Intraperitoneal corticosteroids for recurrent ascites in patients with Fontan circulation: Initial clinical experience.

Individuals with single-ventricle congenital heart disease who are palliated to a Fontan circulation are at risk for heart failure and liver disease, with recurrent ascites being a potentially debilitating cause of late morbidity. Although ascites associated with heart failure or liver failure is usually characterized by a high serum-ascites albumin gradient (SAAG), we have observed multiple instances of ascites in Fontan patients with low SAAG, suggesting an inflammatory process. We present three cases in which recalcitrant ascites severely and adversely impacted the quality of life and describe our initial experience with intraperitoneal corticosteroids in this setting.

Peripartum Maternal Hepatitis B Care in a US Nationwide Data Set.

BACKGROUND: Hepatitis B virus (HBV) screening during pregnancy is standard of care to prevent vertical transmission to infants, yet the mothers themselves may not receive appropriate follow-up. GOALS: Using a national database, we sought to determine rates of maternal peripartum follow-up with a HBV specialist and identify factors associated with a lack of follow-up. MATERIALS AND METHODS: We identified women who delivered in 2000 to 2012 and were diagnosed with HBV according to International Classification of Diseases-9 codes using a national database (Optum) derived from commercial insurance claims with ∼46 million members ages 0 to 64 in all 50 states. Our primary outcome was follow-up during or after pregnancy with a HBV specialist (gastroenterology/infectious diseases). RESULTS: The prevalence of HBV was 0.27% (2558/959,747 pregnancies), and median follow-up was 45 months. Only 21% of women had peripartum HBV specialist follow-up. On multivariable regression, predictors of peripartum follow-up at 1-year included younger age [odds ratio (OR), 0.97/y; 95% confidence interval (CI), 0.94, 0.99], Asian race/ethnicity (OR, 1.56 vs. white; 95% CI, 1.13, 2.17), and residing in the Northeast (OR, 1.70; 95% CI, 1.09, 2.66) and Midwest (OR, 1.73; 95% CI, 1.07, 2.81) versus West. Predictors of testing for HBV DNA and alanine aminotransferase at 1 year included Asian race (OR, 1.72; 95% CI, 1.23, 2.41), a primary care physician visit within 2 years of delivery (OR, 1.63; 95% CI, 1.19, 2.22), and peripartum HBV specialist follow-up within 1 year (OR, 15.68; 95% CI, 11.38, 21.60). CONCLUSIONS: Maternal HBV specialist follow-up rates were extremely low in this large, diverse cohort representing all United States regions. Referral to a HBV specialist was the strongest predictor of appropriate postpartum HBV laboratory testing. Follow-up rates may be even lower in uninsured populations.

Imatinib-induced drug reaction with eosinophilia and systemic symptoms in solid tumors: a patient with dermatofibrosarcoma protuberans and successful desensitization management.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe, potentially life-threatening drug-induced hypersensitivity reaction, characterized by cutaneous eruptions, fever, diffuse lymphadenopathy, along with hypereosinophilia, and elevated liver function tests, which in severe cases may lead to fulminant hepatic failure and death. Although DRESS syndrome has been associated with over 50 different drugs including imatinib, it has never been reported in association with imatinib treatment in solid tumors. We recently treated a patient with metastatic dermatofibrosarcoma protuberans, a rare cutaneous mesenchymal tumor characterized by constitutive activation of the PDGFß receptor and high sensitivity to imatinib therapy, who had a DRESS reaction to imatinib. Given an initial dramatic clinical and radiological response to treatment and lack of effective alternative targeted therapies, following imatinib discontinuation and resolution of DRESS, we cautiously reintroduced imatinib therapy using a desensitization protocol under the care of the allergy and immunologic clinic. Imatinib was carefully titrated from an initial dose of 50 mg to a target dose of 400 mg daily, while tapering down the prednisone dose. The patient was able to tolerate the treatment without recurrent episodes of DRESS or interruptions, and gained additional 6 months of clinical benefit from imatinib treatment. Although suspected causative drugs should not be reintroduced in DRESS whenever possible, in this case of metastatic disease and lack of effective alternative treatments, a carefully designed drug rechallenge helped minimize the risk of overt clinical reaction and resulted in an overall clinical benefit.

Peripartum Care for Mothers Diagnosed with Hepatitis B During Pregnancy: A Survey of Provider Practices.

