We report herein a case with acute hepatitis due to hepatitis B virus genotype Ae, concurrent with
amebic colitis. A 39-year-old homosexual Japanese man was admitted to our hospital with jaundice.
Laboratory tests showed an elevation of transaminase and positivity for hepatitis B surface antigen and IgM-type antibody to hepatitis B core antigen. The hepatitis B virus genotype was determined to be Ae. Furthermore, a mud-like stool with blood and mucous had sometimes been noted during the
past 3 years, and amebic colitis was shown by colonofi berscopy during hospitalization. The patient was diagnosed with acute hepatitis B, concurrent with amebic colitis, and was successfully treated with lamivudine and metronidazole. In Japanese patients with acute hepatitis B virus genotype A infection, homosexual activity tends to be high. Furthermore, in Japanese homosexual men, amebiasis
has been increasing. Thus, in Japanese patients with acute hepatitis B, a determination of genotype should be performed in order to investigate the route of transmission of hepatitis B virus, and a search for amebiasis should be performed in patients with acute hepatitis due to hepatitis B virus genotype A. Furthermore, education of homosexual men regarding hepatitis B virus, hepatitis B
virus vaccination, and amebiasis is urgently required

Ishikawa, Shin

Iwasaki, Yoshiaki

Kato, Jun

Kobashi, Haruhiko

Miyake, Yasuhiro

Nawa, Toru

Sakaguchi, Kohsaku

Shiratori, Yasushi

Takaki, Akinobu

Tatsukawa, Masashi

Okayama University Scientific Achievement Repository

Acta Medica OkayamaVolume 61, Issue 1 2007 Article 5FEBRUARY 2007A homosexual japanese man with acutehepatitis due to hepatitis B virus genotype ae,concurrent with amebic colitisYasuhiro Miyake, Okayama UniversityYoshiaki Iwasaki, Okayama UniversityShin Ishikawa, Okayama UniversityMasashi Tatsukawa, Okayama UniversityToru Nawa, Okayama UniversityJun Kato, Okayama UniversityAkinobu Takaki, Okayama UniversityHaruhiko Kobashi, Okayama UniversityKohsaku Sakaguchi, Okayama UniversityYasushi Shiratori, Okayama UniversityCopyright c©1999 OKAYAMA UNIVERSITY MEDICAL SCHOOL. All rights reserved.A Homosexual Japanese Man with Acute Hepatitis Due to Hepatitis B Virus Genotype Ae,  Concurrent with Amebic ColitisYasuhiro Miyake＊,  Yoshiaki Iwasaki,  Shin Ishikawa,  Masashi Tatsukawa,  Toru Nawa,  Jun Kato,  Akinobu Takaki,  Haruhiko Kobashi,  Kohsaku Sakaguchi,  and Yasushi ShiratoriDepartment of Gastroenterology and Hepatology,  Okayama University Graduate School of Medicine,  Dentistry and Pharmaceutical Sciences,  Okayama 700ﾝ8558,  Japancute hepatitis B virus infection acquired in adulthood,  has been recognized to be self-lim-ited.  Hepatitis B virus DNA is successfully cleared in more than 95ｵ of adult patients with the acute infection [1].　　The hepatitis B virus genotype has been deter-mined to be associated with the clinical course of patients with acute hepatitis B.  Hepatitis B virus is classiﬁ ed into 8 genotypes exhibiting distinct geo-graphic distributions [2,  3].  Throughout East Asia, including Japan,  genotypes B and C are prevalent [2, 3].　　Recently,  infection with hepatitis B virus geno-type A,  which is prevalent in North Western Europe, North America,  and South Africa,  has become fre-quent in Japan.  In Japanese patients with acute hepa-titis B viral infection,  the proportion of patients infected with hepatitis B virus genotype A was AWe report herein a case with acute hepatitis due to hepatitis B virus genotype Ae,  concurrent with amebic colitis.  A 39-year-old homosexual Japanese man was admitted to our hospital with jaundice. Laboratory tests showed an elevation of transaminase and positivity for hepatitis B surface antigen and IgM-type antibody to hepatitis B core antigen.  The hepatitis B virus genotype was determined to be Ae.  