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Treatment of Chronic Hepatitis B Infection.doc.doc Treatment of Chronic Hepatitis B Infection.doc.doc Document Transcript

  • Treatment of Chronic Hepatitis B Infection A CME by Fax Program Presented by the Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition Vanderbilt School of MedicineRelease date: October 15, 2007 IntroductionExpiration date: October 15, 2008 Since its discovery about 40 yrs ago, hepatitis BAuthorMichael K. Porayko, MD continues to be a major public health challenge.Associate Professor, Medicine Worldwide, more than 400 million people haveMedical Director of Liver Transplantation chronic hepatitis B (CHB), with a major concentrationVanderbilt School of Medicine of those infected living in or coming from the Asia- Pacific region. The overall prevalence of the virus inEditor the United States is around 5% but the prevalence ofJoseph Awad, MD CHB in various urban populations containing a greaterAssociate Professor, MedicineAssociate Professor, Pharmacology number of immigrants from Asia can range from 10%Vanderbilt School of Medicine to 24%. It has been estimated that 15% to 40% of these chronically infected individuals will eventuallyDisclosure develop complications of liver injury includingMichael K. Porayko - Speaker Fee: Roche, Schering, Gilead cirrhosis and hepatocellular cancer. With emphasis onJoseph Awad - Nothing to disclose. screening and immunization programs, the annualObjectives incidence of new cases of HBV infection in the U.S.After completion of this CME program, the reviewer should be has decreased by more than 50% over the last decade.able to: With the discovery of multiple potent antiviral• Identify different clinical courses of hepatitis B for medications, there has been a renewed interest in the purposes of deciding on the need for antiviral therapy treatment of chronic hepatitis B infections as another• Identify risk factors for more progressive chronic hepatitis way to control the virus and its complications within B the population.• Distinguish differences in management of patients with chronic HBV infection identified as either positive or This CME by Fax program has been written to negative for HBeAg provide the “bare bones” guidelines of managing• Gain an understanding of how to avoid the development of viral resistance to therapy and how to treat patients chronic hepatitis B. For those who want more detailed once resistance mutations have emerged information, we have provided several citations in a• Recognize different classes of HBV antiviral medications bibliography at the end of this article, which includes that can be utilized alone or in combination based on the most recent AASLD practice guidelines on the efficacy against resistance mutations subject.InstructionsParticipants should read all portions of this fax, including alltables and references. A post-test and an evaluation formfollow this activity, both of which require completion. Toreceive your continuing education credit, you will need a scoreof at least 80% on the post-test. The post-test and evaluationform must be completed and returned by October 15, 2008. Itshould take approximately 1 hour to complete this activity asdesigned. There is no registration fee for this activity.Certificates will be mailed within 3-4 weeks of receipt of thepost-test.AcknowledgmentVanderbilt School of Medicine gratefully acknowledges anunrestricted educational grant from Roche in support of thisactivity.Administered by the Vanderbilt Division of CME. Continued on page 2. 1
  • Natural History and Detection of Chronic autoimmune or metabolic liver diseases. ClinicalHepatitis B Infection indicators of chronic liver disease should be sought, including radiological imaging of the liver andWhen initially encountering a patient with HBV abdomen, so that treatment will not be delayed ininfection, it is important to decide whether the patient those with evidence of chronic ongoing liver injury. Ifhas acute or chronic infection to avoid treating confusion persists regarding the duration of infectionsomeone with antiviral medications that may interrupt and degree of liver injury after your initial evaluationthe natural evolution of the infection to an inactive or and serological testing, a liver biopsy may help clarifynonreplicative state. A good working knowledge of the extent of damage and the need for treatment,the various serological markers of HBV infection