Jessica P. Hwang

AASLD guidelines for treatment of chronic hepatitis B.

Aasld Guidelines for Treatment of Chronic Hepatitis B Norah Terrault;Natalie Bzowej;Kyong-Mi Chang;Jessica Hwang;Maureen Jonas;Hassan Murad; Hepatology

Hepatitis B Virus Screening for Patients With Cancer Before Therapy: American Society of Clinical Oncology Provisional Clinical Opinion Update

PURPOSE This updated provisional clinical opinion presents a revised opinion based on American Society of Clinical Oncology panel consensus in the context of an evolving database. CONTEXT Despite the 2010 provisional clinical opinion recommendation, there is still evidence of suboptimal hepatitis B virus (HBV) screening among patients at high risk for HBV infection or HBV reactivation after chemotherapy. This updated provisional clinical opinion introduces a risk-adaptive strategy to identify and treat patients with HBV infection to reduce their risk of HBV reactivation. PROVISIONAL CLINICAL OPINION Medical providers should screen by testing patients for HBV infection before starting anti-CD20 therapy or hematopoietic cell transplantation. Providers should also screen patients with risk factors for HBV infection. Screening should include both hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc), because reactivation can occur in patients who are HBsAg positive/anti-HBc positive or HBsAg negative/anti-HBc positive. Either total anti-HBc or anti-HBc immunoglobulin G (not immunoglobulin M) test should be used. Clinicians should start antiviral therapy for HBsAg-positive/anti-HBc-positive patients before or contemporaneously with cancer therapy and monitor HBsAg-negative/anti-HBc-positive patients for reactivation with HBV DNA and ALT levels, promptly starting antivirals if reactivation occurs. Clinicians can initiate antivirals for HBsAg-negative/anti-HBc-positive patients anticipating cancer therapies associated with a high risk of reactivation, or they can monitor HBV DNA and ALT levels and initiate on-demand antivirals. For patients who neither have HBV risk factors nor anticipate cancer therapy associated with a high risk of reactivation, current evidence does not support HBV screening before initiation of cancer therapy. Two panel members provided a minority viewpoint, involving a strategy of universal HBsAg and selective anti-HBc testing.

Acute exacerbation and reactivation of chronic hepatitis C virus infection in cancer patients

BACKGROUND & AIMS Data on acute exacerbation and reactivation of chronic hepatitis C virus (HCV) infection following chemotherapy are very limited. We sought to characterize the episodes of acute exacerbation and viral reactivation of HCV infection in cancer patients. METHODS The medical records of HCV-infected patients seen at our institution (2008-2009) were analyzed retrospectively. Acute exacerbation was defined as greater than 3-fold increase in serum level of alanine aminotransferase, and viral reactivation as ≥ 1 log(10) IU/ml increase of HCV viral load following chemotherapy. RESULTS Acute exacerbation occurred in 33 (11%) of 308 patients with proven HCV infection. Patients with acute exacerbation more often had underlying hematological malignancies (73% vs. 29%; p<0.001) and lymphopenia (6% vs. 0%; p=0.01) than patients without it. In multivariate analysis, underlying hematological malignancies (p=0.02; odds ratio, 3.2; 95% confidence interval, 1.2-8.7) and use of rituximab (p=0.004; odds ratio, 4.2; 95% confidence interval, 1.6-10.9) were associated with acute exacerbation. Patients with acute exacerbation received higher median cumulative dose of rituximab than those without exacerbation. Discontinuation of chemotherapy due to liver dysfunction was more common in patients with acute exacerbation than in patients without it (45% vs. 11%; p<0.001). Eight (36%) of 22 patients with known pre- and post-chemotherapy viral load had viral reactivation. CONCLUSIONS Acute exacerbation and reactivation of chronic HCV infection occur often after chemotherapy. Liver dysfunction can lead to discontinuation of potentially life-saving chemotherapy in nearly one-half of the patients with exacerbation of HCV infection.

Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance

This AASLD 2018 Hepatitis B Guidance is intended to complement the AASLD 2016 Practice Guidelines for Treatment of Chronic Hepatitis B and update the previous hepatitis B virus (HBV) guidelines from 2009. The 2018 updated guidance on chronic hepatitis B (CHB) includes (1) updates on treatment since the 2016 HBV guidelines (notably the use of tenofovir alafenamide) and guidance on (2) screening, counseling, and prevention; (3) specialized virological and serological tests; (4) monitoring of untreated patients; and (5) treatment of hepatitis B in special populations, including persons with viral coinfections, acute hepatitis B, recipients of immunosuppressive therapy, and transplant recipients. The AASLD 2018 Hepatitis B Guidance provides a data-supported approach to screening, prevention, diagnosis, and clinical management of patients with hepatitis B. It differs from the published 2016 AASLD guidelines, which conducted systematic reviews and used a multidisciplinary panel of experts to rate the quality (level) of the evidence and the strength of each recommendation using the Grading of Recommendations Assessment, Development and Evaluation system in support of guideline recommendations. In contrast, this guidance document was developed by consensus of an expert panel, without formal systematic review or use of the Grading of Recommendations Assessment, Development, and Evaluation system. The 2018 guidance is based upon the following: (1) formal review and analysis of published literature on the topics; (2) World Health Organization guidance on prevention, care, and treatment of CHB; and (3) the authors’ experience in acute hepatitis B andCHB. Intended for use by health care providers, this guidance identifies preferred approaches to the diagnostic, therapeutic, and preventive aspects of care for patients with CHB. As with clinical practice guidelines, it provides general guidance to optimize the care of the