Objectives Hepatitis B (HBV) remains a significant public health burden, despite effective therapy. Routine HBV screening is recommended during pregnancy to reduce the risk of vertical transmission, but the rates of follow-up care peri-partum are low. The aim of this study was to evaluate physician practices and knowledge regarding HBV in women diagnosed perinatally. Methods A survey was distributed to obstetricians and midwives within the Partners HealthCare system at Brigham and Women's Hospital and Massachusetts General Hospital. Results Of 118 survey respondents (response rate 56%), 97% reported that they always tested for hepatitis B, and 77% referred new diagnoses of HBV during pregnancy to a HBV specialist for further care. Only 10% of respondents reported that there was formal referral mechanism in place to facilitate follow-up care for mothers diagnosed with hepatitis B infection. 91% of survey respondents selected hepatitis B surface antigen as the correct screening test, and 76% selected hepatitis B immune globulin with vaccination for the newborn as the correct prophylaxis regimen. Only 40 and 51% of respondents accurately identified serologies that were consistent with acute and chronic infection, respectively. Conclusions for Practice Routine screening for HBV in this population presents an important opportunity to identify cases and to reduce the public health burden of this disease. Providers were somewhat knowledgeable about HBV, but the lack of formal referral mechanism may explain why HBV follow-up is suboptimal in this healthcare system. Supplemental provider education and formal linkage to care programs may increase rates of follow-up HBV care.

Spontaneous bacterial peritonitis is a risk factor for renal failure requiring dialysis in waitlisted liver transplant candidates.

AIMS: To examine the relationship between and impact of spontaneous bacteria peritonitis (SBP) and renal failure requiring dialysis in waitlisted liver transplant (LT) candidates. BACKGROUND: Renal failure is a common and severe complication in cirrhotic patients with SBP. Approximately one-third of patients with SBP develop renal failure despite treatment of infection. However, the incidence of renal failure requiring dialysis in LT waitlisted patients who have developed SBP is unknown. The high mortality observed in this group has also raised debate about resource utilization in the care of these patients. METHODS: Data from the United Network for Organ Sharing Standard Transplant and Research files were collected retrospectively between 1994 and 2012. The primary endpoint measured was first time initiation of dialysis while on the LT wait list. Secondary endpoints included waitlist time and mortality on wait list. RESULTS: A total of 42,085 patients were included. SBP at time of listing was diagnosed in 2,352 patients (5.6%) and first time initiation of dialysis while on the wait list occurred in 2,367 patients (6.2%). Unadjusted OR for requiring dialysis for patients listed with SBP was 1.66 (p < 0.001). When controlled for age, gender, BMI, diabetes mellitus, baseline creatinine, MELD score, serum albumin at listing, the adjusted OR for dialysis was 1.24 (p = 0.007) in waitlisted patients with SBP. Patients with SBP at time of listing had a mean waitlist time 142.1 d vs. 198.7 d in non-SBP patients (p < 0.001). CONCLUSIONS: Spontaneous bacteria peritonitis patients have a significantly increased likelihood to require dialysis and mean shorter waitlist time. Furthermore, the combined occurrence of SBP and dialysis is a strong risk factor for all-cause mortality while on the LT wait list.

Postpartum Laboratory Follow-up in Women With Hepatitis B in Massachusetts From 2007 to 2012.

GOALS: To determine postpartum hepatitis B virus (HBV) laboratory testing rates and identify factors associated with a lack of follow-up testing in Massachusetts. BACKGROUND: Screening for HBV infection in pregnant women is standard of care. Guidelines recommend that patients with chronic HBV have ongoing care and laboratory testing, but little is known about postpartum maternal HBV care outcomes. STUDY: We conducted a retrospective cohort study using Massachusetts Virtual Epidemiologic Network, an electronic public health surveillance system maintained by the Massachusetts Department of Public Health. We identified women who tested hepatitis B surface antigen positive during their first reported (index) pregnancy in Massachusetts from 2007 to 2012 and measured HBV-related laboratory tests reported to Massachusetts Department of Public Health during and after pregnancy. RESULTS: We identified 983 hepatitis B surface antigen positive pregnant women. Half (492/983) did not have evidence of additional postpartum HBV laboratory testing following their index pregnancy. Women who had postpartum laboratory tests reported were younger [mean age (SD): 29 (5.3) vs. 31 (5.5) y, P=0.0001] and more likely to have >1 pregnancy during the study period (41% vs. 1%, P<0.0001). There were no differences in race, ethnicity, and US born status. On multivariable logistic regression, older age predicted a lower likelihood of having postpartum laboratory testing (odds ratio, 0.77; 95% confidence interval, 0.70-0.90). CONCLUSIONS: Postpartum maternal HBV follow-up laboratory testing occurred in only half of Massachusetts women and did not vary by race, ethnicity, or US born status. Our results were limited to a single state surveillance database, which likely underestimates the number of tests ordered.

Postpartum care for mothers diagnosed with hepatitis B during pregnancy.

