Expanding the Donor Pool: First Use of Hepatitis B Virus Nat Positive Solid Organ Allografts Into Seronegative Recipients.

OBJECTIVES: The aim of this study was to assess the 1-year safety and effectiveness of HBV Nucleic Acid Test positive (HBV NAT+) allografts in seronegative kidney transplant (KT) and liver transplant (LT) recipients. SUMMARY BACKGROUND DATA: Despite an ongoing organ shortage, the utilization of HBV NAT+ allografts into seronegative recipients has not been investigated. METHODS: From January 2017 to October 2020, a prospective cohort study was conducted among consecutive KT and LT recipients at a single institution. Primary endpoints were post-transplant HBV viremia, graft and patient survival. RESULTS: With median follow-up of 1-year, there were no HBV-related complications in the 89 HBV NAT+ recipients. Only 9 of 56 KTs (16.1%) and 9 of 33 LTs (27.3%) experienced post-transplant HBV viremia at a median of 185 (KT) and 269 (LT) days postoperatively. Overall, viremic episodes resolved to undetected HBV DNA after a median of 80 days of entecavir therapy in 16 of 18 recipients. Presently, 100% of KT recipients and 93.9% of LT recipients are HBV NAT- with median follow-up of 13 months, whereas 0 KT and 8 LT (24.2%) recipients are HBV surface antigen positive indicating chronic infection. KT and LT patient and allograft survival were not different between HBV NAT+ and HBV NAT- recipients (P > 0.05), whereas HBV NAT+ KT recipients had decreased waitlist time and pretransplant duration on dialysis (P < 0.01). CONCLUSIONS: This is the largest series describing the transplantation of HBV NAT+ kidney and liver allografts into HBV seronegative recipients without chronic HBV viremia or decreased 1-year patient and graft survival. Increasing the utilization of HBV NAT+ organs in nonviremic recipients can play a role in decreasing the national organ shortage.

Safety and Efficacy of Budesonide for Liver Transplant Immune Suppression: Results of a Pilot Phase 2a Trial.

Despite adverse effects like hyperglycemia, new-onset diabetes after transplant (NODAT), and infectious complications, corticosteroid use remains an important part of liver transplantation (LT) immune suppression. Budesonide, a synthetic corticosteroid, undergoes extensive first-pass hepatic metabolism with only 10% systemic bioavailability, providing an opportunity for an improved toxicity-therapeutic ratio. Although effective in the treatment of autoimmune hepatitis, the effects of budesonide for LT immune suppression are unknown. We conducted a single-center phase 2a trial to study the safety and efficacy of budesonide immunosuppressive therapy. From July 2017 to November 2018, 20 patients undergoing a first LT received budesonide tapering doses (from 9 to 3 mg) for 12 weeks. Patients were compared with matched control patients who received prednisone from the same time period. Additionally, both groups received calcineurin inhibitors and mycophenolate mofetil. Outcome measures at week 24 included rates of biopsy-proven acute cellular rejection (ACR), NODAT (hemoglobin A1c >6.4%), and infectious complications. In the budesonide arm, 1 patient developed ACR at week 5 and was removed from the study. Another patient stopped the study drug at week 8 due to persistent nausea. Rates of ACR were similar between the budesonide and control groups (5% versus 5%, P = 1.00). Three patients in the control group developed NODAT versus none in the budesonide group (15% versus 0%; P = 0.23). There were 6 infections in the control group compared with none in the budesonide group (30% versus 0; P = 0.02). These pilot data suggest that budesonide has the potential to be a safe and effective alternative to prednisone for LT immune suppression while reducing steroid-induced infections and NODAT. Randomized controlled trials are required to validate these findings.

Delayed Sleeve Gastrectomy Following Liver Transplantation: A 5-Year Experience.

Obesity has become an epidemic in the United States over the past decade, and recent studies have shown this trend in the liver transplantation (LT) population. These patients may be candidates for laparoscopic sleeve gastrectomy (LSG) to promote significant and sustained weight loss to prevent recurrence of nonalcoholic steatohepatitis. However, safety remains a concern, and efficacy in this setting is uncertain. A single-institution database from 2014 to 2018 was queried for patients undergoing LSG following LT. The selection criteria for surgery were consistent with National Institutes of Health guidelines, and patients were at least 6 months after LT. A total of 15 patients (median age, 59.0 years; Caucasian, 86.7%; and female, 60%) underwent LSG following LT. Median time from LT to LSG was 2.2 years with a median follow-up period of 2.6 years. The median hospital length of stay (LOS) was 2 days after LSG. Mortality and rate of liver allograft rejection was 0, and there was 1 postoperative complication (a surgical site infection). Following LSG, body mass index (BMI) decreased from 42.7 to 35.9 kg/m2 (P < 0.01), and in 12 patients with at least 1 year of follow-up, the total body weight loss was 20.6%. Following LSG in patients with diabetes, the median daily insulin requirements decreased from 98 (49-118) to 0 (0-29) units/day (P = 0.02), and 60% discontinued insulin. Post-LT patients had a similar decrease in BMI and reduction in comorbidities at 1 year compared with a matched non-LT patient cohort. In the largest patient series to date, we show that LSG following LT is safe, effective, and does not increase the incidence of liver allograft rejection. Larger longer-term studies are needed to confirm underlying metabolic changes following LSG.

