TUESDAY, May 6 (HealthDay News) -- The grapefruit flavonoid naringenin inhibits the secretion of Hepatitis C virus (HCV) in infected cells and could offer a new approach for treating the disease, according to a Harvard Medical School study.

About 3 percent of the global population is infected with HCV, which can lead to cirrhosis and liver cancer. The current standard therapy of interferon and ribavirin is only effective in about 50 percent of cases and can cause major side effects, according to background information in the study.

Recent research suggests that HVC may be "hitching a ride" along the lipoprotein life cycle, and that compounds and dietary supplements that influence lipoprotein metabolism may also affect HCV.

In this new study, researchers demonstrated that HCV is actively secreted by infected cells while bound to a very low-density lipoprotein.

"Silencing apolipoprotein B (Apo-B) mRNA in infected cells causes a 70 percent reduction in the secretion of both ApoB-100 and HCV. This ApoB-dependent HCV secretion pathway suggests a novel therapeutic approach for the treatment of HCV infection," the researchers wrote.

They then tested the grapefruit flavonoid naringenin and found it reduced HCV secretion in infected cells by 80 percent.

"The concept of supplementing HCV patients' diets with naringenin is appealing," the researchers wrote. But they noted the intestinal wall doesn't absorb naringenin well, which means therapeutic doses of the flavonoid would have to be given by injection or combined with other compounds to boost its absorption by the intestines.

The researchers also noted that naringenin and several other compounds in grapefruit have significant drug-drug interactions.

"Future studies would focus on long-term ability of naringenin and perhaps other citrus flavonoids to reduce viral load in animal models and long-term cultures of primary human hepatocytes," the researchers concluded.

The study was published in the May issue of Hepatology.

More information

The U.S. Centers for Disease Control and Prevention has more about hepatitis C.

An increasing number of patients have kidney dysfunction while awaiting liver transplantation, which has led to debate among transplant experts about which patients are likely to develop kidney dysfunction after liver transplant and should be considered for combined liver/kidney transplantation.

This kind of decision is extremely difficult due to the lack of a reliable predictive model and the increasing shortage of organs available for transplant, according to background information in the study, led by Ranjeeta Bahirwani, of the University of Pennsylvania.

The study included 60 people who had liver transplants between March 2000 and August 2005, and had serum creatinine of at least 1.5 mg/dl for at least two weeks prior to, and at the time of, transplantation.

The patients were followed for a median of 36 months after their transplant, and only eight of them had significant kidney dysfunction. Those who had kidney dysfunction for more than 12 weeks before transplant were at increased risk for severe post-transplant kidney problems.

Diabetes and serum creatinine level at the time of transplant were other major predictors of severe post-transplant kidney problems.

"Our data are reassuring that the vast majority of patients with pre-transplant renal insufficiency do not develop advanced stage 4 or 5 chronic kidney disease," after liver transplant, the study authors wrote.

Serious post-transplant kidney disease was particularly rare among patients whose pre-transplant serum creatinine was elevated for less than 12 weeks. The researchers suggested that elevated serum creatinine levels for more than 12 weeks before transplant, the presence of diabetes, and the serum creatinine value at the time of transplant could help identify patients who might be considered for combined liver-kidney transplantation.

The study was published in the May issue of Liver Transplantation.

More information

The American Liver Foundation has more about liver transplantation.

Researchers evaluated 1,732 children, average age 42, of participants in the Framingham Heart Study, a long-term study of families in Framingham, Mass. The researchers found that people whose fathers were clinically obese at an early age were more likely to have increased liver enzyme (serum alanine aminotransferase -- ALT) levels, an indicator of liver disease.

When the researchers conducted a secondary analysis that didn't include obese offspring, they still found a strong link between elevated serum ALT levels and paternal early-onset obesity. This demonstrates that the link between obesity in the father and elevated serum ALT levels in children is independent of the offspring's body-mass index (BMI) and persists among non-obese children, the researchers said.

No relationship was found between early-onset obesity in mothers and ALT levels in their children.

"These findings show that familial factors may play a role in elevated serum ALT levels in the general population," study senior author Dr. Caroline S. Fox, medical officer with the Framingham Heart Study, said in a prepared statement.

The study was published in the April issue of Gastroenterology.

Serum ALT levels are a marker of liver disease in the general population, and previous studies have shown that there's a strong link between obesity and elevated serum ALT levels, according to background information in the study.

Up to 7 percent of the adult U.S. population has unexplained elevated ALT serum levels, according to the U.S. National Health and Nutrition Examination Survey. These elevated ALT serum levels may be due to nonalcoholic fatty liver disease (NAFLD), which is believed to be the most common cause of elevated ALT serum levels, which can lead to inflammation of the liver (hepatitis), scarring of the liver (cirrhosis), and liver cancer.

"Serum ALT elevations and NAFLD are more prevalent than ever in the U.S., though we don't know specifically what's causing the increase. Our results point to a genetic connection between early-onset paternal obesity and increased ALT levels," Fox said.