OBJECTIVE: We sought to determine rates of maternal postpartum hepatitis B virus (HBV) follow-up with a HBV specialist and identify factors associated with poor follow-up, as prior research has focused on infant outcomes and not maternal care. STUDY DESIGN: We conducted a retrospective review of data from Partners HealthCare system, the largest health care system in Massachusetts, and identified women with chronic HBV who delivered from 2002 through 2012. RESULTS: We identified 291 women (mean age 31.5 years, 51% Asian) with incident HBV during pregnancy. In all, 47% had postpartum follow-up with a HBV specialist, but only 19% also had appropriate laboratory tests (hepatitis B e antigen [HBeAg], hepatitis B e antibody, HBV DNA, and ALT) within 1 year of their HBV diagnosis. Mothers with HBV follow-up were more likely to have a primary care physician (PCP) within the Partners HealthCare system (66% vs 38%, P < .0001), a positive HBeAg (20% vs 8%, P = .004), and elevated AST values (17% vs 8%, P = .02). On multivariable logistic regression analysis, a mother who had a PCP (odds ratio, 2.50; 95% confidence interval, 1.37-4.59) or positive HBeAg (odds ratio, 4.45; 95% confidence interval, 1.64-12.06) had a greater likelihood of having HBV follow-up. CONCLUSION: Only 19% of HBV-infected mothers met care guidelines 1 year after being diagnosed with HBV. Inadequate postpartum HBV care affects women of all races/ethnicities. Women who had a PCP as well as those who were HBeAg positive were more likely to be referred for postpartum follow-up with a HBV specialist, suggesting that providers might be referring patients when they perceive HBV to be more serious or complex.

MRI-based radiomic feature analysis of end-stage liver disease for severity stratification.

PURPOSE: We aimed to develop a predictive model of disease severity for cirrhosis using MRI-derived radiomic features of the liver and spleen and compared it to the existing disease severity metrics of MELD score and clinical decompensation. The MELD score is compiled solely by blood parameters, and so far, it was not investigated if extracted image-based features have the potential to reflect severity to potentially complement the calculated score. METHODS: This was a retrospective study of eligible patients with cirrhosis ([Formula: see text]) who underwent a contrast-enhanced MR screening protocol for hepatocellular carcinoma (HCC) screening at a tertiary academic center from 2015 to 2018. Radiomic feature analyses were used to train four prediction models for assessing the patient's condition at time of scan: MELD score, MELD score [Formula: see text] 9 (median score of the cohort), MELD score [Formula: see text] 15 (the inflection between the risk and benefit of transplant), and clinical decompensation. Liver and spleen segmentations were used for feature extraction, followed by cross-validated random forest classification. RESULTS: Radiomic features of the liver and spleen were most predictive of clinical decompensation (AUC 0.84), which the MELD score could predict with an AUC of 0.78. Using liver or spleen features alone had slightly lower discrimination ability (AUC of 0.82 for liver and AUC of 0.78 for spleen features only), although this was not statistically significant on our cohort. When radiomic prediction models were trained to predict continuous MELD scores, there was poor correlation. When stratifying risk by splitting our cohort at the median MELD 9 or at MELD 15, our models achieved AUCs of 0.78 or 0.66, respectively. CONCLUSIONS: We demonstrated that MRI-based radiomic features of the liver and spleen have the potential to predict the severity of liver cirrhosis, using decompensation or MELD status as imperfect surrogate measures for disease severity.

Accelerated chronic skin changes without allograft vasculopathy: A 10-year outcome report after face transplantation.

BACKGROUND: Long-term outcomes after face transplantation are rarely reported in the scientific literature. Here we present outcome data of a partial face allograft recipient 10 years after transplantation. METHODS: Medical records were reviewed for functional and psychosocial outcomes as well as complications. Histopathologic analyses of autopsy tissues and characterization of skin immune cells were performed. RESULTS: The patient retained long-term motor and sensory function, though with a noticeable drop in sensory function after year 5. Social reintegration of the patient was marked by reconnection with his family and participation in public social activities. Immunosuppressive therapy consisted of tacrolimus (target levels 6-8 ng/mL after the first year), mycophenolate, and prednisone, while steroids were completely weaned between years 1 and 7. One acute cellular rejection episode of grade II or higher occurred on average per year and led to chronic skin changes (papillary dermal sclerosis with superficial hyalinization, epidermal thinning with loss of rete ridges, perieccrine fibrosis), but the allograft vessels, muscles, adipose tissue, and bone were spared. Allograft skin was characterized by increased number of CD4+ TNF-α/IL17A producing T-cells as compared with native skin. Long-term kidney function was maintained at 60 mL/min estimated glomerular filtration rate. Unfortunately, the preexisting hepatitis C virus infection with liver cirrhosis was resistant to 3 treatments with new direct-acting antivirals and eventually hepatocellular carcinoma developed, causing the patient's death 10 years after transplantation. CONCLUSION: This report suggests that face transplants can maintain their function for at least 10 years. Chronic skin changes can occur independently of allograft vasculopathy.

