Case of primary hepatic leiomyosarcoma successfully treated with laparoscopic right hepatectomy.

We describe the case of a 77-year-old woman, presenting with non-specific epigastric pain. Physical examination and subsequent imaging revealed the presence of a large mass in the right liver lobe. This was shown to be a leiomyosarcoma on biopsy histology. Further investigation confirmed this to be a primary hepatic leiomyosarcoma with no evidence of metastases. The patient underwent successful surgical resection. She is currently under imaging follow-up, with no evidence of disease recurrence.

Fibrinogen measurement in liver disease: validation of the functional fibrinogen thromboelastography assay and a novel mathematical predictive model.

BACKGROUND: Fibrinogen is produced in the liver and tends to be reduced in liver cirrhosis. Quantitative and qualitative tests exist to measure fibrinogen. We aimed to validate the functional fibrinogen thromboelastography assay (FF-TEG) and propose a new model to estimate fibrinogen levels via the Clauss method (Clauss) using data from a prothrombin time-derived fibrinogen assay (PT-Fg) in patients with liver cirrhosis. MATERIALS AND METHODS: Clauss, PT-Fg, fibrinogen antigen (Fib-Ag) and FF-TEG were studied in 55 patients with liver cirrhosis (26 with Child-Turcotte-Pugh [CTP]-A disease, 14 with CTP-B and 15 CTP-C) and 20 healthy individuals. RESULTS: The results of all four assays correlated strongly with each other, but gave significantly different mean levels in all cohorts. PT-Fg gave the highest levels whereas the Clauss gave the lowest levels. The FF-TEG performed well with results which were in between the Clauss and the PT-Fg. Significant differences were only observed between CTP-A and CTP-C for the Clauss, PT-Fg and Fib-Ag but not functional fibrinogen level. We devised a simple linear regression model in order to estimate Clauss from the PT-Fg. DISCUSSION: The results of the FF-TEG correlate well with those of routine fibrinogen assays in patients with liver cirrhosis. However, the FF-TEG assay does not discriminate between early and late stages of disease, pointing to a preserved fibrin clot strength in cirrhosis. Through linear regression models, fibrinogen levels can be accurately estimated using the Clauss method based on fibrinogen levels obtained in the cheaper PT-Fg.

Restrictions for reimbursement of interferon-free direct-acting antiviral drugs for HCV infection in Europe.

All-oral direct-acting antiviral drugs (DAAs) for hepatitis C virus, which have response rates of 95% or more, represent a major clinical advance. However, the high list price of DAAs has led many governments to restrict their reimbursement. We reviewed the availability of, and national criteria for, interferon-free DAA reimbursement among countries in the European Union and European Economic Area, and Switzerland. Reimbursement documentation was reviewed between Nov 18, 2016, and Aug 1, 2017. Primary outcomes were fibrosis stage, drug or alcohol use, prescriber type, and HIV co-infection restrictions. Among the 35 European countries and jurisdictions included, the most commonly reimbursed DAA was ombitasvir, paritaprevir, and ritonavir, with dasabuvir, and with or without ribavirin (33 [94%] countries and jurisdictions). 16 (46%) countries and jurisdictions required patients to have fibrosis at stage F2 or higher, 29 (83%) had no listed restrictions based on drug or alcohol use, 33 (94%) required a specialist prescriber, and 34 (97%) had no additional restrictions for people co-infected with HIV and hepatitis C virus. These findings have implications for meeting WHO targets, with evidence of some countries not following the 2016 hepatitis C virus treatment guidelines by the European Association for the Study of Liver.

Lack of Spatial Immunogenetic Structure among Wolverine (Gulo gulo) Populations Suggestive of Broad Scale Balancing Selection.

