emergency cases such as fulminant hepatic failure (FHF).
METHODS: Thirty-eight patients with FHF were treated between May 1992 and April 1999. Causes of acute liver failure were non-A, non-B hepatitis in 27 patients, hepatitis B virus in seven, and hepatitis A virus, Epstein-Barr virus, herpes simplex virus, and chrome poisoning in one each.
RESULTS: Four patients did not undergo LDLT because of severe brain damage or combined multiple organ failure. The remaining 34 patients underwent a total of 36 LDLTs, including two retransplantations; 16 children received transplants of 17 lateral segments, three children and eight adults transplants of 11 left lobes, and seven adults transplants of eight right lobes. A total of 15 recipients died, four of primary graft dysfunction, three of refractory acute rejection, two of pneumonia, and one each of ductopenic rejection, sepsis, aplastic anemis, recurrence of Epstein-Barr virus hepatitis, multiple organ failure by chrome poisoning, and unknown hepatic failure. Primary graft dysfunction developed in adult recipients with small-for-size graft transplants, whereas refractory acute rejection and ductopenic rejection occurred in six grafts each of children with non-A, non-B FHF.
CONCLUSIONS: LDLT can be safely expanded to cases of FHF in adult patients. Primary graft dysfunction in adult recipients with small-for-size left lobe grafts can be overcome by using right lobes. However, refractory acute rejection and ductopenic rejection in children remain a major problem.
Sato S, Suzuki K, Takikawa Y, Endo R, Omata M; Japanese National Study Group of Fulminant Hepatitis.
Clinical epidemiology of fulminant hepatitis in Japan before the substantial introduction of liver transplantation: an analysis of 1309 cases in a 15-year national survey.
Hepatol Res. 2004 Nov;30(3):155-161. doi: 10.1016/j.hepres.2004.08.003.
Abstract/Text
BACKGROUND:: The low incidence of fulminant hepatitis (FH) makes it difficult to accurately assess its viral etiology and clinical characteristics. Additionally, the therapeutic options for FH have markedly changed over the years because of the substantial introduction of living-donor liver transplantation. AIM:: To analyze and summarize a large-scale national survey on FH in the pretransplantation era in Japan. METHOD:: An analysis of answers to an annual questionnaire sent to 313 centers for liver diseases in Japan between 1983 and 1997. RESULTS:: During the study period, 1309 patients were registered as having fulminant hepatitis. The causes of FH were: hepatitis A virus (HAV) in 7.8%, hepatitis B virus (HBV) in 23.8%, probable HBV (positive for serum HBs antigen or HBV DNA and negative for the IgM anti-hepatitis B core antibody) in 13.8%, non-A, non-B hepatitis in 29.3%, drug-induced in 9.3, and unknown in 16.0% of these patients. The incidence of HBV-related cases did not decrease during the study period. The acute type had a significantly better prognosis than the subacute type (survival rate, 36.2% versus 15.3%, P < 0.001). The survival rate tended to improve in the third 5-year period for the acute type (28.6% [1983-1987] versus 43.3% [1994-1997]), but not for the subacute type (15.4% versus 12.3%). CONCLUSIONS:: HBV remains a major cause of fulminant hepatitis in Japan. New therapeutic modalities, including liver transplantation, are required for improving the prognosis, in particular, for the subacute type of fulminant hepatitis.
Kim HW, Yu MH, Lee JH, Chang JW, Yang WS, Kim SB, Lee SK, Park JS, Park SK.
Experiences with acute kidney injury complicating non-fulminant hepatitis A.
Nephrology (Carlton). 2008 Dec;13(6):451-8. doi: 10.1111/j.1440-1797.2008.00974.x. Epub 2008 Jun 1.
Abstract/Text
AIM: To describe the clinical features and to identify factors related to development of acute kidney injury in acute hepatitis A patients.
METHODS: The study and control groups consisted of 21 and 425 patients who did or did not develop acute kidney injury, respectively, after acute hepatitis A from January 1997 to May 2007.