Furthermore,  a mud-like stool with blood and mucous had sometimes been noted during the past 3 years,  and amebic colitis was shown by colonoﬁ berscopy during hospitalization.  The patient was diagnosed with acute hepatitis B,  concurrent with amebic colitis,  and was successfully treated with lamivudine and metronidazole.  In Japanese patients with acute hepatitis B virus genotype A infection,  homosexual activity tends to be high.  Furthermore,  in Japanese homosexual men,  amebia-sis has been increasing.  Thus,  in Japanese patients with acute hepatitis B,  a determination of geno-type should be performed in order to investigate the route of transmission of hepatitis B virus,  and a search for amebiasis should be performed in patients with acute hepatitis due to hepatitis B virus genotype A.  Furthermore,  education of homosexual men regarding hepatitis B virus,  hepatitis B virus vaccination,  and amebiasis is urgently required.Key words : hepatitis B virus,  genotype,  homosexual,  amebic colitis,  lamivudineActa Med.  Okayama,  2007Vol.  61,  No.  1,  pp.  35ﾝ39http ://www.lib.okayama-u.ac.jp/www/acta/CopyrightⒸ 2007 by Okayama University Medical School.Case ReportReceived March 17, 2006 ; accepted September 22, 2006. ＊Corresponding author. Phone : ＋81ﾝ86ﾝ235ﾝ7219 ; Fax : ＋81ﾝ86ﾝ225ﾝ5991E-mail : miyakeyasuhiro@hotmail.com (Y. Miyake)1Miyake et al.: A homosexual japanese man with acute hepatitis due toProduced by The Berkeley Electronic Press, 2007reported at 9ｵ prior to 1991,  but 55ｵ after 1991 [4].  Furthermore,  it has been reported that,  prior to 1991,  the main infectious route was post-transfu-sion hepatitis,  but thereafter has been sexual trans-mission [5].　　In this report,  we describe the case of a homo-sexual Japanese man with acute hepatitis due to hep-atitis B virus genotype Ae,  concurrent with amebic colitis,  who was successfully treated with lamivudine and metronidazole.Case Report　A 39-year-old Japanese man was admitted to our hospital on January 2005 due to jaundice,  general fatigue,  and anorexia.  The patient was a homosexual man,  who reported having sexual contact with multi-ple unidentiﬁ ed partners since the age of 33.  A mud-like stool with blood and mucous had sometimes been note during the past 3 years.  Ten days previously, the patient had a sore throat.  For the past week,  he had felt general fatigue and anorexia,  and for the past 5 days he had noticed the dark color of his urine.　　On physical examination at admission,  the patient’s consciousness was clear,  and the bulbar conjunctiva was icteric.  Neither ascites nor pretibial edema was recognized.  Laboratory data on admission were as follows : total bilirubin,  10.7 mg/dL ; aspar-tate aminotransferase,  1,507 IU/L ; alanine amino-transferase,  2,448 IU/L ; albumin,  4.5 g/dL ; and prothrombin activity,  89ｵ.  Tests for hepatitis B surface antigen and IgM-type antibody to hepatitis B core antigen were positive,  although in a medical checkup administered in June 2004,  hepatitis B sur-face antigen had tested negative.  Serum hepatitis C virus-RNA,  antibody to hepatitis C virus,  antibody to human immunodeﬁ ciency virus,  and Treponema pallidum hemagglutination tests were all negative. The patient was diagnosed with acute hepatitis B, and daily administration of 200 mg of lamivudine was initiated.　　The genotype of the hepatitis B virus was ana-lyzed using serum obtained on the day of admission and was stored at － 40 °C.  Informed consent for the analysis was obtained from the patient.  The genotype of the hepatitis B virus was determined based on the complete genome sequence [6,  7],  and was shown to be Ae.　　Two weeks later,  the patient’s serum alanine ami-notransferase levels began to decrease,  and his gen-eral fatigue and anorexia improved.  The dosage of lamivudine was reduced to 100 mg/day 3 weeks after the introduction of lamivudine treatment.  