Byrne, Thomas

ABSTRACT Capillary malformation-arteriovenous type 2 syndrome (CM-AVM2) is a rare, genetic vascular disorder associated with abnormal capillary malformations and arteriovenous malformations. We present a case of CM-AVM2 with refractory diarrhea and failure to thrive due to aberrant, telangiectatic capillaries, and subepithelial collagen deposition found throughout the GI tract on bidirectional endoscopy. The patient was recalcitrant to standard therapies, so bevacizumab was trialed, but the patient expired. This is the first case of CM-AVM2 with diffuse GI mucosal involvement resulting in malabsorption. There is no treatment for this pathology, but treatment with bevacizumab or a mammalian target of rapamycin inhibitor may be efficacious.

Abstract Background: Sorafenib (Sor) remains a first-line option for hepatocellular carcinoma (HCC) or refractory renal cell carcinomas (RCC). PLC/PRF/5 HCC model showed upregulation of hypoxia with enhanced efficacy when Sor is combined with hypoxia-activated prodrug evofosfamide (Evo). Methods: This phase IB 3 + 3 design investigated 3 Evo dose levels (240, 340, 480 mg/m2 on days 8, 15, 22), combined with Sor 200 mg orally twice daily (po bid) on days 1-28 of a 28-day cycle. Primary objectives included determining maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of Sor + Evo. Results: Eighteen patients were enrolled (median age 62.5 years; 17 male /1 female; 12 HCC/6 RCC) across three dose levels (DL0: Sor 200 mg bid/Evo 240 mg/m2 [n=6], DL1:Sor 200 mg bid/Evo 480 mg/m2 [n=5], DL1a: Sor 200 mg bid/Evo 340 mg/m2 [n=7]). Two dose-limiting toxicities (DLTs) were reported with Evo 480 mg/m2 (grade 3 mucositis, grade 4 hepatic failure). Grade 3 rash DLT was observed in one patient at Evo 240 mg/m2. No DLTs were observed at Evo 340 mg/m2. MTD and RP2D were established as Sor 200 mg/Evo 340 mg/m2 and Sor 200/Evo 240 mg/m2, respectively. The most common treatment-related adverse events included fatigue, hand-foot syndrome, hypertension, and nausea/vomiting. Two partial responses were observed, one each at DL0 and DL1a.; disease control rate was 55%.Conclusions: RP2D was established as sorafenib 200 mg bid + Evo 240 mg/m2. While preliminary anti-tumor activity was observed, future development must account for advances in immunotherapy in HCC/RCC. NCT01497444Date of registration December 20, 2011

Drug induced liver injury is a very frequent cause of hepatotoxicity and within that group, herbal and dietary supplements are a well described subcategory. The following clinical vignette describes the case of a young man with acute hepatitis secondary to the use of Ilex paraguariensis, also known as yerba mate, which is a herbal product commonly drunk in South America. This is the first written case of mate tea induced hepatotoxicity.

AbstractSarcopenia, or loss of skeletal muscle mass, is associated with increased mortality and morbidity in liver transplant (LT) candidates. Six‐minute walk distance (6MWD) and health‐related quality of life (HRQOL) as assessed by short form 36 scores (SF‐36) also impact clinical outcomes in these patients. This study explored the relationship between the sarcopenia, 6MWD, and HRQOL in LT candidates. Sarcopenia was evaluated based on skeletal muscle mass index (SMI) quantified from abdominal computed tomography. Patients were followed until death, removal from the wait list or the end of the study period. Two hundred and thirteen patients listed for LT were included. The mean SMI, 6MWD and mean gait speed were 54.3 ± 9.7, 370.5 m and 1 m/s, respectively. Sarcopenia was noted in 22.2% of LT candidates. There was no correlation between sarcopenia, 6MWD, and SF‐36 scores. The 6MWD, but not sarcopenia, was an independent predictor of mortality (hazard ratio = 2.1 [0.9–4.7]). In summary, sarcopenia did not emerge as a significant predictor of waitlist mortality and also failed to correlate with either functional capacity or HRQOL in LT candidates. In patients with ESLD awaiting LT, 6MWD appears to be a more useful prognostic indicator than the presence of sarcopenia.