is especially if active inflammation and fibrosis arenecessary when making this determination. These found. In some instances, even the individual withHBV serological markers can be found in most acute hepatitis B who is deteriorating rapidly may be ageneral textbooks and will not be reviewed in this candidate for antiviral therapy. Patients with aarticle. The presence of anti-HBcore IgM antibody fulminant course of hepatitis B (01% - 0.5% ofcan be a clue to recent infection; however in patients adults), should be referred to a liver transplant centerwith delayed clearance of HBsAg, the IgM core if they appear to be appropriate candidates forantibody can persist, with as many as 20% of patients transplantation surgery.showing positivity after 2 years of follow-up. Therisk of developing chronic infection in Evaluation of Patients With Chronic HBVimmunocompetent adults is considered to be quite low Infection(< 1%) but the overall risk ranges between 5% - 10%,with greater risks of chronic infection in individuals Initial evaluationexposed perinatally (90%) and during childhood • History and physical examination(20%). Persistence of the hepatitis B virus (HBsAg • Laboratory tests to assess of liver disease:positive) for greater than 6 months has been complete blood count with platelets, hepaticconsidered indicative of chronic infection but does not panel, and prothrombin timenecessarily indicate the presence of or development of • Tests for HBV replication: HBeAg/anti-HBe,liver damage. Considering that the HBV viral DNA HBV DNAcan eventually become integrated into the genome of • Consider testing for HBV genotypethe host’s hepatocytes, many investigators feel that • Tests to rule out other causes of liver disease (e.g.even the patient who develops “immune clearance” of anti-HCV, anti-HDV)the virus should not be considered free of the • Test for HAV immunity: anti-HAVpossibility of reversion to an active replicative state • Test for human immunodeficiency viral infection:with the reappearance of HBeAg, especially under anti-HIVcircumstances where the immune system is • Tests to screen for HCC in high-risk patients:suppressed such as in patients receiving chemotherapy alpha fetoprotein tumor marker, radiologicalor immunosuppressive medications. Measurements of imaging of the abdomen/liver (e.g. contrast CTliver enzymes (eg. alanine aminotransferase – ALT), scan)HBe antigen/antibody, HBV DNA levels and liverhistology help define the individual’s course of • Liver biopsy to grade and stage liver disease, ifdisease and the need for antiviral therapy. criteria for chronic hepatitis are met (adopted from Lok and McMahon, Hepatology 2007)When evaluating that patient for the first time whoyou feel has hepatitis B, remember to check for Definitions of Chronic HBV Infectionalternative reasons for liver enzyme elevations,particularly active inflammation resulting from co- Difficulties in defining the natural history of chronicinfection or super-infection with viruses other than hepatitis B include the indolent course of the disease,HBV. These would include hepatitis A, hepatitis C, the lack of symptoms during the early stages and thehepatitis D or delta hepatitis, HIV and rarely hepatitis heterogeneous presentations of the disease. ChronicE in individuals from the appropriate endemic areas. hepatitis B has been categorized into three generalOther causes of liver disease should be excluded as groups based on serological markers, quantitativewell, such as alcohol abuse, hepatotoxic drug use, HBV DNA levels and liver enzymes: see Table 1.Continued next column. Continued on page 3. 2
  • Table 1.Classification Serological Markers HBV DNA (copies/mL)* ALTImmune tolerant HBsAg positive > 107 Normal HBeAg positiveInactive carrier HBsAg positive < 10 5 Normal Anti-HBe positive§ Immunoactive hepatitis HBsAg positive > 105 Elevated HBeAg positive or anti-HBe positive*(5.6 copies/mL = 1 IU/mL)§ This category includes patients who are HBeAg-negative with active viral replication.A sentinel event in the natural history of HBeAg- Determination of HBV genotypes can be helpful inpositive chronic hepatitis is HBeAg seroconversion to predicting responses to therapy. Eight HBVanti-HBe. This is usually associated with a marked genotypes have been identified and have characteristicreduction of HBV replication along with biochemical geographic distributions.and histological remission of inflammatory activity ina majority of