Outcomes of initial therapy for synchronous brain metastases from small cell lung cancer: a single-institution retrospective analysis.

Small cell lung cancer (SCLC) has a propensity for brain metastases, which is associated with poor prognosis. We sought to determine predictors of overall survival (OS) and brain progression-free survival (bPFS) in SCLC patients with synchronous brain metastases at the time of initial SCLC diagnosis. A total of 107 SCLC patients with synchronous brain metastases treated at a single institution were included in this retrospective analysis. These patients had brain lesions present on initial staging imaging. Survival was estimated using the Kaplan-Meier method with log-rank test. Factors predictive of OS and bPFS were analyzed using Cox proportional hazards regression model. Median OS for the entire cohort was 9 months (interquartile range, 4.2-13.8 months) and median bPFS was 7.3 months (interquartile range, 3.5-11.1 months). OS was 30.3% at 1 year and 14.4% at 2 years, while bPFS was 22.0% at 1 year and 6.9% at 2 years. The median number of brain lesions at diagnosis was 3 (interquartile range, 2-8), and the median size of the largest metastasis was 2.0 cm (interquartile range, 1.0-3.3 cm). Increased number of brain lesions was significantly associated with decreased OS. Patients who received both chemotherapy and whole brain radiation therapy (WBRT) had improved OS (P=0.02) and bPFS (P=0.005) compared to those who had either chemotherapy or WBRT alone. There was no significant difference in OS or bPFS depending on the sequence of therapy or the dose of WBRT. Thirteen patients underwent upfront brain metastasis resection, which was associated with improved OS (P=0.02) but not bPFS (P=0.09) compared to those who did not have surgery. The combination of chemotherapy and WBRT was associated with improved OS and bPFS compared to either modality alone. Upfront brain metastasis resection was associated with improved OS but not bPFS compared to those who did not have surgery.

The Impact of Prophylactic Cranial Irradiation and Consolidative Thoracic Radiation Therapy for Extensive Stage Small-Cell Lung Cancer in the Transition to the Chemo-Immunotherapy Era: A Single Institution Series.

INTRODUCTION: Extensive-stage small-cell lung cancer (ES-SCLC) continues to have poor survival due to its aggressive behavior, despite improvements with incorporation of immunotherapy with standard chemotherapy. Controversy exists regarding the role of consolidative thoracic radiation therapy (TRT) and prophylactic cranial irradiation (PCI) in ES-SCLC due to high recurrence rates. We report our institutional result of the benefit of PCI and TRT in ES-SCLC. METHODS: Patients with ES-SCLC without intracranial metastasis at diagnosis (N = 163) were included. All patients completed systemic therapy with or without immunotherapy based on time of standard of care. Cohorts were divided by systemic therapy use and further subdivided by treatment with PCI and TRT. Overall survival (OS) and progression-free survival (PFS) were estimated by the Kaplan-Meier method with log-rank test for comparison. The effects of TRT and PCI were estimated by multivariable (MVA) Cox regression. RESULTS: Seventy-four patients (45.4%) received TRT, and 33.1% (n = 54) received PCI. The median follow-up was 11 months (3-85 months). PCI improved median OS to 15 months from 10 months, P = .02) and median PFS to 8.5 months from 5 months (P = .02) which remained significant on MVA, P = .02 and P = .02, respectively. TRT improved OS on UVA (P = 0.002) but was not significant on MVA. TRT did not improve PFS. CONCLUSION: This study including chemotherapy and chemo-immunotherapy suggests improved outcomes with addition of PCI in patients with ES-SCLC while TRT did not show benefit to either OS or PFS. A future trial is needed to evaluate the role of TRT and PCI in the era of chemo-immunotherapy.

A Novel Setup Technique for Radiation Treatment of a Severely Obese Patient With a Primary Brain Tumor.

