RxPG News : Hepatitis

Factors for developing IPF in Hepatitis C patients

Thu, 23 Oct 2008 14:12:21 PST

( from http://www.rxpgnews.com ) Hepatitis C virus (HCV) is one of the more common causes of chronic liver disease in world with a variety of extrahepatic complications such as essential mixed cryoglobulinemia, membranoproliferative glomerulonep hritis, autoimmune thyroiditis, sialadenitis, and cardiomyopathy. IPF is present in patients with chronic HCV infection. However, there is little or no information on the yearly cumulative incidence and risk factors on the development rate of IPF in patients with HCV.

A research team led by Yasuji Arase from Toranomon Hospital of Japan addresses this question and this will be published on October 14, 2008 in the World Journal of Gastroenterology. In this study, they studied 6150 HCV infected patients who were between 40-70 years old (HCV-group). Another 2050 patients with hepatitis B virus (HBV) were selected as control (HBV-group). The mean observation period was 8.0 ± 5.9 years in HCV-group and 6.3 ± 5.5 years in HBV-group.

They found that fifteen patients in HCV-group developed IPF. On the other hand, none of the patients developed IPF in HBV-group. In HCV-group, the cumulative rates of IPF development were 0.3% at 10th year and 0.9% at 20th year. The IPF development rate in HCV-group was higher than that in HBV-group (P = 0.021). The IPF development rate in patients with HCV or HBV was high with statistical significance in the following cases: (1) patients ≥ 55 years (P < 0.001); (2) patients who had smoking index (package per day × year) of ≥ 20 (P = 0.002); (3) patients with liver cirrhosis (P = 0.042). This result indicated that age, liver cirrhosis and smoking enhance the development of IPF in patients with chronic hepatitis C infection.

Could statins be a new option for hepatitis C patients?

Tue, 22 May 2007 09:59:37 PST

( from http://www.rxpgnews.com ) WASHINGTON, D.C. (May 20, 2007) -- Research presented today at Digestive Disease Week? 2007 (DDW?) demonstrates the potential of statins, important cholesterol management therapies, for improving the management of hepatitis C ? a disease that affects nearly four million Americans. Although there have been no new treatments for hepatitis C since the introduction of pegylated interferon in 2001, the opportunity to develop a new generation of therapies that offer better outcomes may be imminent. DDW is the largest international gathering of physicians and researchers in the fields of gastroenterology, hepatology, endoscopy and gastrointestinal surgery.

Studies such as these are designed to improve the effectiveness of antivirals ? the standard of care therapy for hepatitis C, said John Vierling, M.D., Baylor College of Medicine. The findings from these studies support the rationale and need for larger, controlled trials that may provide additional and more advantageous hepatitis C treatment options.

Chronic hepatitis in pediatric liver transplant patients

Wed, 03 May 2006 01:21:37 PST

( from http://www.rxpgnews.com ) A new study on the long-term outcome of children undergoing liver transplants found that chronic hepatitis (CH) was common and that it was not detectible using standard blood tests. The presence of autoantibodies (antibodies that attack the body's own tissues) in these patients indicates that although not fully understood, CH may be related to the immune response.

The results of this study appear in the May 2006 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). Published by John Wiley & Sons, Inc., Hepatology is available online via Wiley InterScience.

Children normally undergo liver transplants for diseases that do not recur and are potentially curable by the procedure. Although their long-term survival rates are over 80 percent, little is known about tissue changes that occur over time in these young patients. "An important question within the field of paediatriac liver transplantation is whether children who have undergone successful transplantation can expect a normal life expectancy or whether there will be a gradual decline in liver function and eventual graft loss," the authors write.

Led by Helen M. Evans of the Birmingham Children's Hospital in Birmingham, United Kingdom, the study involved children who received liver transplants at the hospital's Liver Unit between 1983 and 1996. Patients underwent standard liver function tests, sonograms and liver biopsies at approximately 1, 5 and 10 years following transplant, and autoantibodies were measured at 5 and 10 years. A total of 113 children had liver biopsies at the one year mark, 135 had biopsies after 5 years, and 64 underwent biopsies at 10 years.