RESULTS: There were 13 men and eight women; their mean age at diagnosis was 28.8 +/- 8.2 years in the study group. Peak values for renal and liver function impairment consisted of a median serum creatinine of 4.6 mg/dL (range, 1.5-15.3 mg/dL) on day 6 (range, days 1-20) and a median total bilirubin of 10.7 mg/dL (range, 2.6-57.5 mg/dL) on day 8 (range, day 1-19). Serum creatinine concentrations returned to baseline level by a median of 16 days and total bilirubin levels returned to normal by a median of 62 days. Six of 21 (29%) patient underwent haemodialysis. Renal biopsies performed in two patients showed acute tubular necrosis and interstitial nephritis, respectively. Logistic regression analysis showed that a lower haematocrit, the presence of coagulopathy and high C-reactive protein concentration on admission, and higher peak bilirubin value during the illness were associated with development of acute kidney injury.
CONCLUSION: Acute hepatitis A should be considered in the differential diagnosis of patients with acute kidney injury, even without fulminant hepatic failure. A lower haematocrit, the presence of coagulopathy and high C-reactive protein level at presentation, and higher peak bilirubin level during the illness were associated with development of acute kidney injury in acute hepatitis A patients.
Locarnini S.
A virological perspective on the need for vaccination.
J Viral Hepat. 2000 May;7 Suppl 1:5-6. doi: 10.1046/j.1365-2893.2000.00020.x.
Abstract/Text
Superinfecton of chronic carriers of hepatitis B virus (HBV) or hepatitis C virus (HCV) with hepatitis A virus (HAV) is often associated with more severe liver disease than infection with HAV alone. Superinfection commonly causes markers of HBV and HCV replication to fall to significantly lower levels. The pathogenesis of acute liver damage characteristic of viral hepatitis is thought to be mediated by host cytotoxic T-lymphocytes (CTLs) directed against virus-infected hepatocytes. It has been proposed that the more aggressive liver disease observed in individuals infected with HAV in addition to chronic HBV/HCV is a result of the induction of interferon (IFN)-alpha during acute HAV infection. This accounts for the antiviral effect on the active markers of HBV/HCV replication, and the enhanced CTL response against HBV/HCV-infected hepatocytes. Alternatively, HAV may indirectly stimulate the T helper 1 (Th1)-type cytokine responses, such as interleukin (IL)-2, IFN-gamma and tumour necrosis factor (TNF)-alpha, which directly promote the antiviral CTL response. Clearance of HBV infection, and possible HAV and HCV, is associated with a specific CTL response, while viral persistence in chronic HBV and HCV infection has been attributed to an imbalance in the Th1-Th2 arms of the immune response. Vaccination against hepatitis A should be considered for patients with chronic HBV/HCV infection, to minimize the risk of exacerbating underlying liver disease.
Baba M, Hasegawa H, Nakayabu M, Fukai K, Suzuki S.
Cytolytic activity of natural killer cells and lymphokine activated killer cells against hepatitis A virus infected fibroblasts.
J Clin Lab Immunol. 1993;40(2):47-60.
Abstract/Text
The role of Natural Killer (NK) cells, Lymphokine Activated Killer (LAK) cells and the induction of cytokines in the hepatocellular injury of hepatitis A were studied in vitro using a 51Cr release assay in hepatitis A virus (HAV) infected MRC-5 cells (MRC-HAV). When fresh peripheral mononuclear cells (PBMC) from healthy, anti-HAV antibody (-) and (+) human donors, or patients with acute hepatitis A were used as effector cells, MRC-HAV were lysed more extensively than uninfected cells. Similarly, in models using recombinant interleukin-2 (rIL-2) pretreated PBMC from HAV antibody (-) and (+) donors or patients with hepatitis A as effector cells, MRC-HAV were lysed more extensively than uninfected MRC. Both fresh PBMC and rIL-2 pretreated PBMC from anti-HAV antibody (+) donor lysed MRC-HAV cells more effectively than PBMC collected from anti-HAV antibody (-) patients. PBMC from patients with hepatitis A during the acute phase demonstrated more severe lysis of both uninfected MRC and MRC-HAV target cells. However, MRC-HAV lysis was enhanced to a greater degree. In an attempt to identify which cells were involved in cell lysis, cytotoxicity assays were performed by separating PBMC by cell sorter using monoclonal antibodies against all T cells, NK and B-cell fractions and culturing each with supplemental rIL-2. The NK cell fraction selectively destroyed MRC-HAV, but the lytic activity of both the pan T-cell and B-cell fractions was too weak to demonstrate any significant difference. Therefore, NK-LAK cells appeared to play a more significant role in cytolysis than did T-LAK cells. Morphologic observations of cellular damage were accomplished with PBMC obtained from healthy anti-HAV antibody (+) donors. PBMC were suspended in media containing rIL-2 and incubated for 4 days on monolayers of uninfected MRC and MRC-HAV. IFN-alpha and IFN-gamma in the supernatant of the cultured media were simultaneously assayed. Severe damage to HAV-infected cells was observed. Moreover, strong induction of IFN-alpha and IFN-gamma was found with high levels measured in the supernatant. Therefore, it is likely that non-specific immune mechanisms involving NK and LAK cells play a central role in hepatocellular damage prior to the initiation of damage due to Cytotoxic T Lymphocytes (CTL).