Modern external beam radiation therapy (EBRT) techniques rely on the accurate positioning of the patient using the treatment couch. These motorized couches have weight limits that have decreased over time and are not able to support severely obese patients requiring EBRT. We aimed to develop a technique to support obese patients who are above their weight tolerance while accurately delivering radiation treatment to a brain tumor. This technique was used on a patient receiving adjuvant radiation for gliosarcoma, a variant of glioblastoma. The patient was CT scanned, and the 3D conformal radiation therapy plan was created. A custom treatment couch was created using a transport stretcher, Styrofoam, a CT couch-top, and an IMRT board, which allowed for a thermoplastic mask to be used for a reproducible setup. AP and lateral portal films were taken prior to each treatment to confirm the accuracy of the manual daily setup of the patient on the custom couch. The patient received 60 Gy in 30 daily fractions of 3DCRT in a reproducible fashion. The average deviation from the isocenter fell within the 10 mm and 8 mm planning margins applied to the clinical target volume (CTV) for the initial and boost fields, respectively. The average daily shifts in the anterior-posterior (AP) direction for the patient were 7.97 (-16.19 to 12.04) mm and 1.98 mm (-1.1 to 4.3) mm for the initial and boost treatments, respectively. The average daily shifts in the superior-inferior (SI) direction were 2.2 (-5.08 to 9.04) mm and 3.88 (-2.9 to 8.0) mm for the initial and boost treatments, respectively. This novel approach allowed treatment at 60 Gy for a gliosarcoma patient who had previously been denied treatment due to his weight. By utilizing readily available materials within the department, our team was able to create a reproducible setup technique to safely treat the patient.

Treating Recurrent Brain Metastases Using GammaTile Brachytherapy: A Case Report and Dosimetric Modeling Method.

One of the treatment options for recurrent brain metastases is surgical resection combined with intracranial brachytherapy. GammaTile® (GT) (GT Medical Technologies, Tempe, Arizona) is a tile-shaped permanent brachytherapy device with cesium 131 (131Cs) seeds embedded within a collagen carrier. We report a case of treating a patient with recurrent brain metastases with GT and demonstrate a dosimetric modeling method.

Limited brain metastases: a narrative review.

Limited brain metastases refer to an oligometastatic state in the brain for which focal therapy with stereotactic radiosurgery (SRS) is appropriate. The definition of what is considered "limited" for brain metastases, however, is not well defined. Multiple recent randomized trials show that metastasis-directed therapy with surgery or stereotactic radiation can prolong survival for patients with 1-5 metastases from various primary tumors, but patients with untreated brain metastases were largely excluded from these trials. Stereotactic radiosurgery allows for the treatment of multiple brain metastases while avoiding whole brain radiation (WBRT), which has a known negative impact on neurocognitive function. Randomized trials have shown that stereotactic radiation alone is effective for the treatment of up to 4 brain metastases with decreased neurocognitive side effects and no detriment to overall survival (OS). These data have led to our current definition of "limited" brain metastases. However, more recent data suggests that patients with up to 10 brain metastases can benefit from SRS. Ongoing trials are investigating if patients with up to 15-20 brain metastases may similarly benefit from SRS alone. Advances in systemic therapies which penetrate the blood-brain barrier and have greater activity in central nervous system (CNS) may also expand the population for whom radiosurgery is an appropriate treatment. Immunotherapy may also be synergistic with radiosurgery in some cases. This narrative review will discuss the evolving definition and management of limited brain metastases.

