University of Birmingham researchers may have found a way to halt the Hepatitis C virus (HCV) that causes liver failure in 95% of transplant patients.

liver

Re-infection of transplanted livers with the HCV virus can irreparably damage the new organ. The research team headed up by Professor Jane McKeating, Professor David Mutimer and Dr Ian Rowe have demonstrated that, if HCV can be stopped by a drug which blocks the virus entering the liver, the chances of the liver transplant being a success is greatly improved.

Dr Ian Rowe, who presented the research, said:  “This is the first trial in patients undergoing liver transplantation of a drug [known as ITX5061] that blocks HCV entry into the new liver. Until now we have only been able to study this process in the laboratory and this study has allowed us to learn about this process as it happens in patients.  ITX5061 treatment was safe and we hope that further studies of this drug in combination with others in development will improve the outcomes for this challenging group of patients.”

People who receive a new liver to replace an organ damaged by HCV infection are 95 per cent likely to experience recurrent infection after the transplant. The virus can be fast developing and can surpass pre-transplant levels within a few days.  More importantly, viral replication and ensuing injury can be more aggressive after the liver transplantation. This often means that the new liver becomes damaged, and to a level at which it can cease to function in just a few years. As many as a quarter of HCV infected patients who receive a transplant will experience liver failure, possibly leading to death, within ten years.

HCV is the second biggest cause of chronic liver disease leading to a transplant in the UK, and the leading cause in the USA. The Health Protection Agency (HPA) estimate that by 2020 15,840 individuals will be living with hepatitis C-related cirrhosis or cancer in England, more than 4,200 with decompensated cirrhosis or cancer for whom a liver transplant may be the only option.

Until now, doctors have been unable to prevent HCV, which circulates in the bloodstream, from entering the new liver – however results from a trial at Birmingham evaluating a HCV entry inhibitor drug, ITX5061, given before, during and after the transplant dramatically slows down the progress of the virus re-infecting the liver. Although the drug did not clear HCV completely from the blood of the patients, the results of this research suggest that it could be used as a treatment in conjunction with more conventional strategies.

The trial involved 23 patients undergoing liver transplantation.

Read more at the University of Birmingham

Image by: Clarita


New insights into the causes of our raging obesity epidemic are coming from an unusual source: locusts.

Australian scientist Stephen Simpson’s speaking at Harvard University explained how an animal on a calorie-rich, but protein-poor diet will keep eating until it gets the protein it needs and balloon. “We found that same pattern in a whole range of other animals,” Simpson said. “The other omnivore we found it in was us.”

Years of research into insect swarming behavior led Simpson, a leading obesity, diabetes and cardiovascular scientist, step by step from physiology to nutritional needs to a wider investigation of animal nutrition and, finally, to the human diet. Simpson began his research trying to understand why and how an ordinary grasshopper morphs into a locust, changing from a camouflaged, solitary animal into a social, aggressive, strikingly black-and-yellow member of an insect swarm. Early work showed that population density triggered the behavioral and physical changes. When populations of the grasshoppers, gathering because they’d been attracted by a food source, reached a critical threshold, they switched from being shy and avoiding contact to being social and swarming.

Then came an examination of the organization of swarms, and the finding that though the behavior is coordinated, the swarms contain no leaders. Instead, swarm behavior is driven by that of the individual reacting to nearby conditions. The major force among those local conditions is proximity to neighbours, because, it turns out, locusts are afraid of cannibalism.

Simpson examined the dietary needs of a related insect with similar swarming behavior, the Mormon cricket, by putting samples of carbohydrate, protein, mixed protein and carbohydrate, and a control without either in the path of a swarm that was marching rather than flying. The insects invariably gathered around the protein and the protein-carbohydrate meals, but ignored the all-carbohydrate meal and the one lacking both.

That work provided insight into swarms’ hunt for protein. And the largest protein source in a Mormon cricket swarm is the individual cricket. This explains not only their occasional cannibalism, but also the regimented behavior of the swarm, with the insects lining up a particular distance from one another and keeping a safe distance from hungry companions while marching or flying.

“It’s a forced march,” Simpson said. “These animals are protein-deprived in their habitat so chasing their neighbour and avoiding their neighbour is the driving motivation during swarms.”

A closer examination of the locust diet showed that the insects will seek out a balanced ratio of carbohydrates and protein. However, protein (critical in reproduction) is the most important driver.

When locusts were kept on diets high in carbohydrates but low in protein, they would overeat until they got their ideal protein level. That was not the case, however, when they were put on a protein-rich diet low in carbohydrates. Then, the animals would overeat, but would stop before they reached the ideal carbohydrate level, probably because of the potential toxicity of large amounts of protein byproducts. That meant that the animals lost weight on the high-protein diet, which provides insight into the effectiveness of the Atkins and other high-protein fad diets, Simpson said. An examination of other herbivores and omnivores — carnivores did not fit the mold — showed that mice, fish, birds, and one other important species followed that trend.

Simpson found the  same pattern in a range of other omnivorous animals - including humans.

An examination of the long-term effects of these diets showed the problems with staying on a high-protein diet for long periods of time, Simpson said. "While diets rich in protein are ideal for reproductive success, egg-laying in insects, they also shorten lifespan."

The Lecture: “Law of the Locusts: What Insect Swarms Teach Us about Cannibalism, Aging, and Human Obesity,” was sponsored by the Harvard Museum of Natural History,