patients. The probability of HBeAg HBV Genotypes and Their Geographic Originsseroconversion has been observed to be about 50%and 70% in 5 and 10 years respectively from the time • A – Northwest Europe, North America, Centralof diagnosis. For HBeAg-positive patients, high Africapretreatment ALT is the best predictor of a treatment • B and C – Asiaresponse. • D – Worldwide; highest prevalence in the Mediterranean area, Middle East and South AsiaFactors Associated With Higher Rates of • E – Sub-Saharan AfricaSpontaneous HBeAg Seroconversion • F – South and Central America• Older age • H – Northern part of Latin America• Female gender• Higher ALT levels at presentation (> 5x ULN) A majority of practitioners are not utilizing HBV• Acute exacerbations/spontaneous flares genotypes in their practices at this time but these• HBV genotype (B > C) determinations are becoming more important as we• Ethnicity (other than Asian) learn more about the individual responses to therapy. For example, studies show that genotypes A and B areSome individuals will present with HBeAg-negative characterized by a higher sustained response to alfa-chronic hepatitis B. They will show evidence of interferon when compared to genotype C and D.active inflammation despite the presence of anti-HBe Therefore, since genotype A is more prevalent in theand can have lower quantitative levels of HBV DNA United States, the use of pegylated interferon in the(104 – 105 copies/mL). This atypical serological treatment of this HBV genotype can result in goodresponse is related to the predominance of HBV rates of seroconversion and sustained viral responses.variants unable to express HBeAg due to mutations in Alternatively, the rates of viral resistance tothe precore and core promoter regions of the viral Lamivudine are higher among patients with genotypegenome. HBeAg-negative chronic hepatitis B is more A when compared to genotype D. Treatment ofprevalent in individuals from the Mediterranean basin, patients with genotypes A, B, C and D with adefovirMiddle East and Asia. Liver disease in these has been shown in one large clinical trial to resultindividuals tends to be more active and advanced significant decreases in serum HBV DNA levels in allwhen compared to those with HBeAg-positive chronic patients regardless of genotype. Additional studieshepatitis. Severe necroinflammation on liver biopsy is will need to be performed to provide a better guide toseen in more than 50% of HBeAg-negative patients at the use of HBV genotypes in general practice but thisthe time of diagnosis and sustained spontaneous is likely to occur in the near future. Commercial testsremissions are rare. for HBV genotyping are now available through referral laboratories.Continued next column. Continued on page 4. 3
  • The development of cirrhosis in patients actively level (> 104 copies/mL) was a strong predictor of HCCinfected with HBV and left untreated has been independent of HBeAg, serum ALT and liverinvestigated more extensively in HBeAg-positive cirrhosis.patients. The 5-year cumulative incidence ofprogression to cirrhosis ranges from 8% to 20% in Treatment of Chronic Hepatitis Bthese individuals and the 5-year cumulative incidence Currently, there are six drugs that have been approvedof hepatic decompensation once cirrhosis is identified for the treatment of chronic hepatitis B infection in thehas been estimated to be about 16%. Once United States. These are interferon alfa-2b (Introndecompensation occurs, the prognosis is poor. The A®), lamivudine (Epivir®), adefovir (Hepsera-HBV®),probability of survival ranges from 55% - 70% at 1 entecavir (Baraclude®), peginterferon alfa-2ayear and decreases to 14% - 28% at 5 years. The (Pegasys®) and telbivudine (Tyzeka®). The goal ofvariability in the rate of progression to cirrhosis is therapy for chronic HBV infection is to eliminate ordependent on multiple factors some of which are significantly suppress replication of the virus in anlisted below. effort to prevent progression of liver disease to cirrhosis that may result in liver failure or theRisk Factors for Progression to Cirrhosis development of HCC leading to death or the need for• HBeAg-negative liver transplantation. When and who to treat is based• Older age on a combination of clinical and biochemical data• Genotype C compared to genotype B obtained from the patient as mentioned above.