Hepatitis: A silent killer Peter Chan, 55, is what we'd call a walking miracle.He falls under the one percentage of individuals who no longer have Hepatitis B after suffering many years of infection.He was 30 when he was first diagnosed with chronic hepatitis B.
Saturday
Weekend Hepatitis News;One in 12 people worldwide are living with chronic hepatitis B or C.
Hepatitis: A silent killer Peter Chan, 55, is what we'd call a walking miracle.He falls under the one percentage of individuals who no longer have Hepatitis B after suffering many years of infection.He was 30 when he was first diagnosed with chronic hepatitis B."It was only after I read an article about hepatitis in New Straits Times that I had a better understanding of the disease.My father died of liver cancer and my siblings had jaundice at some point or another.Based on the information given in the write-up, I knew I was a likely candidate for hepatitis B.
Although I had no symptoms, I decided to get tested, to be on the safe side, and found that I was infected," says Chan.
He began treatment immediately and in the beginning stage, he had to inject the medication himself daily for a few months.After a few years, he moved on to oral medication for a period.
Today, Chan is completely free of the virus and is testament to the importance of early detection through awareness.
"I had to make certain lifestyle changes, like giving up alcohol totally as I didn't want to risk any liver damage," he adds.He goes for regular check-ups and urges everyone to go for hepatitis screening.
"Hepatitis is a silent killer as there are no symptoms.Once the symptoms show, it's too late.So you need to be aware of the disease and go and get yourself tested," he advises.
When you meet C.Chia, you will not be able to tell he is a Hepatitis C patient.The 66-year-old looks as fit as a fiddle when he walks into the room for the interview.Scheduled to fly to the United States later in the day, he speaks about his journey with Hepatitis C.
"I was diagnosed with hepatitis C in 2005.I was shocked because I had gone in for a regular heart examination and came out discovering I had hepatitis C," he relates.
Sometime in 1979, Chia had to have blood transfusion after suffering from stomach ulcers.Six years later, in 1986, he again had a transfusion.He believes the blood transfusions would have been the most likely cause of his contracting hepatitis C.Testing for hepatitis C only became available worldwide in the early 1990s.
"By the time I found out I had hepatitis C, it was 20 years later and my liver was already in the early stage of cirrhosis," he says.
He began treatment immediately and six months after completion, Chia was completely cured of the virus.He still undergoes regular blood tests and ultrasound of his liver as advised by his doctor."I would never have known I had hepatitis C had I not gone for my heart exam.So my message to people out there is to get tested, especially if you are at any risk of getting it.The earlier you get diagnosed, the earlier you can treat it," he advises.
"People don't really know what hepatitis is," says Professor Dr Rosmawati Mohamed, consultant hepatologist (liver specialist) at University of Malaya Medical Centre.She is also the executive council member of the Coalition To Eradicate Viral Hepatitis In Asia Pacific (CEVHAP).
"It is caused by viruses.There are five types: Hepatitis A to E.As many as two billion people have been exposed, although not all of them are chronic.
What is alarming is that 75 per cent are in Asia.
"It is caused by viruses.There are five types: Hepatitis A to E.As many as two billion people have been exposed, although not all of them are chronic.
What is alarming is that 75 per cent are in Asia.
One in four will end up with serious liver disease but what is an important fact is that hepatitis is cancer-causing.The time frame of progression is about 30-50 years before you end up with liver damage and, most of the time, there are no symptoms.It is a silent disease," she adds.
According to Dr Rosmawati, five per cent of our population have hepatitis B.
"We can do something about reducing the prevalence,'' she says fervently."If you look at the worldwide figure, a large part of the population has not yet been diagnosed or screened.Only one per cent is diagnosed."
Sadly, the burden of hepatitis B and C is in Asia.Dr Rosmawati says it is very important for those who have been infected for sometime, and after they have been a*sessed, to seek treatment.
As we approach World Hepatitis Day on July 28, we are reminded of a condition that is far more prevalent than HIV and cancer.The figures show that one in 12 people worldwide are living with chronic hepatitis B or C.It kills 150 million people each year globally and yet, it is largely neglected for one simple reason - most of those infected don't even know that they carry the virus.
"This is something we want to highlight on World Hepatitis Day.We will be having a nationwide campaign for six weeks, beginning June 15 to July 30 that will involve 26 participating centres in every state of the country.Free hepatitis B and C testing will be available and non-invasive tests will also be available for people who already diagnosed with hepatitis," she says.
Dr Rosmawati stresses that, in this part of the world, the most common way hepatitis B is transmitted is from mother to child.As such, vaccination of newborns play an important role.