The results showed that there was a decrease over time in the proportion of biopsies considered to be normal, with chronic hepatitis being the most common abnormality (22 percent at 1 year, 43 percent at 5 years, 64 percent at 10 years). While liver function tests at 5 years were not significantly different in children who had CH, the presence of autoantibodies was significantly higher at 5 and 10 years in children with CH (72 percent and 80 percent respectively). In addition, there was a strong association between the presence of CH and the development of progressive fibrosis (the formation of scar-like tissue). The authors note that "the finding of increasing fibrosis in children with chronic hepatitis has not been reported before and has potentially important implications for long term graft function."

The authors note that transient autoantibody production following transplant sometimes occurs during episodes of rejection. In addition, late rejection may be associated with tissue changes that are different to those normally seen in acute rejection but more closely resemble those seen in chronic viral or autoimmune hepatitis. "It is therefore possible that some cases of otherwise unexplained chronic hepatitis in the liver allograft may represent a form of late cellular rejection," the authors suggest.

The results of the present study indicate that important tissue abnormalities can be detected in biopsies obtained from children who are clinically well and have normal liver function tests, the authors state. "Screening for chronic allograft hepatitis using liver biochemistry is therefore not possible and may instead require regular measurement of autoantibodies," they conclude.

Vaccinating Infants of Hepatitis B Mothers Prevents Infection - Systematic Review

Tue, 31 Jan 2006 18:59:37 PST

( from http://www.rxpgnews.com ) Immunising newborn infants of mothers with hepatitis B prevents infection being transmitted from mother to child, finds a study published online by the BMJ.

There are around 350 million hepatitis B carriers worldwide. The virus is transmitted by contact with blood or body fluids of an infected person. Mother to child transmission around the time of birth is common and accounts for up to half of all carriers.

Researchers analysed randomised trials to assess the beneficial and harmful effects of hepatitis B vaccines (active production of antibodies) and hepatitis B immunoglobulin (passive transfer of antibodies) in newborn infants of mothers positive for hepatitis B surface antigen.

They found that hepatitis B vaccine, hepatitis B immunoglobulin, or the combination of vaccine plus immunoglobulin given to the newborn infants of mothers positive for hepatitis B surface antigen prevents the occurrence of hepatitis B. Furthermore, the combination of vaccine plus immunoglobulin was superior to vaccine alone.

There was no difference between the two types of vaccine currently available.

Although this study confirms that vaccines and immunoglobulin are effective, more research is needed to identify the optimal dose and treatment schedule of hepatitis B immunisation, conclude the authors.

Need for treatment modification in older hepatitis C patients

Fri, 06 Jan 2006 03:34:37 PST

( from http://www.rxpgnews.com ) A new study in Japan examining the effects of combination therapy on older patients with hepatitis C found more adverse effects necessitating discontinuation of treatment, lowering of dosages, and lower long-term benefits in this age group.
The results of this study appear in the January 2006 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). (published by John Wiley & Sons, Inc)

Chronic hepatitis C virus (HCV), the most common cause of liver disease, affects approximately 300 million people worldwide. The virus was seen in the Japanese population decades before the U.S., with the result that HCV patients in Japan are 10 to 15 years older than patients in western countries. The standard treatment is combination therapy with interferon or pegylated interferon (a newer form of the drug that is thought to be more effective) and the antiviral drug ribavirin. However, this treatment tends to be associated with adverse effects that lead to either a dose reduction or discontinuation of therapy in up to 28 percent of patients.