The nor-malization of serum levels of alanine aminotransami-nase was achieved 5 weeks after the introduction of lamivudine treatment.  Hepatitis B e antigen disap-peared from serum 12 weeks after the introduction of lamivudine treatment,  and hepatitis B surface antigen was cleared 7 months after the introduction of lamivudine treatment (Fig.  1).  However,  antibody to hepatitis B surface antigen did not develop 14 months after the introduction of lamivudine treat-ment,  and lamivudine treatment was continued.　　Meanwhile,  the peripheral hemoglobin concentra-tions fell gradually to 11.4 g/dL 4 weeks after admis-sion,  and colonoﬁ berscopy showed multiple ulcers covered with whitish exudates in the cecum (Fig. 2A).  Histological features showed mucosa with lym-phocytic and eosinophilic accumulations,  and tropho-zoites of Entamoeba histolytica ingesting red blood cells (Fig.  2C,  D).  The patient was diagnosed with amebic colitis,  and daily administration of 500 mg of metronidazole was initiated.  Colonoﬁ berscopy per-formed after 3 weeks showed normal cecal mucosa (Fig.  2B).  During the treatment of amebic colitis using metronidazole,  no aggravation of the transami-nases was recognized.Discussion　　In the present case,  the mode of transmission of hepatitis B virus was considered to be homosexual contact.  Sexual transmission of hepatitis B virus is frequent among homosexual men because multiple partnerships are common and anal sex is inherently more traumatic than vaginal intercourse,  fostering exposure to blood [8].  Thus,  immunization against hepatitis B virus is recommended for homosexual men.  However,  the present case did not know any-thing about hepatitis B virus or hepatitis B virus vaccination.  In Japan,  education of homosexual men regarding hepatitis B virus and hepatitis B virus vac-cination is urgently required.　　Recently in Japan,  approximately 30ﾝ40ｵ of men with acute hepatitis due to hepatitis B virus genotype 36 Acta Med.  Okayama　Vol.  61,  No.  1Miyake et al.2Acta Medica Okayama, Vol. 61 [2007], Iss. 1, Art. 5http://escholarship.lib.okayama-u.ac.jp/amo/vol61/iss1/5A are reported to be homosexual [4,  9].  Among the human immunodeﬁ ciency virus type 1-positive popula-tion in Japan,  approximately 90ｵ of homosexual men infected with hepatitis B virus have genotype A [10].  In patients with acute hepatitis B viral infec-tion,  a determination of genotype should be per-formed in order to investigate the route of transmis-sion of hepatitis B virus and to determine a medical treatment plan.　　It has been reported that acute hepatitis due to hepatitis B virus genotype A tends to be persistent, compared with that due to other genotypes,  and hep-atitis B surface antigen is cleared in only a small proportion of patients receiving lamivudine treat-ment,  although approximately half of these patients respond with a loss of hepatitis B e antigen [9]. However,  hepatitis B surface antigen was cleared with lamivudine treatment in the present case. Suzuki et al. [9] have reported that low maximum alanine aminotransferase levels ( ＜ 500 IU/L) are predictive of the perpetuation of acute hepatitis due to hepatitis B virus genotype A.  The clinical course of the present case was thus consistent with their report.　　Although a randomized,  prospective study of lamivudine in patients with acute hepatitis B has not been reported,  lamivudine treatment has been reported to be safe and well-tolerated in these 37A Homosexual Man with Acute Hepatitis BFebruary 2007ColonoﬁberscopyMetronidazole 500mg/dayALT (IU/L) Lamivudine 200mg/day 100mg/dayPT (%)T.Bil (mg/dL)PTALTT.Bil(weeks)Clinical course after admission3,0002,5002,0001,5001,00050000 4 8 12 16 20 24 28120100806040200HBs Ag (COI) 2000.0 (＋) 2000.0 (＋) 1018.8 (＋) 24.9 (＋) 1.1 (＋)  0.4 (－)anti-HBs (COI) 0.1 (－) 0.1 (－) 0.1 (－) 0.1 (－) 0.1 (－)  0.1 (－)HBe Ag (COI) 958.8 (＋) 13.0 (＋) 2.5 (＋) 0.2 (－) 0.1 (－)  0.1 (－)anti-HBe (%) 0.1 (－) 47.6 (－) 76.4 (＋) 91.8 (＋) 91.3 (＋) 88.8 (＋)HBV DNA (log10copies/mL) 6.8 3.7 3.3 ＜2.6  　 ＜2.6  　 ＜2.6  　Fig. 1　　Patient clinical course.  