Fatty liver is not independently associated with the rates of complete response to oral antiviral therapy in chronic hepatitis B patients.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis B (CHB) are common liver diseases. Concurrent NAFLD may affect antiviral treatment outcomes in CHB patients. The aim of this study is to investigate the impact of NAFLD on complete viral suppression ([CVS], HBV DNA <20-100 IU/mL) and/or biochemical response ([BR], ALT of ≤25 U/L for females; 35 U/L for males) in CHB patients who received oral antiviral therapy. METHODS: A retrospective study of 555 treated CHB patients (187 NAFLD; 368 non-NAFLD) from 2000 to 2016 at a USA medical centre. NAFLD was diagnosed by imaging and/or histology after ruling out secondary causes of hepatic steatosis. RESULTS: The majority of patients were male (60.7%), Asian (87.56%) and HBeAg-negative (66.7%). NAFLD patients compared to non-NAFLD were more likely HBeAg negative (74.3% vs 62.8%, P = .02), hypertensive (33.2% vs 22.8%, P = .009) and male (67.4% vs 57.3%, P = .02) with a higher mean BMI (25.4 ± 4.3 vs 23.8 ± 4.0 kg/m2 , P < .001). Both cohorts achieved similar rates of CVS (86% vs 88%) and BR (38% vs 41%) during the follow-up of up to 60 months (P > .05), but NAFLD had higher cumulative rates of CVS + BR, compared with non-NAFLD patients (32.5% vs 22.8%, P = .03). In multivariate analyses, NAFLD was not independently associated with CVS and/or BR outcomes. Receipt of entecavir or tenofovir (vs older therapies) and lower baseline HBV DNA or higher ALT were positively associated with achieving CVS or BR. CONCLUSION: Concomitant NAFLD had no impact on the long-term rates of CVS and/or BR in treated CHB patients.

Risk Factors for Abnormal Cervical Cytology in Women Undergoing Kidney Transplant Evaluation.

OBJECTIVES: Cervical cytology screening has been successful in reducing deaths from cervical cancer. We sought to determine risk factors for abnormal Pap test results in women undergoing kidney transplant evaluation. MATERILAS AND METHODS: We retrospectively examined women undergoing kidney transplant evaluations from 2008 to 2011. Patients were stratified based on normal cytology and atypical/malignant cytology. RESULTS: Of 404 patients, 293 patients (72.5%) had normal cytologic findings, whereas 111 (27.5%) had abnormal findings. On univariate logistic regression analyses, patients who had chronic kidney disease with an autoimmune cause (odds ratio = 2.71 [95% confidence interval, 1.41-5.19]; P = .003), previous renal transplants (odds ratio = 2.64 [95% confidence interval, 1.20-5.82], P = .016), or age ≤ 50 years (odds ratio = 1.68 [95% confidence interval, 1.08-2.61], P = .022) were more likely to have abnormal findings. Patients with normal and abnormal findings had similar rates of dialysis use. On multivariate logistic regression, patients who had chronic kidney disease with autoimmune causes (odds ratio = 2.48 [95% confidence interval, 1.26-4.88]; P = .008) and who had previous renal transplants (odds ratio = 2.67 [95% confidence interval, 1.20-5.95]; P = .017) were more likely to have abnormal findings. CONCLUSIONS: Previous kidney transplant, autoimmune disease, and age ≤ 50 years were associated with abnormalities on cervical cancer screening in our female group of patients. Patients with these characteristics may benefit more from routine cervical cancer screening than other patients evaluated for kidney transplant.

The Utility of Screening Colonoscopy During Kidney Transplant Evaluation.