Researchers led by Yoshiaki Iwasaki of the Department of Gastroenterology and Hepatology at Okayama University in Okayama, Japan conducted a study involving 208 HCV patients between December 2001 and July 2003. They classified the patients into three groups: younger than 50 years of age, 50 to 59 years old, and 60 years of age or older and scheduled them for 24 weeks of combination therapy with interferon and ribavirin. Of the 208 patients, 56 percent had to discontinue therapy or reduce their dosage due to adverse effects such as decreased appetite, retinal hemorrhage, and low white blood cell count and the older the patient, the more likely it was that this was the case. In addition, there was a tendency toward a lower sustained virological response (SVR, the absence of HCV for more than 6 months after completing therapy) in the older patient group.

The dose reductions and discontinuation of therapy in this study were much more frequent than in previous studies, which the researchers attribute to the more advanced age of the patients. The fact that older patients had higher rates of impaired kidney function and high blood pressure may have led to more frequent adverse effects. In addition, they note that patients were given high-dose induction therapy of standard interferon, which may render them more susceptible to adverse effects than HCV patients in western countries, where lower doses of interferon or pegylated interferon are the norm.

The results also indicated that for more than 70 percent of the patients, dose reduction and discontinuation of therapy was necessary within the first 12 weeks of therapy, which had a negative impact on SVR, especially in older patients and in cases where the doses of both drugs were reduced. Of the two drugs, reducing ribavirin during the first 12 weeks of therapy seemed to have a greater impact on SVR than reducing interferon.

"The present data demonstrated the importance of considering patient age when treating hepatitis C via combination therapy, especially for patients more than 60 years old," the authors state. "The treatment schedule should be modified, or other therapeutic modalities should be considered for older patients with chronic hepatitis C." They stress the importance of patient education and support to maximize patient compliance in completing the treatment regimen. Although the study involved only Japanese patients, it should be noted that approximately 35,000 new HCV infections occur each year in the U.S.; the proper treatment of older patients with chronic hepatitis C may therefore become an emerging problem in this country.

Therapy may not be necessary for asymptomatic autoimmune hepatitis

Mon, 15 Aug 2005 21:07:38 PST

( from http://www.rxpgnews.com ) It is not uncommon for patients with autoimmune hepatitis (AIH), a disease in which the patient's own immune system attacks the liver, to have no symptoms. Such cases are being diagnosed more frequently due to the increased practice of administering routine liver enzyme and antibody tests. Whether or not to treat asymptomatic AIH remains unclear--therapy with immunosuppressants could potentially slow progress of the disease but involves side effects that are sometimes toxic.

In order to determine if immunosuppressive therapy is indicated when no symptoms are present, researchers led by Jordan J. Feld, M.D. of the Departments of Medicine and Pathology at the University Health Network of the University of Toronto, compared the natural course of asymptomatic AIH with symptomatic AIH.

The study included 124 patients diagnosed with AIH at the Toronto Western Hospital Liver Clinic between 1970 and 2002 31 of whom were asymptomatic. Researchers reviewed the patients' clinical records to document the presence or absence of symptoms. Patients were considered asymptomatic if they were free of all symptoms, even non-specific ones such as fatigue or abdominal pain. Immunosuppressive therapy was recommended for all symptomatic patients, while asymptomatic patients were not treated, unless treatment had already been initiated. Patients who developed symptoms during the study period were started on immunosuppressive therapy. If they remained in remission for two years with no relapse the therapy was discontinued, but it was restarted if the disease recurred off treatment.

The results of the study indicated that asymptomatic patients had lower liver enzyme and IgG antibody levels, as well as lower scores on the hepatic activity index (HAI), which measures liver inflammation, but otherwise did not differ from patients with symptoms. Half of the asymptomatic patients ended up receiving treatment either because it was already started by their physicians or because they eventually developed symptoms. "Our data suggest that it may be safe to follow asymptomatic patients with a strategy to institute immunosuppressive treatment if symptoms develop over time," the authors state, although they note that patients with no symptoms were less likely to respond to treatment than those that had symptoms.

