<?xml version="1.0" encoding="utf-8"?>
<recommendedContent xmlns="http://api.mspoke.com">
    <recommendedItem id="20100101_19_3213"
                     title="Cirrhosis Outcomes Better When Tx Guidelines Followed (CME/CE)"
                     score="0.01"
                     href="http://www.medpagetoday.com/Gastroenterology/GeneralHepatology/tb/21964?impressionId=1283747212143"
                     
      &lt;p&gt;Routinely screening liver cirrhosis patients for esophageal varices and treating them according to published guidelines led to lower-than-expected rates of subsequent variceal hemorrhage, researchers found.&lt;/p&gt;
&lt;p&gt;A review of patient charts in a center that showed strong compliance with cirrhosis management guidelines found that the actuarial two-year likelihood of variceal bleeding was 13%  --  compared with a predicted rate of 27% calculated on the basis of liver dysfunction severity, variceal size, and so-called &quot;red wale markings&quot; seen on endoscopy (&lt;em&gt;P&lt;/em&gt;&amp;lt;0.05), according to Jayavani Moodley, MD, of the Cleveland Clinic, and colleagues.&lt;/p&gt;
&lt;p&gt;&quot;In our population, management according to principles endorsed by a recently published practice guideline was associated with a lower bleeding rate than that expected in untreated patients,&quot; Moodley and co-authors wrote in the August issue of &lt;em&gt;Clinical Gastroenterology and Hepatology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;Guidelines issued in 2007 jointly by the American Gastroenterological Association and the American Association for the Study of Liver Disease call for screening cirrhosis patients for esophageal varices and beta-blocker treatment or variceal ligation for patients found to be at risk for bleeding, along with periodic follow-up endoscopy.&lt;/p&gt;
&lt;p&gt;Moodley&apos;s team reviewed charts from 179 patients evaluated for cirrhosis at the Cleveland Clinic from 2003 to 2006 and found that 80% had endoscopic screens for esophageal varices within six months of their initial visit, and a total of 94% had such screens at some point during treatment at the clinic.&lt;/p&gt;
&lt;p&gt;A chart review of endoscopy results revealed that 83 patients had varices  --  including 35 with medium to large lesions.&lt;/p&gt;
&lt;p&gt;The review also indicated that treatments conforming to the AGA/AASLD guidelines were given to 91% of patients with medium or large varices. On the other hand, compliance with the guidelines was lower (60%) among patients with small varices.&lt;/p&gt;
&lt;p&gt;Of those patients without bleeding episodes during follow-up, 82% had their screening endoscopy within six months of their initial visit  --  whereas only 50% of the patients suffering hemorrhages received such prompt screening (&lt;em&gt;P&lt;/em&gt;=0.016).&lt;/p&gt;
&lt;p&gt;Hemorrhage from esophageal varices occurred in nine patients with varices at screening of 12 total bleeding episodes that occurred during the follow-up period.&lt;/p&gt;
&lt;p&gt;Moodley and colleagues had calculated a two-year actuarial probability of 13% that patients with varices would have hemorrhages. In comparison  --  under the standard North Italian Endoscopy Club model for predicting variceal hemorrhage rates  --  27% of the Cleveland Clinic patients with varices would have been expected to develop hemorrhages in two years. This model takes into account the severity of liver dysfunction, the size of varices, and whether red wale markings are present.&lt;/p&gt;
&lt;p&gt;Moodley and colleagues noted that 80% of the clinic&apos;s patients with medium to large varices underwent ligation procedures as opposed to beta-blocker therapy.&lt;/p&gt;
&lt;p&gt;In their report, they wrote that the clinic&apos;s institutional preference was &quot;influenced by two meta-analyses which indicate superiority of esophageal variceal ligation in preventing initial bleeding.&quot; But they also noted that a study published last year found better outcomes for beta-blockers.&lt;/p&gt;
&lt;p&gt;&quot;This finding, if verified, will likely alter our treatment strategy in the future,&quot; Moodley and colleagues commented.&lt;/p&gt;
&lt;p&gt;In an accompanying editorial, two physicians at Boston&apos;s Beth Israel Deaconess Medical Center noted an odd paradox in the study&apos;s findings.&lt;/p&gt;