• Co-infection with HDV, HCV or HIV• Alcohol abuse Treatment endpoints • Improve liver histologyAnother serious complication of chronic HBVinfection is the development of hepatocellular • Decrease serum HBV DNA to low orcarcinoma (HCC). In areas of high endemicity the undetectable levelsincidence of liver tumor per 100 person-years is about • Decrease or normalize serum ALT0.1 for the asymptomatic HBsAg carrier, 1.0 for • Induce HBeAg loss or seroconversion to anti-HBeuntreated patients with chronic HBV without • Induce HBsAg loss or seroconversion to anti-HBspreexisting cirrhosis and 3 – 8 for untreated Asian A summary of potential treatment recommendationspatients with compensated HBV-cirrhosis. Alcohol for various patient subgroups is outlined below.and concurrent infection with HCV or HDV increasethe risk of developing HCC. A more recent study Treatment recommendations are provided given thefrom Taiwan revealed that an elevated HBV DNA data regarding the development of resistance to the various approved oral HBV antiviral medications.Continued next column. See Table 2.Table 2.Antiviral Therapy Rates of Genotypic ResistanceNucleoside-naïve patients Lamivudine (LAM) 15% - 30% after 1 yr; ~70% after 5 yrs Adefovir (ADV) 0% after 1 yr; 29% after 5 yrs Entecavir (ETV) 0% after 1 yr; ~1% after 2 yrs and 3 yrs Telbivudine (LdT) 5% - 11% after 1 yrLamivudine-resistant viruses Adefovir ~20% after 2 yrs Entecavir 1%, 9%, ~17% after 1, 2, and 3yrs respectively 4
  • Continued on page 5.Given these viral genotypic resistance rates to the has a resistance rate that exceeds those found with thevarious available oral agents used to treat HBV, many use of Adefovir and Entecavir; therefore, it has notinvestigators have suggested that Lamivudine is no been considered a preferred treatment option in thelonger to be considered as first line therapy for treatment naïve patient. Viral resistance does nottreatment of chronic hepatitis B. Also, Telbivudine appear to develop against interferon therapy.Continued next column.HBeAg-positive and HBeAg-negative patient treatment algorithm: HBeAg-positive patient HBeAg-negative patient >20,000 IU/mL HBV DNA by PCR < 20,000 IU/mL > 2000 IU/mL < 2000 IU/mL No treatment; monitor every 6-12 months (Consider treatment if evidence of significant histological disease) ALT Normal Elevated Consider biopsy (older patient) Treat: ADV, ETV or PEG-IFN are and treat if disease present. first-line options. In absence of biopsy, monitor for Consider biopsy to stage disease. elevated ALT Long-term treatment required if oral Strongly consider liver biopsy and agents are used. treat if disease present.(Adopted from Keeffe et al. Clinical Gastroenterology and Hepatology 2006)Continued on page 6. 5
  • Treatment options for patient with HBV cirrhosis: Compensated Cirrhosis HBV DNA HBV DNA by HBV DNA > 2000 IU/mL PCR < 2000 IU/mL May choose to treat or observe; adefovir or entecavir are preferred for treatment. Adefovir or entecavir are first-line options Long-term therapy required Combination therapy may be preferred________________________________________________________________________ Decompensated Cirrhosis (jaundice, ascites, variceal hemorrhage, encephalopathy) HBV detectable by Yes No PCR Combination therapy with adefovir plus lamivudine or possibly adefovir plus entecavir is preferred first-line option.Continued on page 7. 6
  • In the setting of cirrhosis, the patient is not For patients who have HBeAg-negative chronicalways able to tolerate HBV viral replication and hepatitis B, the endpoints of treatment are less wellhepatic inflammation without rapidly developing defined due to the lack of a marker to help define theworsening liver function. Hence, the threshold for end of treatment. Certainly, treatment for periods oftreatment is lowered to avoid the development of liver 48 weeks is associated with a loss of serum HBVfailure. Pegylated interferon can be used in selected DNA and normalization of ALT in a majority ofpatients with well-compensated cirrhosis but the side patients but the durability of the response after theeffects associated with use of this medication often medication is discontinued ranges between 20%lead the physician to start with oral agents. To avoid (Peginterferon) to less than 5% (adefovir). Longerthe development of resistance mutations and “escape” duration therapy is clearly indicated for these patientsfrom the beneficial effects of antiviral therapy, many but the recommended duration and potential durabilityinvestigators have recommended