POSTERS Alcoholic-cirrhosis and autopsy based normal liver (N = 5each). HAV RNA was detected by RT-PCR and genotyped by PCRsequencing-phylogenetic analysis method. hOGG1ser326cys and XRCC1codon399 mutation were analyzed by PCR-RFLP. Estimation of cellular oxidative stress in the plasma samples was analyzed using 8-OH-dG EIA kit. XRCC1 protein expression in tissue sections was evaluated by immunohistochemistry. Statistical analysis was performed by SPSSv13 software. Results: HAV-RNA was detectable in 61.11% (33/54) and 100% of the AVH and FHF cases respectively. HAV genotype IIIA was the predominantly present in both groups. Presence of mutant hOGG1 genotype was significantly higher in HAV-FHF cases compared to controls (p = 0.026) and AVH (p = 0.035). Risk of HAV-FHF was doubled by the presence of mutated hOGG1 {OR = 2.5 (1.170– 5.341) at 95% CI} and XRCC1{OR = 2.0 (0.134–29.808)} compared to HAV-AVH cases. Risk of Alcoholic-cirrhosis was increased multiple folds by the presence of mutated hOGG1 (OR = 7.5, p = 0.076) and XRCC1 (OR = 2.5, p = 0.305) compared to controls. hOGG1 mutation also enhanced the risk of HAV related liver injury (OR = 2.5) and ALD (OR = 2.143) compared to controls. The 8-oxoG levels were significantly elevated in HAV-FHF cases compared to controls (p = 0.002) and HAV-AVH (p = 0.035); and in alcoholic-cirrhosis cases compared to controls (p = 0.001); and liver disease cases compared to controls (p = 0.010). Higher 8-oxoG levels correlated significantly with mutant hOGG1 genotype (p < 0.001). XRCC1 expression was down-regulated in 2/5 (40%) cases of alcoholic-cirrhosis compared to controls (p = NS). Conclusion: Genetic alteration of BER pathway genes and oxidative stress critically influences HAV and alcohol related liver disease severity. 8-oxoG levels and hOGG1 genotype may be used as prognostic markers for liver disease predisposition. 554 EPIDEMIOLOGICAL, VIROLOGICAL AND CLINICAL FEATURES OF 112 HEPATITIS E VIRUS INFECTIONS DIAGNOSED OVER A 5-YEAR PERIOD IN SOUTH-EASTERN FRANCE P. Colson1 , V. Moal2 , M. Kaba1 , P. Borentain3 , M. Mola1 , N. Tivoli1 , 3 1 A. Motte1 , R. Gerolami ´ . Pˆ ole des Maladies Infectieuses et Tropicales Clinique et Biologique, F´ed´eration de Bact´eriologie-Hygi`ene-Virologie, Centre Hospitalo-Universitaire Timone, 2 Aix-Marseille Universit´e, Assistance-Publique des Hˆ opitaux de Marseille, Centre de N´ephrologie et Transplantation R´enale, Hˆ opital Conception, 3 Service d’H´epatoGastro-Ent´erologie, Centre Hospitalier Universitaire Conception, Marseille, France E-mail:
[email protected] Background and Aims: Hepatitis E is found mostly in developing countries. In developed countries, the number of sporadic autochthonous cases has increased dramatically during the past decade; there is a porcine reservoir and possible zoonotic transmission. In addition, chronic hepatitis E has emerged in severely immunocompromised persons. We studied the epidemiological, virological and clinical characteristics of autochthonous hepatitis E diagnosed in Marseille University hospitals over the last 5-year period. Methods: From April 2006 through March 2011, hepatitis E virus (HEV) infection were diagnosed in patients who did not travel to countries with HEV hyperendemicity during 2–10 weeks before transaminasitis by detecting in serum HEV RNA (in house realtime PCR) and anti-HEV IgM anti-HEV (ELISA kits Adaltis EIAGen). HEV genotype was determined by population sequencing then phylogenetic analysis. Case-patients were interviewed about their occupation, contacts with animals, food, exposure to water, travel abroad, and transfusion. Results: 112 autochthonous HEV infections were diagnosed. Casepatients included 109 adults and 3 children (7, 10, and 13 yearold); 83 (74%) were men and their mean age was 51±15 years S220
(52±15 years for men). Two-third of the patients were living in Marseille. Mean alanine aminotransferase level was 851±1312 IU/l; mean bilirubin level was 89±128 mmol/l. Hepatitis E was more common during winter and summer (37 and 27 cases, respectively) than during spring and fall (22 and 21 cases, respectively). Mean test/cut-off optical density ratios for anti-HEV IgG and IgM were 5.9 and 7.7, respectively. Among 89 genotyped HEV, 85 were of genotype 3, including 1 subtype a, 20 subtypes c, 4 subtype e and 60 subtypes f. Jaundice and asthenia were the most frequently observed clinical symptoms. HEV infection was diagnosed in 13 renal transplant recipients and 9 HIV-infected patients. Chronic HEV infection occurred in 7 kidney transplant recipients and 2 HIV-seropositive patients. Five patients died within 3 months of acute hepatitis. Conclusion: Incidence of HEV infection has been not negligible in Marseille University hospitals, 20–30 cases having been diagnosed/year. This prompts to perform larger studies to assess the actual incidence, sources/modes of transmission, and clinical outcome of HEV infection in our geographical area. 555 A RAPID TEST TO DETECT IMMUNOGLOBULIN M ANTIBODY TO HEPATITIS E VIRUS 2 ´ , P. Colson1 . 1 Pˆ ole des M. Kaba1 , M. Bronnert1 , A. Motte1 , R. Gerolami Maladies Infectieuses et Tropicales Clinique et Biologique, F´ed´eration de Bact´eriologie-Hygi`ene-Virologie, Centre Hospitalo-Universitaire Timone, 2 Service d’H´epato-Gastro-Ent´erologie, Centre Hospitalier Universitaire Conception, Marseille, France E-mail:
[email protected] Background and Aims: Hepatitis E virus (HEV) is a leading cause of acute hepatitis in tropical/subtropical countries and has been increasingly identified during the past decade in autochthonous hepatitis in developed countries. A rapid and/or point-of-care assay for anti-HEV IgM might be of interest by increasing the convenience and opportunities for testing and by decreasing the time to result. We assessed the performance in a clinical microbiology laboratory in Marseille, France, of a rapid assay detecting anti-HEV IgM antibodies. Methods: We tested a capture solid-phase immunochromatographic commercial rapid assay (ASSURE HEV IgM Rapid Test, MP Diagnostics) (HEVM-RT) that detects anti-HEV IgM on the serum of 41 patients with PCR-documented acute HEV infection (in 38 cases, HEV genotype was 3, indicating autochthonous infection), 40 patients with acute viral hepatitis unrelated to HEV (10 hepatitis A, 6 hepatitis B, 6 hepatitis C, 5 hepatitis B reactivations, 7 Epstein-Barr virus infections, 6 acute cytomegalovirus infections), 19 patients with liver cytolysis in whom no viral aetiology was diagnosed and HEV RNA was not detected, and on 50 sera addressed to our lab due to liver cytolysis. Acute hepatitis E was diagnosed concurrently using anti-HEV IgM detection with an enzymoimmunoassay (Adaltis) and HEV RNA detection and sequencing with in-house protocols. Results: The HEVM-RT was positive in 38 (92.7%) of 41 sera from patients with acute hepatitis E infection. Two false-negative results were obtained for autochthonous HEV-3 infections with high test/cut off optical density ratios (>10) for both anti-HEV IgG and anti-HEV IgM. A false-positive result was obtained for 2/98 non HEV-related liver cytolysis (specificity, 98.0%), including a concurrent primary co-infection with cytomegalovirus and hepatitis C virus. Conclusion: The rapid anti-HEV IgM assay tested here can be considered of interest for the diagnosis of autochthonous HEV infections in the setting of acute hepatitis in our developed country, despite using as antigen a conformational epitope of a genotype 1 strain which circulates in tropical and subtropical. It may be helpful in developing countries, including for detecting and monitoring
Journal of Hepatology 2012 vol. 56 | S71–S224
POSTERS HEV outbreaks, and may also deserve further evaluation in such context. 556 PREVALENCE OF HEPATITIS E IN NEW YORK AMONG HIV NEGATIVE CHRONIC LIVER DISEASE POPULATION “IS IT AN INNOCENT BYSTANDER” P.P. Basu1,2 , T. Nair3 , M. Jafri4 , S. Farhat3 , S. Faustin3 , L. Ang3 , K. Mittimani3 , N. James Shah3 . 1 Gastroenterology and Liver Transplant, Columbia University Medical Center, 2 Gastroenterology and Liver Transplant, 3 Internal Medicine, North Shore University Hospital, Forest Hills, 4 Internal Medicine, NYMC Richmond University Medical Center, Staten Island, NY, USA E-mail:
[email protected] Objectives: Hepatitis E is an oro-fecal infection with high prevalence in developing countries. The study evaluates the prevalence of HEV antibody IgG/IgM in New York in patients with CLD. Methods: Four hundred forty (n) were divided into 2 groups: A – control 140 patients without any liver disease. Group B, 300 patients with liver disease: hepatitis B 125/300 (41%), chronic hepatitis C 60/300 (20%), fatty liver 70/300 (23%), Alcoholic liver disease 29/300 (10%), HBV/HCV co-infection 9/300 (3%), autoimmune hepatitis 2/300 (0.6%), PBC/PSC 5/300 (2%). HEV antibody IGM & IGG were measured & HEV genotyping. 22/300 (7%) patients were liver transplant recipients. Results: Group A, HEV IgG positive 13%(18/140), Group B, HEV IgG positive 40.6% (122/300) including 3.7% (4/122) having both IgM & IgG positive. The prevalence of HEV IgG was 54% (12/22) in liver transplant recipients. Demographic of patients in Group B Characteristics
Chronic Chronic Fatty Liver Alcoholic Liver Hepatitis C Hepatitis B Disease
Sex: M/F BMI (Mean) Race African American Asian Latin American South European North American Asian Pacific
40/20 27%
94/31 26%
42/28 29%
27/2 28%
33 4 12 NA NA NA
9 79 15 16 6 NA
7 6 34 10 NA 13
NA 6 11 12 NA NA
History and genotypic characteristics of patients Characteristics
Chronic Hep C
Chronic Hep B
Fatty Liver
Alcoholic Liver Disease
IVDU Promiscuity Transfusion Genotype G1 G2 G3 G4 G5
36/43 (83%) 23/42 (52%) 6/20 (30%)
7/43 (16%) 10/42 (23%) 14/20 (70%)
NA NA NA
NA 9/42 (2!%) NA
2/30 (7%) 1/30(3%) 26/30 (87%) 1/30 (3%) NA
60/69(87%) 8/69(11%) 1/69 (1%) NA NA
3/10 (30%) 3/10(30%) 4/10(40%) NA NA
1/13(7%) 4/13(30%) 8/13(62%) NA NA
Conclusion: The study demonstrates the prevalence of HEV infection in NY and HEV antibody in CLD including transplant patients. Question remains the impact of acute or chronic liver disease with concomitant HEV in pre, peri, and post liver transplant recipient. Larger study needed to validate.