&lt;p&gt;Although the rate of variceal hemorrhage was low in patients receiving guideline-compliant recommendations (8%), wrote Michelle Lai, MD, MPH, and Nezam Afdhal, MD, it was even lower (6%) among 54 patients who were screened but did not receive the recommended treatment.&lt;/p&gt;
&lt;p&gt;Lai and Afdhal also suggested that findings at a tertiary care center such as the Cleveland Clinic may not apply to community gastroenterology practices. As a result, they indicated, &quot;the findings, therefore, need to be confirmed ... in future studies.&quot;&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;No external funding for the analysis was reported.&lt;/p&gt;&lt;p&gt;The authors and editorialists declared they had no potential conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_3107"
                     title="Hepatitis E Vaccine Candidate Completely Blocked Disease (CME/CE)"
                     score="0.005"
                     href="http://www.medpagetoday.com/InfectiousDisease/Hepatitis/tb/21823?impressionId=1283747212143"
                     
      &lt;p&gt;An investigational vaccine against hepatitis E was shown to be completely effective in a large randomized trial in China, researchers reported.&lt;/p&gt;
&lt;p&gt;The trial, involving more than 100,000 patients, found that none of the patients who received the full three doses of the vaccine (HEV 239 or Hecolin) developed hepatitis E over a 12-month follow-up, according to Ning-Shao Xia, MD, of Xiamen University in Xiamen, China, and colleagues.&lt;/p&gt;
&lt;p&gt;In contrast, there were 15 cases of hepatitis E among the participants in the placebo arm (who were given a licensed hepatitis B vaccine)  --  for an efficacy rate of 100%, Xia and colleagues reported online in &lt;em&gt;The Lancet&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The vaccine efficacy was equally high when the analysis was expanded to include participants who only got two doses and reached 95.5% among those who got at least one dose, the researchers reported.&lt;/p&gt;
&lt;p&gt;Although the existence of hepatitis E has been known for years, research into the virus has largely been neglected. (See &lt;a href=&quot;http://www.medpagetoday.com/MeetingCoverage/ICAAC/16022&quot; mce_href=&quot;http://www.medpagetoday.com/MeetingCoverage/ICAAC/16022&quot; target=&quot;_blank&quot;&gt;ICAAC: Hepatitis E Virus Finally Gets Some Respect&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;But hepatitis E is widespread  --  estimates suggest that a third of the world&apos;s people are infected  --  and can cause serious disease and death, especially in the developing world, according to background provided by the researchers.&lt;/p&gt;
&lt;p&gt;The double-blind, randomized, placebo-controlled trial was done between August, 2007, and June, 2009 in Jiangsu Province in China, where the virus is endemic. In fact, a preliminary analysis of more than 11,000 of the trial participants showed that 47% already had antibodies against hepatitis E, the researchers reported.&lt;/p&gt;
&lt;p&gt;All told, the investigators randomly assigned 56,302 volunteers to get three doses of the vaccine (delivered intramuscularly at baseline, one, and six months) and 56,302 to get the hepatitis B vaccine on the same schedule.&lt;/p&gt;
&lt;p&gt;The main analysis included those who got all three doses -- 86% in each arm -- and were followed for 12 months starting the 31st day after the last dose.&lt;/p&gt;
&lt;p&gt;In that group, there were no cases in the vaccine arm and 15 in the placebo arm.&lt;/p&gt;
&lt;p&gt;As well, five additional volunteers  --  all in the placebo group  --  developed hepatitis E during the period from 14 days after the second dose and before the third dose, the researchers reported, yielding an efficacy rate of 100% among trial participants who got two doses of vaccine.&lt;/p&gt;
&lt;p&gt;In the entire cohort, there were 23 cases of hepatitis E recorded during the follow-up  --  including a case in one volunteer in the vaccine group who had received only one dose, and 22 cases among participants in the placebo group, producing an efficacy rate of 95.5%.&lt;/p&gt;
&lt;p&gt;The high efficacy rate after two doses suggests that the vaccine can be deployed quickly and would be effective in the context of an outbreak or for travelers to an endemic area, the researchers argued.&lt;/p&gt;
&lt;p&gt;The researchers concluded that the vaccine was well tolerated and effective among a general adult population. &quot;Further studies are needed to assess the safety and to support the benefits of the vaccine for pregnant women and for people younger than 15 years or older than 65 years.&quot; they added.&lt;/p&gt;
