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Researchers make advances in understanding causes, treatments and outcomes of liver disease

( Digestive Disease Week ) Non-alcoholic fatty liver disease (NAFLD), which may soon be the leading indication for liver transplant, is found to be significantly associated with worse transplant outcomes. In addition, a new tool for diagnosing NAFLD represents an alternative to liver...

NEW ORLEANS, LA (May 2, 2010) - Non-alcoholic fatty liver disease (NAFLD), which may soon be the leading indication for liver transplant, is found to be significantly associated with worse transplant outcomes. In addition, a new tool for diagnosing NAFLD represents an alternative to liver biopsy, which is more expensive and prone to complications, and ultrasound and alfafeprotein blood test screening are an effective alternative to CT scan and MRI for patients with cirrhosis at high risk for hepatocellular cancer. These are among the research findings being presented at Digestive Disease Week® (DDW®) 2010. DDW is the largest international gathering of physicians and researchers in the field of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.

"NAFLD is a growing concern in the U.S. and the research presented here gives us a better understanding of its influence on transplant outcomes as well as alternatives in diagnosing the condition," said Frank Anania, MD, AGAF, Emory University School of Medicine, associate professor of medicine, director of hepatology.

The Influence of NAFLD and Its Associated Comorbidities on Liver Transplant Outcomes (Abstract #S1858)

NAFLD is significantly associated with worse transplant outcomes (death and graft failure) within the first 30 days after transplant, according to new research from the University of North Carolina (UNC), Chapel Hill.

NAFLD is a rising epidemic in the U.S., fueled in part by the dual epidemics of obesity and diabetes. As NAFLD increases in incidence and prevalence, researchers say they expect it to become the leading indication for liver transplantation in the next two decades. Unfortunately, the same risk factors for NAFLD - diabetes, obesity, high blood pressure and high cholesterol - are also risk factors for heart disease.

Researchers used a retrospective cohort study design to analyze 118 liver transplants over a three-year period. Besides NAFLD, diabetes was also associated with worse outcome and having poorer survival at three years after transplant. High blood pressure, high cholesterol and obesity were not independently associated with death or graft failure.

The study builds on previous research published in 2009, which reached similar conclusions. However, the group at UNC was able to use a stronger study design with a more extensive accounting of donor, operative and patient characteristics.

"Patients with NAFLD may need a more thorough pre-operative assessment prior to listing for liver transplant," said A. Sidney Barritt IV, MD, MSCR, fellow in advanced hepatology and liver transplant, UNC, Chapel Hill. "Future work should determine strategies to decrease perioperative mortality among patients with NAFLD."

That said, the study is a single center experience with a relatively small number of patients, so the researchers are actively building a consortium of transplant centers to research liver transplant outcomes. They aim to repeat a similar study on a much larger scale to validate their findings.

Dr. Barritt said despite the findings, patients with NAFLD will continue to be considered for liver transplant. "Our intent is to find ways to improve transplant outcomes for this population and to ensure that liver transplantation remains a viable, cost-effective intervention for all people with liver disease," he said.

Dr. Barritt will present these data on Sunday, May 2 at 8 a.m. CT in Hall F, Ernest N. Morial Convention Center.

Can the NAFLD Fibrosis Score be used as a Prognostic Predictor for Poor Outcomes of NAFLD Patients? (Abstract #S1848)

Researchers from Chulalongkorn University, Bangkok, Thailand, and the Mayo Clinic have developed a scoring system that for the first time appears to predict liver complications or even death in patients with NAFLD.

NAFLD is one of the most common causes of chronic liver disease and its prevalence is rising, in part because of the increasing incidence of obesity. Liver biopsy is widely considered the gold standard to diagnose the severity of NAFLD, but it is expensive, invasive and associated with a number of complications. Currently, there are no medications to treat fatty liver effectively.

To address this issue, researchers developed a simple tool, the "NAFLD fibrosis score," a composite score of variables, including medical history, age, high blood sugar and body mass index, as well as variables from blood tests including platelet count, albumin and AST/ALT ratio (liver tests). These factors were found to be an indicator for separating NAFLD patients with and without advanced or severe liver fibrosis at the initial NAFLD diagnosis. Participants were predominantly middle-aged (47 years; range 21 to 86 years), were white (95 percent) and 44 percent were male. Obesity was present in 73 percent of the population. History of high blood sugar and high blood pressure were found in 16 percent and 41 percent respectively.

Researchers used data from a cohort study of fatty liver patients diagnosed from 1980 to 2000 including 302 patients with an average follow-up of 12 years and found: the NAFLD fibrosis score change per year in patients who died was significantly higher than in those who survived; intermediate to high probability of advanced liver fibrosis assessed by NAFLD fibrosis score were found in 40 percent of patients; and higher NAFLD fibrosis score at baseline, less often use of metformin and higher creatinine at the end of follow up significantly predicted death or development of liver complication in patients with fatty liver. Results also showed that 40 percent of patients with fatty liver were in an intermediate or high probability of advanced liver fibrosis at baseline and most of them (94 percent) were still in advanced liver fibrosis group at the end of follow up.

"This quantitative scoring system should be calculated for all patients with NAFLD at initial consultation to estimate the probability of advanced liver fibrosis without additional costs," said Sombat Treeprasertsuk, MD, a gastroenterologist from Chulalongkorn University, Bangkok, Thailand, and the Mayo Clinic, Rochester, MN. "Once providers identify patients with fatty liver who have a high score or high risk of poor outcomes, they can set up a customized follow-up regimen for these patients." The test can then be recalculated to monitor progress.

