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Cirrhosis
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Predicting Progression to Cirrhosis
in Chronic HCV Infection Researchers undertook a systematic evaluation of published studies to identify factors associated with accelerated fibrosis progression in patients with chronic hepatitis C virus (HCV) infection. An ecologic analysis was used to estimate relative risk (RR) of cirrhosis across four study methodologies: liver clinic series, post-transfusion cohorts, community-based studies and blood donor series. In each study category, the following factors were independently associated with disease progression:
After adjusting for these cofactors, older age at HCV infection and acquisition of HCV through blood transfusion were not implicated in influencing disease outcome. Although not able to be examined in this study, co-infection with HIV, and to a lesser extent HBV, is also likely to result in worse outcomes for patients with chronic HCV infection. Virological factors such as HCV genotype, viral load and quasi-species diversity are less likely to be important. A Weibull distribution was used to model disease progression at a population level. The influence of cofactors on individual prognosis was examined and an algorithm to predict the risk of subsequently developing cirrhosis is presented. 08/04/03
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Platelet count/spleen diameter ratio: proposal and validation of a non-invasive parameter to predict the presence of oesophageal varices in patients with liver cirrhosis
Gut 2003;52:1200-1205 © 2003 by BMJ Publishing Group & British Society of Gastroenterology LIVER Platelet count/spleen diameter ratio: proposal and validation of a non-invasive parameter to predict the presence of oesophageal varices in patients with liver cirrhosis E Giannini1, F Botta1, P Borro1, D Risso2, P Romagnoli1, A Fasoli1, M R Mele1, E Testa1, C Mansi1, V Savarino1 and R Testa1 1 Gastroenterology Unit, Department of Internal Medicine, University of Genoa, Italy 2 Medical Statistics Section, Department of Health Sciences, University of Genoa, Italy Correspondence to: Professor R Testa, Gastroenterology Unit, Department of Internal Medicine (DIMI), Viale Benedetto XV No 6, 16132 Genova, Italia; rtesta@unige.it ABSTRACT Background and aims: Cirrhotic patients frequently undergo screening endoscopy for the presence of oesophageal varices (OV). In the future, this social and medical burden will increase due to the greater number of patients with chronic liver disease and their improved survival. In this study, our aims were (1) to identify clinical, biochemical, and ultrasonographic parameters which might non-invasively predict the presence of OV in patients with liver cirrhosis; (2) to evaluate the reproducibility of the obtained results in a different, although related, further group of patients; and (3) to assess the predictiveness of the identified rules in patients with compensated cirrhosis. Methods: In the first part of the study we retrospectively evaluated the presence of OV in 145 cirrhotic patients, and in the second part we evaluated the reproducibility of the study results in a subsequent group of 121 patients. Finally, we evaluated these parameters in a subgroup of 145 patients with compensated disease. All 266 patients underwent a complete biochemical workup, upper digestive endoscopy, and ultrasonographic measurement of spleen bipolar diameter. Platelet count/spleen diameter ratio was calculated for all patients. Results: The prevalence rates of OV were 61% and 58% in the first and second groups of patients, respectively. In the first part of the study, we found that platelet count, spleen diameter, platelet count/spleen diameter ratio, and Child- Pugh class were significantly different among patients with or without OV, although the platelet count/spleen diameter ratio was the only parameter which was independently associated with the presence of OV in a multivariate analysis. A platelet count/spleen diameter ratio cut off value of 909 had 100% negative predictive value for a diagnosis of OV. This result was reproduced in the second group of patients as well as in patients with compensated disease. In a cost-benefit analysis, screening cirrhotic patients according to the "platelet count/spleen diameter ratio strategy" was far more cost effective compared with the "scope all strategy". Conclusions: The platelet count/spleen diameter ratio is the only parameter which is independently associated with the presence of OV, and its negative predictive value is reproducible. Its use is of value even in the subgroup of patients with compensated disease, and it is also cost effective. |
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Protein
markers could shed light on the origins of liver cancer
Author: NewsRx.com via Pinnacor Author Date: 7/28/2003 Protein markers could shed light on the pathogenesis of liver cancer
Protein markers could shed light on the
pathogenesis of liver cancer.
"Many of the emerging technologies for the
global evaluation of gene expression, at both the RNA and protein level,
are being applied to the problem of finding biomarkers for human disease
progression. These analyses can be made difficult, however, by variation
between samples that arises from both technical and nondisease related
physiological or genetic causes.
"In an effort to identify serum polypeptides
whose presence or absence correlates with the clinical status of patients
at high risk for hepatocellular carcinoma (HCC), we have developed a
strategy that helps to focus the analysis on meaningful changes in protein
levels above the background of variation," researchers in the United
States report.