&lt;p&gt;Adverse events were mostly mild and local, including pain and swelling at the injection site, Xia and colleagues reported.&lt;/p&gt;
&lt;p&gt;The study is &quot;an important event in the prevention and control of hepatitis E.&quot; according to Scott Holmberg, MD, of the CDC.&lt;/p&gt;
&lt;p&gt;In an accompanying comment, Holmberg said that a safe and effective vaccine  --  if it&apos;s affordable  --  &quot;raises the prospect&quot; of routine vaccination to reduce the impact of chronic hepatitis E, as well as epidemic outbreaks.&lt;/p&gt;
&lt;p&gt;Vaccines, he argued, should not substitute for improvements in sanitation. But, given that sanitary conditions in many places have been slow to improve, &quot;this vaccine might be our best new stopgap in the effort to control the scourge of (hepatitis E) in many parts of the world,&quot; he concluded.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study had support from the Chinese National High-tech R&amp;amp;D Programme, the Chinese National Key Technologies R&amp;amp;D Programme, the Chinese National Science Fund for Distinguished Young Scholars, the Fujian Provincial Department of Sciences and Technology, the Xiamen Science and Technology Bureau, and the Fujian Provincial Science Fund for Distinguished Young Scholars.&lt;/p&gt;&lt;p&gt;Two of the authors are employees of Xiamen Innovax Biotech, which is developing the vaccine. The remaining authors, including Xia, said they had no conflicts.&lt;/p&gt;&lt;p&gt;Holmberg said he had no conflicts.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_3063"
                     title="HBV Damage Disappears With Long-Term Therapy (CME/CE)"
                     score="0"
                     href="http://www.medpagetoday.com/Gastroenterology/Hepatitis/tb/21736?impressionId=1283747212143"
                     
      &lt;p&gt;Long-term treatment with entecavir (Baraclude) at least partially reverses cirrhosis and fibrosis in most chronic hepatitis B patients, according to extended follow-up of a clinical trial.&lt;/p&gt;
&lt;p&gt;In nucleoside-naive patients, liver biopsies taken at least six years after starting on three or more years of entecavir treatment revealed histologic improvement in 96% of patients.&lt;/p&gt;
&lt;p&gt;Fibrosis score improved by at least one point in 88% of patients as well, found Ting-Tsung Chang, MD, of National Cheng Kung University Hospital in Tainan, Taiwan, and colleagues.&lt;/p&gt;
&lt;p&gt;All 10 patients with advanced disease at baseline saw improvements in fibrosis and cirrhosis long term, the researchers reported in the September issue of &lt;em&gt;Hepatology&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;These results add to evidence challenging the idea that fibrosis is an irreversible and relentlessly progressive process, they noted.&lt;/p&gt;
&lt;p&gt;The researchers analyzed outcomes from 69 patients who provided a long-term biopsy sample after having received entecavir for a total of at least three years as part of one of two identical phase III randomized trials, followed by rollover into an open-label study in which all patients got 1.0 mg entecavir daily.&lt;/p&gt;
&lt;p&gt;The &lt;a href=&quot;http://www.medpagetoday.com/Gastroenterology/Hepatitis/2818&quot; mce_href=&quot;http://www.medpagetoday.com/Gastroenterology/Hepatitis/2818&quot; target=&quot;_blank&quot;&gt;randomized phase&lt;/a&gt; of the trials showed entecavir superior to lamivudine (Epivir) for both patients with chronic e antigen-negative hepatitis B and those with e antigen-positive infections. All patients were nucleoside-naive before the trial.&lt;/p&gt;
&lt;p&gt;Among the 57 patients who met criteria for the long-term efficacy analysis, the median time on entecavir was approximately six years (range three to seven).&lt;/p&gt;
&lt;p&gt;The rate of histologic improvement compared with baseline rose to 96% at the long-term assessment, compared with 73% after just 48 weeks of therapy.&lt;/p&gt;
&lt;p&gt;The same was true for the proportion with at least a one-point improvement in Ishak fibrosis score, rising from 32% at 48 weeks to 88% at the long-term assessment.&lt;/p&gt;
&lt;p&gt;For those with necroinflammation by the Knodell classification at baseline, 75% dropped down to no or minimal necroinflammation long term. Among those with fibrosis at baseline, 72% had no or minimal fibrosis long term.&lt;/p&gt;
