Evidence-based consensus guidelines for the diagnosis and management of erythropoietic protoporphyria and X-linked protoporphyria.

Erythropoietic protoporphyria and X-linked protoporphyria are rare genetic photodermatoses. Limited expertise with these disorders among physicians leads to diagnostic delays. Here, we present evidence-based consensus guidelines for the diagnosis, monitoring, and management of erythropoietic protoporphyria and X-linked protoporphyria. A systematic literature review was conducted, and reviewed among subcommittees of experts, divided by topic. Consensus on guidelines was reached within each subcommittee and then among all members of the committee. The appropriate biochemical and genetic testing to establish the diagnosis is reviewed in addition to the interpretation of results. Prevention of symptoms, management of acute phototoxicity, and pharmacologic and nonpharmacologic treatment options are discussed. The importance of ongoing monitoring for liver disease, iron deficiency, and vitamin D deficiency is discussed with management guidance. Finally, management of pregnancy and surgery and the safety of other therapies are summarized. We emphasize that these are multisystemic disorders that require longitudinal monitoring. These guidelines provide a structure for evidence-based diagnosis and management for practicing physicians. Early diagnosis and management of these disorders are essential, particularly given the availability of new and emerging therapies.

Illuminating Dersimelagon: A Novel Agent in the Treatment of Erythropoietic Protoporphyria and X-Linked Protoporphyria.

Erythropoietic protoporphyria (EPP) is a genetic disorder stemming from reduced ferrochelatase expression, the final enzyme in the pathway of heme biosynthesis. A closely related condition, X-linked protoporphyria (XLP), bears similar clinical features although it arises from the heightened activity of δ-aminolevulinic acid synthase 2 (ALAS2), the first and normally rate-controlling enzyme in heme biosynthesis in developing red blood cells. Both of these abnormalities result in the buildup of protoporphyrin IX, leading to excruciating light sensitivity and, in a minority of cases, potentially fatal liver complications. Traditionally, managing EPP and XLP involved sun avoidance. However, the emergence of innovative therapies, such as dersimelagon, is reshaping the therapeutic landscape for these conditions. In this review, we summarize salient features of the properties of dersimelagon, shedding light on its potential role in advancing our understanding of treatment options for EPP and XLP.

Management of Decompensated Cirrhosis in the Surgical ICU: an American Association for the Surgery of Trauma Critical Care Committee Clinical Consensus Document.

Management of decompensated cirrhosis (DC) can be challenging for the surgical intensivist. Management of DC is often complicated by ascites, coagulopathy, hepatic encephalopathy, gastrointestinal bleeding, hepatorenal syndrome, and difficulty assessing volume status. This Clinical Consensus Document created by the American Association for the Surgery of Trauma Critical Care Committee reviews practical clinical questions about the critical care management of patients with DC to facilitate best practices by the bedside provider.

Current state of endohepatology: Diagnosis and treatment of portal hypertension and its complications with endoscopic ultrasound.

The diagnosis and management of cirrhosis and portal hypertension (PH) with its complications including variceal hemorrhage, ascites, and hepatic encephalopathy continues to evolve. Although there are established "standards of care" in liver biopsy and measurement of PH, gastric varices remain an area without a universally accepted therapeutic approach. The concept of "Endo Hepatology" has been used to describe of the applications of endoscopic ultrasound (EUS) to these challenges. EUS-liver biopsy (EUS-LB) offers an alternative to percutaneous and transjuglar liver biopsy without compromising safety or efficacy, and with added advantages including the potential to reduce sampling error by allowing biopsies in both hepatic lobes. Furthermore, EUS-LB can be performed during the same procedure as EUS-guided portal pressure gradient (PPG) measurements, allowing for the collection of valuable diagnostic and prognostic data. EUS-guided PPG measurements provide an appealing alternative to the transjugular approach, with proposed advantages including the ability to directly measure portal vein pressure. In addition, EUS-guided treatment of gastric varices (GV) offers several possible advantages to current therapies. EUS-guided treatment of GV allows detailed assessment of the vascular anatomy, similar efficacy and safety to current therapies, and allows the evaluation of treatment effect through doppler ultrasound visualization. The appropriate selection of patients for these procedures is paramount to ensuring generation of useful clinical data and patient safety.

Porphyric neuropathy.

Acute hepatic porphyrias are inherited metabolic disorders that may present with polyneuropathy, which if not diagnosed early can lead to quadriparesis, respiratory weakness, and death. Porphyric neuropathy is an acute to subacute motor predominant axonal neuropathy with a predilection for the upper extremities and usually preceded by a predominantly parasympathetic autonomic neuropathy. The rapid progression and associated dysautonomia mimic Guillain-Barré syndrome but are distinguished by the absence of cerebrospinal fluid albuminocytologic dissociation, progression beyond 4 wk, and associated abdominal pain. Spot urine test to assess the porphyrin precursors delta-aminolevulinic acid and porphobilinogen can provide a timely diagnosis during an acute attack. Timely treatment with intravenous heme, carbohydrate loading, and avoidance of porphyrinogenic medications can prevent further neurological morbidity and mortality.

Liver transplantation beyond or downstaging within the Milan criteria for hepatocellular carcinoma.

