Julie A. Thompson

Esophageal capsule endoscopy for screening and surveillance of esophageal varices in patients with portal hypertension

Bleeding from esophageal varices (EV) is a serious consequence of portal hypertension. Current guidelines recommend screening patients with cirrhosis with esophagogastroduodenoscopy (EGD) to detect varices. However, the unpleasantness and need for sedation of EGD may limit adherence to screening programs. Pilot studies have shown good performance of esophageal capsule endoscopy in detecting varices. This multicenter trial was designed to assess the diagnostic performance of capsule endoscopy in comparison with EGD. Patients undergoing EGD for screening or surveillance of EV underwent a capsule study previously. The study was designed as an equivalence study, assuming that a difference of ≤10% between capsule endoscopy and EGD in diagnosing EV would demonstrate equivalence. Two hundred eighty‐eight patients were enrolled. Endoscopy was for screening in 195 patients and for surveillance of known EV in 93. Overall agreement for detecting EV between EGD and capsule endoscopy was 85.8%; the kappa score was 0.73. Capsule endoscopy had a sensitivity, specificity, positive predictive value, and negative predictive value of 84%, 88%, 92%, and 77%, respectively. The difference in diagnosing EV was 15.6% in favor of EGD. There was complete agreement on variceal grade in 227 of 288 cases (79%). In differentiating between medium/large varices requiring treatment and small/absent varices requiring surveillance, the sensitivity, specificity, positive predictive value, and negative predictive value for capsule endoscopy were 78%, 96%, 87%, and 92%, respectively. Overall agreement on treatment decisions based on EV size was substantial at 91% (kappa = 0.77). Conclusion: We recommend that EGD be used to screen patients with cirrhosis for large EV. However, the minimal invasiveness, good tolerance, and good agreement of capsule endoscopy with EGD might increase adherence to screening programs. Whether this is the case needs to be determined. (HEPATOLOGY 2008;47:1595–1603.)

Induced abortion and breast cancer risk.

Results from case-control studies suggest that induced abortion may be associated with a small increase in risk of breast cancer. While risk estimates from cohort studies have generally not observed such an association, these studies have had limited information regarding abortion and possible confounding variables. Therefore, we conducted a study among a cohort of post-menopausal women from whom detailed information regarding pregnancy outcomes as well as risk factors for breast cancer had been collected. The study sample included 37,247 Iowa Womens Health Study participants, 55-64 years of age at baseline in 1986, who reported no history of breast, or other, cancer (except non-melanoma skin cancer), and for whom information regarding pregnancy outcomes (that is, live birth, stillbirth, spontaneous abortion, ectopic pregnancy or induced abortion) was available. We used linkage with records of the State Health Registry of Iowa, part of the National Cancer Institutes Surveillance, Epidemiology, and End Results (SEER) program, to estimate the incidence of breast cancer among cohort members through 1995. We calculated age-adjusted relative risks and 95% confidence intervals using Cox proportional hazards regression. Only 653 women (1.8%) reported an induced abortion. The age-adjusted relative risk of breast cancer among women with prior induced abortion compared with those without was 1.1 (95% CI = 0.8-1.6). Relative risks were higher among women whose age at first abortion was less than 20 or at least 30 years, for those whose abortion took place after their first birth or who never gave birth, and for those with early termination (0-2 months). These estimates varied from 1.3-1.7, but the confidence intervals around each were wide. Since most women in this cohort were beyond their reproductive years when abortion became legal in 1973, the low prevalence of induced abortion argues for a cautious interpretation.

Extracorporeal cellular therapy (ELAD) in severe alcoholic hepatitis: A multinational, prospective, controlled, randomized trial

Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma‐derived C3A cells express anti‐inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin ≥8 mg/dL, Maddreys discriminant function ≥ 32, and Model for End‐Stage Liver Disease (MELD) score ≤ 35 were randomized to receive standard of care (SOC) only or 3‐5 days of continuous ELAD treatment plus SOC. After a minimum follow‐up of 91 days, overall survival (OS) was assessed by using a Kaplan‐Meier survival analysis. A total of 203 subjects were enrolled (96 ELAD and 107 SOC) at 40 sites worldwide. Comparison of baseline characteristics showed no significant differences between groups and within subgroups. There was no significant difference in serious adverse events between the 2 groups. In an analysis of the intent‐to‐treat population, there was no difference in OS (51.0% versus 49.5%). The study failed its primary and secondary end point in a population with sAH and with a MELD ranging from 18 to 35 and no upper age limit. In the prespecified analysis of subjects with MELD < 28 (n = 120), ELAD was associated with a trend toward higher OS at 91 days (68.6% versus 53.6%; P = .08). Regression analysis identified high creatinine and international normalized ratio, but not bilirubin, as the MELD components predicting negative outcomes with ELAD. A new trial investigating a potential benefit of ELAD in younger subjects with sufficient renal function and less severe coagulopathy has been initiated. Liver Transplantation 24 380–393 2018 AASLD.

