The molecular interactions between hosts, vectors and pathogens drive the etiology of infectious diseases. At first sight, the Guillain-Barré and Alpha-Gal syndromes have quite different etiologies but, as proposed here, a closer look into the immune response to galactose-containing oligosaccharide structures that characterizes these two diseases reveals striking commonalities. In this Opinion paper, we address the main molecular drivers of two apparently unrelated diseases, and how the characterization of the immune response and immunological tolerance would advance the control and prevention of these diseases.

To evaluate the effects of gastric coronary venous embolization with TH glue (developer-containing octyl-α-cyanoacrylate) in combination with splenectomy for the treatment of cirrhotic portal hypertension and gastroesophageal varices.

From April 2002 to July 2016, 81 patients with cirrhotic portal hypertension who underwent this procedure were subject to perioperative (within 2 weeks), short-term (within 2 weeks to 1 month) and long-term (1 month thereafter) efficacy analyses. Complications, rebleeding rate, and long-term survival rate were evaluated.

No patients developed embolism caused by TH glue ectopia. Eleven patients experienced perioperative complications, including high esophageal expenditure blood (1%), subphrenic effusion (1%) and abdominal infection (1%), which affected one case each respectively. Pulmonary infection (2%) and portal system thrombosis (2%) affected two cases respectively. There were 4 patients who experienced ascites (5%). All patients had small amounts of melena and were healed after conservative medical treatment. The 1-, 3-, 5- and 10-year postoperative rebleeding rates were 4.9%, 8.6%, 11.1% and 18.5% respectively. The 1-, 3-, 5- and 10-year postoperative survival rates were 97.5%, 92.6%, 90.1% and 80.2% respectively. No hepatic encephalopathy occurred within 1 year after operation in any case.

The postoperative rebleeding rate was lower than that reported in the literature and the subjects achieved good perioperative, short-term and long-term effects. The method of operation in the treatment of cirrhotic portal hypertension and gastroesophageal varices is characterized by a good safety profile, less invasiveness, rapid postoperative recovery, and a lower rebleeding rate than other devascularization procedures. Thus, it is an option that can be first considered by patients requiring emergency surgery to stop bleeding or patients with poor liver function, and even some patients with Child-Pugh grade C.

Acute soft skull syndrome is an uncommon complication of patients with sickle cell anemia. Here, we report a case of an adult patient in Sudan with the acute soft syndrome, with our aim of providing more knowledge on this type of complication. The 20-year old patient, with a known history of sickle cell anemia, presented with a 1-day history of headache and joint pain. The complaint continued after admission, with increasing headache severity and development of rapid skull swelling, which indicated the rare sickle cell disease complication known as an acute soft head syndrome. Conservative management resulted in good response and rapid recovery of this case of acute soft skull syndrome with sickle cell anemia mainly related to skull infraction.

Early outcomes following solid organ transplantation have markedly improved in recent years. Antibody-mediated rejection caused by donor specific anti-human leukocyte antigen antibodies (HLA-DSA) is widely recognized to be a risk factor for rejection episode, graft loss and decreased graft survival. The presence of HLA-DSA before transplantation and the appearance of these antibodies after transplantation can induce a wide spectrum of allograft injuries, ranging from the absence of allograft lesions with normal biopsy histopathologies to indolent subclinical processes to acute rejection with early allograft loss. However, the interpretation of the current DSA results is not easy and has led to many discussions and controversies. Current challenges exist in identification of pathologic DSA, monitoring and diagnostic algorithms, appropriate risk stratification, minimization for preformed or de novo DSA by proper use of immunosuppression. This article summarizes recent advances concerning the impact of preformed and de novo DSA in solid organ transplantation, with a focus on the clinical significance of DSA and available treatment modalities. Areas requiring further investigation are also identified.

Background and Aims: The aim of this study was to investigate the effect(s) of meteorological factors on the prevalence of acute-on-chronic liver failure (ACLF) based on 10-years’ worth of population data.

Methods: We retrospectively collected ACLF case data from January 2007 to December 2016 from three major hospitals in Fuzhou City, China. Climatic data, including rainfall, mean temperature, differences in temperature (delta temperature) and mean humidity for each month were downloaded from the China Climatic Data Service Center. Following data collection, Poisson regression analysis was used to estimate the effect(s) of climatic factors on the risk of the prevalence of ACLF.

Results: The population consisted of a total of 3510 cases, with a mean age of 44.7 ± 14.8 years-old and with 79.8% being male. Upon analyzing the population data, we found a growing trend and seasonal pattern of monthly counts of ACLF-related hospitalization throughout the past decade. Specifically, the primary peak of ACLF prevalence was in January and the secondary peak was in July. Poisson regression showed mean temperature (risk ratio = 0.991, 95%CI = 0.986–0.996) and mean humidity (risk ratio = 1.011, 95%CI = 1.006–1.017) to be independently correlated with the monthly cases of ACLF. The results suggest that every unit increase of mean temperature (1°C) and mean humidity (1%) are associated with 0.991- and 1.011-fold changes of ACLF cases, respectively. Rainfall and delta temperature did not appear to affect the prevalence of this disease.