OBJECTIVES: Transplant centers often recommend, but not necessarily require, screening colonoscopies for people over 50 years of age in accordance with the US Preventative Services Task Force guidelines for the general population. We sought to identify risk factors affecting colonoscopy results in renal failure patients undergoing kidney transplant evaluation. MATERIALS AND METHODS: We retrospectively examined patients undergoing kidney transplant evaluation from 2009 to 2012 (n = 469 patients). Comparisons were made between colonoscopy reports categorized as normal (no finding or hyperplastic polyp) or abnormal (adenomatous polyp or carcinoma). RESULTS: Of 469 patients who met the study criteria, 303 (64.6%) had normal colonoscopies and 166 (35.4%) had abnormal colonoscopies. Logistic regression analysis showed that male sex (odds ratio = 2.09; 95% confidence interval, 1.37-3.20; P = .001) and increasing age (odds ratio = 1.04; 95% confidence interval, 1.01-1.08; P = .019) were more likely to correspond to abnormal findings. Those with dialysis vintage (length of time on dialysis) up to 3 years (odds ratio = 2.10; 95% confidence interval, 1.09-4.06; P = .027) and hypertension as the cause of renal failure (odds ratio = 1.79; 95% confidence interval, 1.05-2.87; P = .002) had more abnormal findings. No differences in length of evaluation, rate of being listed for transplant, and rate of transplant were shown. CONCLUSIONS: The overall rate of adenomatous findings on colonoscopy was higher among patients with pretransplant end-stage renal disease than in the general population, as shown in other studies. Age, sex, dialysis vintage up to 3 years, and hypertensive renal failure were associated with adenomatous polyps of the colon in this study population. Because adenomatous polyp rates are high in patients with chronic kidney disease who are undergoing transplant evaluation and colonoscopic findings do not appear to delay transplant evaluations or listing rates, screening colonoscopies should be encouraged.

Lower liver cancer risk with antiviral therapy in chronic hepatitis B patients with normal to minimally elevated ALT and no cirrhosis.

For chronic hepatitis B (CHB), alanine aminotransferase (ALT) ≥2 × upper limit of normal (ULN) is often used as a major criteria to initiate treatment in absence of cirrhosis, though patients with lower ALT may not be free from future risk of hepatocellular carcinoma (HCC). We aimed to examine the effect of antiviral therapy on HCC incidence based on ALT levels.We performed a retrospective study on 3665 patients consisting of United States and Taiwanese REVEAL-HBV cohort who were consecutive, treatment-naïve, noncirrhotic CHB patients aged ≥40 years. Patients were categorized by ALT cutoffs (≥2 × ULN vs <2 × ULN) and subgrouped by treatment status. Kaplan-Meier and Cox proportional hazards models were used to calculate cumulative incidence and hazard ratio (HR) of HCC adjusting for REACH-B scores.A total of 202 patients developed HCC. Antiviral treatment significantly reduced HCC risk: HR 0.24, 95% confidence interval 0.10-0.58; P = 0.001. HCC incidence per 100,000 person-years was significantly higher in untreated versus treated patients, even for those with ALT < 2 × ULN: 314.46 versus 0 per 100,000 person-years, P = 0.0042. For patients with Hepatitis B Virus (HBV) Deoxyribonucleic Acid (DNA) ≥ 2000 IU/mL, the number-needed-to-treat (NNT) were 15 and 14 to prevent 1 incident HCC at year 10 for patients with ALT < 2 × ULN and ≥2 × ULN, respectively.After adjustment by REACH-B score, antiviral treatment significantly decreased HCC incidence even in patients with ALT < 2 × ULN. NNT to prevent 1 incident HCC after 10 years of therapy was low (14-15) in patients with mildly elevated HBV DNA ≥ 2000 IU/mL regardless of ALT levels.

Alternative Therapies for Chronic Hepatitis B Patients With Partial Virological Response to Standard Entecavir Monotherapy.