Serum apoptosis markers in acute liver failure: a pilot study.

BACKGROUND & AIMS: We sought to determine whether circulating apoptotic markers are altered in acute liver failure (ALF), differ with etiology, or predict clinical outcome in this condition. METHODS: Serum levels of soluble Fas (sFas), tumor necrosis factor-alpha (TNF-alpha), hepatocyte growth factor (HGF), and interleukin-6 (IL-6) were measured in 67 acute liver failure patients, as well as controls. In a subset of the groups, we measured serum M-30 antigen, an exposed neoepitope from caspase cleavage. We also assessed M-30 immunoreactivity in liver tissue of ALF patients and controls. RESULTS: Median levels for TNF-alpha, HGF, IL-6, and M-30 antigen were at least 10-fold greater in ALF than in hepatitis C virus or normal controls (P < .0001). Median day 1 sFas, day 3 sFas, and day 1 HGF levels varied according to etiology of acute liver failure (P = .004, P = .011, and P = .019, respectively), with values for drug-induced liver injury and acetaminophen-related ALF higher than other etiologies. Median M-30 antigen levels were significantly higher in patients who were transplanted and/or died (2183 U/L) than spontaneous survivors (1004 U/L) (P = .026). M-30 immunoreactivity in liver tissue was significantly greater in ALF patients than HCV controls (P = .004). CONCLUSIONS: TNF-alpha, HGF, IL-6, and M-30 antigen were significantly elevated in ALF. High levels of sFas and HGF might help to confirm a diagnosis of drug-induced liver injury or acetaminophen-related ALF. Higher levels of M-30 antigen are associated with poor clinical outcomes in ALF.

Efficacy and Safety of Direct Acting Antivirals in Kidney Transplant Recipients with Chronic Hepatitis C Virus Infection.

The prevalence of Hepatitis C Virus (HCV) infection is significantly higher in patients with end-stage renal disease compared to the general population and poses important clinical challenges in patients who undergo kidney transplantation. Historically, interferon-based treatment options have been limited by low rates of efficacy and significant side effects, including risk of precipitating rejection. Limited data exist on the use of all-oral, interferon-free direct-acting antiviral (DAA) therapies in kidney transplant recipients. In this study, we performed a retrospective chart review with prospective clinical follow-up of post-kidney transplant patients treated with DAA therapies at three major hospitals in Boston, MA. A total of 24 kidney recipients with HCV infection received all-oral DAA therapy post-transplant. Patients were predominantly male (79%) with a median age of 60 years (range 34-70 years), median creatinine of 1.2 mg/dL (0.66-1.76), and 42% had advanced fibrosis or cirrhosis. The majority had HCV genotype 1a infection (58%). All patients received full-dose sofosbuvir; it was paired with simeprevir (9 patients without and 3 patients with ribavirin), ledipasvir (7 patients without and 1 patient with ribavirin) or ribavirin alone (4 patients). The overall sustained virologic response (SVR12) was 91% (21 out of 23 patients). One patient achieved SVR4 but demised prior to SVR12 check point due to treatment unrelated cause. Two treatment failures were successfully retreated with alternative DAA regimens and achieved SVR. Both initials failures occurred in patients with advanced fibrosis or cirrhosis, with genotype 1a infection, and prior HCV treatment failure. Adverse events were reported in 11 patients (46%) and were managed clinically without discontinuation of therapy. Calcineurin inhibitor trough levels did not significantly change during therapy. In this multi-center series of patients, all-oral DAA therapy appears to be safe and effective in post-kidney transplant patients with chronic HCV infection.

Cholestasis and cholestatic syndromes.

PURPOSE OF REVIEW: This review highlights recent advances in understanding the regulation of bile acid transport in cholestasis and in the pathogenesis, outcomes, epidemiology, and treatment of a variety of cholestatic liver diseases and their associated complications. RECENT FINDINGS: Highlights include additional understanding of the role of the nuclear receptors farsenoid X receptor, pregnane X receptor, and constitutive androstane receptor in bile acid homeostasis, new understanding of the pathogenesis of primary biliary cirrhosis, familial intrahepatic cholestasis, biliary atresia, and primary sclerosing cholangitis, and clinical trials of therapies for intrahepatic cholestasis of pregnancy, primary biliary cirrhosis, and primary sclerosing cholangitis. SUMMARY: Our understanding of the molecular mechanisms, epidemiology and pathogenesis of cholestasis continues to advance. These advances will hopefully lead to more effective therapies for specific cholestatic conditions.