&lt;p&gt;Only one of the 57 patients showed an increase in Ishak fibrosis score (1 at baseline versus 2 at long-term biopsy) despite undetectable HBV DNA, normal liver enzymes, and an improvement in necroinflammatory score long term.&lt;/p&gt;
&lt;p&gt;Virologic suppression  --  HBV DNA under 300 copies/mL  --  was maintained for all patients at the time of long-term biopsy, while 86% had normalized alanine transaminase (ALT).&lt;/p&gt;
&lt;p&gt;As expected from the sustained virologic response, there was no evidence of virologic rebound or development of antiviral drug resistance, the researchers noted.&lt;/p&gt;
&lt;p&gt;Although 55% of patients lost e antigen and 33% had seroconversion during long-term treatment, those who didn&apos;t also showed improved liver histology and reversal of fibrosis, which Chang&apos;s group pointed to as evidence that &quot;these outcomes are more closely associated with HBV DNA suppression than with immunologic response to therapy.&quot;&lt;/p&gt;
&lt;p&gt;Moreover, the results confirm the value of long-term treatment for chronic hepatitis B, they concluded.&lt;/p&gt;
&lt;p&gt;&quot;The safety profile, potent suppression of HBV replication, and low potential for antiviral drug resistance in nucleoside-naive patients make long-term treatment of chronic hepatitis B with entecavir monotherapy possible,&quot; they wrote in the paper.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was sponsored by the Bristol-Myers Squibb Pharmaceutical Research Institute.&lt;/p&gt;&lt;p&gt;Chang reported having research funding from Gilead Sciences, Bristol-Myers Squibb, GlaxoSmithKline, Schering-Plough, and Pfizer, as well as receiving speech honoraria from Bristol-Myers Squibb and Schering-Plough.&lt;/p&gt;&lt;p&gt;Several co-authors reported being employees of Bristol-Myers Squibb.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_2936"
                     title="Novel HCV Drug Can Double Response Rate (CME/CE)"
                     score="-0.006"
                     href="http://www.medpagetoday.com/InfectiousDisease/Hepatitis/tb/21570?impressionId=1283747212143"
                     
      &lt;p&gt;An investigational protease inhibitor aimed at blocking hepatitis C replication can double the response rate compared with standard care, researchers said.&lt;/p&gt;
&lt;p&gt;In an open-label randomized phase II trial, adding the compound  --  boceprevir  --  to standard therapy in various combinations increased the so-called sustained virological response compared with a control group who got only standard care, according to Paul Kwo, MD, of the Indiana University School of Medicine in Indianapolis, and colleagues.&lt;/p&gt;
&lt;p&gt;But the response rate was doubled when patients were first treated with four weeks of standard therapy  --  peginterferon alfa-2b and ribavirin  --  before boceprevir was added for another 44 weeks, they reported online in &lt;em&gt;The Lancet&lt;/em&gt;.&lt;/p&gt;
&lt;p&gt;The current standard therapy for hepatitis C aims to stimulate the immune system in general without specific interference in viral replication. For patients with the difficult-to-treat genotype 1 of the virus, the therapy yields a sustained virological response in between 40% and 50% of patients.&lt;/p&gt;
&lt;p&gt;In contrast, boceprevir (and a second drug, telaprevir, being investigated separately) blocks the action of the NS3 protease enzyme of hepatitis C, directly preventing viral replication. Early results of this trial were reported last year. (See &lt;a href=&quot;http://www.medpagetoday.com/InfectiousDisease/Hepatitis/13894&quot; mce_href=&quot;http://www.medpagetoday.com/InfectiousDisease/Hepatitis/13894&quot; target=&quot;_blank&quot;&gt;Sustained Response Seen with New Hepatitis C Drug&lt;/a&gt;)&lt;/p&gt;
&lt;p&gt;The researchers tested various drug combinations and treatment schedules in 520 treatment-naive patients with genotype 1 virus. They were randomly assigned to get: &lt;ul&gt; &lt;li&gt;A control standard therapy of peginterferon alfa-2b plus ribavirin for 48 weeks &lt;/li&gt; &lt;li&gt;Standard care for four weeks, then standard care plus boceprevir (at 800 milligrams three times a day) for 24 weeks&lt;/li&gt; &lt;li&gt;Standard care for four weeks, then standard care plus boceprevir (at the same dosage) for 44 weeks&lt;/li&gt; &lt;li&gt;Standard care and boceprevir for 28 weeks &lt;/li&gt; &lt;li&gt;Standard care and boceprevir for 48 weeks&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;In a second part of the study, 75 patients were randomly assigned to get 48 weeks of the triple combination or a 48-week variant in which the ribavirin dose was reduced from 800 to 1,400 milligrams daily to 400 to 1,000 milligrams.&lt;/p&gt;
