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Research Briefs May 2018

Antiviral Treatment May Not Matter To Mother–Child HBV Transmission

Tenofovir disoproxil fumarate (TDF), an antiviral used to treat hepatitis B virus (HBV) infection, does not significantly reduce mother-to-child transmission of the virus when taken during pregnancy and after delivery, according to a recent study.

The limited evidence of benefit from antiviral drugs to prevent mother-to-child transmission of HBV has led to conflicting practice recommendations, said Nahida Chakhtoura, MD, a member of the study team. The World Health Organization recommends that all newborns receive their first dose of HBV vaccine within 24 hours of delivery. Those born to HBV-infected mothers are also given hepatitis B immune globulin (HBIG) for added protection. However, they’re still at risk for the virus if the mother has high levels of the virus or a mutated version.

The phase 3 study, conducted at 17 hospitals in Thailand, enrolled 331 pregnant women with HBV. The women received placebo or TDF at intervals from 28 weeks of pregnancy to two months after delivery. All 294 infants received HBIG and five doses of the HBV vaccine, and were followed through the age of 6 months, at which time three infants in the placebo group and none in the TDF group had HBV infection.

“Our study suggests that adding TDF to the current regimen seems to have little effect on infant infection rates when transmission rates are already low,” Dr. Chakhtoura said.

Source: National Institutes of Health, March 2018

Ultra-Short TB Prophylaxis

It might take only one month of antibiotics—not nine months—to prevent tuberculosis (TB) in people with human immunodeficiency virus (HIV) infection, according to researchers from the National Institute of Allergy and Infectious Diseases (NIAID).

A phase 3 trial enrolled 3,000 people 13 years of age and older living with HIV. All participants lived in an area with a high TB burden or had a skin or blood test indicating latent infection. Among people with latent TB infection, HIV infection is the greatest risk factor for progression to active TB disease. About half of the patients were taking antiretroviral therapy. The patients were randomly assigned to a one-month course of rifapentine (Priftin, Sanofi-Aventis U.S.) plus isoniazid or nine months of isoniazid alone. They were monitored for an average of three years.

TB incidence was lower than expected and similar in both treatment groups: 32 participants in the one-month group and 33 in the nine-month group developed active TB. Regardless of treatment, TB rates were higher among participants who were not taking antiretrovirals when the study began and among those with positive TB tests.

Adherence was high in both groups, but significantly better with the shorter regimen, and fewer adverse events were reported in the one-month group.

Anthony Fauci, MD, Director of NIAID, and Robert Eisinger, PhD, Special Assistant for Scientific Projects at NIAID, have called for systems biology approaches using large datasets and modeling to understand how Mycobacterium tuberculosis infection causes disease. Noting that lengthy and complex treatment regimens make the disease increasingly difficult to cure, they say the ultimate treatment goal should be drug combinations administered for shorter time periods, as well as a safe and more broadly effective vaccine and rapid, inexpensive diagnostic tests for drug-resistant TB.

Source: National Institutes of Health, March 2018

Genes, Cigarettes, and Blood Pressure

Cigarette smoking may be the key that unlocks more genetic mysteries of blood pressure. Using a technique called “gene–environment interaction analysis,” National Institutes of Health researchers zeroed in on areas of the genome associated with blood pressure. Cigarette smoking, known to raise blood pressure, was an environmental “marker.”

The researchers tested different points of the genome in more than 610,000 people from five ancestry groups to find where cigarette smoking and blood pressure interacted.

They confirmed 56 known genetic regions and identified 83 new ones. Ten of the newly discovered genes appeared to have a much larger impact on smokers’ blood pressure versus nonsmokers’, the researchers said—levels were as much as eight times higher.

Previous genetic studies have identified genes and genetic regions associated with blood pressure, but have not explored the interplay between genes and environmental factors, the researchers said. Moreover, the broad cohort of the new study makes the findings more widely useful: Most of the known genetic regions linked to blood pressure were identified through European descendants. In this study, several novel regions were identified through African ancestry analysis, “highlighting the importance of pursuing genetic studies in diverse populations.”

Source: National Institutes of Health, March 2018

A Brief History of Death Rates Among Women

Life expectancy at birth for women increased by more than 32 years from the beginning of the 20th century to the beginning of the 21st. Much of the improvement happened in a relatively short time—between 1900 and 1950. Sanitation improved, bringing clean drinking water and safe disposal of sewage, which reduced deaths due to infection and chronic diseases. Improved housing, better education, greater income, and reduced poverty also influenced the incidence of infectious diseases and reduced contagion.