Low Rates of Hepatitis B Virus Screening at the Onset of Chemotherapy

PURPOSE Patients with hepatitis B virus (HBV) infection are at risk for reactivation after chemotherapy. Effective prophylaxis is available but depends on detection of prior infection. Previous studies have shown low screening rates, but no large-scale US studies have been conducted. We sought to determine predictors of screening and positive HBV test results in patients receiving chemotherapy. METHODS We conducted a retrospective cohort study of patients with newly diagnosed cancer who received chemotherapy between January 2004 and September 2007 at a comprehensive cancer center. We determined rates and predictors of screening for HBV infection with HB surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti-HBc) tests as well as the prevalence and predictors of positive results. We explored rates of acutely elevated liver function tests and liver decompensation after chemotherapy. RESULTS Of 10,729 new patients who received chemotherapy, 1,787 (16.7%) underwent HBsAg or anti-HBc screening. Less than 20% of patients with HBV risk factors were screened, even though their odds of HBV infection were increased four-fold compared with those without risk factors. The prevalence of chronic HBV infection was 1.5%. whereas 7.4% had positive anti-HBc only. The strongest predictors of HBV screening were having a history of HBV infection, hematologic malignancy, and rituximab treatment (P < .001). Asian ethnicity was not a significant predictor of screening, despite being a strong and highly significant predictor of positive test results (P < .001). CONCLUSION HBV screening among patients with cancer is low, especially among those known to be at high risk for HBV infection. Future research directed toward identifying best screening methods and HBV risk tools will be necessary to reduce the risk of reactivation of HBV infection after chemotherapy.

Improving Wait Time for Chemotherapy in an Outpatient Clinic at a Comprehensive Cancer Center

PURPOSE We conducted our study at the Ambulatory Treatment Center (ATC) of the MD Anderson Cancer Center, a network of six outpatient treatment units for patients receiving infusion therapies. Excessive patient wait time for chemotherapy was a primary source of ATC patient dissatisfaction. ATC employees expressed frustration, because often, patients arrived physically on time but were not treatment ready. Additionally, ATC staff emphasized challenges associated with obtaining finalized treatment orders for prescheduled appointments (ie, placeholder appointments without associated physician treatment orders). We aimed to decrease mean patient wait time from check-in to treatment in one ATC unit by 25%. METHODS We studied appointment cycle time in the ATC Green Unit, stratifying appointments by type (ie, prescheduled [no finalized treatment orders] and scheduled [finalized treatment orders]). We obtained mean wait times at baseline (control) and again after our intervention period. We conducted interviews and observations in ATC Green, from which we developed a three-part plan to reduce wait time: increase process efficiency within ATC Green, enhance communications with MD Anderson clinics and centers, and incorporate information technology applications. RESULTS After our intervention, we observed a 15% decrease in wait time for patients with prescheduled appointments and a 29% decrease for those with scheduled appointments. Overall, there was a 26.8% reduction in mean patient wait time relative to baseline (control). CONCLUSION We observed a significantly decreased mean patient wait time after implementing our intervention. This decrease may improve patient satisfaction, relieve employee frustration with appointment scheduling, and create opportunities for increasing institutional revenue.

Hepatitis B and Hepatitis C Prevalence and Treatment Referral Among Asian Americans Undergoing Community-Based Hepatitis Screening

OBJECTIVES We sought to identify cross-sectional hepatitis B virus (HBV) and HCV prevalence among Asian Americans at a community health fair and to assess referral rates. METHODS We determined HBV prevalence with hepatitis B surface antigen (HBsAg), antibodies to hepatitis B core antigen (anti-HBc), and antibodies to hepatitis B surface antigen (anti-HBs). We determined HCV prevalence with hepatitis C antibodies. Successful referral occurred when participants with HBV or HCV were contacted, medically evaluated, and given contact information of liver specialists for care. RESULTS Of 202 people screened, 118 were Asian Americans (65 Chinese and 39 Vietnamese). Twelve had chronic HBV with positive HBsAg. However, chronic HBV prevalence increased from 10.2% to 13.6% by concomitant HBsAg, anti-HBc, and anti-HBs testing. Prevalence of HCV was 6% overall but 15.4% among Vietnamese. Overall, 83% of patients with chronic HBV and 100% of patients with occult HBV or HCV were successfully referred. CONCLUSIONS Concomitant HBsAg, anti-HBc, and anti-HBs testing permits diagnosis of chronic, occult HBV infections missed by testing with HBsAg alone. Persons identified with HBV or HCV at community health fairs can be successfully referred.

