Everolimus Related Fulminant Hepatitis in Pancreatic Neuroendocrine Tumor With Liver Metastases: A Case Report and Literature Review.

Background: Everolimus, an immunosuppressant, is approved for the treatment of advanced renal cell carcinoma, metastatic hormone receptor-positive breast cancer, and pancreatic neuroendocrine tumors (P-NETs) but has been reported to be related to hepatitis B reactivation. Here, we present the first case of fatal fulminant hepatitis B reactivation in a man with P-NET accompanied by multiple liver metastases who received everolimus and octreotide long-acting repeatable (LAR). Case Presentation: A 45-year-old male had a history of chronic hepatitis B infection. He was found to have a complicated liver cyst incidentally, and then he underwent biopsy, which disclosed a grade 2 neuroendocrine tumor (NET). Subsequent MRI of the abdomen and PET revealed a solid mass at the pancreatic tail with numerous liver tumors favoring metastases and peripancreatic lymph node metastases. Transarterial chemoembolization (TACE) of the right lobe of the liver was performed, and he started to take 5 mg everolimus twice a day and 20 mg octreotide LAR every month 8 days after the 1st TACE. No hepatitis B virus (HBV) prophylaxis treatment was administered. He then underwent laparoscopic distal pancreatectomy and splenectomy three and half months after the initial treatment of everolimus. He continued everolimus 5 mg twice a day and octreotide 20 mg every month after the operation. Three months later, hepatic failure occurred due to acute hepatitis B flare-up-related fulminant hepatic failure since other possible causes of hepatic failure were excluded. Five days after hepatic failure presented, hepatic failure was apparent, and pulseless ventricular tachycardia occurred. The patient expired after failed resuscitation. Conclusion: A literature review of everolimus-related hepatitis B reactivation was conducted. In P-NET patients with chronic hepatitis B who will undergo everolimus treatment, HBV prophylaxis should be considered since fatal hepatitis B reactivation might occur under rare conditions.

Outcomes of kidney transplant recipients admitted to the intensive care unit: a retrospective study of 200 patients.

BACKGROUND: Risk of over-immunosuppression or immunization may mitigate the overall and long-term renal outcomes of kidney transplant recipients (KTR) admitted to the ICU in the modern era but remain poorly described. Thus, there is an unmet need to better characterize the survival of KTR admitted to the ICU, but also the renal and immunological outcomes of survivors. METHODS: Retrospective observational study that included 200 KTR admitted between 2010 and 2016 to the ICU of a teaching hospital (median age 61 years [IQR 50.7-68]; time from transplantation 41 months [IQR 5-119]). Survival curves were compared using the Log-rank test. RESULTS: Mortality rates following admission to the ICU was low (26.5% at month-6), mainly related to early mortality (20% in-hospital), and predicted by the severity of the acute condition (SAPS2 score) but also by Epstein Barr Virus proliferation in the weeks preceding the admission to the ICU. Acute kidney injury (AKI) was highly prevalent (85.1%). Progression toward chronic kidney disease (CKD) was observed in 45.1% of survivors. 15.1% of survivors developed new anti-HLA antibodies (donor-specific antibodies 9.2% of cases) that may impact the long-term renal transplantation function. CONCLUSIONS: Notwithstanding the potential biases related to the retrospective and monocentric nature of this study, our findings obtained in a large cohort of KTR suggest that survival of KTR admitted in ICU is good but in-ICU management of these patients may alter both survival and AKI to CKD transition, as well as HLA immunization. Further interventional studies, including systematic characterization of the Epstein Barr virus proliferation at the admission (i.e., a potential surrogate marker of an underlying immune paralysis and frailty) will need to address the optimal management of immunosuppressive regimen in ICU to improve survival but also renal and immunological outcomes.

Acute Hepatic Necrosis Caused by Salmonella enterica Serotype I 4,5,12:-:1,2 in a Dog.

Acute hepatic necrosis was diagnosed in a dog. Gram staining and fluorescence in situ hybridization identified Salmonella enterica in the liver, subsequently confirmed as S. enterica serotype I 4,5,12:-:1,2. This is the first report of acute hepatic necrosis with liver failure caused by Salmonella in a dog.

Fatal methanol poisoning: features of liver histopathology.

Methanol poisoning has become a considerable problem in Iran. Liver can show some features of poisoning after methanol ingestion. Therefore, our concern was to examine liver tissue histopathology in fatal methanol poisoning cases in Iranian population. In this study, 44 cases of fatal methanol poisoning were identified in a year. The histological changes of the liver were reviewed. The most striking features of liver damage by light microscopy were micro-vesicular steatosis, macro-vesicular steatosis, focal hepatocyte necrosis, mild intra-hepatocyte bile stasis, feathery degeneration and hydropic degeneration. Blood and vitreous humor methanol concentrations were examined to confirm the proposed history of methanol poisoning. The majority of cases were men (86.36%). In conclusion, methanol poisoning can cause histological changes in liver tissues. Most importantly in cases with mean blood and vitreous humor methanol levels greater than 127 ± 38.9 mg/dL more than one pathologic features were detected.

