Causes of hepatitis and potential therapies that may improve care presented in study

Hepatitis, a potentially serious disease caused by a virus that attacks the liver, is a major problem worldwide. Hepatitis A is generally foodborne, while hepatitis B and C spread primarily through parenteral or sexual routes. Hepatitis B and C can be life-long, potentially deadly chronic infections.

In studies presented today at Digestive Disease Week in New Orleans, researchers analyzed the causes of hepatitis and potential therapies that may improve care. Digestive Disease Week (DDW) is the largest international gathering of physicians, researchers and academics in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery. “The hepatitis viruses, primarily A, B and C, are prevalent throughout the world, and safe and effective therapies are not available for many sufferers,” said Anna Lok, M.D., of the University of Michigan. “Once we can fully understand how these viruses cause liver damage, we can develop more effective treatments to manage and cure the disease.”

According to current estimates, coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) is a major worldwide public health problem. Researchers in the VA Healthcare System examined the proportion of chronic HCV-infected patients who had been tested for HIV and related risk factors and found that improved screening programs are needed.

Data was prospectively collected in 4,364 HCV RNA positive patients undergoing evaluation for HCV therapy from 24 medical centers throughout the country over a one-year period. Of these patients, 77.9 percent had been tested for HIV, 15 percent were never tested, 6.7 percent did not know if they were tested, and 0.4 percent declined to answer. Among the HCV-infected patients who were tested for HIV, 8.4 percent were positive, 88.9 percent were negative, 2.5 percent did not know the results of the HIV test, and 0.2 percent declined to answer.

“Although the majority of our HCV-infected patients have been tested for HIV, there is still a substantial proportion who were either not tested or were tested but did not know the results,” said Edmund Bini, M.D., lead author of the study. “Better public health programs to improve HIV awareness among these patients and those at high risk of coinfection are important and should be developed.”

Patients who contract the hepatitis B virus can experience a brief, acute illness or a chronic, life-long infection. Those with chronic hepatitis B (HBV) can have serious complications such as cirrhosis, liver failure and liver cancer. Until now, it has been difficult to identify HBV patients who are likely to develop complications. A team of doctors led by Anna Lok, M.D. from the University of Michigan report today that they have developed a set of models based on laboratory test results to detect inflammation and fibrosis in the liver.

“We’re pleased that for some chronic hepatitis B patients, demographic and laboratory data enable us to predict liver injury thus avoiding the need for a liver biopsy,” said Anna Lok, M.D., lead author of the study. “Ability to determine the severity of liver injury using readily available clinical data will allow us to make more informed treatment decisions and improve quality of life for our patients.”

To identify these predictive models, researchers reviewed baseline data and liver histology from HBV patients who participated in trials of adefovir therapy for both HBeAg+ (hepatitis B e antigen positive, 494 pts) and HBeAg- (hepatitis B e antigen negative, 178 pts).

The analysis identified patients with Knodell inflammatory score of eight or greater, and those with an Ishak fibrosis score of three or higher. Based on logistic regression models, inflammation was predicted using the variables albumin (a protein indicating proper liver function) and aspartate aminotransferase (AST) enzyme levels. Fibrosis was predicted in HBeAg+ patients using age, AST, serum alkaline phosphatase (SAP), prothrombin and bilirubin levels as variables. In HBeAg- patients, the best model used the variables of platelets, AST/ALT (aspartate to alanine aminotransferase) ratio and SAP.

The Knodell inflammatory score is a numerical scoring system (0-18) that grades the degree of inflammation in liver biopsies, and the Ishak fibrosis score (0-6) is a scoring system that stages the degree of fibrosis in liver biopsies.

Current therapies for hepatitis C virus (HCV) have considerable side effects and only induce a sustained virologic response in less than half of patients infected with HCV genotype 1, the most common genotype in the U.S., Europe and Japan (60-70 percent of patients). In this study, researchers from Bach and Godofsky found that a novel hepatitis therapy, NM283, has consistent antiviral activity and is well tolerated in HCV-1 infected chronic hepatitis C patients.

The phase I/II dose escalation trial is investigating NM283, a novel candidate HCV RNA polymerase inhibitor, which has shown anti-flavivirus activity in vitro, and has suppressed viremia in chimpanzees infected with chronic human-derived HCV-1. This preliminary human study is of treatment-naïve or experienced adults with HCV-1-associated chronic hepatitis C. A total of 48 patients divided into 12-patient cohorts (randomized 10:2) received NM283 or placebo for 15 days with 14 days of follow-up, at doses of either 50, 100, 200, or 400 milligrams per day, orally.

Dose-related decreases in serum HCV RNA were noticed at day 16, and tolerance of the study treatment has been satisfactory, with no serious adverse events, dose-limiting toxicities, or pattern of laboratory abnormalities. The treatment is well-absorbed, with dose-proportional plasma exposure.

“These preliminary results show that this novel therapy may be a superior option for treating HCV-1 hepatitis C patients, with successful performance and tolerance levels,” said Eliot Godofsky, M.D., lead author of the study. “While we strive to improve the efficacy of treatments for this large patient population, we also believe in the importance of helping patients maintain a better quality of life.”

Comments

The opinions expressed here are the views of the writer and do not necessarily reflect the views and opinions of News Medical.
Post a new comment
Post

While we only use edited and approved content for Azthena answers, it may on occasions provide incorrect responses. Please confirm any data provided with the related suppliers or authors. We do not provide medical advice, if you search for medical information you must always consult a medical professional before acting on any information provided.

Your questions, but not your email details will be shared with OpenAI and retained for 30 days in accordance with their privacy principles.

Please do not ask questions that use sensitive or confidential information.

Read the full Terms & Conditions.

You might also like...
Global and Local Efforts to Take Action Against Hepatitis