choosing agents that is still being investigated.have been shown to have lower rates of HBV Regardless of the patient’s HBeAg status orgenotypic resistance when used over longer duration. seroconversion, individuals with cirrhosis of the liverThe use of sequential therapy (i.e. one drug used after should remain on HBV antiviral therapy indefinitelythe next when resistance develops) is discouraged given the severe consequences of a reversion to activebecause resistance to a number of oral agents is likely viral replication and additional hepatic injury.to develop more rapidly. Treatment with acombination of oral agents that do not overlap in their Antiviral Resistant HBVresistance mutation profiles is appealing for thosepatients with a hepatitis B virus that has shown Understanding the concepts of and knowing how togenotypic resistance to one or more agents already or manage drug resistant mutant HBV is an importantin patients who can not tolerate any viral component of your treatment strategy anytime youbreakthrough, such as those with decompensated come encounter a patient infected with hepatitis B.cirrhosis. For example, viral resistance to the One must be familiar with the types of drug-resistantcombination of lamivudine and adefovir has not been mutations that can develop to any of the oral agentsdocumented. and what treatment options are available to you once resistance develops. Resistance genotyping isResponses to Approved Antiviral Therapies becoming more popular as the testing has become more readily available.One of the goals of therapy for patients with anHBeAg-positive serology is to induce a durableseroconversion to anti-HBe or HBeAg clearance.After a defined treatment interval (usually 48 weeks)in various clinical trials the seroconversion ratesresulting from treatment with various availablemedications ranges between 16% and 27%: pegylatedinterferon (27%), lamivudine (16% - 21%), adefovir(12%), entecavir (21%) and telbivudine (22%). OnceHBeAg seroconversion is achieved, the response isusually durable with a relatively low rate of reversionto an active replicative state. The durability of thisseroconversion is 80% - 90% for interferon, 50% -80% for lamivudine, 90% for adefovir, 69% forentecavir, 80% for telbivudine. Once seroconversionoccurs, it is generally recommended that the patient betreated for another 6 – 12 months as consolidationtherapy to achieve more durable viral suppression. Amore robust seroconversion can develop in somepatients as indicated by the emergence of anti-HBs;however it is more unusual given that it only occurs inabout 0.5% of patients per year. 7
  • Continued next column. Continued on page 8.In Vitro Cross-Resistance Patterns for Anti-HBV Drugs Resistance Mutation LAM Resistant ADV Resistant ADV Resistant (L180M + M204V) (N236T) (A181V)Mutation confers some degree of • Entecavir • Clevudine • Lamivudinereduced sensitivity to listed • Emtricitabine • Tenofovir • Entecavirdrugs • Clevudine • Telbivudine • ElvucitabineDrugs remaining fully active • Adefovir • Lamivudine • Tenofovir • Tenofovir • Emtricitabine • Entecavir • TelbivudineWhen a resistant mutation develops that the patient more of these medications is becoming morebegins to show active replication in the face of taking prevalent. Even though the patient may be treatment-the medication correctly, the physician must consider naïve, the hepatitis B virus that he or she has acquiredan alternative drug or combination of drugs. Picking a may be treatment-experienced with the ability todrug from a class of drugs not susceptible to the rapidly mutate to resistant forms.mutation that has developed is crucial (see tableabove). Adding a drug so that the patient is covered Tenofovir and emtricitabine have been used inby two drugs with individual resistance profiles, rather combination (eg. Truvada®) to treat patients infectedthan stopping current therapy and starting a new drug with HIV ± HBV but have not yet been approved for(i.e. sequential therapy) is rapidly becoming the use for HBV infection alone. These medications havepreferred management strategy for patients developing been used alone or in combination by experiencedresistant viral genotypes. physicians to treat patients with more resistant strains of HBV when other options have been exhausted.Also important to remember, with the widespread use With appropriate management of infected patientsof these oral medications, viral exposure to one or with