ALT,  alanine aminotransferase ; anti-HBe,  antibody to hepatitis B e antigen ; anti-HBs,  antibody to hepatitis B surface antigen ; COI,  cut oﬀ  index ; HBe Ag,  hepatitis B e antigen ; HBs Ag,  hepatitis B surface antigen ; HBV DVA, hepatitis B virus DNA ; PT,  prothrombin activity ; T.Bil,  total bilirubin.3Miyake et al.: A homosexual japanese man with acute hepatitis due toProduced by The Berkeley Electronic Press, 2007patients [11,  12].  Furthermore,  lamivudine treat-ment is considered to induce a prompt clinical,  bio-chemical,  serological,  and virological response in immunocompetent patients with acute hepatitis B [11, 12].  We considered that,  in patients with acute hep-atitis due to hepatitis B virus genotype A,  lamivu-dine should be administered upon diagnosis,  in order to prevent the progression of acute hepatitis to ful-minant hepatitis,  and to achieve a normalization of transaminase levels and a clearance of hepatitis B virus infection,  if they are not infected with a human immunodeﬁ ciency virus type 1.　　In the present case,  lamivudine treatment was continued even after hepatitis B surface antigen dis-appeared from serum.  Yotsuyanagi et al.  [13] have reported that,  in the serum of patients after recov-ery from acute hepatitis B,  free hepatitis B virus persists at low levels in the window period when both hepatitis B surface antigen and antibody to hepatitis B surface antigen are absent from serum,  although immunoglobulin-bound hepatitis B virus is predomi-nant,  and that free hepatitis B virus is not detectable after the seroconversion to antibody to hepatitis B surface antigen.  The absence of free hepatitis B virus in serum generally indicates a loss of infectiv-ity.  Thus,  we consider that lamivudine treatment should be continued until a protective titer of anti-body to hepatitis B surface antigen develops.　　Amebiasis is the second leading cause of death from parasitic disease worldwide,  and an estimated 40,000ﾝ100,000 people die yearly from the disease [14].  Worldwide,  most individuals with amebiasis are infected by ingestion of food or water contami-nated with feces containing Entamoeba histolytica 38 Acta Med.  Okayama　Vol.  61,  No.  1Miyake et al.A BC DFig. 2　　Demonstration of amebic colitis by colonoﬁ berscopy and histological features.  A,  Colonoﬁ berscopy before treatment with metronidazole shows multiple ulcers covered with whitish exudates in the cecum ; B,  Colonoﬁ berscopy after treatment with metronidazole shows normal cecal mucosa ; C,  Histological feature shows mucosa with lymphocytic and eosinophilic accumulations (HE ; original magniﬁ cation,×50) ; D,  Histological feature shows trophozoites of Entamoeba histolytica ingesting red blood cells (arrow,  HE ; original magniﬁ cation,  ×400).4Acta Medica Okayama, Vol. 61 [2007], Iss. 1, Art. 5http://escholarship.lib.okayama-u.ac.jp/amo/vol61/iss1/5cycts.  However,  in Japan,  amebiasis is domestically transmitted by 2 populations : homosexual men and mentally handicapped persons,  which is remarkably diﬀ erent from most other developed countries [15]. Recently,  in Japanese homosexual men,  amebiasis has been increasing [16].  In order to prevent the outbreak of amebiasis infection,  the control of ame-biasis in homosexual men is considered to be neces-sary.　　In the present case,  when metronidazole was initi-ated,  the serum bilirubin levels were as high as 14.1 mg/dL.  Metronidazole was prescribed for 3 weeks,  and the serum bilirubin levels decreased to 5.0 mg/dL at the conclusion of metronidazole treat-ment.  