Emmet B. Keeffe

A Treatment Algorithm for the Management of Chronic Hepatitis B Virus Infection in the United States: 2008 Update

Chronic HBV infection is an important public health problem worldwide and in the United States. A treatment algorithm for the management of this disease, published previously by a panel of U.S. hepatologists, has been revised on the basis of new developments in the understanding of the disorder, the availability of more sensitive molecular diagnostic tests, and the licensure of new therapies. In addition, a better understanding of the advantages and disadvantages of new treatments has led to the development of strategies for reducing the rate of resistance associated with oral agents and optimizing treatment outcomes. This updated algorithm was based primarily on available evidence by using a systematic review of the literature. Where data were lacking, the panel relied on clinical experience and consensus expert opinion. The primary aim of antiviral therapy is durable suppression of serum HBV DNA to low or undetectable levels. Assays can now detect serum HBV DNA at levels as low as 10 IU/mL and should be used to establish a baseline level, monitor response to antiviral therapy, and survey for the development of drug resistance. Interferon alfa-2b, lamivudine, adefovir, entecavir, peginterferon alfa-2a, telbivudine, and tenofovir are approved as initial therapy for chronic hepatitis B and have certain advantages and disadvantages. Although all of these agents can be used in selected patients, the preferred first-line treatment choices are entecavir, peginterferon alfa-2a, and tenofovir. Issues for consideration for therapy include efficacy, safety, rate of resistance, method of administration, and cost.

A treatment algorithm for the management of chronic hepatitis B virus infection in the United States

BACKGROUND AND AIMS Chronic hepatitis B is an important public health problem worldwide and in the United States. A treatment algorithm for chronic hepatitis B virus (HBV) infection was developed by a panel of US hepatologists based on new developments in the understanding of the virology of HBV, availability of more sensitive molecular diagnostic testing, and advantages and disadvantages of currently approved therapies. METHODS This algorithm is based on available evidence, but where data are lacking, the panel relied on clinical experience and consensus expert opinion. RESULTS Serum HBV DNA can be detected at levels as low as 100-1000 copies/mL by using molecular assays and should be determined to establish a baseline level before treatment, monitor response to antiviral therapy, and survey for the development of drug resistance. The primary aim of antiviral therapy is durable suppression of serum HBV DNA to the lowest level possible. The threshold level of HBV DNA for determination of candidacy for therapy is >/=10(5) copies/mL for patients with hepatitis B e antigen (HBeAg)-positive chronic hepatitis B. A lower serum HBV DNA threshold is appropriate for patients with HBeAg-negative chronic hepatitis B and those with decompensated cirrhosis, and the panel recommends thresholds of 10(4) copies/mL and 10(3) copies/mL, respectively. CONCLUSIONS Interferon alfa-2b, lamivudine, and adefovir dipivoxil are all approved as initial therapy for chronic hepatitis B and have certain advantages and disadvantages. Issues for consideration include efficacy, safety, incidence of resistance, method of administration, and cost. Studies are under way to explore the safety and efficacy of combination therapy, which may prove to be more effective than monotherapy in suppressing viral replication and may decrease or delay the incidence of drug resistance.

Hepatitis B virus genotypes in the United States: results of a nationwide study

BACKGROUND & AIMS Hepatitis B virus (HBV) genotypes may be related to severity of liver disease and treatment response. The aims of this nationwide study were to determine the prevalence of HBV genotypes in the United States and the association between HBV genotypes and patient demographics, mode of infection, and clinical status. METHODS A total of 694 consecutive chronic HBV-infected patients seen in 17 U.S. liver centers during a 1-year period were enrolled. Demographic, clinical, and laboratory data were collected. Sera were tested for HBV genotyping, precore, and core promoter variants by line-probe assays. RESULTS All 7 HBV genotypes (A-G) were found, with genotypes A and C the most common. The prevalence of HBV genotypes was different in different regions of the United States. A strong correlation was found between HBV genotypes and ethnicity. HBV genotype A was prevalent among white and black patients, whereas genotypes B and C were most common among Asian patients. The predominant genotype among patients born in the United States, Europe, the Far East, and Southeast Asia were A, D, C, and B, respectively. Genotypes A and C were associated with a higher prevalence of hepatitis B e antigen. Precore variant was detected in 27% of patients and core promoter variant in 44% of patients. CONCLUSIONS Our study suggests that the epidemiology of HBV infection in the United States may have changed over time as a result of immigration from countries with a high prevalence of HBV infection. HBV genotypes may account for the heterogeneity in disease manifestations among patients with chronic HBV infection.