the medications now available, the development of multi-drug resistant strains of the virus can beContinued next column. avoided.Strategies for Treating Antiviral-Resistant HBVType of Resistance Rescue TherapyLamivudine (LAM)/Telbivudine resistance  Add adefovir or tenofovir  Switch to emtricitabine plus tenofovir  Switch to entecavir (with risk of subsequent entecavir resistance and multidrug resistance)Adefovir (ADV) resistance  Add lamivudine or switch to emtricitabine plus tenofovir  Add entecavir (if no prior lamivudine resistance)Entecavir (ETV) resistance  Add adefovir or tenofovirMultidrug resistance (MDR)  MDR to LAM + ADV – consider tenofovir + emtricitabine or tenofovir + entecavir  MDR to LAM + ETV – consider tenofovir or tenofovir plus emtricitabine(Emtricitabine + Tenofovir = Truvada®) 8
  • Continued on page 9.Summary BibliographyHopefully, this CME program has given you some 1. Lok AS, McMahon BJ. AASLD Practiceinsight into the current thinking regarding the Guidelines. Chronic hepatitis B. Hepatologymanagement of patients with chronic HBV infection. 2007;45:507–539.The recent influx of several new antiviral medications 2. Keeffe EB, Dieterich DT, Han SB, et al. Clinand the anticipated continued growth of our Gastroenterol Hepatol 2006;4:936–962.armamentarium has led to increased complexities in 3. Lok AS. Navigating the maze of hepatitis Bour way of managing hepatitis B as well as confusion treatments. Gastroenterologyfor some. However, if you can appreciate a few of the 2007;132:1586-1594.basic principles of therapy as introduced in this brief 4. Palumbo E. Hepatitis B genotypes and responsereview and expanded by more comprehensive practice to antiviral therapy: a review. American Jguidelines available to you through recent Therapeutics 2007;14:302-309.publications (see bibliography), you will be better able 5. Akuta N, Kumada H. Influence of hepatitis Bto improve patient outcomes and quality of life of virus genotypes on the response to antiviralthose infected with HBV. Knowing whom and when therapies. J Antimicrobial Chemotherapyto treat the HBV infection can be challenging at times 2005;55:139-142.but simply stated, if there is evidence of progressive 6. Lok AS, Zoulim F, Locarnini S, et al. Antiviralliver damage or severe patient decline, therapy is drug-resistant HBV:standardization ofindicated even if you risk the chance of aborting the nomenclature and assays and recommendationsdevelopment of the patient’s own natural immunity to for management. Hepatology 2007;46:254-265.the virus. Patients showing active inflammation withhigh viral loads or HBeAg-negative serologies are 7. Gish RG, Locarnini SA. Chronic hepatitis B:likely to be candidates for therapy given the increased current testing strategies. Clin Gastroenterolrisk of progressive liver disease and hepatocellular Hepatol 2006;4:666-676.cancer. When starting a medication to treat your 8. Hoofnagle JH, Doo E, Liang TJ, et al.patient, consider the stage of liver disease and the Management of hepatitis B:summary of a clinicalpossibility of HBV resistance. Choosing a drug or research workshop. Hepatologycombination of drugs to reduce the chance of 2007;45:1054-1075.resistance development is preferable. However, the 9. Keeffe EB, Marcellin P. New and emergingpatient must be followed continually to insure ongoing treatment of chronic hepatitis B. Clinviral suppression. It must be remembered that the Gastroenterol Hepatol 2007;5:285-294.virus is never cleared from the body completely; we 10. Gish RG, Perrillo RP, Jacobson IM. Customizingjust manage to suppress it into inactivity. Patients the management of chronic hepatitis B viruswith HBsAg have defined endpoints of treatment due infection. Semin Liver Dis 2007;27 (Supplto the ability to show a seroconversion to anti-HBe; 1):9-17.continuing treatment for another 6 – 12 months after 11. Chen CJ, Yang HI, Su J, et al. Risk ofseroconversion has been associated with long-term hepatocellular carcinoma across a biologicaldurable responses after the medication is discontinued. gradient of serum hepatitis B virus DNA level.The treatment endpoints for patients who have chronic JAMA 2006;295:65-73.infection but are negative for HBeAg are not welldefined and require more investigation to providemore concrete recommendations about duration oftherapy and long-term responses. Rapid viralsuppression with potent medications appears to beassociated with the best outcomes. Finally, patientswith cirrhosis or more advanced-stage liver diseasemay need to be treated more aggressively andindefinitely given the potential consequences ofongoing liver injury. 9