&lt;p&gt;All of the combinations that included boceprevir did better than standard therapy, the researchers reported, with sustained virological response rates ranging from 54% to 75%, compared with 39% for patients in the control arm.&lt;/p&gt;
&lt;p&gt;The 75% response rate occurred in the patients who got standard care for four weeks, followed by peginterferon alfa-2b, ribavirin, and boceprevir for 44 weeks. The difference from the control arm was significant at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001.&lt;/p&gt;
&lt;p&gt;Next best was a 67% response rate seen in patients who got all three drugs for 48 weeks. The difference from the control arm was also significant at &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001.&lt;/p&gt;
&lt;p&gt;In the second part of the trial, the low-dose ribavirin combination yielded a response rate of 36% and was associated with a high rate of both viral breakthrough (caused by resistance mutations) and relapse, the researchers wrote.&lt;/p&gt;
&lt;p&gt;In both parts of the study, they reported, boceprevir-based groups had higher rates of anemia and dysgeusia (altered sense of taste) than did the control group  --  55% versus 34% and 27% versus 9%, respectively.&lt;/p&gt;
&lt;p&gt;The new NS3 protease inhibitors are a step forward in the treatment of hepatitis C, according to Laura Milazzo, MD, and Spinello Antinori, MD, both of the University of Milan.&lt;/p&gt;
&lt;p&gt;Writing in an accompanying editorial, they said the results of the study suggest that adding boceprevir to the standard treatment substantially improves outcomes, &quot;although not to the desired proportion.&quot;&lt;/p&gt;
&lt;p&gt;But, they added, the emergence of resistance is an issue that needs to be addressed. &quot;Such resistance will be the biggest challenge in the future,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;Lessons from the HIV pandemic, they commented, demonstrate that only complete suppression of viral replication can prevent drug resistance, so that new strategies are needed to explore combinations of drugs, improve adherence, improve the pharmacokinetics of the drugs, and develop resistance testing.&lt;/p&gt;
&lt;p&gt;Limitations of the study included its open-label design (although the authors noted that the endpoints were hepatitis C RNA levels which were blinded laboratory measurements) and classification of patients as with or without cirrhosis based on liver biopsy, which could have been as much as five years old.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;The study was supported by Merck.&lt;/p&gt;&lt;p&gt;Kwo reported financial links with Schering-Plough/Merck, Vertex, Tibotec, Roche, Abbott, Bristol-Myers Squibb, Gilead, Idenix, Valeant, Novartis, Anadys, GlaxoSmithKline, and Human Genome Sciences. Several other authors reported financial links with Schering-Plough/Merck, as well as with a range of other pharmaceutical companies.&lt;/p&gt;&lt;p&gt;The editorialists declared they had no competing interests.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
    <recommendedItem id="20100101_19_2909"
                     title="Chronic HBV Raises Lymphoma Risk (CME/CE)"
                     score="-0.007"
                     href="http://www.medpagetoday.com/InfectiousDisease/Hepatitis/tb/21538?impressionId=1283747212143"
                     
      Chronic hepatitis B virus infection  --  common throughout Asia and Africa and often present since early in life  --  raises the risk for non-Hodgkin&apos;s lymphoma, a large South Korean study confirmed.&lt;br&gt;
&lt;br&gt;Among individuals who were positive for hepatitis B surface antigen (HBsAg), the adjusted hazard ratio for non-Hodgkin&apos;s lymphoma was 1.74 (95% CI 1.45 to 2.09, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001), compared with those who tested negative, according to Eric A. Engels, MD, of the National Cancer Institute in Rockville, Md., and colleagues.&lt;br&gt;