Elinav E, Ben-Dov IZ, Shapira Y, Daudi N, Adler R, Shouval D, Ackerman Z.
Acute hepatitis A infection in pregnancy is associated with high rates of gestational complications and preterm labor.
Gastroenterology. 2006 Apr;130(4):1129-34. doi: 10.1053/j.gastro.2006.01.007.
Abstract/Text
BACKGROUND & AIMS: Hepatitis A virus (HAV) infection is the most common cause of acute hepatitis but is rarely reported during pregnancy. Our aim was to evaluate the impact of acute HAV infection on pregnancy outcome.
METHODS: Consecutive admissions of 79,458 pregnant females during a 25-year period were retrospectively reviewed.
RESULTS: Thirteen cases of second and third trimester HAV infection were found and evaluated. Nine of the 13 patients (69%) developed gestational complications, including premature contractions (n = 4), placental separation (n = 2), premature rupture of membranes (n = 2), and vaginal bleeding (n = 1). In 8 of these patients, complications led to preterm labor, at a median of 34 gestational weeks (range, 31-37 weeks). Delivery was vaginal in 12 of the 13 cases; fetal distress was noted in a single case, and meconium in amniotic fluid in 2 cases. Median birth weight was 1778 grams and 3040 grams in preterm and term deliveries, respectively (P < .05). Child outcome was favorable in all cases. In 4 cases, neonatal serum HAV RNA levels were measured and found negative. The presence of fever and hypoalbuminemia were associated with delivery at an earlier gestational week. There was a positive relation between gestational week at diagnosis of HAV infection and birth week (r = 0.68, P = .02), suggesting a causality relationship. All mothers featured full recovery from HAV infection.
CONCLUSIONS: Acute HAV infection during pregnancy is associated with high risk of maternal complications and preterm labor. HAV serology and maternal vaccination during prepregnancy evaluation should be considered in areas of the world in which susceptible adult populations exist.
Urganci N, Arapoglu M, Akyildiz B, Nuhoğlu A.
Neonatal cholestasis resulting from vertical transmission of hepatitis A infection.
Pediatr Infect Dis J. 2003 Apr;22(4):381-2. doi: 10.1097/00006454-200304000-00023.
Abstract/Text
Tejada-Strop A, Costafreda MI, Dimitrova Z, Kaplan GG, Teo CG.
Evaluation of Potencies of Immune Globulin Products Against Hepatitis A.
JAMA Intern Med. 2017 Mar 1;177(3):430-432. doi: 10.1001/jamainternmed.2016.9057.
Abstract/Text
Nelson NP.
Updated Dosing Instructions for Immune Globulin (Human) GamaSTAN S/D for Hepatitis A Virus Prophylaxis.
MMWR Morb Mortal Wkly Rep. 2017 Sep 15;66(36):959-960. doi: 10.15585/mmwr.mm6636a5. Epub 2017 Sep 15.
Abstract/Text
GamaSTAN S/D (Grifols Therapeutics, Inc., Research Triangle Park, North Carolina) is a sterile, preservative-free solution of immune globulin (IG) for intramuscular administration and is used for prophylaxis against disease caused by infection with hepatitis A, measles, varicella, and rubella viruses (1). GamaSTAN S/D is the only IG product approved by the Food and Drug Administration for hepatitis A virus (HAV) prophylaxis. In July 2017, GamaSTAN S/D prescribing information was updated with changes to the dosing instructions for hepatitis A preexposure and postexposure prophylaxis indications. These changes were made because of concerns about decreased HAV immunoglobulin G antibody (anti-HAV IgG) potency, likely resulting from decreasing prevalence of previous HAV infection among plasma donors, leading to declining anti-HAV antibody levels in donor plasma (2). No changes in dosing instructions were made for measles, varicella, or rubella preexposure or postexposure prophylaxis.