557 ACUTE HEPATITIS E (HEV) IN A REGION OF NORTHERN SPAIN 1 M.L. Gonzalez-Di ´ eguez ´ , C. Navascues ´ 1 , R. Garc´ıa2 , J. De la Vega3 , P. Garc´ıa4 , H. Alonso1 , Mercedes Rodr´ıguez5 , M. Varela1 , Manuel Rodr´ıguez1 . 1 Liver Unit, Hospital Universitario Central de Asturias, Oviedo, 2 Gastroenterology Department, Hospital de Cabue˜ nes, Gij´ on, 3 Gastroenterology Department, Hospital San Agust´ın, Avil´es, 4 Gastroenterology Department, Hospital Valle del Nal´ on, Langreo, 5 Microbiology Department, Hospital Universitario Central de Asturias, Oviedo, Spain E-mail:
[email protected]
Hepatitis E virus causes both epidemics and sporadic cases of acute hepatitis in many developing countries. In recent years, an increasing number of cases of autochthonous hepatitis E have been recognized in different western countries. Aim: To determine the incidence, risk population and ways of transmission of acute hepatitis E in our region. Patients and Methods: We collected prospectively all cases of acute hepatitis attended in four hospitals from January 2010 to October 2011. Ischemic hepatitis were excluded. Age, sex, nationality, clinical, analytical, serological and epidemiological variables were analyzed. Acute hepatitis was defined as ALT >10× ULN and the etiology was established according to standard criteria. Acute hepatitis E diagnosis was based on Anti-HEV IgM positive. AntiHEV IgG and HEV RNA were also tested. Results: 122 patients(78 males/44 females) were diagnosed with acute hepatitis. The mean age was 49.8±18 years [14–90]. One hundred seventeen(96%) were born in Spain. Jaundice was present in 77%. 16% had a severe hepatitis and 5% developed a fulminant liver failure; 3 of them needed a liver transplant. Two patients(1.6%) died. The main etiology was toxic(23%), followed by HAV(18%), HBV(16.4%), autoimmune(12.3%), cryptogenic(9%), HEV(8.2%), HCV(5.7%) and others(3%). Among patients with acute hepatitis E, 90% were male and they were older than those with other viral hepatitis(64.9±14.2 vs 43.9±15.7; p = 0.000). All of them were Spaniards and none had traveled outside Spain in the previous 6 months. Five(50%) reported having contact with domestic or wild animals while only 10% did so among the other viral hepatitis(p = 0.03). They also had taken medications more frequently(40% vs 14%, p = 0.07). Hepatitis E patients presented higher GGT (500±305 vs 297±271; p = 0.03) without significant differences in the rest of the analytical parameters analyzed. HEVRNA was positive in 60% of them. Only one patient died, he had a chronic alcoholic liver disease. Conclusions: The incidence of acute hepatitis E in our community is low but not negligible, so serologic testing for HEV infection should be performed in all toxic and cryptogenic acute hepatitis. The patients with Hepatitis E in our area are more often elderly men in contact with domestic or wild animals 558 WINDOW PERIOD OF ANTI-HAV IGM ANTIBODIES IN DIAGNOSING ACUTE HEPATITIS A K.-A. Kim, H.K. Lee, J.S. Lee, T.J. Song, W.K. Bae, N.-H. Kim. Internal Medicine, Inje University College of Medicine, Ilsan Paik Hospital, Goyang, Republic of Korea E-mail:
[email protected] Background: The diagnosis of acute hepatitis A virus (HAV) infection is based on the presence of anti-HAV IgM antibodies in patients presenting with acute hepatitis. Some patients show negative serology at initial presentation, which may confuse the diagnosis of HAV infection. We investigated the characteristics of hepatitis A patients whose initial serology tests for HAV were negative. Methods: Patients with symptomatic acute hepatitis who had anti-HAV IgM tested from January 2008 to December 2010 at a
Journal of Hepatology 2012 vol. 56 | S71–S224
S221