"For the current study we divided the patient
population into four clinically defined diagnostic groups that represent a
generally increasing risk for HCC. Chronic infection with hepatitis B
virus (HBV) is a major risk factor for HCC and our groups included
patients with no indication of liver disease (healthy), those with
inactive chronic HBV, those with active chronic HBV, and patients with a
diagnosis of HCC and history of chronic HBV infection," wrote L.F. Steel
and colleagues, Thomas Jefferson University, Jefferson Center for
Biomedical Research.
"Serum polypeptides from these patients were
first analyzed in two-dimensional gels by combining the serum from
patients in each of the four groups to generate composite gel profiles.
Analysis of these composite gels allowed us to identify two relatively
abundant features that were reduced in the HCC group as compared to the
healthy group. Tryptic fragment mass fingerprinting identified the
features as a carboxy terminal fragment of complement C3 and an isoform of
apolipoprotein A1," they said.
"These two features were examined by
two-dimensional gel electrophoresis of serum from each individual in the
four groups in order to verify that the inter-group differences seen in
composite gels reported changes in abundance for most members of the
group, rather than extreme changes for a small fraction of the group.
These preliminary studies suggest that a proteomic methodology can be used
for the identification of serum biomarkers for HCC and other liver
disease," Steel and coworkers stated.
Steel and colleagues published their study in
Proteomics (A strategy for the comparative analysis of serum proteomes for
the discovery of biomarkers for hepatocellular carcinoma. Proteomics,
2003;3(5):601-609).
The information in this article comes under
the major subject areas of Hepatology, Liver Cancer, Oncology, Proteomics,
RNA Research and World Disease. This article was prepared by Biotech Week
editors from staff and other reports.
To see more of the NewsRx.com, or to
subscribe, go to
http://www.newsrx.com.
©Copyright 2003, Biotech Week via NewsRx.com & NewsRx.net.
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Peripheral neuropathy in liver cirrhosis. Kharbanda PS, Prabhakar S, Chawla YK, Das CP, Syal P. Postgraduate Institute of Medical Education and Research, Chandigarh, India. BACKGROUND AND AIMS: Neuropathy in association with chronic liver disease, including cirrhosis, is recognized; however, there are differences in the incidence and type of neuropathy reported. The causal relationship of liver disease to neuropathy has been questioned. This study was designed to evaluate the incidence and character of peripheral neuropathy in patients with liver cirrhosis. The effect of alcohol consumption, severity of liver disease and encephalopathy on the incidence and severity of neuropathy were also studied. METHODS: Patients having an identifiable cause of peripheral neuropathy, except alcohol, were excluded from the study. Patients with evidence of vitamin B12 deficiency or diabetes were also excluded from the study. In this study, 33 patients with liver cirrhosis were evaluated clinically and electrophysiologically to detect any evidence of peripheral neuropathy. Nerve conduction studies were performed in the upper and lower limbs using surface electrodes. These patients also underwent a detailed clinical examination. RESULTS: Clinical signs of peripheral neuropathy were found in seven (21%) patients. Nerve conduction studies were abnormal in 24 (73%) patients. The pattern of involvement was predominantly of an axonal sensory motor polyneuropathy. Neuropathy was found both in patients with alcohol-related and non-alcohol-related cirrhosis. The presence of encephalopathy did not have a significant bearing on the incidence and severity of neuropathy. The neuropathy was also not significantly related to the severity of liver disease. CONCLUSIONS: The present study reveals that a
significant number of patients with liver cirrhosis show evidence of
peripheral neuropathy, which is present regardless of the etiology of
cirrhosis, and is subclinical in a majority of these patients. The cause of
neuropathy was probably the liver disease itself, as the incidence and
severity of neuropathy in the alcohol-related cirrhosis, although higher,
was not significantly different from the neuropathy in patients with
non-alcohol-related cirrhosis.
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Axcan Licenses Drug for the Treatment of Hepatic Encephalopathy from Merz Pharmaceuticals TSX SYMBOL (Toronto Stock Exchange): AXP
Nasdaq SYMBOL (Nasdaq National Market): AXCA
MONT-SAINT-HILAIRE and FRANKFURT, July 22 /CNW Telbec/ - Axcan Pharma
Inc. ("Axcan" or the "Company") and Merz Pharmaceuticals GmbH ("Merz")
announced today that they have signed an agreement under which Axcan acquires
an exclusive license to use, develop and submit for approval injectable and
oral granule formulations containing L-ornithine and L- aspartate for the
treatment of hepatic encephalopathy associated with early to late-stage liver
cirrhosis. Under the license agreement Axcan also has the right to develop the
product for additional indications. This product, once approved, will be
distributed in the United States Canada, France and Italy. Prevalence of
hepatic encephalopathy in the United States is estimated by the US Center for
Disease Control at between 60,000 to 100,000 patients. This drug is currently
marketed in Germany and several other countries under the name Hepa-Merz.
Terms of the agreement were not disclosed.
"We are very happy to partner with Merz, an innovative privately owned
pharmaceutical company that developed Hepa-Merz," commented Léon F. Gosselin,
President and Chief Executive Officer of Axcan. "We expect to quickly initiate
and conduct two controlled Phase III studies in North America and complete
them in 2004. This would allow Axcan to launch the injectable form as soon as
possible thereafter," he concluded.