Prevalence and Treatment of Hepatitis C Virus Genotypes 4, 5, and 6

Infection with hepatitis C virus (HCV) genotypes 4-6 (with the previously named genotypes 7-9 included as subtypes of genotype 6) is distributed and studied less widely than genotypes 1-3. However, genotypes 4-6 are very common in geographic areas where chronic hepatitis C is highly prevalent. In fact, the majority (87%) of the 169.7 million HCV-infected individuals worldwide are from western Pacific countries (62.2 million), southeast Asia (32.3 million), Africa (31.9 million), and eastern Mediterranean countries (21.3 million). It is among this large population outside of the Americas and Europe that these less well known genotypes are found: genotype 4 in Egypt and Africa, genotype 5 in South Africa, and genotype 6 in southeast Asia. The existing literature, although limited, suggests that patients with chronic hepatitis C genotypes 4-6 may exhibit different clinical courses and treatment outcomes. Ethnicity-related factors may contribute to the presence of more advanced disease in patients with genotype 4, who also tend to have a poor response to interferon-based therapy. HCV genotype 5 appears to be an easy-to-treat virus with response rates similar to those of genotypes 2 and 3 after a 48-week course of therapy. Response to treatment in patients with HCV genotype 6 may be at an intermediate level between that seen with genotype 1 and genotype 2 or 3. The optimal duration of treatment (24 vs 48 wk) for HCV genotype 6 is unclear and currently is under investigation.

Development and evaluation of the liver disease quality of life instrument in persons with advanced, chronic liver disease - The LDQOL 1.0

Development and evaluation of the liver disease quality of life instrument in persons with advanced, chronic liver disease—the LDQOL 1.0

Cost-effectiveness of screening for hepatocellular carcinoma in patients with cirrhosis due to chronic hepatitis C.

Background : Screening for hepatocellular carcinoma in cirrhotic patients using abdominal ultrasonography and alpha‐foetoprotein levels is widely practiced.

Review article: current antiviral therapy of chronic hepatitis B

Background  The long‐term goals of therapy for chronic hepatitis B are to reduce serum HBV DNA to low or undetectable levels and ultimately reduce or prevent the development of cirrhosis and hepatocellular carcinoma.

The epidemiology of hepatitis C virus infection.

The prevalence of hepatitis C virus (HCV) infection varies in different populations, ranging from as low as 0.6% in volunteer blood donors to as high as 80% in injection drug users. The prevalence of HCV in a population can be predicted by risk factors associated with the transmission of infection. These risk factors include injection drug use, blood product transfusion, organ transplantation, hemodialysis, occupational injury, sexual transmission, and vertical transmission. We review the literature regarding the incidence and prevalence of HCV infection and the evidence supporting various modes of HCV transmission.

Improved Virologic Response in Chronic Hepatitis C Genotype 4 Treated With Nitazoxanide, Peginterferon, and Ribavirin

BACKGROUND & AIMS Sustained virologic response (SVR) rates of 50%-60% have been achieved in patients with chronic hepatitis C genotype 4 treated with peginterferon plus ribavirin. The safety and efficacy of nitazoxanide plus peginterferon alfa-2a, with or without ribavirin, were evaluated in a randomized controlled trial at 2 centers in Egypt. METHODS Previously untreated patients with chronic hepatitis C and genotype 4 infection were assigned randomly to groups that were given standard of care (peginterferon alfa-2a and ribavirin for 48 weeks, n = 40), nitazoxanide monotherapy for 12 weeks followed by nitazoxanide plus peginterferon alfa-2a for 36 weeks (n = 28), or nitazoxanide monotherapy for 12 weeks followed by nitazoxanide plus peginterferon alfa-2a and ribavirin for 36 weeks (n = 28). Therapeutics included nitazoxanide (500 mg) twice daily, peginterferon alfa-2a (180 microg) once weekly, and weight-based ribavirin (1000-1200 mg/day). RESULTS The percentages of rapid virologic response (RVR), defined as undetectable HCV RNA at week 4 of combination therapy, and SVR were significantly higher in patients given the triple therapy compared with the standard of care (64% vs 38%, P = .048; and 79% vs 50%, P = .023; respectively). Patients given nitazoxanide plus peginterferon alfa-2a had intermediate rates of RVR (54%) and SVR (61%). Adverse events were similar across treatment groups except for higher rates of anemia in the groups receiving ribavirin. CONCLUSIONS The combination of nitazoxanide, peginterferon alfa-2a, and ribavirin increased the percentages of patients with RVR and SVR, compared with patients given peginterferon plus ribavirin, without an increase in adverse events.

Systematic review : lamivudine prophylaxis for chemotherapy- induced reactivation of chronic hepatitis B virus infection

Background  Reactivation of hepatitis B virus infection in asymptomatic hepatitis B surface antigen carriers undergoing chemotherapy or immunosuppressive therapy is a well‐documented and potentially fatal complication. Data supporting the use of lamivudine for primary prophylaxis have emerged, but its use remains controversial and is not standardized.