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Impact of Occult HBV Infection in Hepatocellular Carcinoma Presentation in HCV-Related Cirrhosis
POSTER PRESENTATIONS THU-151 IMPACT OF OCCULT HBV INFECTION IN HEPATOCELLULAR CARCINOMA PRESENTATION IN HCV-RELATED CIRRHOSIS N. Coppola1, V. Iodice2, M. Starace1, C. Minichini1, N. Farella2, L. Onorato1, G. Liorre2, E. Sagnelli1, G. De Stefano2. 1Mental Health and Public Medicine, Second University of Naples; 2IX Interventional Ultrasound Unit for Infectious Diseases, AORN dei Colli- P.O. Cotugno-, Naples, Italy E-mail: [email protected] Background and Aims: The role of the occult HBV infection (OBI) as an additional risk factor for hepatocellular carcinoma (HCC) has not been fully investigated. The aim of this study was to evaluate the virological and clinical characteristics of OBI (HBV DNA in liver tissue in HBsAg negative patients) in HBsAg negative subjects with HCC. Methods: 68 consecutive HBsAg negative patients with HCC were enrolled at two centers from June 2013 to December 2014: 57.3% males; mean age 70.2 ± 6.24 years; 58 (85.3%) with HCV-related cirrhosis and 10 (14.7%) with non-alcoholic fatty liver diseasesrelated cirrhosis; 85.3% with a Child-A stage cirrhosis; 69.1% at first diagnosis of HCC, 2.9% with portal thrombosis; 89.7% with a BCLC stage-A HCC. For each patient HBV DNA was sought by PCR in plasma, HCC-liver tissue and non-HCC-liver tissue, using sets of primers for core, surface and x regions of HBV genome. Occult HBV infection was defined by the presence of HBV DNA in at least two different PCRs. Results: OBI was identified in 3 patients (4.4%) both in HCC-liver tissue and non-HCC-liver tissue and in 10 (14.7%) only in HCC-liver tissue; no patient showed OBI in plasma. OBI was detected more frequently in the 11 anti-HBs negative/anti-HBc positive and in the 17 anti-HBs/anti-HBc positive than in the 40 anti-HBs/anti-HBc negative patients (54.5%, 29.4% and 5%, respectively; p < 0.0005). The analysis of pre-S1, pre-S2 and S regions showed the presence of aa substitutions in S region (F19L, S59F, T131I, Q129H), deletions in position 4.8 an 17 in pre-S1region and aa substitution in pre-S2 region (P41H). The demographic, biochemical and clinical (unifocal or multifocal HCC, diameter of HCC, HCC localization) were similar in the 13 patients with OBI and in the 55 without. However, the 13 patients with OBI than the 55 without showed a more severe cirrhosis (Child B or C stage: 53.9% vs. 5.5%, p < 0.0001) and more advanced HCC (BCLC B or C stage: 46.1% vs. 1.8%, p < 0.0001). Conclusions: OBI was found in 19.1% of the HBsAg negative patients with HCC, more frequently in anti-HBc positive patients. The OBI seems to have a clinical impact in HCC presentation and HBsAg mutations correlated with HCC progression and failure in HBsAg detection. THU-152 ACUTE LIVER FAILURE CAUSED BY HEPATITIS A VIRUS (HAV) INFECTION IN JAPAN: RECENT STATUS BASED ON NATIONWIDE SURVEYS N. Nakayama1, M. Nakao1, Y. Uchida1, H. Tsubouchi2, H. Takikawa3, S. Mochida1. 1Department of Gastroenterology & Hepatology, Saitama Medical University, Moroyama-Machi; 2Kagoshima City Hospital, Kagoshima; 3Department of Medicine, Teikyo University, Tokyo, Japan E-mail: [email protected] Background and Aims: Diagnostic criteria for “acute liver failure (ALF) and late onset hepatic failure (LOHF)” were established in 2011 in Japan (Hepatol Res 2011; 41: 805), and nationwide surveys were done annually for patients seen in 2010 and later according to these criteria. In these surveys, we found that the outcome of patients due to HAV infection have become unfavorable compared to that in fulminant hepatitis patients seen before 2009. The reasons for such tread were investigated. Methods: A total of 71 patients with HAV infection were enrolled between 1998 and 2013. All patients showed a prothrombin time (INR) of 1.5 or more and hepatic coma; within 8 weeks after the onset of disease symptoms in 70 patients (ALF) and from 8 to 24 weeks in 1 patient (LOHF). Demographic and clinical features of 26 patients seen S374
