Non-alcoholic fatty liver disease(NAFLD) is an important health problem worldwide. NAFLD encompasses a histological spectrum ranging from bland liver steatosis to severe steatohepatitis(nonalcoholic ...steatohepatitis, NASH) with the potential of progressing to cirrhosis and its associated morbidity and mortality. NAFLD is thought to be the hepatic manifestation of insulin resistance(or the metabolic syndrome); its prevalence is increasing worldwide in parallel with the obesity epidemic. In many developed countries, NAFLD is the most common cause of liver disease and NASH related cirrhosis is currently the third most common indication for liver transplantation. NASH related cirrhosis is anticipated to become the leading indication for liver transplantation within the next one or two decades. In this review, we discuss how liver transplantation is affected by NAFLD, specifically the following:(1) the increasing need for liver transplantation due to NASH;(2) the impact of the increasing prevalence of NAFLD in the general population on the quality of deceased and live donor livers available for transplantation;(3) the long term graft and patient outcomes after liver transplantation forNASH,and finally;and(4)the de novo occurrence of NAFLD/NASH after liver transplantation and its impact on graft and patient outcomes.
The European trial investigating normothermic ex vivo liver perfusion (NEVLP) as a preservation technique for liver transplantation (LT) uses gelofusine, a non–US Food and Drug ...Administration–approved, bovine‐derived, gelatin‐based perfusion solution. We report a safety and feasibility clinical NEVLP trial with human albumin–based Steen solution. Transplant outcomes of 10 human liver grafts that were perfused on the Metra device at 37 °C with Steen solution, plus 3 units of erythrocytes were compared with a matched historical control group of 30 grafts using cold storage (CS) as the preservation technique. Ten liver grafts were perfused for 480 minutes (340‐580 minutes). All livers cleared lactate (final lactate 1.46 mmol/L; 0.56‐1.74 mmol/L) and produced bile (61 mL; 14‐146 mL) during perfusion. No technical problems occurred during perfusion, and all NEVLP‐preserved grafts functioned well after LT. NEVLP versus CS had lower aspartate aminotransferase and alanine aminotransferase values on postoperative days 1‐3 without reaching significance. No difference in postoperative graft function between NEVLP and CS grafts was detected as measured by day 7 international normalized ratio (1.1 1‐1.56 versus 1.1 1‐1.3; P = 0.5) and bilirubin (1.5; 1‐7.7 mg/dL versus 2.78; 0.4‐15 mg/dL; P = 0.5). No difference was found in the duration of intensive care unit stay (median, 1 versus 2 days; range, 0‐8 versus 0‐23 days; P = 0.5) and posttransplant hospital stay (median, 11 versus 13 days; range, 8‐17 versus 7‐89 days; P = 0.23). Major complications (Dindo‐Clavien ≥ 3b) occurred in 1 patient in the NEVLP group (10%) compared with 7 (23%) patients in the CS group (P = 0.5). No graft loss or patient death was observed in either group. Liver preservation with normothermic ex vivo perfusion with the Metra device using Steen solution is safe and results in comparable outcomes to CS after LT. Using US Food and Drug Administration–approved Steen solution will avoid a potential regulatory barrier in North America. Liver Transplantation 22 1501–1508 2016 AASLD.
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•Most patients with single HCC ≤3 cm treated by RFA will eventually develop recurrent HCC distant to the ablation site.•Many patients treated with HCC will recur beyond the Milan ...criteria despite close post-RFA surveillance.•Patients with tumors >2 cm and higher serum alpha-fetoprotein are at greater risk of recurrence beyond Milan criteria.
Radiofrequency ablation (RFA) is an effective treatment for single hepatocellular carcinoma (HCC) ≤3 cm. Disease recurrence is common, and in some patients will occur outside transplant criteria. We aimed to assess the incidence and risk factors for recurrence beyond Milan criteria in potentially transplantable patients treated with RFA as first-line therapy.
We performed a retrospective cohort study of potentially transplantable patients with new diagnoses of unifocal HCC ≤3 cm that underwent RFA as first-line therapy between 2000-2015. We defined potentially transplantable patients as those aged <70 years without any comorbidities that would preclude transplant surgery. Incidence of recurrence beyond Milan criteria was compared across 2 groups according to HCC diameter at the time of ablation: (HCC ≤2 cm vs. HCC >2 cm). Competing risks Cox regression was used to identify predictors of recurrence beyond Milan criteria.
We included 301 patients (167 HCC ≤2 cm and 134 HCC >2 cm). Recurrence beyond Milan criteria occurred in 36 (21.6%) and 47 (35.1%) patients in the HCC ≤2 cm and the HCC >2 cm groups, respectively (p = 0.01). The 1-, 3- and 5-year actuarial survival rates after RFA were 98.2%, 86.2% and 79.0% in the HCC ≤2 cm group vs. 93.3%, 77.6% and 70.9% in the HCC >2 cm group (p = 0.01). Tumor size >2 cm (hazard ratio 1.94; 95%CI 1.25–3.02) and alpha-fetoprotein levels at the time of ablation (100–1,000 ng/ml: hazard ratio 2.05; 95%CI 1.10–3.83) were found to be predictors of post-RFA recurrence outside Milan criteria.
RFA for single HCC ≤3 cm provides excellent short- to medium-term survival. However, we identified patients at higher risk of recurrence beyond Milan criteria. For these patients, liver transplantation should be considered immediately after the first HCC recurrence following RFA.
Radiofrequency ablation and liver transplantation are treatment options for early stages of hepatocellular carcinoma (HCC). After ablation some patients will experience recurrence or metastatic spread of the initial tumor or may develop new tumors within the liver. Despite close follow-up, these recurrences can progress rapidly and exceed transplant criteria, preventing the patient from receiving a transplant. We identified that patients with HCC >2 cm and higher serum alpha-fetoprotein are at greater risk of recurrence beyond the transplant criteria. These data suggest that liver transplantation should be considered immediately after the first HCC recurrence for these patients.