"This study is the first to look at the connection between parental early-onset obesity and elevated serum ALT levels in their children using objective clinical measurements of parental BMI instead of self-reports," study first author Dr. Rohit Loomba, of the Liver Diseases Branch of the U.S. National Institute of Diabetes and Digestive and Kidney Diseases, said in a prepared statement.

"Though we are looking at a very specific, community-based sample in our work, the results suggest an association between elevated serum ALT levels and early-onset paternal obesity. Additional studies are needed to assess whether this connection suggests a genetic predisposition to developing liver disease in larger populations," Loomba said.

More information

The American Liver Foundation explains the progression of liver diseases.

The increases occur from 1995 through 2004, the most recent year for which data are available. Death rates peaked in 2002, then declined slightly overall, according to the report, published in the April issue of Hepatology.

The most dramatic age-specific increases were observed among 45- to 54-year-olds who had an increase of 376 percent, and 55- to 64-year-olds who had an increase of 188 percent. For the latter group, rates rose for the duration of the study.

"The highest mortality rates were observed among males, persons aged 45 to 54 and 55 to 64 years, Hispanics, non-Hispanic blacks and non-Hispanic Native American/Alaska Natives," the authors wrote in the report. They suggested that demographic differences are related to prevalence among the various populations.

Hepatitis C virus (HCV) is the most common blood-borne infection in the United States, affecting about 1.3 percent of the population. Up to one in five sufferers develop liver cirrhosis, and up to one in 20 develop liver cancer.

HCV is the top reason for liver transplantation, and the 16th leading cause of premature death in the country. Recent evidence has suggested that disease burden and mortality from chronic HCV infection may increase in the coming years, as the number of persons with longstanding infections continues to rise.

During the study period, HCV-related mortality rates increased from 1.09 deaths per 100,000 persons in 1995 to 2.57 per 100,000 in 2002, before declining slightly to 2.44 per 100,000 in 2004. Average annual increases were smaller from 2000 to 2004 than 1995 to 1999.

The new figures came from researchers analyzing mortality rates derived from U.S. Census and multiple-cause-of-death data from 1995 to 2004. They included 56,409 HCV related deaths.

The observed increases likely reflect both true increases in mortality and the growing use of serologic tests for HCV, the authors said.

"The relatively young age of persons dying from hepatitis C-related liver disease has made hepatitis C-related disease a leading infectious cause of years of potential life lost as well as an important cause of premature mortality overall," the authors concluded.

More information

The National Institute of Diabetes and Digestive and Kidney Diseases has more about Hepatitis C .

WEDNESDAY, March 5 (HealthDay News) -- Mice given the weight-loss drug rimonabant became resistant to alcohol's fat-building effects in the liver, which suggests the medication may help fight alcoholic fatty liver in humans, says a U.S. study.

Alcoholism is the leading cause of liver disease in Western societies, according to background information in the study.

Rimonabant, which blocks cannabinoid receptors, is approved for weight loss in several European countries but has not been approved in the United States. Last June, a U.S. Food and Drug Administration panel recommended that rimonabant should not be given the FDA's blessing because of continuing concerns about increased risks for suicidal thoughts among some users.

In this latest study, the researchers found that mice fed a low-fat diet and ethanol showed an increase in the gene encoding the CB1 cannabinoid receptor and in liver levels of an endocannabinoid called 2-arachidonoylglycerol (2-AG). These mice developed fatty livers.

Another group of mice that received the same diet plus rimonabant did not differ from mice fed a control diet. And mice lacking CB1 receptors, either throughout the body or only in the liver, were protected from alcoholic fatty liver.

"What makes these findings particularly interesting from our perspective is that they may have practical implications," said study author George Kunos, of the U.S. National Institute on Alcohol Abuse and Alcoholism. "Treatment of animals with a [cannabinoid receptor] antagonist largely prevented alcohol's effect. It suggests that the development of fatty liver in those who use alcohol could be interfered with, or perhaps reversed, with such treatment."

The findings were published in the March issue of Cell Metabolism.

"Although alcoholic fatty liver is reversible in the early stages by cessation of drinking, this is often not feasible," the study authors wrote. "The present findings suggest that treatment with a CB1 antagonist may slow the development of fatty liver and thus prevent its progression to more severe and irreversible forms of liver disease."

Drugs that selectively act on CB1 receptors found outside of the brain might help fight fatty liver with less risk of side effects such as anxiety and depression, they said.

"Rimonabant has recently been introduced in Europe for the treatment of visceral obesity and the metabolic syndrome, which themselves are known risk factors for [liver disease]. Clinical trials testing the effectiveness of CB1 receptor blockers in the treatment of both alcoholic and nonalcoholic fatty liver and their more severe sequelae may be warranted," the researchers concluded.

More information

The American Liver Foundation has more about fatty liver.