&lt;br&gt;Among subtypes of lymphoma, HBsAg positivity was associated with an increased risk of diffuse large B-cell lymphoma (HR 2.01, 95% CI 1.48 to 2.75, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001) and a category referred to as &quot;other or unknown&quot; subtypes (HR 1.65, 95% CI 1.29 to 2.11, &lt;em&gt;P&lt;/em&gt;&amp;lt;0.0001), the investigators reported online in &lt;em&gt;Lancet Oncology&lt;/em&gt;.&lt;p&gt;&lt;/p&gt;
&lt;p&gt;Several small studies have hinted at an association between non-Hodgkin&apos;s lymphoma and hepatitis B, similar to that which has been established between lymphoma and hepatitis C.&lt;/p&gt;
&lt;p&gt;To explore this possible link, Engels and colleagues recruited 603,585 participants from the Korean Cancer Prevention Study, following them for up to 14 years.&lt;/p&gt;
&lt;p&gt;A total of 53,045 (9%) were HBsAg positive at baseline. These were more likely to be men and to be younger than those who were HBsAg negative, and more likely to have elevated liver enzymes.&lt;/p&gt;
&lt;p&gt;Subsequently, 133 of antigen-positive patients and 905 antigen-negative patients developed non-Hodgkin&apos;s lymphoma.&lt;/p&gt;
&lt;p&gt;Incidence rates for the outcomes that were significantly associated with HBsAg positive versus negative status were: &lt;ul&gt; &lt;li&gt;Overall non-Hodgkin&apos;s lymphoma, 19.4 versus 12.3 per 100,000 person-years&lt;/li&gt; &lt;li&gt;Diffuse large B-cell lymphoma, 6.86 versus 3.79 per 100,000 person-years&lt;/li&gt; &lt;li&gt;Other/unknown subtypes, 10.5 versus 7.07 per 100,000 person-years&lt;/li&gt; &lt;/ul&gt;&lt;/p&gt;
&lt;p&gt;In an unadjusted model, HBsAg positivity was not significantly associated with an increased risk of malignant immunoproliferation, Hodgkin&apos;s lymphoma, multiple myeloma, or leukemia, but after adjustment for sex, age, and calendar year of hepatitis testing, a significant association was seen for malignant immunoproliferation (HR 3.79, 95% CI 1.05 to 13.7).&lt;/p&gt;
&lt;p&gt;Also in an unadjusted model, participants whose aspartate aminotransferase concentration was elevated were at higher risk for non-Hodgkin&apos;s lymphoma and several other hematologic malignancies.&lt;/p&gt;
&lt;p&gt;However, after adjustment for HBsAg status and demographic variables, the association with liver enzymes was attenuated, while HBsAg positivity remained a significant predictor.&lt;/p&gt;
&lt;p&gt;These findings suggest that hepatitis B may play a causal role in non-Hodgkin&apos;s lymphoma, although the mechanism is unknown, according to the investigators.&lt;/p&gt;
&lt;p&gt;&quot;One plausible mechanism could be chronic activation of B cells in HBV-related hepatitis, predisposing to DNA damage and transformation into lymphoma,&quot; they wrote.&lt;/p&gt;
&lt;p&gt;In an accompanying comment, Sook-Hyang Jeong, MD, of Seoul National University, offered further explanation.&lt;/p&gt;
&lt;p&gt;&quot;Many of the genes involved in B-cell lymphomagenesis are normally regulated by signals from the B-cell antigen receptor, and the infectious agents could play a part by directly inducing polyclonal B-cell hyperactivation or providing a chronic antigenic stimulus,&quot; Jeong wrote.&lt;/p&gt;
&lt;p&gt;Jeong also pointed out that oncologists should be alert to the high prevalence of hepatitis B in non-Hodgkin&apos;s lymphoma, because antiviral therapy is needed during and after cancer chemotherapy to prevent reactivation of the virus -- a potentially lethal event.&lt;/p&gt;
&lt;p&gt;Strengths of the study include the size of the cohort and prospective documentation of antibody status.&lt;/p&gt;
&lt;p&gt;The study investigators noted, however, that the associations seen with specific lymphoma subtypes should be interpreted with caution, particularly with the large number of cases classified as other or unknown.&lt;/p&gt;
&lt;p&gt;Some patients may have had more than one subtype, possibly unrecognized diffuse large B-cell lymphoma or low-grade subtypes such as marginal zone lymphoma.&lt;/p&gt;
&lt;p&gt;Additional research will be needed to determine lymphoma causality and whether treatment of hepatitis B in the context of low-grade lymphoma can obviate the need for chemotherapy, according to the investigators.&lt;/p&gt;
&lt;div style=&quot;float:left;border-style:solid;border-width:1px;border-color:#8dabbc;font-family:arial;font-size:12px;background-color:#DBE9F2;padding:5px;&quot;&gt;&lt;p&gt;Authors of the paper and comment all declared no conflicts of interest.&lt;/p&gt;&lt;/div&gt;&lt;div style=&quot;clear:both;&quot;&gt;&lt;/div&gt;
    </recommendedItem>
</recommendedContent>