Nowaday, zoonoses are an important cause of human parasitic diseases worldwide and a major threat to the socio-economic development, mainly in developing countries. Importantly, zoonotic helminths ...that affect human eyes (HIE) may cause blindness with severe socio-economic consequences to human communities. These infections include nematodes, cestodes and trematodes, which may be transmitted by vectors (dirofilariasis, onchocerciasis, thelaziasis), food consumption (sparganosis, trichinellosis) and those acquired indirectly from the environment (ascariasis, echinococcosis, fascioliasis). Adult and/or larval stages of HIE may localize into human ocular tissues externally (i.e., lachrymal glands, eyelids, conjunctival sacs) or into the ocular globe (i.e., intravitreous retina, anterior and or posterior chamber) causing symptoms due to the parasitic localization in the eyes or to the immune reaction they elicit in the host. Unfortunately, data on HIE are scant and mostly limited to case reports from different countries. The biology and epidemiology of the most frequently reported HIE are discussed as well as clinical description of the diseases, diagnostic considerations and video clips on their presentation and surgical treatment. Homines amplius oculis, quam auribus credunt Seneca Ep 6,5 Men believe their eyes more than their ears
Toxocariasis is a preventable parasitic disease that is caused by the dog and cat roundworms Toxocara cani and T. cati, respectively. Humans become infected when they accidently ingest infectious ...Toxocara eggs commonly found in contaminated soil; children are most often affected. Clinical manifestations of Toxocara infection in humans include ocular toxocariasis and visceral toxocariasis. Although infection with Toxocara can cause devastating disease, the burden of toxocariasis in the United States population remains unknown. In addition, risk factors for acquiring infection need to be better defined, and research needs to be conducted to better understand the pathophysiology and clinical course of toxocariasis. Development of diagnostic tests would enable clinicians to detect active infection, and determination of optimal drug regiments would ensure patients were appropriately treated. Addressing these public health gaps is necessary to understand and address the impact of toxocariasis in the United States.
Hepatitis C virus (HCV) re-infection of the graft is universal and interferon based antiviral therapy remains at present the treatment of choice in HCV liver transplant recipients. Apart from the ...antiviral effects, interferon and ribavirin have both potent immunomodulatory properties resulting in a broad range of immune-related disorders including acute cellular rejection and chronic ductopenic rejection as well as de novo autoimmune hepatitis. Further complicating the picture, HCV infection per se is associated with a variety of autoimmune phenomena. We discuss here the immune-mediated complications and their relationship to chronic HCV and interferon based antiviral therapy.
Following almost 10 years of no reported cases, Guinea worm disease (GWD or dracunculiasis) reemerged in Chad in 2010 with peculiar epidemiological patterns and unprecedented prevalence of infection ...among non-human hosts, particularly domestic dogs. Since 2014, animal infections with Guinea worms have also been observed in the other three countries with endemic transmission (Ethiopia, Mali, and South Sudan), causing concern and generating interest in the parasites' true taxonomic identity and population genetics. We present the first extensive population genetic data for Guinea worm, investigating mitochondrial and microsatellite variation in adult female worms from both human and non-human hosts in the four endemic countries to elucidate the origins of Chad's current outbreak and possible host-specific differences between parasites. Genetic diversity of Chadian Guinea worms was considerably higher than that of the other three countries, even after controlling for sample size through rarefaction, and demographic analyses are consistent with a large, stable parasite population. Genealogical analyses eliminate the other three countries as possible sources of parasite reintroduction into Chad, and sequence divergence and distribution of genetic variation provide no evidence that parasites in human and non-human hosts are separate species or maintain isolated transmission cycles. Both among and within countries, geographic origin appears to have more influence on parasite population structure than host species. Guinea worm infection in non-human hosts has been occasionally reported throughout the history of the disease, particularly when elimination programs appear to be reaching their end goals. However, no previous reports have evaluated molecular support of the parasite species identity. Our data confirm that Guinea worms collected from non-human hosts in the remaining endemic countries of Africa are Dracunculus medinensis and that the same population of worms infects both humans and dogs in Chad. Our genetic data and the epidemiological evidence suggest that transmission in the Chadian context is currently being maintained by canine hosts.
Heartworm disease, caused by Dirofilaria immitis, remains a significant threat to canines and felines. The development of parasites resistant to macrocyclic lactones (ML) has created a significant ...challenge to the control of the infection. The goal of this study was to determine if mice lacking a functional immune response would be susceptible to D. immitis. Immunodeficient NSG mice were susceptible to the infection, sustaining parasites for at least 15 weeks, with infective third-stage larvae molting and developing into the late fourth-stage larvae. Proteomic analysis of host responses to the infection revealed a complex pattern of changes after infection, with at least some of the responses directed at reducing immune control mechanisms that remain in NSG mice. NSG mice were infected with isolates of D. immitis that were either susceptible or resistant to MLs, as a population. The susceptible isolate was killed by ivermectin whereas the resistant isolate had improved survivability, while both isolates were affected by moxidectin. It was concluded that D. immitis survives in NSG mice for at least 15 weeks. NSG mice provide an ideal model for monitoring host responses to the infection and for testing parasites in vivo for susceptibility to direct chemotherapeutic activity of new agents.
To inform Dracunculus medinensis (Guinea worm) eradication efforts, we evaluated the role of fish as transport hosts for Dracunculus worms. Ferrets fed fish that had ingested infected copepods became ...infected, highlighting the importance of recommendations to cook fish, bury entrails, and prevent dogs from consuming raw fish and entrails.
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