Immunosuppression, cancer, and the long‐term outcomes after liver transplantation: Can we do better?

Most of the focus of orthotopic liver transplantation (OLT) research, since its inception as a treatment for end-stage liver disease in 1968, has been on factors that influence short-term outcomes (specifically acute cellular rejection). Five-year survival after transplantation improved to 72% from 59% in one center between 1981 and 1998; 10-year survival improved to 60% from 52% in the same center. These improvements can be attributed to a number of factors: better risk stratification of OLT candidates and perioperative care after transplant (infectious prophylaxis, management of surgical complications, among others), as well as improved understanding and application of immunosuppression. Although early survival after OLT has improved significantly, the factors which influence the long-term outcomes, ie, survival at >10 years after OLT, are less well-defined and studied. A growing body of evidence on factors influencing the long-term outcomes after OLT bears a common theme. As patients who undergo OLT live longer, common causes of mortality in the general population become increasingly important, such as cardiovascular disease, diabetes mellitus, chronic kidney disease, and malignancy. Although early threats to survival have been positively affected by improvements in immunosuppression, improved immunosuppression could have a negative effect on long-term outcomes. Indeed, the incidence of cardiovascular disease, diabetes mellitus, chronic kidney disease, and malignancy all may be increased by certain immunosuppressive agents and regimens. The increased risk of de novo malignancy (DNM) after OLT is particularly a cause for concern and may in part be the result of an important trade-off to preserve early survival: trading reduction in acute rejection for relative oversuppression of immune surveillance. An ideal immunosuppressive regimen would minimize the risk of acute rejection while maximizing long-term survival. Current immunosuppressive regimens are far less aggressive than they were in the early years of transplantation, but it is clear that current techniques still leave patients with risk of DNM. All immunosuppressive regimens may not portend the same risk for DNM, and other confounding factors may contribute to malignancy risk as well. For example, rapamycin, initially an antineoplastic agent, was not addressed in this study. Some recent reports have theorized a lower cancer risk in patients treated with rapamycin; however, convincing data has not yet been realized. Furthermore, this risk is affected by a number of factors: age, etiology of liver disease, history of alcohol and tobacco use, to name a few. It is unclear how much of a role the timing, amount, duration, and selection of various immunosuppressive agents play in the development of DNM. Previous data suggest that a more proactive approach to limiting immunosuppressant exposure might confer some benefit. In this issue of Liver Transplantation, Tjon and colleagues examined the monitoring and adjustment of

Mortality and costs associated with alcoholic hepatitis: A claims analysis of a commercially insured population

Rising mortality in the United States due to alcoholic liver disease (ALD) and the dearth of effective treatments for ALD have led to increased research in this area, particularly in alcoholic hepatitis. To understand the burden of illness and potential economic value of effective treatments, we conducted a health care claims analysis of over 15,000 commercially insured adults who were hospitalized with alcoholic hepatitis (AH) between 2006 and 2013 and followed for up to 5 years. Their average age was 54 years and 68% were male. Over 5 years, about two-thirds of these adults died (44% in the first year), and fewer than 500 received liver transplants. There were nearly 40,000 re-hospitalizations, with over 50% of the survivors re-hospitalized within a year and nearly 75% through the second year. The total costs were nearly

Interferon graft dysfunction: A final chapter for interferon and hepatitis C

145,000 per patient, with costs decreasing over time from over

Genetic Services for Familial Cancer Patients: A Survey of National Cancer Institute Cancer Centers

50,000 in the first year (including the index hospitalization) to about

The impact of MELD allocation on simultaneous liver-kidney transplantation.

10,000 per year in the later years. Total costs for the cohort over 5 years were

Impact of early biliary complications on long-term outcomes in adult-to-adult living donor liver transplant recipients

2.2 billion. Patients who received a liver transplant averaged about

BRCA1 Susceptibility Markers and Postmenopausal Breast Cancer: The Iowa Women’s Health Study

300,000 in transplant-related costs and over