"For the first time, we are offering huge screenings in both the northern and southern regions, with 12 out of 14 states participating in the campaign.We want to spread the message to people that if they know they have hepatitis, effective and immediate treatment is available.Some will achieve a cure and will be able to eradicate the virus completely.
The campaign tagline is Know Your Liver, B Aware and C A Doctor.
Dr Rosmawati says: "We would like to request everyone to get their liver tested.If it is already infected, they need to get it treated.Public understanding is of utmost importance at this stage and much needs to be done as one of the key issues identified at CEVHAP's inaugural meeting in Taipei last October was low patient and public understanding of the disease and its implications." For details on the nationwide campaign, visit http://www.myhepatitisday.com/.
Viral infection of the liver
Hepatitis B is a viral infection that attacks the liver and can cause both acute and chronic diseases.The virus is transmitted not through casual contact but through contact with the blood or other bodily fluids of an infected person.
About two billion people worldwide are infected with the virus and about 350 million live with chronic infection.An estimated 600,000 people die each year due to the acute or chronic consequences of hepatitis B.About 25 per cent of adults who are chronically infected during childhood will die of liver cancer or cirrhosis (scarring of the liver) caused by the chronic infection.
Hepatitis B is a viral infection that attacks the liver and can cause both acute and chronic diseases.The virus is transmitted not through casual contact but through contact with the blood or other bodily fluids of an infected person.
About two billion people worldwide are infected with the virus and about 350 million live with chronic infection.An estimated 600,000 people die each year due to the acute or chronic consequences of hepatitis B.About 25 per cent of adults who are chronically infected during childhood will die of liver cancer or cirrhosis (scarring of the liver) caused by the chronic infection.
The hepatitis B virus is 50 to 100 times more infectious than HIV.A vaccine has been available since 1982 and is 95 per cent effective in preventing infection and its chronic consequences.It is the first vaccine against a major human cancerThe mechanisms underlying the Hepatitis C virus (HCV) resistance to interferon alpha (IFN-alpha) are not fully understood.We used IFN-alpha resistant HCV replicon cell lines and an infectious HCV cell culture system to elucidate the mechanisms of IFN-alpha resistance in cell culture.The IFN-alpha resistance mechanism of the replicon cells were addressed by a complementation study that utilized the full-length plasmid clones of IFN-alpha receptor 1 (IFNAR1), IFN-alpha receptor 2 (IFNAR2), Jak1, Tyk2, Stat1, Stat2 and the ISRE- luciferase reporter plasmid.We demonstrated that the expression of the full-length IFNAR1 clone alone restored the defective Jak-Stat signaling as well as Stat1, Stat2 and Stat3 phosphorylation, nuclear translocation and antiviral response against HCV in all IFN-alpha resistant cell lines (R-15, R-17 and R-24) used in this study.
Moreover RT-PCR, Southern blotting and DNA sequence analysis revealed that the cells from both R-15 and R-24 series of IFN-alpharesistant cells have 58 amino acid deletions in the extracellular sub domain 1 (SD1) of IFNAR1.In addition, cells from the R-17 series have 50 amino acids deletion in the sub domain 4 (SD4) of IFNAR1 protein leading to impaired activation of Tyk2 kinase.Using an infectious HCV cell culture model we show here that viral replication in the infected Huh-7 cells is relatively resistant to exogenous IFN-alpha.HCV infection itself induces defective Jak-Stat signaling and impairs Stat1 and Stat2 phosphorylation by down regulation of the cell surface expression of IFNAR1 through the endoplasmic reticulum (ER) stress mechanisms.The results of this study suggest that expression of cell surface IFNAR1 is critical for the response of HCV to exogenous IFN-alpha
"Limited data also suggest that lifestyle interventions may hold benefits for histopathology," Dr.Michael Trenell and colleagues from Newcastle University, Newcastle upon Tyne, United Kingdom report in a paper in the Journal of Hepatology, available online now.
NAFLD, they note in their paper, is a "serious and growing clinical problem" affecting an estimated 20% to 33% of the adult population, depending on criteria and country.
Diet and physical activity are often recommended in patients with NAFLD, despite a lack of systematic evaluations of the efficacy of this approach.
This prompted Dr.Trenell and colleagues to search Medline, Scopus, and the Cochrane Controlled Trials Register for studies looking at the effect of diet, physical activity, and/or exercise modification in adults with NAFLD.
"The outcome markers of interest were indicators of steatosis, histological evidence of inflammation and fibrosis, and glucose control/insulin sensitivity," they wrote in their paper.