Van Herck K, Jacquet JM, Van Damme P.
Antibody persistence and immune memory in healthy adults following vaccination with a two-dose inactivated hepatitis A vaccine: long-term follow-up at 15 years.
J Med Virol. 2011 Nov;83(11):1885-91. doi: 10.1002/jmv.22200. Epub 2011 Aug 23.
Abstract/Text
Long-term persistence of vaccine-induced immune response in adults was assessed annually for 15 years following primary immunization with a two-dose inactivated hepatitis A vaccine. In 1992, 119 and 194 subjects aged 17-40 years and naïve for hepatitis A virus (HAV) were enrolled in two studies to receive 1,440 ELISA units (El.U) of inactivated hepatitis A vaccine (Havrix™, GlaxoSmithKline Biologicals, Belgium) according to a standard 0, 6 or an extended 0, 12 months schedule, respectively. Serum samples were taken 1 month after the second vaccine dose and every consecutive year up to 15 years after primary vaccination for measurement of anti-HAV antibody concentrations (NCT00291876 and NCT00289757). At year 15, 100% (48/48) and 97.3% (108/111) of subjects vaccinated at 0, 6 or 0, 12 months remained seropositive for anti-HAV antibodies, with geometric mean concentrations (GMCs) of 289.2 and 367.4 mIU/ml, respectively. An additional dose of HAV vaccine (1,440 El.U) was administered to the six subjects who had become seronegative for anti-HAV antibodies since year 11. All subjects mounted a humoral immune response to the additional HAV challenge dose, although post-challenge anti-HAV antibody levels remained low in one subject. These studies represent the longest annual follow-up of hepatitis A vaccine in healthy adults. The immune response induced by two doses of this inactivated HAV vaccine was shown to persist for at least 15 years. No difference in long-term antibody persistence was observed between the two primary vaccination schedules, reinforcing the potential for flexibility in the timing of the second primary vaccine dose.
Copyright © 2011 Wiley-Liss, Inc.
Sharapov UM, Bulkow LR, Negus SE, Spradling PR, Homan C, Drobeniuc J, Bruce M, Kamili S, Hu DJ, McMahon BJ.
Persistence of hepatitis A vaccine induced seropositivity in infants and young children by maternal antibody status: 10-year follow-up.
Hepatology. 2012 Aug;56(2):516-22. doi: 10.1002/hep.25687. Epub 2012 Jun 11.
Abstract/Text
UNLABELLED: Persistence of seropositivity conferred by hepatitis A vaccine administered to children <2 years of age is unknown and passively transferred maternal antibodies to hepatitis A virus (maternal anti-HAV) may lower the infant's immune response to the vaccine. One hundred ninety-seven infants and young children were randomized into three groups to receive a two-dose hepatitis A vaccine: group 1 at 6 and 12 months, group 2 at 12 and 18 months, and group 3 at 15 and 21 months of age. Within each group, infants were randomized by maternal anti-HAV status. Anti-HAV levels were measured at 1 and 6 months and at 3, 5, 7, and 10 years after the second dose of hepatitis A vaccination. Children in all groups had evidence of seroprotection (>10 mIU/mL) at 1 month after the second dose. At 10 years, all children retained seroprotective anti-HAV levels except for only 7% and 11% of children in group 1 born to anti-HAV-negative and anti-HAV-positive mothers, respectively, and 4% of group 3 children born to anti-HAV-negative mothers. At 10 years, children born to anti-HAV-negative mothers in group 3 had the highest geometric mean concentration (GMC) (97 mIU/mL; 95% confidence interval, 71-133 mIU/mL) and children born to anti-HAV-positive mothers in group 1 had the lowest GMC (29 mIU/mL; 95% confidence interval, 20-40 mIU/mL). Anti-HAV levels through 10 years of age correlated with initial peak anti-HAV levels (tested at 1 month after the second dose).