Sarcoidosis Involving the Gastrointestinal Tract: Diagnostic and Therapeutic Management.

Involvement of the gastrointestinal (GI) tract is an infrequent extrathoracic presentation of sarcoidosis. We reviewed 305 cases of GI involvement reported in 238 patients, in whom GI sarcoidosis was the first sign of the disease in half the cases. The disease does not affect the GI tract uniformly, with a clear oral-anal gradient (80% of reported cases involved the esophagus, stomach, and duodenum). Clinicopathological mechanisms of damage may include diffuse mucosal infiltration, endoluminal exophytic lesions, involvement of the myenteric plexus, and extrinsic compressions. Ten percent of patients presented with asymptomatic or subclinical disease found on endoscopy. The diagnosis is relevant clinically because 22% of cases reviewed presented as life threatening. In addition, initial clinical/endoscopic findings may be highly suggestive of GI cancer. The therapeutic approach is heterogeneous and included wait-and-see or symptomatic approaches, glucocorticoid/immunosuppressive therapy, and surgery. Sarcoidosis of the gut is a heterogeneous, potentially life-threatening condition that requires a multidisciplinary approach and early clinical suspicion to institute personalized therapeutic management and follow-up.

Downstaging therapy followed by liver transplantation for hepatocellular carcinoma beyond Milan criteria.

BACKGROUND: Orthotopic liver transplantation is a curative treatment for hepatocellular carcinoma within Milan criteria, but these criteria preclude many patients from transplant candidacy. Recent studies have demonstrated that downstaging therapy can reduce tumor burden to meet conventional criteria. The present study reports a single-center experience with tumor downstaging and its effects on post-orthotopic liver transplantation outcomes. METHODS: All patients with hepatocellular carcinoma who were evaluated by our multidisciplinary liver services team from 2012 to 2016 were identified (N = 214). Orthotopic liver transplantation candidates presenting outside of Milan criteria at initial radiographic diagnosis and/or an initial alpha-fetoprotein >400 ng/mL were categorized as at high risk for tumor recurrence and post-transplant mortality. RESULTS: Of the 214 patients newly diagnosed with hepatocellular carcinoma, 73 (34.1%) eventually underwent orthotopic liver transplantation. The majority of patients who did not undergo orthotopic liver transplantation were deceased or lost to follow-up (47.5%), with 14 of 141 (9.9%) currently listed for transplantation. Among transplanted patients, 21 of 73 (28.8%) were considered high-risk candidates. All 21 patients were downstaged to within Milan criteria with an alpha-fetoprotein <400 ng/mL before orthotopic liver transplantation, through locoregional therapies. Recurrence of hepatocellular carcinoma was higher but acceptable between downstaged high-risk and traditional candidates (9.5% vs 1.9%; P > .05) at a median follow-up period of 17 months. Downstaged high-risk candidates had a similar overall survival compared with those transplanted within Milan criteria (log-rank P > .05). CONCLUSIONS: In highly selected cases, patients with hepatocellular carcinoma outside of traditional criteria for orthotopic liver transplantation may undergo downstaging therapy in a multidisciplinary fashion with excellent post-transplant outcomes. These data support an aggressive downstaging approach for selected patients who would otherwise be deemed ineligible for transplantation.

"Ohio River valley fever" presenting as isolated granulomatous hepatitis: a case report.

Histoplasmosis is endemic to the midwestern and east central states in the United States near the Mississippi and the Ohio River valleys. Ninety-nine percent of patients exposed to histoplasmosis develop only subclinical infection. Liver involvement as a part of disseminated histoplasmosis is well known; however, isolated hepatic histoplasmosis without any other stigmata of dissemination is extremely rare and the literature is limited to only two case reports. We present a rare case of isolated granulomatous hepatitis due to histoplasmosis in a 35-year-old female with dermatomyositis receiving low-dose prednisone and methotrexate. There was no evidence of fungal dissemination elsewhere. High clinical suspicion is critical for early diagnosis and treatment.