between 2004 and 2013 (group-A) were compared to those of 45 patients seen between 1998 and 2003 (B). Results: Among patients in group-A, 14 patients including 12 patients (46%) without receiving liver transplantation (LT) were rescued, whereas 33 patients (73%) were rescued without LT and 3 patients with LT in group-B ( p < 0.05). Regarding patients without receiving LT, male patients were more frequent in group-A (83%) than in group-B (60%) ( p < 0.05) and ages (years old; mean ± SD) of patients in groupA (58 ± 12) were higher than those in group-B (48 ± 13) ( p < 0.01). A percentage of patients with underlying diseases such as metabolic syndrome diseases was 63% in group-A, which was significantly greater than that in group-B (22.0%, p < 0.01); especially those with diabetes mellitus and hypertension were increased. Patients with diabetic mellitus were more frequent in those deceased without receiving LT than in those rescued without LT (30% vs 9%; p < 0.05). Conclusions: Survival rates of ALF patients with HAV infection became deteriorated due to increase of elderly male patients with underlying diabetic mellitus. Nationwide vaccination for HAV is required to improve prognosis of ALF patients in Japan where aging of population progresses. THU-153 HEPATITIS E VIRUS GENOTYPE 3 IN SEWAGE AND GENOTYPE 1 IN SPORADIC ACUTE HEPATITIS CASES IN ISRAEL D. Ram1, Y. Manor1, Y. Gozlan1, E. Schwartz2, Z. Ben-Ari3, E. Mendelson1, O. Mor1. 1Central Virology Laboratory, Ministry of Health; 2Center for Geographic Medicine and Tropical Diseases; 3Liver Diseases Center, Sheba Medical Center, Ramat Gan, Israel E-mail: [email protected] Background and Aims: Hepatitis E virus (HEV) is yearly responsible for approximately 20 million acute hepatitis cases worldwide. Transmitted by the fecal-oral route it is classified into four genotypes: genotypes 1 and 2 infect humans onlyand genotypes 3 and 4 infect both humans and animals. HEV appears to be an emerging problem in an increasing number of industrialized countries where both genotype 1 viruses, mostly related to travel to developing countries and genotype 3 autochthonous infections have been reported. In recent years, environmental surveillance has become a very useful tool for population-based alert and monitoring of viral activity. In Israel, there is no monitoring for HEV, although the prevalence of anti HEV IgG antibodies was found to be 10.6%. Our aim was to investigate the presence of the virus in sewage environmental samples and in patients presenting with acute hepatitis during 2013–2015. Methods: 169 sewage samples, collected from 36 treatment facilities and sewage lines which cover 102 communities and span 30–40% of the population of Israel and 49 samples from hospitalized patients that presented with acute hepatitis were assessed. RealStar HEV RTPCR V 1.0 kit (Altona Diagnostics) was used for molecular HEV diagnosis. HEV genotype was determined by sequencing. Results: Altogether, 8.3% (14/169 samples) of all sewage samples were HEV PCR positive. Positivity was located mainly in the Israeli Haifa (11/18 samples), Tel Aviv (2/29 samples) and Beer Sheva (1/38 samples) regions. These regions are known for their good sanitary conditions and middle- high socioeconomic population. No clear seasonal pattern was identified. 6.1% (3/49) of patients with acute hepatitis were also HEV positive. Sequencing revealed HEV G3 in sewage samples and HEV G1 in patients. Conclusions: HEV G3 was identified only in sewage samples. Though mostly in Haifa region in the north-west of the country, HEV G3 sequences were also found in other areas suggesting a wider spread in Israel. The few clinical cases, all travelers returning from endemic countries, were infected with HEV G1. The consistent identification of HEV G3 in sewage, the absence of any G3 in patients together with the high prevalence of anti HEV antibodies may suggest silent circulation or lack of awareness to HEV and justifies better surveillance for this emerging pathogen. The possibility of zoonotic HEV G3 infection should also be explored.
