Race/ethnicity difference in the pharmacogenetics of bilirubin-related atazanavir discontinuation.

BACKGROUND: Atazanavir causes plasma indirect bilirubin to increase. We evaluated associations between Gilbert's polymorphism and bilirubin-related atazanavir discontinuation stratified by race/ethnicity. PATIENTS AND METHODS: Patients had initiated atazanavir/ritonavir-containing regimens at an HIV primary care clinic in the southeastern USA, and had at least 12 months of follow-up data. Metabolizer group was defined by UGT1A1 rs887829 C→T. Genome-wide genotype data were used to adjust for genetic ancestry in combined population analyses. RESULTS: Among 321 evaluable patients, 15 (4.6%) had bilirubin-related atazanavir discontinuation within 12 months. Homozygosity for rs887829 T/T was present in 28.1% of Black, 21.4% of Hispanic, and 8.6% of White patients. Among all patients the hazard ratio (HR) for bilirubin-related discontinuation with T/T versus C/C genotype was 7.3 [95% confidence interval (CI): 1.7-31.5; P=0.007]. Among 152 White patients the HR was 14.4 (95% CI: 2.6-78.7; P=0.002), but among 153 Black patients the HR was 0.8 (95% CI: 0.05-12.7; P=0.87). CONCLUSION: Among patients who initiated atazanavir/ritonavir-containing regimens, UGT1A1 slow metabolizer genotype rs887829 T/T was associated with increased bilirubin-related discontinuation of atazanavir in White but not in Black patients, this despite T/T genotype being more frequent in Black patients.

Difference in clinical presentation, immunology profile and treatment response of type 1 autoimmune hepatitis between United Kingdom and Singapore patients.

BACKGROUND: Autoimmune hepatitis (AIH) is an immune-mediated liver disease of unknown etiology. Increasing incidence of AIH in Asian patients has been reported. However, the phenotypic difference of Asian patients in Europe and Asia has still not been explored. AIM: To evaluate the clinical presentation, biochemical and immunological profiles, treatment response and survival outcome of type 1 AIH from two tertiary liver transplant centres (United Kingdom and Singapore). METHOD: Patients who fulfilled the simplified diagnostic scoring criteria of AIH were included in the study. Patients with overlap syndrome were excluded. RESULTS: Totals of 40 Asian patients and 159 Caucasian patients from the University Hospital of Birmingham National Health Service Foundation Trust, UK, were compared with 57 Asian patients from Singapore General Hospital, Singapore. Asian patients from Singapore present significantly much later (median 55 vs. 32 years, p < 0.001), had higher MELD (p < 0.001) with lower albumin (p < 0.001) and higher bilirubin (p < 0.001) and lower ASMA positivity (p < 0.001) at diagnosis compared to UK Asian. Jaundice at presentation was much higher in Singapore Asian patients compared to UK Asian (53 vs. 30 %) but cirrhosis at diagnosis was more common in UK patients. Associated autoimmune conditions were less commonly seen in Singapore Asians. Comparing between UK cohorts, Asian patients present at younger age and have higher IgG level compared to Caucasian. Overall, 5-year transplant-free survival in all three cohorts was similar (p = 0.846). CONCLUSION: We demonstrate that AIH patients from Singapore present at older age with jaundice and have a low positivity of SMA. Despite these differences, transplant-free survival is similar in the two groups.

Ethnobotany of medicinal plants used in Antakya: A multicultural district in Hatay Province of Turkey.

ETHNOPHARMACOLOGICAL RELEVANCE: We have compiled information about the medicinal plants used in folk medicine in the district of Antakya. Since its establishment by King Seleucus I in 300 B.C., Antakya (old Antioch) has hosted nearly 20 civilizations. Antakya, neighboring Northwestern Syria, is located on the western end of the "Silk Road" and was one of the great centers of Graeco-Roman world. Today, Antakya is a cosmopolitan city in which Arabic and Turkish are widely spoken, and where distinct ethnic and religious communities, such as Arab Alawite, Arab Christian, Arab Sunni, Turk Sunni, Armenian, and Jewish, have been living together in harmony for centuries. In addition, the rich flora in the vicinity of Antakya also renders the area interesting in terms of ethnobotanical fieldwork. AIM OF THE STUDY: This study aimed to compile the information about plants used for medicinal purposes by local people in the district of Antakya. This city is a significant region in terms of ethnobotanical fieldwork, owing to its cosmopolitan structure, long history, relatively preserved traditional community structure, and rich flora. Furthermore, we sought to compare the ethnomedicinal data geographically, cross-culturally, and historically. MATERIALS AND METHODS: The ethnobotany of medicinal plants used in the district of Antakya has been investigated through two separate studies; one was conducted in 1975, interviewing 29 people, and the other was conducted in 2011-2013, interviewing 182 people. The use value (UV) and informant consensus factor (FIC) values of the plants were calculated. In order to interpret the authenticity and sources of the compiled ethnomedicinal information, previous publications that contain information about the similar medicinal uses of plants identified in our region were reviewed and evaluated meticulously. A comparison with the data obtained from other regions of Turkey and from other Mediterranean regions, as well as a cross-cultural analysis between the ethnic groups within the study area, was performed by implementation of the Jaccard index (JI) RESULTS: Throughout the study, information about 202 medicinal plant taxa was compiled. Among these plants, 39 have either not yet been mentioned in ethnobotanical or medicinal studies, or have been used for a medicinal purpose other than those encountered in the literature review. The ethnomedicinal information we gathered from the study area exhibits close similarities to the ethnomedicinal information of other Southern and Eastern Mediterranean countries where Arabic is spoken, as well as to that of Northern and Western Mediterranean countries where Latin languages are spoken. In addition to these similarities, in most cases, this ethnomedicinal information shows hybrid features of ethnomedicinal knowledge from Eastern and Western Mediterranean countries. CONCLUSION: Based on a literature survey, we found that the cited medicinal uses for 43 plants have also been corroborated by other various biological testings. This finding strongly suggests the importance of ethnobotanical studies in the development of new medicines. We believe that this study has compiled rich ethnomedicinal information that reflects the cosmopolitan structure of Antakya in a very good way.