AbstractVitamin D deficiency is common among patients with end‐stage liver disease (ESLD). The primary aim of our study was to assess the prevalence of vitamin D deficiency, secondary hyperparathyroidism, and bone disease in patients with ESLD awaiting LT.MethodsWe retrospectively studied 190 patients at our center. Serum total 25‐hydroxyvitamin D (25‐OH D), parathyroid hormone (PTH), calcium, and bone mineral analysis (BMA) were recorded. Standard World Health Organization (WHO) criteria were used to diagnose osteopenia/osteoporosis. Only patients with normal serum creatinine were analyzed.ResultsThirty‐two of 190 patients were excluded from the final analysis (missing serum total 25‐OH D levels in three patients and elevated serum creatinine, 29 patients). 105 of 158 (66.4%) evaluable patients had 25‐OH D levels <25 ng/mL. Patients included in the analysis (n = 158) were divided according to serum total 25‐OH D levels: 0–10 ng/mL (n = 23), 11–20 ng/mL (n = 64), and >20 ng/mL (n = 71). There were no significant differences in mean serum PTH and corrected calcium levels among the three subgroups. Only three patients had elevated serum PTH. Patients with total 25‐OH D ≤ 10 ng/mL had higher model for end‐stage liver disease (MELD) scores vs. those with 25‐OH D > 20 ng/mL (13.3 ± 3, range 8–21, vs. 11.9 ± 3.4, range 6–29, p = 0.004). Irrespective of vitamin D status, bone disease was present in 64.6% of patients.ConclusionLow vitamin D levels and bone disease are common among patients with ESLD awaiting LT. Despite a high prevalence of low serum total 25‐OH D, our cohort maintained normal corrected calcium levels and did not develop secondary hyperparathyroidism. We propose that free serum 25‐OH D and vitamin D‐binding protein may be necessary to accurately establish the diagnosis of vitamin D deficiency in the setting of ESLD. Additional studies are needed to further define mechanisms of bone disease in patients with ESLD.

New onset diabetes after transplantation (NODAT) occurs less frequently in living donor liver transplant (LDLT) recipients than in deceased donor liver transplant (DDLT) recipients. The aim of this study was to compare the incidence and predictive factors for NODAT in LDLT versus DDLT recipients. The Organ Procurement and Transplant Network/United Network for Organ Sharing database was reviewed from 2004 to 2010, and 902 LDLT and 19,582 DDLT nondiabetic recipients were included. The overall incidence of NODAT was 12.2% at 1 year after liver transplantation. At 1, 3, and 5 years after transplant, the incidence of NODAT in LDLT recipients was 7.4, 2.1, and 2.6%, respectively, compared to 12.5, 3.4, and 1.9%, respectively, in DDLT recipients. LDLT recipients have a lower risk of NODAT compared to DDLT recipients (hazard ratio = 0.63 (0.52–0.75),P<0.001). Predictors for NODAT in LDLT recipients were hepatitis C (HCV) and treated acute cellular rejection (ACR). Risk factors in DDLT recipients were recipient male gender, recipient age, body mass index, donor age, donor diabetes, HCV, and treated ACR. LDLT recipients have a lower incidence and fewer risk factors for NODAT compared to DDLT recipients. Early identification of risk factors will assist timely clinical interventions to prevent NODAT complications.

New-onset diabetes after transplantation (NODAT) is common after liver transplant and associated with poorer outcomes. The aim of this study was to identify risk factors for NODAT in liver transplant recipients off corticosteroids. In 225 adult nondiabetic liver transplant recipients, the mean age was 51.7 years, the majority were men (71%), and half had HCV (49%). The mean calculated MELD score at transplantation was 18.7, and 19% underwent living-donor transplant (LDLT). One year after transplantation, 17% developed NODAT, and an additional 16% had impaired fasting glucose. The incidence of NODAT in patients with HCV was 26%. In multivariate analysis, HCV, pretransplant FPG, and LDLT were significant. Each 10 mg/dL increase in pretransplant FPG was associated with a twofold increase in future development of NODAT. The incidence of NODAT after liver transplant in patients off corticosteroids is 17%. Risk factors for developing NODAT include HCV and pretransplant FPG; LDLT is protective.