The analysis included 23 studies.Seven had control groups, but only six were randomized.Eleven groups received diet-only interventions, two received exercise-only, and 19 received diet and physical activity/exercise.The interventions lasted from one to six months.The physical activity interventions consisted largely of moderate intensity aerobic activity.
Overall, the studies reviewed show that a range of lifestyle modifications are effective in reducing elevated intrahepatic triacyglycerol concentration (IHTAG) the first step in the development of steatohepatitis, liver fibrosis, liver cirrhosis and hepatocellular carcinoma.
Overall, reductions in body weight averaged 4% to 14% and resulted in statistically significant IHTAG reductions of 35% to 81%.The magnitude of change correlated strongly with the amount of weight lost.
The reviewed studies also "consistently showed reductions in liver fat and/or liver aminotransferase concentration," the investigators say, "with the strongest correlation being with weight reduction."
In most of the studies, glucose control and/or insulin sensitivity improved after lifestyle intervention.
Five studies reported changes in histopathology and all showed a trend toward decreased inflammation.In two studies, this was statistically significant, the researchers report."Changes in fibrosis were less consistent with only one study showing a significant reduction," they add.
There was, however, considerable heterogeneity across studies in specific interventions and a*sessment methods employed and diagnostic criteria for NAFLD applied.
In addition, monitoring of adherence to diet or exercise was often limited, and no study employed objective measures of physical activity such as accelerometers.Instead, they all used questionnaires.Dietary a*sessments were not reported in enough detail to a*sess likely accuracy.
"Given the clinical impact of NAFLD and the lack of therapies for its management, developing effective, reproducible lifestyle interventions is crucial," the investigators conclude.
Unfortunately, published studies to date looking at lifestyle interventions in adults with NALFD "do not allow clear differentiation of the effects of physical activity relative to diet, or the importance of diet composition," they write.
They suggest future studies employ "accurate methods to establish the most effective means of producing a sustained reduction in liver fat, necroinflammation, and, if possible, fibrosis and report their interventions, including objective indicators of adherence, in sufficient detail to be readily translatable to clinical practice."
J Hepatol.Published online July 4, 2011.
For many years, the Institute of Human Genetics, Helmholtz Zentrum Munich and the Technische UniversitГ
The complete article is available as a provisional PDF.Anemia is not predictive of sustained viral response in HCV-liver transplant recipients treated with peg-interferon and ribavirinIn the immune competent setting, antiviral therapy-related anemia has been recently shown to be a*sociated with sustained viral response (SVR).We aimed to a*sess whether the same occurs in liver transplantation (LT).
In order to test this, 164 LT patients {75% men, 55 years (range: 35-75) infected with HCV (87% genotype 1a or 1b)} with recurrent hepatitis C (advanced fibrosis in 64%) treated with peg-interferon (pegIFN) and ribavirin (RBV) between 2002-2010 were included.Baseline immuosuppression consisted of tacrolimus (Tac) in 56%.
Mycophenolate mofetil (MMF) was used in 15%.Anemia was defined as haemoglobin (Hb) below 10 g/d.Significant anemia was present when Hb drop was higher than 5 g/dl.Seventy percent and 40% developed anemia and significant anemia, respectively.Erythropoietin was used in 61%.Factors independently a*sociated with significant anemia, included low estimated creatinine clearance (RR:0.97, 95% CI: 0.95-0.99; p=.03), longer time from LT to therapy (RR: 1.001, 95% CI:1.000-1.001; p=.002), high baseline viremia (RR:3.2, 95% CI:1.3-8.1, p=.01), cyclosporine (CsA)-based immunosuppression (RR:0.4, 95% CI:0.2-0.99; p=.049), and use of MMF (RR:3.4, 95% CI: 1.1-10.7; p=.03).
An SVR occurred in 42%; factors a*sociated with SVR were baseline variables (younger recipient and donor age, infection with non-1 genotypes, body ma*s index, mild fibrosis) and on-treatment factors related to adherence or viral kinetics.
Anemia resulted in RBV dose reductions but was not a*sociated with viral response at any time point.
In conclusion, in LT patients anemia is a very frequent complication during antiviral therapy a*sociated with increased RBV dose reduction but not with SVR.Predictors of anemia include MMF or CsA immunosuppression, high viremia and renal insufficiency.
Liver Transpl, 2011.В© 2011 AASLD.
'Humanized' Mice - A New Way To Study Side Effects Of New Drugs Before They Reach Clinical Trials
14 July 2011
14 July 2011
Despite the fact that mice are very commonly used in biomedical research, not much help has been gained by their use in the testing of new drugs.The reason for this is that a mouse's liver reacts differently to drugs as...[read article] NEW YORK (Reuters Health) July 15, 2011 Weight loss or increased physical activity "consistently" reduce liver fat and improve glucose control and insulin sensitivity in patients with non-alcoholic fatty liver disease (NAFLD), according to a systematic review of published studies.