Hyperbilirubinemia in healthy newborns born to immigrant mothers from southeastern Asia compared to Italian ones.

OBJECTIVE: To compare the characteristics of jaundice and hyperbilirubinemia in the newborn population of both immigrant and Italian mothers. METHODS: The authors studied a group of 1,680 infants born at "A. Gemelli" hospital during 1 y. All were with appropriate weight for gestational age, weighting more than 2,500 g, born to low-risk pregnancy. Maternal ethnicity, clinically evident jaundice (that is total serum bilirubin (TSB) > 7 mg/dL), hyperbilirubinemia (TSB > 12 mg/dL), the duration of hospital stay and their need of phototherapy were evaluated. RESULTS: In infants born to Asian mothers, hyperbilirubinemia was significantly more frequent (48.8 % vs. 26.5 %, p = 0.003) and they reached mean TSB peak significantly later (86.5 ± 38.5 vs. 74.5 ± 20.6 h, P = 0.0001) compared with Italian infants. The average length of hospitalization of infants of Asian and Latin American mothers is significantly longer compared to Italian newborns (4.5 ± 1.9 vs. 3.6 ± 1.1, p <0.0001 and 4.2 ± 1.6 vs. 3.6 ± 1.1, p = 0.0004). With regard to the use of phototherapy, and to its duration, there are no significant differences between the populations studied. CONCLUSIONS: Having studied all infants at low risk, the greater length of hospitalization is due to later peak and the higher frequency of jaundice in newborns of immigrant mother, especially in Asia. Therefore, as it happens to the Italian newborns, it would be desirable to build forecasting nomograms in these populations, to reduce the length of hospitalization and facilitate protected discharge.

Febre amarela: Rio Grande do Sul e o risco da reurbanização / Yellow fever: rio grande do sul and the risk of reurbanização

A Febre Amarela e uma doença infecciosa aguda não - contagiosa de curta duração e de gravidade variável. É causada por um flavivírus, para o qual está disponível uma vacina altamente eficaz. A transmissão é feita por intermédio de mosquitos. O surgimento de novos casos de febre amarela, no Brasil é uma ameaça constante. A possível expansão desta doença infecciosa para o Rio Grande do Sul é a preocupação de muitos sanitaristas, uma vez que o vetor está presente nas cidades gaúchas. Em 2001, a vacinação contra a febre amarela em 43 municípios da Região das Missões foi realizada após comprovação de quea febre amarela fora a causa de morte de bugius em muitos municípios, sendo estes classificados como áreas de risco para endemias. Neste contexto, torna-se essencial aos médicos o conhecimento da Febre Amarela: fisiopatologia, áreas de risco, manejo da doença e, sobretudo, mecanismos de prevenção. Cabe lembrar que a Febre Amarela é uma doença de notificação compulsória aos órgãos públicos.

Jaundice in African-American and Hispanic patients with AIDS.

Although abnormalities in hepatic biochemical tests are common in patients with acquired immunodeficiency syndrome (AIDS), overt jaundice is infrequent. The aim of this study was to investigate the etiology and outcome of jaundice in African-American and Hispanic patients with AIDS. We retrospectively reviewed medical records of 1,238 HIV-infected patients with abnormal liver chemistry over a 10-year period. Data were abstracted and analyzed for demography, medications, laboratory tests, abdominal ultrasonography, computerized tomography (CT), magnetic resonance imaging (MRI), endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic cholangiography (PTC) and liver biopsy results. Of 1,238 patients with abnormal liver chemistry and HIV infection, 1,040 (84%) had AIDS. Of the 1,040 AIDS patients, 102 (10%) had jaundice (serum bilirubin >3 mg/dL). Of the 198 HIV-positive patients without AIDS and with abnormal liver chemistry, none had jaundice. The common causes of jaundice were drugs (29%) and infections (28%). Liver biopsy was performed in 20 AIDS patients, and the common findings included granulomas, Mycobacterium avium complex (25%) and Kaposi's sarcoma (25%). Of 102 patients with AIDS and jaundice, 72 (70%) died. Of the 198 patients without AIDS and without jaundice, 14 (7%) died. In conclusion, liver-associated enzyme abnormality was common among our patients with AIDS; however, jaundice was infrequent and associated with a high mortality; drugs, infections and alcohol were the common culprits.

Red blood cell alloantibodies and liver transplantation in Chinese patients.

Red blood cell (RBC) alloantibodies are present in up to 14% of white recipients of liver transplants and can cause severe delayed hemolysis. A retrospective survey showed 17 cases (8.8%) of RBC alloantibodies in 192 consecutive Chinese recipients of liver transplants, compared with a 3.7% background hospital incidence. The spectrum of RBC alloantibodies was different from that in white recipients, with no anti-D or anti-K antibodies but with a significant incidence of anti-Mi (29%) antibodies. There was significantly increased transfusion in RBC alloantibody positive cases. Delayed hemolysis also resulted in higher day-7 bilirubin levels. A total of 7 to 86 antigen-positive units were issued in five RBC alloantibody cases, including three early deaths. Seven cases in the RBC alloantibody negative group, but none in the positive group, were salvaged by regraft. Blood banks servicing transplant centers should be aware of ethnic patterns in RBC alloantibodies. Delayed hemolysis may jeopardize patient survival as a result of difficult postoperative stabilization, especially in cases requiring massive transfusion.