  • Continued on page 10.Sponsorship Statement:Sponsored by Vanderbilt School of Medicine; Department of Medicine, Division of Gastroenterology,Hepatology and NutritionAccreditation Statement:Vanderbilt School of Medicine is accredited by the Accreditation Council for Continuing MedicalEducation to provide continuing medical education for physicians.Designation Statement:Vanderbilt School of Medicine designates this educational activity for a maximum of 1.0 AMA PRACategory 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of theirparticipation in the activity.Disclosure Statement:It is the policy of Vanderbilt School of Medicine that participants in CME activities be made aware ofany affiliation or financial interest that may affect the content of presentation(s). Each author/editor hascompleted and signed a conflict of interest statement. The author’s/editor’s relationships have beendisclosed below: • Joseph Awad cited no actual or potential conflict of interest in relation to his involvement in this CME activity. • Michael Porayko indicated that he has the following financial relationship: Speaker Fee: Roche, Schering, Gilead Vanderbilt CME has determined that there are no conflicts of interest.Acknowledgment:Vanderbilt School of Medicine gratefully acknowledges an unrestricted educational grant from Roche insupport of this activity.Americans with Disabilities Act:It is the policy of Vanderbilt School of Medicine not to discriminate against any person on the basis ofdisabilities. If you feel you need services or auxiliary aids mentioned in this act in order to fullyparticipate in this continuing education activity, please call Nanette Bahlinger at 615-322-0672.For Additional Information:Please contact the Vanderbilt Division of Continuing Medical Education: 877-CME-VUMC (toll free),615-322-0672 or fax 615-322-4526. 10
  • Continued on page 11. 11
  • Treatment of Chronic Hepatitis B Infection Post Test/Evaluation Form Presented by the Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition Vanderbilt School of Medicine1. A 55 year old patient with Chronic Hepatitis B, eAg 5. Patients with Hepatitis B are not considered candidates negative, eAb positive, viral load of 1000 Units/mL for liver transplantation. and ALT of 45 IU/L is discovered to have Lymphoma a. True and is starting chemotherapy. Which of the following is b. False recommended regarding Hepatitis B? a. No treatment 6. This review met the objectives listed on page 1. b. Entecavir  Agree  Disagree c. Hepatitis B immune globulin d. Interferon 7. The instructional quality of this review is good.  Agree  Disagree e. Ribavirin 8. There is no evidence of commercial bias in this review.2. Which of the following Hepatitis B sAg positive patients  Agree  Disagreewould you be least likely to consider for antireplicativeHepatitis B therapy? 9. Will you be making any changes in your practice as a result a. 25 year old eAg+, VL 100,000 Units/mL, ALT of your participation in this CME activity? 3000, Bilirubin 20 mg/dL, INR 2.0  No  Yes b. 35 year old eAg+, VL 25 MU/mL, ALT 35/mL, Bilirubin 1.0 mg/dL If yes, please share with us what you intend to change: c. 45 year old eAg+, VL 12 MU/mL, ALT 185 IU/mL, Bilirubin 1.5 mg/dL d. 55 year old eAb+, VL 5000 Units/mL, ALT 60, Bilirubin 2.0, Albumin 3.2 mg/dL, platelet count 120K, some ascites3. Hepatitis B sAg/eAg positive patients without prior anti-replicative therapy cannot have a drug-resistant strain ofHepatitis B. a. True 10. Additional comments: b. False4. The viral load threshold for treatment in Hepatitis B sAgpositive patients with imunoactive hepatitis is lower if theyare eAg negative. a. True b. FalseTo receive continuing medical education credit, return this completed form to Vanderbilt Division of CME. Fax: 615-322-4526 Mail: CME by Fax, 320 Light Hall, Nashville, TN 37232-0260Name/Degree: ______________________________________________________________________________Address: _______________________________________ City/State/Zip: __________________________Email address (REQUIRED): _______________________________________________________________Phone: ____________________________________ Fax: ___________________________________________ 12
  • Last four digits of your Social Security Number (REQUIRED): _________________ 13