This is the ﬁ rst report that,  in patients with acute hepatitis,  metronidazole can be administered together with lamivudine to treat concurrent amebic colitis.  Metronidazole may be well-tolerated,  even in icteric patients with acute hepatitis B.　　In summary,  this report describes a homosexual Japanese man with acute hepatitis due to hepatitis B virus genotype Ae,  concurrent with amebic colitis, who was successfully treated with lamivudine and metronidazole.  In the present case,  the mode of transmission of hepatitis B virus genotype Ae and Entamoeba histolytica was considered to be homosex-ual contact.  In Japanese patients with acute hepatitis B virus genotype A infection,  the statistical proba-bility of homosexuality is high.  Thus,  a determina-tion of genotype should be performed in order to investigate the route of transmission of hepatitis B virus,  and a search for amebiasis should be per-formed in patients with acute hepatitis due to hepati-tis B virus genotype A.  Furthermore,  education of homosexual men regarding hepatitis B virus,  hepati-tis B virus vaccination,  and amebiasis is urgently required.References 1. Ganem D and Prince AM : Hepatitis B virus infectionﾝnatural his-tory and clinical consequences.  N Engl J Med (2004) 350 : 1118ﾝ1129. 2. Miyakawa Y and Mizokami M : Classifying hepatitis B virus geno-types.  Intervirology (2003) 46 : 329ﾝ338. 3. Schaefer S : Hepatitis B virus : signiﬁ cance of genotypes.  J Viral Hepat (2005) 12 : 111ﾝ124. 4. Kobayashi M,  Suzuki F,  Arase Y,  Akuta N,  Suzuki Y,  Hosaka T, Saitoh S,  Kobayashi M,  Tsubota A,  Someya T,  Ikeda K,  Matsuda M,  Sato J and Kumada H : Infection with hepatitis B virus geno-type A in Tokyo,  Japan during 1976 through 2001.  J Gastroenterol (2004) 39 : 844ﾝ850. 5. Arima S,  Michitaka K,  Horiike N,  Kawai K,  Matsubara H, Nakanishi S,  Abe M,  Hasebe A,  Tokumoto Y,  Yamamoto K and Onji M : Change of acute hepatitis B transmission routes in Japan. J Gastroenterol (2003) 38 : 772ﾝ775. 6. Sugauchi F,  Mizokami M,  Orito E,  Ohno T,  Kato H,  Suzuki S, Kimura Y,  Ueda R,  Butterworth LA and Cooksley WG : A novel variant genotype C of hepatitis B virus identiﬁ ed in isolates from Australian Aborigines : complete genome sequence and phyloge-netic relatedness.  J Gen Virol (2001) 82 : 883ﾝ892. 7. 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Kondili LA,  Osman H and Mutimer D : The use of lamivudine for patients with acute hepatitis B (a series of cases).  J Viral Hepat (2004) 11 : 427ﾝ431.12. Schmilovitz-Weiss H,  Ben-Ari Z,  Sikuler E,  Zuckerman E,  Sbeit W, Ackerman Z,  Safadi R,  Lurie Y,  Rosner G,  Tur-Kaspa R and Reshef R : Lamivudine treatment for acute severe hepatitis B : a pilot study.  Liver Int (2004) 24 : 547ﾝ551.13. Yotsuyanagi H,  Yasuda K, Iino S,  Moriya K,  Shintani Y,   Fujie H, Tsutsumi T,  Kimura S and Koike K : Persistent viremia after recov-ery from self-limited acute hepatitis B.  Hepatology (1998) 27 : 1377ﾝ1382.14. Stanley SL Jr : Amoebiasis.  Lancet (2003) 361 : 1025ﾝ1034.15. Nozaki T,  Kobayashi S,  Takeuchi T and Haghighi A : Diversity of Clinical Isolates of Entamoeba histolytica in Japan.  Arch Med Res (2006) 37 : 276ﾝ278.16. Ohnishi K,  Kato Y,  Imamura A,  Fukayama M,  Tsunoda T, Sakaue Y,  Sakamoto M and Sagara H : Present characteristics of symptomatic Entamoeba histolytica infection in the big cities of Japan.  Epidemiol Infect (2004) 132 : 57ﾝ60.39A Homosexual Man with Acute Hepatitis BFebruary 20075Miyake et al.: A homosexual japanese man with acute hepatitis due toProduced by The Berkeley Electronic Press, 2007

A homosexual japanese man with acute hepatitis due to hepatitis B virus genotype ae, concurrent with amebic colitis

Okayama University Digital Information Repository

A homosexual japanese man with acute hepatitis due to hepatitis B virus genotype ae, concurrent with amebic colitis

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