A Randomized, Double-blind, 2-Period, Placebo-Controlled Crossover Trial of a Sustained-Release Methylphenidate in the Treatment of Fatigue in Cancer Patients

PurposeThis study assessed the efficacy of methylphenidate versus placebo for cancer-related fatigue reduction. Other objectives were to analyze cytokine levels and to determine the effects of methylphenidate on other symptoms, cognitive function, work yield, and patients’ perceptions and preferences. MethodsPatients were randomly assigned (1:1) to receive methylphenidate-placebo or placebo-methylphenidate for 4 weeks. Patients crossed over after 2 weeks. Wilcoxon signed rank tests and McNemar tests were used to assess continuous and categorical variables. The primary efficacy endpoint was change in the level of worst fatigue on the Brief Fatigue Inventory (BFI) at the end of each 2-week period. ResultsThe mean baseline BFI score was moderate (5.7). Methylphenidate treatment did not affect patients’ worst level of fatigue or other symptoms. Results from the Wechsler Adult Intelligence Scale Digit Symbol Test and the Hopkins Verbal Learning Test with BFI interference questions and BFI activity questions showed significant improvement in the methylphenidate-treated patients’ verbal learning, memory, visual perception, analysis, and scanning speed. Patients treated with methylphenidate missed significantly fewer work hours owing to health reasons and worked significantly more hours. After 4 weeks, 64% of patients reported that methylphenidate improved their cancer-related fatigue, and 58% wanted to continue treatment. Significant difference in interleukin 6R (positive), interleukin 10 (negative), and tumor necrosis factor &agr; (positive) was noted between the methylphenidate and the placebo group. ConclusionsLow-dose methylphenidate did not improve cancer-related fatigue. Patients taking methylphenidate had better cognition and were able to work more hours. Patients tolerated methylphenidate well, and the majority felt better and wanted to continue treatment.

Hepatitis B reactivation during cancer chemotherapy: an international survey of the membership of the American Association for the Study of Liver Diseases

Hepatitis B virus reactivation (HBVr) can be a serious complication of cancer chemotherapy. However, underutilization of HBV screening and secondary underutilization of antiviral prophylaxis have been frequently reported. The authors electronically distributed a 30‐point questionnaire to members of the American Association for the Study of Liver Diseases to capture experiences with HBVr during cancer chemotherapy. The questionnaire specified diagnostic criteria and collected information on HBV screening, antiviral prophylaxis and clinical outcomes. Ninety‐nine respondents reported 188 patients who met the criteria for HBV reactivation. Forty‐one practised outside the United States, and most were hepatologists (n = 71) or gastroenterologists (n = 12). One hundred and twenty‐six patients had haematologic malignancies, of which 88 (70%) had lymphoma. Seventy‐five patients (40%) had screening for both hepatitis B surface antigen (HBsAg) and antibody to hepatitis B core antigen (anti‐HBc), and an additional 24 patients (13%) had HBsAg screening alone. Prophylactic antiviral therapy was reported in only 18 patients (10%). Chemotherapy was interrupted in 52 patients (41%) with haematologic malignancies and 26 of 41 patients (63%) with solid tumours (P = 0.01). Rituximab‐treated patients (n = 66) required hospitalization more frequently (P = 0.04), but their overall survival did not differ from individuals not treated with rituximab. Death due to liver failure was reported in 43 patients overall (23%). Underutilization of prophylactic antiviral therapy occured in a substantial number of patients who were found to be HBV infected prior to the initiation of cancer chemotherapy. The reasons for this need further exploration because reactivation results in serious yet preventable outcomes.

Hepatitis B virus management to prevent reactivation after chemotherapy: a review

PurposeReactivation of hepatitis B virus (HBV) infection after chemotherapy can lead to liver failure and death. Conflicting recommendations regarding HBV screening in cancer patients awaiting chemotherapy mean that some patients at risk for HBV reactivation are not being identified and treated with prophylactic antiviral therapy.MethodsWe performed a narrative review of the existing evidence regarding screening for and management of HBV infection among patients with cancer using Ovid Medline, PubMed, and the Cochrane Library.ResultsOur review showed inconsistencies in the definition and management strategies for HBV reactivation. The timeframe of reactivation is variable, and its molecular mechanisms are not clear. There are five effective antiviral agents that can be used as prophylaxis to prevent reactivation of HBV infection in cancer patients; however, the optimal drug and duration of therapy are unknown. Reactivation is more commonly reported in patients with hematologic malignancies receiving rituximab treatment, but reactivation can occur after other chemotherapies and in patients with solid tumors. Screening with all three screening tests—HBsAg, anti-HBc, and anti-HBs—allows the most thorough interpretation of a patient’s serologic profile and assessment of reactivation risk; however, decision-making and cost-effectiveness studies are needed to determine optimal screening strategies.ConclusionsPrevention of reactivation of HBV infection depends on identification of patients at risk and initiation of antiviral prophylaxis, but data to guide screening and treatment strategies are lacking. Additional research is necessary to accurately define and predict reactivation, identify best antiviral treatment strategies, and identify cost-effective HBV screening strategies.