During pregnancy, the energy requirements of the fetus impose changes in maternal metabolism. Increasing insulin resistance in the mother maintains nutrient flow to the growing fetus, while prolactin and placental lactogen counterbalance this resistance and prevent maternal hyperglycemia by driving expansion of the maternal population of insulin-producing β-cells1–3. However, the exact mechanisms by which the lactogenic hormones drive β-cell expansion remain uncertain. Here we show that serotonin acts downstream of lactogen signaling to drive β-cell proliferation. Serotonin synthetic enzyme Tph1 and serotonin production increased sharply in β-cells during pregnancy or after treatment with lactogens in vitro. Inhibition of serotonin synthesis by dietary tryptophan restriction or Tph inhibition blocked β-cell expansion and induced glucose intolerance in pregnant mice without affecting insulin sensitivity. Expression of the Gαq-linked serotonin receptor Htr2b in maternal islets increased during pregnancy and normalized just prior to parturition, while expression of the Gαi-linked receptor Htr1d increased at the end of pregnancy and postpartum. Blocking Htr2b signaling in pregnant mice also blocked β-cell expansion and caused glucose intolerance. These studies reveal an integrated signaling pathway linking β-cell mass to anticipated insulin need during pregnancy. Modulators of this pathway, including medications and diet, may affect the risk of gestational diabetes4.

The recent National Health and Nutrition Examination Survey (NHANES) sampled only the civilian, non-institutionalized population of USA and may have underestimated the prevalence of hepatitis C virus (HCV) in this country. We searched the database MEDLINE, the Bureau of Justice Statistics, Center for Medicare and Medicaid and individual states Department of Corrections for all epidemiological studies regarding the prevalence of HCV in populations not sampled by the NHANES survey namely the incarcerated, homeless, nursing home residents, hospitalized and those on active military duty. Because of their relatively low frequency in the NHANES sample, we also expanded our search to include healthcare workers and long-term dialysis patients. Although included in the NHANES sample, we also performed searches on drug users (injection and non-injection) and veterans to confirm the findings of the NHANES study. Based on the prevalence of studies identified meeting our inclusion criteria, our most conservative estimates state that there at least 142 761 homeless persons, 372 754 incarcerated persons and 6805 persons on active military duty unaccounted for in the NHANES survey. While the NHANES estimates of drug users (both injection and noninjection) appear to be reasonable, the survey seems to have underestimated the number of HCV-positive veterans. Our most conservative estimates suggest that there are at least 5.2 million persons living with HCV in USA today, approximately 1.9 million of whom were unaccounted for in the NHANES survey.Hepatitis C virus (HCV) is the most common bloodborne infection in USA (1) and worldwide (2). Chronic HCV can lead to hepatic fibrosis, cirrhosis and hepatocellular carcinoma (HCC) and is the leading cause of liver transplantation nationwide (3).The National Health and Nutrition Examination Surveys (NHANES) is a series of surveys that have periodically collected data on HCV prevalence, allowing clinicians to target at-risk groups with educational services and therapeutic options. According to the most recent NHANES, 1.6% or 4.1 million persons in USA were anti-HCV positive, most of whom were born between 1945 and 1964 (4). With 15 079 total participants, its information is invaluable and easily the largest epidemiological survey of HCV data in existence regarding HCV prevalence in USA. The NHANES study highlights the burden of HCV infection in the aforementioned birth cohort and the need to diagnose these individuals before complications develop.The survey, however, sampled from a non-institutionalized, civilian population, did not include certain highrisk persons, namely the incarcerated, homeless, nursing homes residents, hospitalized patients, those on active military service and immigrants. Other groups with an expected high prevalence of HCV infection missed by the survey include healthcare workers (HCW) and persons on long-term haemodialysis because of low frequency and lack of availability in the NHANES dataset. As a result, the NHANES has likely underestimated the true preva...

Orthotopic liver transplant (OLT) is an established life saving procedure for both acute and chronic liver failure, but incidences and risk factors for development of these malignancies are yet to be established. To determine the incidences and risk factors associated with de novo malignancy after OLT. We performed a systematic review of relevant epidemiological studies available on MEDLINE, which provided information on the incidences and risk factors for the development malignancies in adult OLT recipients published from 1983 to 2009. All data was compiled from retrospective studies. Independent risk factors for the development of de novo malignancy in adult OLT recipients were identified to be statistically significant including immunosuppression, hepatitis C virus infection, smoking, alcoholic cirrhosis and sun exposure. OLT recipients with smoking and alcohol history are of particular risk for head and neck and lung cancers. Primary sclerosing cholangitis and inflammatory bowel disease were found to be independent risk factors for colon cancer. Adult OLT recipients are at increased risk for the development of posttransplant malignancies and obviates the need for surveillance protocols that are safe and cost-effective. OLT recipients should be advised on taking proper precautions in the sun, smoking cessation, and eliminating alcohol consumption. Given the emergence of alcoholic cirrhosis as a leading indication for liver transplantation, the early detection of lung and head and neck cancers is of particular importance.

