Liver specialists in Nevada are seeing an increase in patients since health officials in February announced an outbreak of hepatitis C cases linked to an endoscopy clinic.

Dr. Robert Gish, a California physician who has had a part-time practice in Nevada for the past two decades, said his patient load has doubled since the outbreak was made public. Some of his new patients underwent procedures at the 700 Shadow Lane facility and have tested positive for hepatitis C. Other patients are just learning they have the disease and are seeking treatment, Gish said.

Dr. Donald Hillebrand, another liver specialist from California with a part-time Nevada practice, said his patient load "has picked up substantially."

Hillebrand was hired by Southwest Medical Associates in April to help with an anticipated growth in liver patients as a result of the outbreak, linked to the Endoscopy Center of Southern Nevada, 700 Shadow Lane.

Hillebrand said he is seeing two general types of liver patients in Southern Nevada. One group is composed of those with end-stage liver disease; the other consists of general hepatology patients, those with hepatitis C or B or who just need a liver doctor.

Author: 

Zobair M. Younossi, MD, MPH, FACP, FACG

Introduction

Chronic hepatitis C continues to be the most important cause of chronic liver disease in the United States, potentially resulting in cirrhosis, hepatocellular carcinoma, and the need for liver transplantation. The only US Food and Drug Administration-approved treatment for hepatitis C is combination therapy with pegylated interferon alfa and ribavirin (standard of care), which leads to a sustained virologic response (SVR) in approximately 80% of patients infected with hepatitis C virus (HCV) genotype 2, approximately 60% to 65% infected with genotype 3, and approximately 40% of patients infected with HCV genotype 1.[1-3] If SVR is achieved, durable response is quite likely, providing patients with an excellent chance for long-term viral eradication.

In addition to a relatively low SVR rate in HCV genotype 1 patients, other challenges associated with the current anti-HCV treatment regimen are its side effects and the required duration of therapy, both of which interfere with patients' adherence to the full course of antiviral therapy. In fact, recent reports suggest that the inability to maintain the optimal dose of both pegylated interferon alfa and ribavirin, especially early in the course of treatment, is associated with a lower rate of response to the current standard of care therapy.[3] This may explain, in part, the difference between response rates reported in randomized clinical trials (indicating the efficacy of treatment) compared with the response rates reported in clinical practices (indicating the effectiveness of treatment). To overcome these challenges, recent investigations have focused on optimal management of treatment-associated side effects such as anemia and depression.[1-3]

In addition to managing side effects, research has also focused on developing models to predict low response probability in an effort to avoid futile treatment, and high response probability in an effort to support a full regimen for patients likely to achieve viral eradication. These predictive models are based on viral kinetic data at weeks 4, 12, and 24. Patients who achieve rapid virologic response (RVR; undetectable HCV RNA [< 10 IU/mL] by polymerase chain reaction [PCR] after 4 weeks of treatment) have an excellent chance of achieving SVR.[1,2] In contrast, failure to achieve an early virologic response by week 12 of treatment (a minimum of 2-log drop in HCV RNA from the baseline value) is a reliable negative predictor of response to this combination therapy regimen.[1,2] Furthermore, patients who continue to have detectable virus after 24 weeks of therapy are unlikely to achieve SVR and are considered "nonresponders" to combination therapy.

Although findings on viral kinetics and adherence can help clinicians individualize therapy and maximize SVR, many patients, especially those infected with HCV genotype 1, fail to respond to the current standard-of-care treatment. This has led to the development of new strategies and medications for HCV treatment. Although a number of approaches are under consideration, 3 strategies appear most promising: (1) improving the pharmacokinetics and side-effect profile of interferon; (2) improving the pharmacokinetics and side-effect profile of ribavirin; and (3) targeting viral enzymes required for HCV viral replication. This report discusses the most recent findings with regard to these new approaches to the treatment of HCV infection, with special focus on specifically targeted antiviral therapy for hepatitis C (STAT-C) regimens.[4,5]

» Long term follow up results from chronically infected Hepatitis C patients strongly confirm and exceed positive data obtained earlier in 2008

» Study is the first to show a statistically significant and long?term antiviral effect of therapeutic Hepatitis C vaccination
» Data pave the way and strongly support move into a second generation vaccine formulated with Intercell?s adjuvant IC31® acting through TLR activation
 

Vienna, Austria, September 3, 2008 – Today, Intercell AG (ICLL) announced the six months follow up data of its exploratory clinical Phase II study targeting treatment?naïve Hepatitis C genotype?1 patients. As previously reported in February 2008, in this trial the therapeutic Hepatitis C vaccine (IC41) comprising five synthetic T?cell peptides and Intercell's firstgeneration poly?Arginine adjuvant (IC30) disclosed a statistically significant reduction of viral load in the blood of chronically infected patients up to 2 weeks after the last vaccination. The current long term follow up results show that this reduction was significantly more pronounced at six months after the final vaccination.

Author - Z. M. Younossi
Aliment Pharmacol Ther.2008;28(1):2-12

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome.
Aim: To assess the epidemiological impact and the current management of patients with NAFLD.
Methods: Published peer-reviewed literature and abstracts concerning NAFLD and non-alcoholic steatohepatitis (NASH) were reviewed. Articles specifically related to epidemiology, diagnosis and current treatment strategies for NAFLD and NASH are summarized.
Results: NAFLD is strongly associated with the epidemic of obesity and type-2 diabetes mellitus, and is estimated to affect about 20-30% of the population in the US. From the spectrum of NAFLD, only patients with biopsy-proven NASH (estimated prevalence in the US population is about 3-5%) have been convincingly shown to progress to cirrhosis, liver failure and hepatocellular carcinoma. The clinical manifestation of NAFLD is usually absent or subtle, with abnormal aminotransferases or incidental radiographic findings of fatty liver. The pathogenesis of NAFLD is attributed to a multi-hit process involving insulin resistance, oxidative stress, apoptotic pathways, and adipocytokines. In 2008, there is no established treatment for NAFLD. Weight loss and treatment for each component of metabolic syndrome. Nevertheless, a large number of agents are being considered in clinical trials of patients with NASH.
Conclusions: Awareness of the tremendous impact of NAFLD as an important cause of chronic liver disease is increasing along with a great deal of information about its pathogenesis. Future, well-designed clinical trials that target specific pathways involved in the pathogenesis of NASH are urgently needed.

The fight against the liver disease hepatitis C has been at something of an impasse for years, with more than 150 million people currently infected, and traditional antiviral treatments causing nasty side effects and often falling short of a cure. Using a novel technique, medical and engineering researchers at Stanford University have discovered a vulnerable step in the virus' reproduction process that in lab testing could be effectively targeted with an obsolete antihistamine.

The new research published in the Aug. 31 online version of Nature Biotechnology.

The advance involves two new discoveries. One is that a protein called NS4B is instrumental in binding some of the genetic material, or RNA, and allowing the hepatitis C virus to replicate. The other is that the former anti-itching drug clemizole hydrochloride could hinder that protein, resulting in a tenfold decrease in virus replication with no apparent harm to infected liver-like cells. Because the drug has already been used by people, it is eligible for human testing.

"We're excited about this and we're actively moving forward toward clinical trials," said virology expert Jeffrey Glenn, MD, PhD, associate professor of gastroenterology and hepatology. Glenn is one of two senior authors of the paper. The lead authors are postdoctoral scholars Shirit Einav, MD, in medicine, and Doron Gerber, PhD, in bioengineering.