BACKGROUND: Entecavir (ETV) is a first-line, oral antinucleoside agent for the treatment of chronic hepatitis B patients. Despite its high potency, some patients may still be viremic after prolonged therapy with ETV monotherapy. Long-term outcome data comparing maintained ETV monotherapy to alternative therapies in persistently viremic patients are limited. Our goal was to compare complete viral suppression (CVS) rates [hepatitis B DNA (HBV DNA)<40 to 60 IU/mL] with alternative therapies to continued ETV monotherapy in ETV partial responders. METHODS: This is a retrospective cohort study consisting of 86 consecutive treatment-naive, ETV=0.5 mg partial responders (detectable HBV DNA after ≥12 mo on ETV) who maintained ETV=0.5 mg daily (n=29) or switched to either ETV=1.0 mg daily (n=32) or ETV/tenofovir (TDF)=0.5 mg/300 mg (n=25) in 3 US GI/liver clinics from January 2005 to January 2012. Patients were identified by International Classification of Diseases, Ninth Revision query and data were collected by individual chart review. For those who remained on ETV=0.5 mg, comparison at regimen "switch time" was done using values at 12 months from initial ETV therapy. Rates of CVS were evaluated using Kaplan-Meier methods. Multivariate Cox proportional hazard models were used to estimate hazard ratio (HR) relating to potential predictors to the desirable outcomes of CVS. RESULTS: In all therapy groups, the majority of patients were Asian (93.1% to 100.0%), male (64.0% to 68.8%), and hepatitis B e antigen-positive (95.8% to 100.0%) and had similar baseline alanine aminotransferase (ALT) levels. However, baseline HBV DNA (7.0 vs. 7.9 vs. 7.8 log10 IU/mL, P=0.05) and HBV DNA at regimen switch point (2.9 vs. 3.7 vs. 3.6 log10 IU/mL, P=0.0014) were lower in the ETV=0.5 mg cohort compared with those switched to ETV=1.0 mg or ETV/TDF, respectively. The ETV=0.5 mg cohort also had the shortest duration of ETV=0.5 mg therapy before switch (11.8 vs. 13.5 vs. 19.2 mo, P<0.0001). After the switch point, more patients on ETV/TDF achieved CVS compared with those on ETV=0.5 mg or ETV=1.0 mg at month 6 (77.3% vs. 13.8% vs. 9.4%), month 12 (86.4% vs. 40.5% vs. 25.0%), and month 18 (100% vs. 70.2% vs. 33.3%). Compared with the ETV=0.5 mg and ETV=1.0 mg groups, the ETV/TDF group also had higher rates of ALT normalization at month 6 (73.0% vs, 46.4% vs. 63.0%), month 12 (79.7% vs. 69.5% vs. 77.9%), and month 18 (100.0% vs. 69.5% vs. 86.8%), respectively. The multivariate analyses, inclusive of baseline age and treatment duration on initial therapy with ETV=0.5 mg, indicated that the ETV/TDF combination (HR=12.19, P<0.0001) was independently and positively associated with CVS, whereas high HBV DNA levels at baseline (HR=0.77, P=0.02) and at switch point (HR=0.46, P=0.002) were negatively associated with CVS. ETV=1.0 mg dose was not a predictor for CVS compared with ETV=0.5 mg. CONCLUSIONS: Following adjustments for HBV DNA levels and prior treatment duration, ETV/TDF combination therapy independently predicted superior viral suppression and ALT normalization in partial responders to ETV=0.5 mg daily compared with ETV=0.5 mg or ETV=1.0 mg monotherapy. In patients who continued to be viremic after 12 months of ETV=0.5 mg, one third were still viremic after another 18 months on the same therapy. Alternative therapies should be considered for these patients.

Tenofovir monotherapy after achieving complete viral suppression on entecavir plus tenofovir combination therapy.

OBJECTIVES: It is unclear whether patients with chronic hepatitis B with partial response to entecavir (ETV) who have achieved complete viral suppression (CVS) with ETV plus tenofovir (TDF) combination therapy maintain CVS if switched to TDF or ETV. Our goal was to examine virologic outcomes in such patients. METHODS: This is a retrospective cohort study of 57 ETV partial responders with chronic hepatitis B who showed CVS on ETV+TDF combination therapy, who were switched back to monotherapy with either ETV (n=16) or TDF (n=18), or continued on combination therapy (n=23). The majority of patients were Asian (91%) and male (65%), with a mean age of 41±12 years. RESULTS: The patients switched back to ETV had significantly higher rates of virologic breakthrough by 6 months after the switch compared with their TDF counterparts (88 vs. 39%, P=0.004). Patients who remained on ETV+TDF also had virologic breakthrough, due to either confirmed or suspected nonadherence. On multivariate analysis inclusive of age, sex, and hepatitis B virus DNA levels at initiation of combination therapy, ETV (compared with TDF) was found to be an independent predictor for virologic breakthrough (odds ratio 112.7, P=0.03), as well as duration of CVS of less than 12 months while on ETV+TDF (odds ratio 60.2, P=0.03). CONCLUSION: TDF monotherapy, especially in those who have had CVS for at least 12 months on combination therapy, may be considered for some ETV partial responders who have achieved CVS with combination therapy, given the financial advantage and convenience of monotherapy.