AIMTo describe racial/ethnic differences in treatment and survival among liver cancer patients in a population-based cancer registry.METHODSInvasive cases of primary hepatocellular carcinoma, n = 33270, diagnosed between January 1, 1988-December 31, 2012 and reported to the California Cancer Registry were analyzed by race/ethnicity, age, gender, geographical region, socio-economic status, time period of diagnosis, stage, surgical treatment, and survival. Patients were classified into 15 racial/ethnic groups: non-Hispanic White (White, n = 12710), Hispanic (n = 8500), Chinese (n = 2723), non-Hispanic Black (Black, n = 2609), Vietnamese (n = 2063), Filipino (n = 1479), Korean (n = 1099), Japanese (n = 658), American Indian/Alaskan Native (AIAN, n = 281), Laotian/Hmong (n = 244), Cambodian (n = 233), South Asian (n = 190), Hawai`ian/Pacific Islander (n = 172), Thai (n = 95), and Other Asian (n = 214). The main outcome measures were receipt of surgical treatment, and cause-specific and all-cause mortality.RESULTSAfter adjustment for socio-demographic characteristics, time period, and stage of disease, compared to Whites, Laotian/Hmong [odds ratio (OR) = 0.30, 95%CI: 0.17-0.53], Cambodian (OR = 0.65, 95%CI: 0.45-0.96), AIAN (OR = 0.66, 95%CI: 0.46-0.93), Black (OR = 0.76, 95%CI: 0.67-0.86), and Hispanic (OR = 0.78, 95%CI: 0.72-0.84) patients were less likely, whereas Chinese (OR = 1.58, 95%CI: 1.42-1.77), Koreans (OR = 1.45, 95%CI: 1.24-1.70), Japanese (OR = 1.41, 95%CI: 1.15-1.72), and Vietnamese (OR = 1.26, 95%CI: 1.12-1.42) were more likely to receive surgical treatment. After adjustment for the same covariates and treatment, cause-specific mortality was higher for Laotian/Hmong [(hazard ratio (HR) = 1.50, 95%CI: 1.29-1.73)], Cambodians (HR = 1.35, 95%CI: 1.16-1.58), and Blacks (HR = 1.07, 95%CI: 1.01-1.13), and lower for Chinese (HR = 0.82, 95%CI: 0.77-0.86), Filipinos (HR = 0.84, 95%CI: 0.78-0.90), Vietnamese (HR = 0.85, 95%CI: 0.80-0.90), Koreans (HR = 0.90, 95%CI: 0.83-0.97), and Hispanics (HR = 0.91, 95%CI: 0.88-0.94); results were similar for all-cause mortality.CONCLUSIONDisaggregated data revealed substantial racial/ethnic differences in liver cancer treatment and survival, demonstrating the need for development of targeted interventions to mitigate disparities.

Breast-feeding is protective against H. pylori infection, especially in middle- and low-income nations.

Background: Fresh frozen plasma (FFP) transfusion is often used in the management of acute variceal haemorrhage (AVH) despite best practice advice suggesting otherwise.Objective: We investigated if FFP transfusion affects clinical outcomes in AVH. Design, setting and patients:We performed a retrospective cohort study of 244 consecutive, eligible patients admitted to five tertiary health care centres between 2013 and 2018 with AVH.Main outcome measurements: Multivariable regression analyses were used to study the association of FFP transfusion with mortality at 42 days (primary outcome) and failure to control bleeding at 5 days and length of stay (secondary outcomes).Results: Patients who received FFP transfusion (n = 100) had higher mean Model for End Stage Liver Disease (MELD) score and more severe variceal bleeding than those who did not received FFP transfusion (n = 144). Multivariable analysis showed that

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Implementation of screening recommendations for chronic hepatitis B (CHB) among foreign-born persons at risk has been sub-optimal. The use of alerts and reminders in the electronic health record (EHR) has led to increased screening for other common conditions. The aim of our study was to measure the effectiveness of an EHR alert on the implementation of hepatitis B surface antigen (HBsAg) screening of foreign-born Asian and Pacific Islander (API) patients. We used a novel technique to identify API patients by self-identified ethnicity, surname, country of origin, and language preference, and who had no record of CHB screening with HBsAg within the EHR. Patients with Medicare and/or Medicaid insurance were excluded due to lack of coverage for routine HBsAg screening at the time of this study. At-risk API patients were randomized to alert activation in their EHR or not (control). A total of 2,987 patients met inclusion criteria and were randomized to the alert ( = 1,484) or control group ( = 1,503). In the alert group, 119 patients were tested for HBsAg, compared with 48 in the control group (odds ratio, 2.64; 95% confidence interval, 1.88-3.73; < 0.001). In the alert group, 4 of 119 (3.4%) tested HBsAg-positive compared with 5 of 48 (10.4%) in the control group ( = 0.12). An EHR alert significantly increased HBsAg testing among foreign-born APIs. Utilization of EHR alerts has the potential to improve implementation of hepatitis B-screening guidelines.