Researchers from the Centers for Disease Control and Prevention analyzed trends for all-cause unadjusted death rates from 1900 through 2010 and computed age-adjusted, all-cause death rates. But as changes in some environmental factors improved life expectancy, other changes took their toll. And often, environmental influences fluctuated. Cigarette smoking, for instance, rose rapidly during the 1930s, peaked between 1965 to 1975, then began to fall. Death rates for heart disease increased 97% in the first five decades, and then declined by 71%. Death rates for cancer rose, then dropped. Stroke rates declined steadily. On the other hand, the researchers found a “dramatic rise” in mortality rates due to respiratory system cancers and chronic respiratory disease.

Rates for infectious diseases dropped the most. In 1900, the five major causes of death for females were pneumonia and influenza, tuberculosis, enteritis and diarrhea, heart disease, and stroke. Of those, only heart disease and stroke were among the five major causes in 2010.

The researchers found a “notable” lack of large increases in unintentional motor vehicle (UI-MV) deaths. Although the number of automobiles and highways increased exponentially, deaths per mile driven reached a low in 1930 and kept dropping thereafter, probably due to safety measures. Since 2007, drug-overdose deaths among women have risen rapidly and overtaken deaths from UI-MV.

Although some causes of death, particularly heart disease and stroke, decreased as a result of behavior change and better health care, the researchers say, decreases in mortality rates are slowing. They caution about the “persistent prevalence” of risky behaviors and underuse of preventive and medical services, especially in racial minority populations.

Source: Preventing Chronic Disease, March 2018

An Easier Way to Track Genetic Influences

The research paradigm had been: Examine a person’s traits or symptoms, then search for genes or gene variants that cause or contribute to them. But it was difficult for researchers to re-contact people with genotypes of interest for “downstream” follow-up.

Now, the National Institutes of Health (NIH) and Inova Health System are launching The Genomic Ascertainment Cohort (TGAC), a two-year pilot project that will allow researchers to recall genotyped people and examine the influence of genes and gene variants on phenotypes. “It’s essentially matchmaking between genes and gene variants and the researchers who study them,” says Richard Siegel, MD, PhD, TGAC Co-Organizer, and Clinical Director and Chief of the Autoimmunity Branch at the National Institute of Arthritis and Musculoskeletal and Skin Diseases. For instance, a researcher might locate a genotype of interest in the database and ask participants with the genotype to come to the NIH Clinical Center in Bethesda.

Participating NIH institutes will contribute genome and exome sequences from existing research programs to the database. Another 1,000 patients will be recruited to have genome sequencing performed.

“We’re trying to advance science in a new, creative, and slightly radical way,” says Leslie Biesecker, MD, TGAC Co-Organizer and Chief of the Medical Genomics and Metabolic Genetics Branch at the National Human Genome Research Institute. “We’re especially interested in using this as a platform to test our ability to predict phenotype from genotype—one of the key underpinnings of predictive genomic medicine.”

Source: National Institutes of Health, March 2018

Life After Liver Transplantation

Liver transplantation is “one of the most resource-intense procedures despite significant improvements in procedures and protocols,” say researchers from Seoul National University Hospital. But little is known about the “practical aspects of life after liver transplantation,” such as unplanned visits to the emergency department (ED) or readmission for complications. So the researchers conducted a study to find out what health care resources are used after discharge.

Of 430 patients, half visited the ED at least once, and 57% were readmitted at least once. The rate of ED visits rose from 15% at 30 days after discharge to 44% at one year. Readmission rates more than tripled from 16% at 30 days to 52% at one year.

Contrary to other research, living donor liver transplantation (LT) was not a risk factor of readmission. Emergency LT was a risk factor for ED visits and readmission within 30 days of discharge. And, while LT using the left liver lobe and preexisting hepatitis C are known risk factors for long-term graft failure, at the researchers’ hospital hepatitis B is the most common indication for living donor LT. Most of their patients undergo LT using the right liver lobe.

Some of the risk factors were unexpected, the researchers say. One was donor age younger than 60 years. Warm ischemic time of 15 minutes or longer was another. The researchers note that prolonged warm ischemic time increases hepatic ischemia and reperfusion injury and is related to postoperative complications, which can be a cause of frequent readmission.

Length of stay (LOS) longer than two weeks was also a risk factor for readmission. In their institution, the average LOS for patients with a warm ischemic time of less than 15 minutes was 15.6 days, shorter than the overall average LOS. Shorter LOS, the researchers add, may reflect fewer immediate postoperative complications.

Although they identified no specific complication as a risk factor for readmission, they did find specific conditions that accounted for a relatively high proportion of readmissions and repeated readmission, including abnormal liver function tests and fever. The researchers suggest those are conditions to monitor and manage.

Notably, patients who did not require readmission or ED visits in the first 20 months almost never required unplanned health care resources thereafter.

Source: Scientific Reports, March 2018