Renal Function in Chronic Hepatitis B Patients Treated With Tenofovir Disoproxil Fumarate or Entecavir Monotherapy: A Matched Case-Cohort Study.

BACKGROUND AND AIMS: Tenofovir (TDF)-associated renal dysfunction has been described in various studies of human immunodeficiency virus-infected patients. Our goal is to examine the incidence and magnitude of decrease in renal function in chronic hepatitis B patients treated with TDF. METHODS: We performed a case-cohort study of 103 patients on TDF 300 mg and 103 patients unexposed to TDF (Entecavir) at 4 centers, who were matched for age±10 years, sex, and baseline estimated glomerular filtration rate (eGFR) group. Calculation and evaluation of eGFR were performed with both the Cockcroft-Gault formula and the Modification of Diet in Renal Disease formula. RESULTS: The exposed and unexposed populations were well matched with a similar mean age (44±10 y), proportion of male patients (63.1%), and baseline eGFR groups (86.4% unimpaired). There was no significant difference in the proportion of patients reclassified to a more severe renal classification (RMSRC) or in the proportion of patients with decrease in eGFR of ≥20% in those exposed to TDF versus control. The incidence density for RMSRC was 7.4 cases per 100 patient-years in the exposed group compared with 11.5 cases per 100 patient-years in the unexposed group (95% CI, 0.31-1.34). The relative risk of exposed to unexposed was 0.64 (95% CI, 0.31-1.34). On Cox proportional hazard analysis following adjustment for sex, age, baseline diagnosis hypertension, diabetes, impaired baseline renal function, and cirrhosis, TDF was not a predictor for RMSRC or decrease in eGFR≥20%. CONCLUSIONS: TDF treatment was not an independent predictor for significant deterioration of renal function. Renal function of chronic hepatitis B patients on antiviral therapy should be monitored, especially in those who are older and/or with mildly impaired renal function.

Similar response to entecavir 0.5 and 1.0 mg in treatment-naïve chronic hepatitis B patients: a case-control study.

BACKGROUND AND AIMS: The dose recommendation for entecavir (ETV) is 0.5 mg daily for treatment-naïve chronic hepatitis B (CHB) patients and 1.0 mg daily for lamivudine-refractory patients; however, few data are available for the efficacy of a 1.0-mg daily dose in treatment-naïve CHB patients. Our goal is to examine the treatment outcome of treatment-naïve patients placed on ETV 0.5 mg or ETV 1.0 mg daily through week 48. METHODS: Cases were 40 consecutive hepatitis B e antigen (HBeAg)-positive CHB patients treated with ETV 1.0 mg daily between January 2005 and September 2010, and controls were 40 consecutive CHB patients treated with ETV 0.5 mg daily between January 2005 and September 2010 at three US gastroenterology/liver clinics. Controls were matched for age (±5 years), sex, HBeAg, and baseline hepatitis B virus (HBV) DNA (±0.5 log10 IU/ml). Complete viral suppression was defined as undetectable HBV DNA by polymerase chain reaction (<100 IU/ml). RESULTS: Both groups had similar distributions of age (38 ± 11 years), male patients (55 %), and mean HBV DNA (7.7 ± 1.1 log10 IU/ml). The complete viral suppression rate was similar in both cases and controls through week 24 (15 vs. 15 %, p = 1.00) and week 48 (22 vs. 36 %, p = 0.17). Non-adherence was reported in three patients in the ETV 1.0 mg daily cohort at week 48. CONCLUSIONS: There were no significant differences in the proportion of patients with complete viral suppression in patients treated with ETV 0.5 mg daily or the higher daily dose of 1.0 mg.