Notably, the current study also showed that patients who had cirrhosis when diagnosed had a worse outcome than those that did not, with a higher incidence of complications or death. Treatment is normally initiated in asymptomatic patients because it is thought to prevent the development of cirrhosis, but whether this is the case remains unclear. Other studies have been inconclusive in this area and based on the current study the authors conclude: "Most [asymptomatic] patients will not develop symptoms during follow-up and they appear to do well without immunosuppressive therapy at least for as long as they remain asymptomatic."

Although the authors note that the results should be considered with caution due to the limited number of patients who underwent liver biopsy, they conclude that severe OSA, independent of being overweight, is a risk factor for liver disease. In addition, they postulate that OSA may contribute to insulin resistance and fatty liver disease, since insulin responsiveness improves after treating OSA. They suggest that the striking relationship between the severity of sleep apnea and liver damage indicates that OSA may play a role in how fatty liver disease develops.

In conclusion, the authors state, OSA is a risk factor for abnormal liver enzymes independently from BMI, and should be investigated in patients without other cause of liver disease. They conclude: Further studies are needed to assess the prevalence of OSA in patients with NASH [nonalcoholic steatohepatitis, or fatty liver disease with inflammation] and to evaluate whether treatment of OSA may improve liver injury.

PegInterferon-alfa-2b with Ribavirin Shows Promise

Tue, 03 May 2005 13:25:38 PST

( from http://www.rxpgnews.com ) More than half of 61 children infected with chronic hepatitis C achieved a sustained viral response after treatment with peginterferon-alfa-2b and ribavirin, report the authors of a new study published in the May 2005 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD).

The combined treatment regimen is considered the best available treatment for adults with chronic hepatitis C, but until now, no published studies have examined its value of for children. To address this lack of information, researchers, led by Stefan Wirth of HELIOS Children's Hospital Wuppertal, Germany sought to evaluate the efficacy and tolerability of the therapy in infected children based on HCV genotype, liver enzyme tests, and route of disease transmission.

The researchers recruited 62 children ranging in age from 2 to 17 years, of mixed genders and races, all with chronic hepatitis C. Researchers determined their HCV genotype, mode of infection, and liver enzyme levels, then initiated the therapy that included a weekly subcutaneous dose of peginterferon-alfa-2b and a daily oral dose of ribavirin. All 62 completed the therapy according to the study protocol, save one who dropped out after developing an allergic reaction at the injection site.

Twelve months later, 39 of the 61 patients (64 percent) had undetectable levels of HCV RNA. Three of these responders relapsed during the 6-month follow-up period, but 36 (59 percent) remained HCV-free. All of the children with HCV genotype 2 or 3 achieved a persistent sustained viral response, in contrast to the fewer than half of the patients with HCV genotype 1. The study also showed that children who had been infected via needle (for example, from a blood transfusion) responded better to treatment than those who were infected by their mothers at birth. Lastly, the researchers found that patients with normal liver enzyme levels before treatment responded better than those with elevated levels.

Most of the children experienced side effects from the treatment ranging from mild flu-like symptoms to weight loss to leucopenia (a decrease in white blood cell count). One girl developed diabetes mellitus, a rare but permanent side effect associated with interferon. She continued treatment and achieved sustained viral response. All other side effects resolved when the treatment protocol ended.

"The data of this uncontrolled study confirms that treatment with recombinant peginterferon-alfa-2b plus ribavirin in children and adolescents with chronic hepatitis C was well tolerated and yielded an encouraging result with 59 percent sustained viral response," the authors report. While the response rate was not significantly higher compared to studies using non-pegylated interferon-alfa-2b plus ribavirin, "it is particularly remarkable that all patients infected by genotype 2 and 3 showed permanent response."

The authors also emphasized the importance of the high viral response rate of children whose liver enzyme tests were normal before treatment began, which suggests that such children should not be excluded from treatment. The lower response rates among children with genotype 1 and in those who were infected by their mothers implies a need for additional research.

"Further studies with larger numbers of patients have to elucidate whether there is a different response rate in relation to mode of transmission," the authors conclude. Other studies "should focus on treatment duration for genotype 2 and 3 patients and particularly on vertically infected children with genotype 1."