"We firmly believe that the treatment of liver diseases will see a future-
oriented demand for new medications. Ornithine-Aspartate will be one of the
promising options and we are looking forward to working with Axcan to make the
product Hepa-Merz a success," said Dr. Jochen Huckmann, Chief Executive
Officer of Merz in Germany.
Dr. Roger Butterworth, PhD, Professor of Neurology and Director of the
Neuroscience Research Unit, Centre Hospitalier de l'Université de Montréal
(Campus Saint-Luc) and a world renowned researcher in hepatic encephalopathy
who contributed to the discovery of the mechanism of action of the product in
this condition, said: "This product has been long awaited in North America. It
has been proven to be very efficacious and very safe for the treatment of
hepatic encephalopathy. Once approved in North America, it should fulfill a
real medical need in the treatment of this disease".
HEPATIC ENCEPHALOPATHY
Hepatic encephalopathy (HE) is characterized by the development of
impaired neurological and mental functions, which can occur with various
degrees of severity (e.g. abnormalities of consciousness, personality,
behavioral and/or intellectual function to deep coma) secondarily to liver
diseases such as liver cirrhosis. HE is caused by a metabolic disturbance and
is therefore potentially reversible.
Ammonia, a substance produced by the body when proteins are digested, is
believed to be toxic to the brain but is normally detoxified by the liver. If
the process does not properly occur which is the case in the above-mentioned
patient population, the liver cannot properly metabolize and detoxify
substances in the body, which then accumulate and cause metabolic
abnormalities that can lead to brain damage and even coma. In otherwise
clinically stable cirrhotic patients, hepatic encephalopathy may be triggered
by episodes of gastrointestinal bleeding, excessive dietary protein,
electrolyte abnormalities, infections and renal diseases.
Within five years of diagnosis of cirrhosis of the liver, approximately
26% of patients are said to experience some symptoms of hepatic
encephalopathy. Reports have suggested that 80% of cirrhotic patients have
subclinical hepatic encephalopathy. Mortality risk in cirrhotics with hepatic
encephalopathy is almost three times greater than it is for patients without
the disease.
Current treatments of hepatic encephalopathy include non-absorbable
antibiotics (eg. neomycine) and non-absorbable disaccharides (e.g. lactulose),
but not every patient responds rapidly to these treatments. Several clinical
studies according to current guidelines and evidence-based medicine critieria
have confirmed the efficacy and safety of L-ornithine L-aspartate in the
treatment of hepatic encephalopathy. This drug stimulates detoxification of
ammonia via glutamine synthesis and urea excretion, thereby lowering high
blood ammonia levels which cause hepatic encephalopathy.
ABOUT MERZ
Merz Pharmaceuticals, as a member of Merz Pharma, is an innovative and
international healthcare company, specializing in the research, development
and marketing of drugs for the treatment of neurological and psychiatric
diseases. Merz is a leader in the field of Alzheimer research and developed
the first drug for the treatment of moderate to severe Alzheimer's. Other
indications that are covered by Merz are hepatology/metabolic diseases and
dermatology and metabolic diseases.
ABOUT AXCAN
Axcan is a leading specialty pharmaceutical company involved in the field
of gastroenterology. The Company markets a broad line of prescription products
sold for the treatment of symptoms in a number of gastrointestinal diseases
and disorders such as inflammatory bowel disease, irritable bowel syndrome,
cholestatic liver diseases and complications related to cystic fibrosis.
Axcan's products are marketed by its own sales force in North America and
Europe. Its common shares are listed on the Toronto Stock Exchange under the
symbol "AXP" and on the Nasdaq National Market under the symbol "AXCA".
"Safe Harbor" statement under the Private Securities Litigation Reform
Act of 1995.
-------------------------------------------------------------------------
To the extent any statements made in this release contain information
that is not historical, these statements are essentially forward looking and
are subject to risks and uncertainties, including the difficulty of predicting
FDA approvals, acceptance and demand for new pharmaceutical products, the
impact of competitive products and pricing, new product development and
launch, reliance on key strategic alliances, availability of raw materials,
the regulatory environment, fluctuations in operating results and other risks
detailed from time to time in the Company's filings with the Securities and
Exchange Commission.
(*) The name Hepa-Merz appearing in this press release is a trademark of
Merz Pharmaceuticals GmbH.
-30-
For further information: David W. Mims, Executive Vice President and Chief Operating Officer, Axcan Pharma Inc., (205) 991-8085 ext. 223; Isabelle Adjahi, Director, Investor Relations, Axcan Pharma Inc., (450) 467-2600 ext. 2000; www.axcan.com; Dr. Andrea Kreisselmeier, Head of Corporate Communications, Merz Pharma GmbH & Co. KgaA, +49-(69)150-3853, www.merz.com
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