Less-established risk factors are common in Asian Americans with hepatitis C virus: a case-controlled study.

BACKGROUND AND AIMS: The Centers for Disease Control and Prevention recommend screening for hepatitis C virus (HCV) in patients with injection drug use, blood transfusion before 1992, stigmata of liver disease, or born between 1945 and 1965. The purpose of this study was to examine risk factors for HCV acquisition in Asian Americans. METHODS: This was a case-controlled study, with 471 consecutive patients testing positive for anti-HCV between January 2001 and December 2008. Controls included 471 patients with negative HCV matched at a one-to-one ratio for sex, age (±5 years), and ethnicity. RESULTS: For Asian patients, the most common risk factors were blood transfusion and acupuncture or exposure to dirty needles (27 and 20 %, respectively). On multiple logistic regression, potential predictors for a positive anti-HCV test in Asians were acupuncture or exposure to dirty needles (OR = 12.9, P < 0.0001), body tattoo (OR = 12.0, P = 0.001), and history of blood transfusion (OR = 5.7, P < 0.0001). DISCUSSION: Acupuncture and exposure to dirty needles are independent risk factors of HCV infection. Asians coming from endemic areas should be screened for HCV even when commonly-known risk factors for Western patients are not present.

High proportion of hepatitis C virus in community Asian American patients with non-liver-related complaints.

GOALS AND BACKGROUND: Besides United States population born between 1945 and 1965, screening for hepatitis C virus (HCV) is not recommended for the general US population. However, HCV may be more prevalent in certain subgroups and screening may be warranted. The goal of this study was to examine the proportion of HCV in a large sample of community Asian American patients presenting for non-liver-related complaints. STUDY: We conducted a cross-sectional study of 1246 patients tested for hepatitis C virus antibodies (anti-HCV) referred to 2 gastroenterology clinics for non-liver-related gastrointestinal reasons between January 2001 and February 2011. We determined HCV status and patient history via electronic medical record review. RESULTS: Of the 1246 study patients tested for anti-HCV, the majority were Asian (81.4%) and 29 Asian patients (2.9%) had positive anti-HCV. HCV proportion in the remaining 232 non-Asians (non-Hispanic whites and Hispanics) was 1.7%. Asians with positive anti-HCV were more likely to have had blood transfusions (31.0% vs. 6.6%, P<0.0001) or acupuncture (10.3% vs. 1.5%, P<0.0001). Of the 976 Asian patients with hepatitis B surface antigen testing, 38 (3.9%) also had detectable hepatitis B surface antigen. CONCLUSIONS: Among patients seen at community gastroenterology clinics for non-liver-related reasons, HCV proportion was 1.7% for non-Asians and 2.9% for Asians. Screening for HCV should be offered to high-risk patients presenting to gastroenterology clinics with unrelated gastrointestinal complaints.

High frequency of recurrent viremia after hepatitis B e antigen seroconversion and consolidation therapy.

BACKGROUND: The primary treatment endpoint for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B is HBeAg seroconversion; however, data on the durability of response are inconsistent. GOALS: Our goal was to investigate the rate of recurrent viremia after HBeAg seroconversion and subsequent discontinuation of therapy. METHODS: We retrospectively studied 88 consecutive Asian American patients who achieved HBeAg seroconversion [loss of HBeAg and development of antibody to HBeAg (anti-HBe)] among 458 HBeAg-positive patients who received oral antiviral therapy at 3 US clinics between March 1998 and November 2010. Recurrent viremia was defined as reappearance of detectable serum hepatitis B virus DNA (>100 IU/mL) on 2 consecutive laboratory tests from previously undetectable levels. RESULTS: Antiviral medications used at the time of HBeAg seroconversion included: lamivudine (23%), adefovir (34%), entecavir (36%), tenofovir (4%), and combination therapy (3%). Antiviral therapy was continued after HBeAg seroconversion in 49 patients (group I) and discontinued in the other 39 patients after consolidation therapy [median=12 months (range, 1 to 55 mo)] (group II). No patients in group I experienced recurrent viremia, whereas 90% in group II did. Elevated alanine aminotransferase also occurred in 38% of group II patients [median peak alanine aminotransferase 249 IU/mL (range, 93 to 1070 IU/mL)]. CONCLUSIONS: Despite consolidation therapy, almost all patients who discontinued therapy after achieving HBeAg seroconversion and complete viral suppression experienced recurrent viremia, and close to half also experienced biochemical flares. HBeAg seroconversion does not seem to be a durable treatment endpoint for many patients, and they should be monitored carefully for virologic relapse and biochemical flares if antiviral therapy is withdrawn.