Elucidating the adaptive genetic potential of wildlife populations to environmental selective pressures is fundamental for species conservation. Genes of the major histocompatibility complex (MHC) are highly polymorphic, and play a key role in the adaptive immune response against pathogens. MHC polymorphism has been linked to balancing selection or heterogeneous selection promoting local adaptation. However, spatial patterns of MHC polymorphism are also influenced by gene flow and drift. Wolverines are highly vagile, inhabiting varied ecoregions that include boreal forest, taiga, tundra, and high alpine ecosystems. Here, we investigated the immunogenetic variation of wolverines in Canada as a surrogate for identifying local adaptation by contrasting the genetic structure at MHC relative to the structure at 11 neutral microsatellites to account for gene flow and drift. Evidence of historical positive selection was detected at MHC using maximum likelihood codon-based methods. Bayesian and multivariate cluster analyses revealed weaker population genetic differentiation at MHC relative to the increasing microsatellite genetic structure towards the eastern wolverine distribution. Mantel correlations of MHC against geographical distances showed no pattern of isolation by distance (IBD: r = -0.03, p = 0.9), whereas for microsatellites we found a relatively strong and significant IBD (r = 0.54, p = 0.01). Moreover, we found a significant correlation between microsatellite allelic richness and the mean number of MHC alleles, but we did not observe low MHC diversity in small populations. Overall these results suggest that MHC polymorphism has been influenced primarily by balancing selection and to a lesser extent by neutral processes such as genetic drift, with no clear evidence for local adaptation. This study contributes to our understanding of how vulnerable populations of wolverines may respond to selective pressures across their range.

Tenofovir as rescue therapy following clinical failure to Lamivudine in severe acute hepatitis B.

Acute hepatitis B (AHB) is a self-limiting condition in more than 95% of cases. Treatment is however recommended in patients with severe AHB (<1% of cases), aiming to prevent liver failure and death. Various nucleos(t)ide analogues (NA) have been found to be effective in severe AHB, although NA-resistant strains causing AHB have been also recently reported. The use of tenofovir in severe AHB has only been described in 3 cases (1 adult and 1 infant with HBV mono-infection, 1 adult with HBV/HIV co-infection). We hereby report a 47-year-old treatment-naïve male, who developed severe AHB and was initially treated with lamivudine (LMV). Initial rapid biochemical response was followed by biochemical breakthrough after 9 days, suggesting LMV resistance. Rescue therapy with 'add-on' tenofovir brought about a sustained improvement in biochemical, serological and virological markers until HBsAg was lost after 4 months. Thus, this is the second adult HBV mono-infected patient, who responded successfully to tenofovir in severe AHB.

Acute Liver Impairment in a Young, Healthy Athlete: Hypoxic Hepatitis and Rhabdomyolysis following Heat Stroke.

Any process that substantially diminishes arterial blood flow or arterial oxygen content to the liver can result in hypoxic (ischaemic) hepatitis. 90% of hypoxic hepatitis occurs in unstable patients in intensive care units with haemodynamic failure secondary to heart failure, respiratory failure and toxic shock. The rate of in-hospital mortality in hypoxic hepatitis is very high with studies recording mortalities of 61.5%. It tends to be very uncommon in healthy, young patients with no underlying medical problems. We report here the case of a young healthy athlete who developed heat stroke associated with rhabdomyolysis and hypoxic hepatitis while he was running the final stages of a marathon. The patient required intensive care admission and inotropic support for a few hours after he was admitted with heat stroke. He underwent a rapid recovery after he was resuscitated with fluids. N-acetyl cysteine was also given during the acute stage of the hepatitis. This case highlights an uncommon case of hypoxic hepatitis in a young, healthy patient secondary to hypotension and heat stroke. Inotropic support might have precipitated the hypoxic hepatitis in this young patient.

Concerted evolution of duplicated mitochondrial control regions in three related seabird species.

BACKGROUND: Many population genetic and phylogenetic analyses of mitochondrial DNA (mtDNA) assume that mitochondrial genomes do not undergo recombination. Recently, concerted evolution of duplicated mitochondrial control regions has been documented in a range of taxa. Although the molecular mechanism that facilitates concerted evolution is unknown, all proposed mechanisms involve mtDNA recombination. RESULTS: Here, we document a duplication of a large region (cytochrome b, tRNAThr, tRNAPro, ND6, tRNAGlu and the control region) in the mitochondrial genome of three related seabird species. To investigate the evolution of duplicate control regions, we sequenced both control region copies (CR1 and CR2) from 21 brown (Sula leucogaster), 21 red-footed (S. sula) and 21 blue-footed boobies (S. nebouxii). Phylogenetic analysis suggested that the duplicated control regions are predominantly evolving in concert; however, approximately 51 base pairs at the 5' end of CR1 and CR2 exhibited a discordant phylogenetic signal and appeared to be evolving independently. CONCLUSIONS: Both the structure of the duplicated region and the conflicting phylogenetic signals are remarkably similar to a pattern found in Thalassarche albatrosses, which are united with boobies in a large clade that includes all procellariiform and most pelecaniform seabirds. Therefore we suggest that concerted evolution of duplicated control regions either is taxonomically widespread within seabirds, or that it has evolved many times.