"Limited data also suggest that lifestyle interventions may hold benefits for histopathology," Dr.Michael Trenell and colleagues from Newcastle University, Newcastle upon Tyne, United Kingdom report in a paper in the Journal of Hepatology, available online now.
NAFLD, they note in their paper, is a "serious and growing clinical problem" affecting an estimated 20% to 33% of the adult population, depending on criteria and country.
Diet and physical activity are often recommended in patients with NAFLD, despite a lack of systematic evaluations of the efficacy of this approach.
This prompted Dr.Trenell and colleagues to search Medline, Scopus, and the Cochrane Controlled Trials Register for studies looking at the effect of diet, physical activity, and/or exercise modification in adults with NAFLD.
"The outcome markers of interest were indicators of steatosis, histological evidence of inflammation and fibrosis, and glucose control/insulin sensitivity," they wrote in their paper.
The analysis included 23 studies.Seven had control groups, but only six were randomized.Eleven groups received diet-only interventions, two received exercise-only, and 19 received diet and physical activity/exercise.The interventions lasted from one to six months.The physical activity interventions consisted largely of moderate intensity aerobic activity.
Overall, the studies reviewed show that a range of lifestyle modifications are effective in reducing elevated intrahepatic triacyglycerol concentration (IHTAG) the first step in the development of steatohepatitis, liver fibrosis, liver cirrhosis and hepatocellular carcinoma.
Overall, reductions in body weight averaged 4% to 14% and resulted in statistically significant IHTAG reductions of 35% to 81%.The magnitude of change correlated strongly with the amount of weight lost.
The reviewed studies also "consistently showed reductions in liver fat and/or liver aminotransferase concentration," the investigators say, "with the strongest correlation being with weight reduction."
In most of the studies, glucose control and/or insulin sensitivity improved after lifestyle intervention.
Five studies reported changes in histopathology and all showed a trend toward decreased inflammation.In two studies, this was statistically significant, the researchers report."Changes in fibrosis were less consistent with only one study showing a significant reduction," they add.
There was, however, considerable heterogeneity across studies in specific interventions and a*sessment methods employed and diagnostic criteria for NAFLD applied.
In addition, monitoring of adherence to diet or exercise was often limited, and no study employed objective measures of physical activity such as accelerometers.Instead, they all used questionnaires.Dietary a*sessments were not reported in enough detail to a*sess likely accuracy.
"Given the clinical impact of NAFLD and the lack of therapies for its management, developing effective, reproducible lifestyle interventions is crucial," the investigators conclude.
Unfortunately, published studies to date looking at lifestyle interventions in adults with NALFD "do not allow clear differentiation of the effects of physical activity relative to diet, or the importance of diet composition," they write.
They suggest future studies employ "accurate methods to establish the most effective means of producing a sustained reduction in liver fat, necroinflammation, and, if possible, fibrosis and report their interventions, including objective indicators of adherence, in sufficient detail to be readily translatable to clinical practice."
J Hepatol.Published online July 4, 2011.
Authors and Disclosures
Journalist
Megan Brooks
Megan Brooks is a freelance writer for Reuters Health.Disclosure: Megan Brooks has disclosed no relevant financial relationships.
Journalist
Megan Brooks
Megan Brooks is a freelance writer for Reuters Health.Disclosure: Megan Brooks has disclosed no relevant financial relationships.
New Gene Identified for Restless Legs Syndrome
ScienceDaily (July 15, 2011) People suffering from restless legs syndrome (RLS) experience unpleasant sensations in the legs at night for which the only remedy is movement.Now, an international consortium from Europe, Canada and the US has identified new genetic risk factors for the disease.Carriers of these risk variants have an increased likelihood of developing RLS.This finding, which will be published on July 14th in the open-access journal PLoS Genetics, presents new opportunities for future research of this disorder.
RLS is amongst the most common neurological diseases.Patients suffer from an urge to move and paresthesia -- tingling, prickling and numbness -- in the legs, occurring mainly in the evening or at night when the body is at rest.These sensations may only be relieved by moving or walking around, which may result in severe sleeping disorders, chronic sleep loss and daytime fatigue.In severe cases the disease can lead to depression and social isolation.The frequency of RLS increases with age: up to ten per cent of those above 65 years of age are affected, albeit in very different forms.Children can, however, also contract the disease.
For many years, the Institute of Human Genetics, Helmholtz Zentrum Munich and the Technische UniversitГ
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