Tenofovir monotherapy and tenofovir plus entecavir combination as rescue therapy for entecavir partial responders.

BACKGROUND AND AIMS: Despite high potency, a significant proportion of patients treated with entecavir achieve only partial viral suppression. Our goal was to examine the complete viral suppression rate (undetectable HBV DNA PCR levels) with alternative therapies in such patients. METHODS: We retrospectively studied 42 consecutive patients with partial response to entecavir (detectable HBV DNA at ≥12 months of therapy) who were treated at three clinics with rescue therapies: entecavir + adefovir (n = 5), tenofovir (n = 6), and entecavir + tenofovir (n = 31). Antiviral resistance was excluded by negative mutation analysis and/or absence of virologic breakthrough (increase >1 log(10)IU/mL from nadir). RESULTS: All patients were Asian and 57 % were male with a median age of 36 (22-64) years. Only a few patients had prior exposure to lamivudine (7 %) or adefovir (7 %). Almost all patients (95 %) had positive HBeAg. Overall, the complete viral suppression rate was 79 %, and the alanine aminotransferase normalization rate was 83 % in entecavir partial responders after 6 months on rescue therapies. Cumulative complete viral suppression rates were significantly different (P = 0.0164) among the entecavir + adefovir, tenofovir, and entecavir + tenofovir treatment groups at 6 months (20 vs. 83 vs. 83 %, respectively) and 12 months (20 vs. 100 vs. 97 %). All three patients without complete viral suppression on entecavir + adefovir became aviremic 6 months after switching to entecavir + tenofovir. CONCLUSIONS: Virologic response to entecavir + tenofovir combination therapy and tenofovir monotherapy appeared to be similar in most patients, but not with the entecavir + adefovir combination.

Medication nonadherence with long-term management of patients with hepatitis B e antigen-negative chronic hepatitis B.

BACKGROUND AND AIMS: Antiviral treatment responses for patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) are well-defined by data from registration trials but may differ from patients seen in community settings where medical adherence is usually not as strictly monitored. The goal of this study was to examine the long-term outcomes of HBeAg-negative patients in a community clinical setting. METHODS: We performed a cohort study of 189 consecutive treatment-naïve patients with CHB who were treated with either entecavir (ETV) 0.5 mg daily (n=107) or adefovir dipivoxil (ADV) 10 mg daily (n=82) from 2002 to 2009 at two community clinics. RESULTS: All patients were Asians. Both ETV and ADV cohorts had similar median baseline ALT and HBV DNA levels. By year 4, a similar proportion of ETV and ADV patients who remained on monotherapy achieved complete viral suppression (91-96%); however, more patients in the ADV cohort required alternative therapy (27 vs. 5%). No patients in the ETV cohort developed resistance while 18% of the ADV cohort did. Cumulative nonadherence rates were 10 and 12% in ADV and ETV cohorts, respectively. CONCLUSIONS: Failure to monotherapy in a community clinical setting is due to both antiviral resistance and patient nonadherence. Medication nonadherence is likely to be a more important contributor to treatment failure than antiviral resistance, especially with new anti-HBV agents such as ETV and tenofovir.