CONCLUSION: The seropositivity induced by hepatitis A vaccine given to children <2 years of age persists for at least 10 years regardless of presence of maternal anti-HAV.
Copyright © 2012 American Association for the Study of Liver Diseases.
Maki Y, Edo N, Mizuguchi M, Ikeda M, Kitano M, Kitagami E, Osa M, Yamamoto S, Ogawa T, Nakamura T, Kawana A, Kimizuka Y.
Impact of frequency and duration of freeze-dried inactivated tissue culture hepatitis A vaccine (Aimmugen®) vaccination on antibody titers; a japanese cross-sectional study.
Vaccine. 2023 Sep 22;41(41):5974-5978. doi: 10.1016/j.vaccine.2023.08.030. Epub 2023 Aug 22.
Abstract/Text
BACKGROUND: The effect of the timing of additional doses and the long-term persistence of lyophilized inactivated tissue culture hepatitis A (HA) vaccine (Aimmugen®) on antibodies is unknown.
METHODS: A single-center, cross-sectional, observational study was conducted in collaboration with the Japan Air Self-Defense Force, whose personnel were immunized with Aimmugen® when deployed to endemic areas. Patients who consented to this study after a medical examination with blood sampling between June 2022 and February 2023 were included; HA-IgG level in the residual serum was measured using the chemiluminescent immunoassay method. The exact vaccination history was investigated based on immunization records maintained by the Ministry of Defense, and a questionnaire was used to collect confounding factors.
RESULTS: Of the 181 participants observed, 49 were in the unvaccinated group, and 132 were in the vaccinated group. Out of the vaccinated group, 6.8 % received either one or two doses, 40.9 % received three doses, and 52.3 % received more than four doses. IgG antibody titers (S/CO value) in each group (0, 1 or 2, 3, and over 4) increased in a frequency-dependent manner, with those vaccinated over four times showing significantly higher IgG antibody titers than all other groups (0.19 ± 0.10 vs 3.66 ± 3.00 vs 7.63 ± 3.57 vs 10.57 ± 1.86, respectively). When the number of months elapsed from the last vaccination to the date of blood collection in each group was plotted against IgG antibody titer, the slope of the regression line flattened out from a decreasing trend in the order 1 or 2, 3, over 4.
CONCLUSIONS: Three doses of Aimmugen® are efficacious, but four or more doses induce more robust and sustained antibody production. Additionally, four or more doses may be effective when there is a need to ensure long-term immunity or risk of prolonged exposure.
Copyright © 2023 Elsevier Ltd. All rights reserved.
Pascoli F, Pezzuto A, Buratin A, Piovesana A, Fortin A, Arcangeli G, Toffan A.
Efficacy of domestic cooking inactivation of human hepatitis A virus in experimentally infected manila clams (Ruditapes philippinarum).
J Appl Microbiol. 2016 Oct;121(4):1163-71. doi: 10.1111/jam.13242. Epub 2016 Aug 28.
Abstract/Text
AIM: The aim of this work was to evaluate the efficacy of domestic cooking in inactivating Manila clams experimentally infected with human hepatitis A virus (HAV).
METHODS AND RESULTS: Electronic temperature probes were positioned to measure the internal temperature of Manila clams during domestic cooking. Two batches were infected with 10(7) and 10(5) TCID50 ml(-1) of HAV. The infected whole-in-shell clams were divided into three replicates and cooked on a conventional stove both singularly and in group and removed from the pan at fixed intervals. Pools of three digestive glands were examined by virus isolation for three blind passages and cell culture supernatant tested with real-time PCR.
CONCLUSION: Results showed that 2-min cooking by a traditional domestic method at a temperature close to 100°C, after the opening up of the valves of all the clams, can completely devitalize the HAV in high viral load-infected clams.
SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first study on inactivation of HAV in experimentally infected Manila clams subjected to domestic cooking. At present, labelling all lagoon products as 'requiring cooking before consumption' is highly recommended, but no specifications are given on how long and at what temperature they should be cooked. Considering the high commercial value of Manila clams, our results can provide both the producers and the consumer with useful indications on how to cook clams to prevent the risk of HAV foodborne illness.
© 2016 The Society for Applied Microbiology.