Dr. Treeprasertsuk cautioned that when the tool shows a high risk of death or development of liver complications, be mindful that every diagnostic test has a true positive or a false positive result. He also encouraged people to improve their liver health through lifestyle, diet and regular exercise.

Dr. Treeprasertsuk will present these data on Sunday, May 2 at 8 a.m. CT in Hall F, Ernest N. Morial Convention Center.

Use of Ultrasound as the Initial Imaging Exam for Hepatocellular Carcinoma in High Risk Population (Abstract #S1278)

Patients with cirrhosis who are at high risk for developing heptatocellular cancer (HCC) can be effectively screened via ultrasound and alfa fetoprotein (AFP) blood test screening, rather than more costly CT or MRI scans. Researchers from the University of Texas Medical Branch at Galveston found that results from ultrasound and AFP screenings were accurate in detecting HCC. High levels of AFP are considered a biomarker for HCC.

To test the accuracy and sensitivity of standard monitoring procedures for patients with cirrhosis for the development of HCC, researchers retrospectively compared standard monitoring of ultrasound with AFP screening to subsequent results from CT or MRI scans performed within six months of the initial screening. Researchers found ultrasound alone was 99 percent specific and 76 percent sensitive in the detection of HCC. When elevated AFP was screened, specificity increased to 100 percent and the sensitivity to 87.5 percent.

"These findings emphasize the importance of using ultrasound, together with alfa fetoprotein, as the initial screening protocol, and provide a road map for when additional screening procedures, like CT and MRI scans should be undertaken," said Roger D. Soloway, MD, Marie B. Gale Centennial professor of internal medicine, University of Texas Medical Branch, gastroenterology, hepatology and nutrition division, department of internal medicine. "This data can lead to decreased use of CT without sacrificing detection rate significantly."

This retrospective analysis of demographic and laboratory data included 160 cases in which an initial ultrasound was performed followed by a CT or MRI within six months; this group included 34 cases of suspected HCC. From these suspected cases, 26 patients were correctly identified as having HCC by ultrasound. In eight cases in which ultrasound was falsely negative and CT found a lesion, the average AFP level was 32,325 ng/mL. In the 125 patients with a true negative ultrasound, the average AFP was 17.14 ng/mL. This group had only 12 patients, with an AFP greater than 20 ng/mL, and only one who had an AFP greater than 400 ng/mL.

For the entire population of patients, the positive predictive value of ultrasound for detecting HCC was 96.3 percent, while the negative predictive value was 94 percent. Only two patients had a negative ultrasound, with a normal AFP level and still had HCC.

These findings demonstrate that even with high risk patients, if ultrasound does not show a focal lesion and the AFP is normal, these standard monitoring tests should be repeated in six months. If the ultrasound does not show a focal lesion but the AFP is elevated (> 20 ng/mL), a CT and AFP should be obtained in three months as follow up.

"Ultrasound can eliminate more expensive imaging studies until confirmation is necessary, helping to reduce the overall cost of medical monitoring for patients in heptatocellular cancer screening populations," said Dr. Soloway. He cautioned that, while ultrasound is an effective screening for this group, it is not as sensitive as CT for detecting HCC.

Dr. Soloway will present these data on Sunday, May 2 at 8 a.m.. CT in Hall F, Ernest N. Morial Convention Center.

The Significance of Buprenorphine Use and Adherence in AntiHCV Treatment Outcome in Drug Users (Abstract # M1883)

A new study shows successful treatment of intravenous drug users (IVDUs) with hepatitis C virus (HCV) when treated concurrently with anti-viral and opioid substitution therapies. Intravenous drug use is a main cause of HCV transmission in Western countries, and IVDU patients with HCV are generally treated on a case-by-case basis according to current guidelines because of concerns regarding low adherence and response rates in treatment.

Investigators from The Greek Organisation Against Drugs (OKANA) and the Medical Schools of Athens and Thessaloniki evaluated common anti-HCV treatment outcomes in IVDUs receiving methadone or buprenorphine. Patients were evaluated on their adherence to treatment and the sustained virologic response (SVR) to medication, meaning no HCV RNA was detectectable by blood tests for an extended period of time following treatment.

From 2002 to 2008, 95 IVDUs with chronic HCV infection started antiviral treatment. All of them were treated with opioid-substitution therapy, 46 with methadone and 49 with buprenorphine. More than 82 percent of patients completed the treatment schedule, while seven patients discontinued treatment due to side effects and nine patients due to their own decision. SVR was observed in 66.3 percent of patients with six months post-treatment data available; 15 patients were non-responders or relapsed and 17 had not completed the treatment schedule or were lost to follow up.

SVR was higher in patients who were adherent to treatment (adherent versus discontinuation side effects versus discontinuation by own decision: 77.9 percent versus 28.6 percent versus 0 percent). Buprenorphine was also found to be associated with higher rates of fulfilling treatment schedule compared to methadone (8.1 percent discontinuation versus 27.3 percent).

"Our research demonstrates that patients with hepatitis C virus infection can be effectively treated as long as they are kept adherent," said Olga Anagnostou, MD, OKANA. "Intravenous drug users with hepatitis C infection should not be excluded from treatment - especially when they are on substitution treatment."

The results of the Greek study suggest the reconsideration of eligibility criteria for initiation of an anti-viral treatment in IVDUs and revealed the crucial role that buprenorphine may play on improving adherence and response rates.

Dr. Anagnostou will present these data on Monday, May 3 at 12 p.m. CT in Ballroom C, Ernest N. Morial Convention Center.