INTRODUCTION: Unresectable hepatocellular carcinoma (HCC) is a common indication for liver transplantation (LT). The Milan criteria became standard criteria but expansion beyond the Milan criteria (tumor size and number) have resulted in similar post-transplant outcomes, thus suggesting LT is a viable treatment option for HCC presenting beyond the Milan criteria Areas covered: Expanded criteria and the use of downstaging therapies to meet Milan criteria are reviewed. Surrogates of tumor biology (including biomarkers and response to therapy) are described in detail. The controversy regarding treatment of HCV infection prior to transplant for HCC is addressed. Predictors of post-transplant recurrence and therapeutic options are explored. English-language manuscripts pertaining to LT criteria for HCC, downstaging, and tumor prognosis were reviewed. Effort was made to include manuscripts from throughout the world to ensure the reader a broad international perspective. Expert commentary: Patients can be successfully transplanted with HCC beyond Milan criteria, or patients beyond Milan criteria can be downstaged to within Milan criteria and achieve successful post-liver transplant outcomes. The current reliance on tumor burden (size and number) alone ignores the mounting data supporting the prognostic use of additional surrogates of tumor biology in identifying appropriate candidates.

A Randomized Controlled Trial of Procedural Techniques for Large Volume Paracentesis

ABSTRACT Introduction. The aim of this study is to investigate large volume therapeutic paracentesis using either a z-tract or axial (coxial) technique in a randomized controlled trial. Materials and methods. In this randomized, single blind study, patients with cirrhosis undergoing outpatient therapeutic paracentesis were randomized to the z-tract or the modified angular (coaxial) needle insertion technique. Subject and procedure characteristics were compared between the groups with ascites leakage as quantified by need for dressing changes with standardized sized gauze pads as a primary endpoint and subject procedural discomfort, operator preference, and procedure complications as secondary endpoints. Results. 72 paracenteses were performed during the study period: 34 to the z-tract and 38 to the coaxial insertion technique. Following exclusions, a total of 61 paracenteses were analyzed: 30 using the z-tract technique and 31 using the coaxial technique. There were equal rates of post-procedural leakage of ascites between groups (13% in both groups, p = 1.00). Using the visual analog scale (0 - 100), there was a statistically significant increase in the subject reported pain score with the z-tract compared with the coaxial method [26.4 (95% CI 18.7 - 34.1) vs. 17.2 (95% CI 10.6 - 23.8), p = 0.04]. Mean physician rated procedure difficulty (1 - 5) was significantly higher for the z-tract vs. the coaxial technique [2.1 (95% CI 1.6 - 2.6) vs. 1.5 (95% CI 1.2 - 1.8), p = 0.04]. Conclusion. When compared to the z-tract technique, the coaxial insertion technique is superior during large volume paracentesis in cirrhosis patients.

Portal vein thrombosis, mortality and hepatic decompensation in patients with cirrhosis: A meta-analysis.

AIM: To determine the clinical impact of portal vein thrombosis in terms of both mortality and hepatic decompensations (variceal hemorrhage, ascites, portosystemic encephalopathy) in adult patients with cirrhosis. METHODS: We identified original articles reported through February 2015 in MEDLINE, Scopus, Science Citation Index, AMED, the Cochrane Library, and relevant examples available in the grey literature. Two independent reviewers screened all citations for inclusion criteria and extracted summary data. Random effects odds ratios were calculated to obtain aggregate estimates of effect size across included studies, with 95%CI. RESULTS: A total of 226 citations were identified and reviewed, and 3 studies with 2436 participants were included in the meta-analysis of summary effect. Patients with portal vein thrombosis had an increased risk of mortality (OR = 1.62, 95%CI: 1.11-2.36, P = 0.01). Portal vein thrombosis was associated with an increased risk of ascites (OR = 2.52, 95%CI: 1.63-3.89, P < 0.001). There was insufficient data available to determine the pooled effect on other markers of decompensation including gastroesophageal variceal bleeding or hepatic encephalopathy. CONCLUSION: Portal vein thrombosis appears to increase mortality and ascites, however, the relatively small number of included studies limits more generalizable conclusions. More trials with a direct comparison group are needed.

The snow-shoveler's ST elevation myocardial infarction.

Heavy snowfall, cold temperatures, and low atmospheric pressure during the winter months have been associated with increased adverse cardiovascular events. However, only a few cases of the "snow shoveler's infarction" have been reported. The investigators describe their experience with 6 patients presenting with ST elevation myocardial infarctions, all within a 24-hour period during an unprecedented snowfall (4 of whom were shoveling snow), and provide a detailed review of previously reported cases of snow shoveler's infarction. Consistent with other reports, most patients reported here had the traditional cardiac risk factors of hypertension, hyperlipidemia, diabetes mellitus, tobacco use, and sedentary lifestyle. Unique to this case series, however, was that the 4 patients who had histories of coronary artery disease and previous coronary artery stenting all presented with subacute stent thromboses documented on coronary angiography performed emergently. Moreover, these patients constituted 25% of all subacute stent thromboses diagnosed in the cardiac catheterization laboratory in the preceding 12 months. In conclusion, these findings suggest that in typically sedentary individuals with cardiac risk factors or histories of coronary artery disease, snow shoveling may trigger ST elevation myocardial infarction and therefore should be avoided. This may be most critical in patients with histories of coronary stent placement, considering that these findings suggest that snow shoveling may precipitate subacute stent thrombosis.