Journal of Hepatology 2016 vol. 64 | S213–S424
between 2004 and 2013 (group-A) were compared to those of 45 patients seen between 1998 and 2003 (B). Results: Among patients in group-A, 14 patients including 12 patients (46%) without receiving liver transplantation (LT) were rescued, whereas 33 patients (73%) were rescued without LT and 3 patients with LT in group-B ( p < 0.05). Regarding patients without receiving LT, male patients were more frequent in group-A (83%) than in group-B (60%) ( p < 0.05) and ages (years old; mean ± SD) of patients in groupA (58 ± 12) were higher than those in group-B (48 ± 13) ( p < 0.01). A percentage of patients with underlying diseases such as metabolic syndrome diseases was 63% in group-A, which was significantly greater than that in group-B (22.0%, p < 0.01); especially those with diabetes mellitus and hypertension were increased. Patients with diabetic mellitus were more frequent in those deceased without receiving LT than in those rescued without LT (30% vs 9%; p < 0.05). Conclusions: Survival rates of ALF patients with HAV infection became deteriorated due to increase of elderly male patients with underlying diabetic mellitus. Nationwide vaccination for HAV is required to improve prognosis of ALF patients in Japan where aging of population progresses. THU-153 HEPATITIS E VIRUS GENOTYPE 3 IN SEWAGE AND GENOTYPE 1 IN SPORADIC ACUTE HEPATITIS CASES IN ISRAEL D. Ram1, Y. Manor1, Y. Gozlan1, E. Schwartz2, Z. Ben-Ari3, E. Mendelson1, O. Mor1. 1Central Virology Laboratory, Ministry of Health; 2Center for Geographic Medicine and Tropical Diseases; 3Liver Diseases Center, Sheba Medical Center, Ramat Gan, Israel E-mail: [email protected] Background and Aims: Hepatitis E virus (HEV) is yearly responsible for approximately 20 million acute hepatitis cases worldwide. Transmitted by the fecal-oral route it is classified into four genotypes: genotypes 1 and 2 infect humans onlyand genotypes 3 and 4 infect both humans and animals. HEV appears to be an emerging problem in an increasing number of industrialized countries where both genotype 1 viruses, mostly related to travel to developing countries and genotype 3 autochthonous infections have been reported. In recent years, environmental surveillance has become a very useful tool for population-based alert and monitoring of viral activity. In Israel, there is no monitoring for HEV, although the prevalence of anti HEV IgG antibodies was found to be 10.6%. Our aim was to investigate the presence of the virus in sewage environmental samples and in patients presenting with acute hepatitis during 2013–2015. Methods: 169 sewage samples, collected from 36 treatment facilities and sewage lines which cover 102 communities and span 30–40% of the population of Israel and 49 samples from hospitalized patients that presented with acute hepatitis were assessed. RealStar HEV RTPCR V 1.0 kit (Altona Diagnostics) was used for molecular HEV diagnosis. HEV genotype was determined by sequencing. Results: Altogether, 8.3% (14/169 samples) of all sewage samples were HEV PCR positive. Positivity was located mainly in the Israeli Haifa (11/18 samples), Tel Aviv (2/29 samples) and Beer Sheva (1/38 samples) regions. These regions are known for their good sanitary conditions and middle- high socioeconomic population. No clear seasonal pattern was identified. 6.1% (3/49) of patients with acute hepatitis were also HEV positive. Sequencing revealed HEV G3 in sewage samples and HEV G1 in patients. Conclusions: HEV G3 was identified only in sewage samples. Though mostly in Haifa region in the north-west of the country, HEV G3 sequences were also found in other areas suggesting a wider spread in Israel. The few clinical cases, all travelers returning from endemic countries, were infected with HEV G1. The consistent identification of HEV G3 in sewage, the absence of any G3 in patients together with the high prevalence of anti HEV antibodies may suggest silent circulation or lack of awareness to HEV and justifies better surveillance for this emerging pathogen. The possibility of zoonotic HEV G3 infection should also be explored.
Journal of Hepatology 2016 vol. 64 | S213–S424