Major hepatic necrosis: a common complication after angioembolization for treatment of high-grade liver injuries.

BACKGROUND: The management of high-grade liver injuries often involves a combination of operative and nonoperative strategies. Angioembolization (AE) is frequently used in the management of these injuries. Morbidity in patients with high-grade hepatic injuries remains high despite improvements in mortality with a multimodality approach. Major hepatic necrosis (MHN) is a morbid, but underappreciated complication of AE in this patient population. This study will examine the risk factors and outcomes of patients with high-grade liver injures managed with AE who developed the complication of MHN. METHODS: Patients admitted to the R Adams Cowley Shock Trauma Center between January 2002 and December 2007 with high-grade blunt or penetrating liver injuries (grades III-VI) were identified from the trauma registry and the medical records were retrospectively reviewed. Demographic and injury specific data, complications, and admission physiologic variables were collected. Patients who had therapeutic AE, either preoperatively or postoperatively, and went on to develop liver-related complications including MHN were reviewed. RESULTS: There were 538 patients with high-grade liver injuries admitted during a 5-year period. One hundred and sixteen patients (22%) underwent angiography, and 71 (13%) had a therapeutic AE. Sixteen patients (22.5%) had grade III injuries, 44 (62%) had grade IV injuries, and 11 (15.5%) had grade V injuries. Overall mortality in this group was 14% with eight patients (11.3%) dying as a result of their liver injury. Complication rates were 18.8%, 65.9%, and 100% in the patients with grades III, IV, and V injuries, respectively, for an overall complication rate of 60.6%. Thirty patients (42.2%) went on to develop MHN. Patients who developed MHN were compared with those who did not. Baseline characteristics, Injury Severity Score, and hemodynamic parameters at admission were no different between the two groups. Patients with MHN had higher grade injuries, required significantly more blood product transfusions, and had a significantly longer length of stay (all p < 0.001). Patients who developed MHN were more likely to have undergone operative intervention (96.7% vs. 41.5%, p < 0.001), with 87% having a damage control laparotomy. Other liver-related complications occurred more frequently in the patients that developed MHN (60.0% vs. 34.1%, p = 0.03). However, mortality was not different in the two groups. CONCLUSION: High-grade liver injuries pose significant challenges to those who care for trauma patients. Many patients can be successfully managed nonoperatively, but there are still patients that require laparotomy. AE is the logical augmentation of damage control techniques for controlling hemorrhage. However, given the nature and severity of these injuries, these therapies are not without complications. MHN was found to be a common complication in our study. It tended to occur in high-grade injures, was associated with higher complication rates, longer hospital length of stay, and higher transfusion requirements. Management of MHN can be challenging. Factors that still need to be elucidated are the role of perihepatic packing and timing of second look operation.

Contribution of transjugular liver biopsy in patients with the clinical presentation of acute liver failure.

PURPOSE: Acute liver failure (ALF) treated with conservative therapy has a poor prognosis, although individual survival varies greatly. In these patients, the eligibility for liver transplantation must be quickly decided. The aim of this study was to assess the role of transjugular liver biopsy (TJLB) in the management of patients with the clinical presentation of ALF. METHODS: Seventeen patients with the clinical presentation of ALF were referred to our institution during a 52 month period. A TJLB was performed using the Cook Quick-Core needle biopsy. Clinical data, procedural complications, and histologic findings were evaluated. RESULTS: Causes of ALF were virus hepatitis B infection in 7 patients, drug toxicity in 4, mushroom in 1, Wilson's disease in 1, and unknown origin in 4. TJLB was technically successful in all patients without procedure-related complications. Tissue specimens were satisfactory for diagnosis in all cases. In 14 of 17 patients the initial clinical diagnosis was confirmed by TJLB; in 3 patients the initial diagnosis was altered by the presence of unknown cirrhosis. Seven patients with necrosis < 60% were successfully treated with medical therapy; 6 patients with submassive or massive necrosis (> or = 85%) were treated with liver transplantation. Four patients died, 3 had cirrhosis, and 1 had submassive necrosis. There was a strict statistical correlation (r = 0.972, p < 0.0001) between the amount of necrosis at the frozen section examination and the necrosis found at routine histologic examination. The average time for TJLB and frozen section examination was 80 min. CONCLUSION: In patients with the clinical presentation of ALF, submassive or massive liver necrosis and cirrhosis are predictors of poor prognosis. TLJB using an automated device and frozen section examination can be a quick and effective tool in clinical decision-making, especially in deciding patient selection and the best timing for liver transplantation.