Conclusions: The hospitalization for ACLF peaks in January and July. Low temperature and high humidity appear to function as factors contributing to this seasonal pattern.

Background and Aims: Accumulated studies have evaluated the effects of glucokinase regulatory protein (GCKR) gene polymorphisms on the risk of nonalcoholic fatty liver disease (NAFLD) and coronary artery disease (CAD), but the association of GCKR polymorphisms with the risk of NAFLD and CAD in the Chinese Han population have remained unclear. The aim of this study was to investigate the association between GCKR gene polymorphisms (rs780094 and rs1260326) and the risk of NAFLD and CAD in NAFLD patients in a Chinese Northern Han population.

Methods:GCKR rs780094 and rs1260326 gene polymorphisms were genotyped by polymerase chain reaction sequencing for B-type ultrasonography-proven NAFLD patients with (n = 82) or without (n = 142) CAD, and in healthy controls (n = 152). Serum lipid profiles’ levels were determined using biochemical methods. Statistical analyses were conducted using SPSS 22.0 statistical software.

Results: As the results showed, significant differences in the serum lipid profiles existed between each group. No significant differences were observed in the distributions of genotypes and alleles of GCKR rs780094 and rs1260326 in each group. The GCKR rs780094 T and rs1260326 T allele carriers possessed decreased body mass index value, and serum fasting plasma glucose and TG levels in the overall subjects, respectively. In addition, the GCKR rs780094 T allele carriers possessed decreased serum fasting plasma glucose level in the controls and NAFLD + CAD patients.

Conclusions:GCKR rs780094 and rs1260326 polymorphisms were found to be not associated with the risk of NAFLD nor of CAD in NAFLD patients in this Chinese Northern Han population. GCKR rs780094 T and rs1260326 T alleles could affect the body mass index value and serum fasting plasma glucose and triglyceride levels.

To elucidate the antihypertensive and hypocholesterolemic effects of fenugreek, cumin, ajowan and their combined extracts along with enalapril maleate and fenofibrate in conscious 1K-1C hypertensive and hypercholesterolemic rats respectively.

Male Sprague-Dawley hypertensive rats were administered fenugreek, cumin, ajowan and their combined alcoholic extracts, which were compared with enalapril maleate (per oral). Blood pressure readings were taken on each of 3 days prior to drug treatment. Rats were divided into groups of six animals per dose, and each animal was used as its own control. Pre-drug and 2 hours post-drug blood pressure readings were recorded using the tail-cuff method. The antihypercholesterolemic study was carried out for 28 days. At the end of the treatment, the animals were fasted for 24 hours prior to the collection of blood samples. Blood was collected on the 8th, 15th and 29th days for measurement of plasma cholesterol, triglycerides and high density lipoprotein-cholesterol estimations using standard kits. The results were analyzed statistically using either paired t-test or ANOVA, followed by Dunnett’s test; p < 0.05 was considered to be significant.

The seeds’ of alcoholic extracts and their combination exhibited significant antihypertensive and antihypercholesterolemic effects at 300 and 500 mg (per os) in conscious 1K-1C hypertensive and hypercholesterolemic rats, at p < 0.05 when compared to enalapril maleate and fenofibrate respectively.

The study reveals the antihypertensive and antihypercholesterolemic activity of fenugreek, cumin, ajowan and their combined extracts in hypertensive and hypercholesterolemic rats. The combined extract seems to be promising for the development of a phytomedicine for hypertension and atherosclerosis.

Gut microbiota has been demonstrated to have a significant impact on the initiation, progression and development of complications associated with multiple liver diseases. Notably, nonalcoholic fatty liver diseases, including nonalcoholic steatohepatitis and cirrhosis, severe alcoholic hepatitis, primary sclerosing cholangitis and hepatic encephalopathy, have strong links to dysbiosis – or a pathobiological change in the microbiota. In this review, we provide clear and concise discussions on the human gut microbiota, methods of identifying gut microbiota and its functionality, liver diseases that are affected by the gut microbiota, including novel associations under research, and provide current evidence on the modulation of gut microbiota and its effects on specific liver disease conditions.

Background and Aims: Non-invasive evaluation of liver necroinflammation in patients with chronic liver disease is an unmet need in clinical practice. The diagnostic accuracy of transient elastography-based liver stiffness measurement (LSM) for liver fibrosis could be affected by liver necroinflammation, the latter of which could intensify stiffness of the liver. Such results have prompted us to explore the diagnosis potential of LSM for liver inflammation.

Methods: Three cross-sectional cohorts of liver biopsy-proven chronic liver disease patients were enrolled, including 1417 chronic hepatitis B (CHB) patients from 10 different medical centers, 106 non-alcoholic steatohepatitis patients, and 143 patients with autoimmune-related liver diseases. Another longitudinal cohort of 14 entecavir treatment patients was also included. The receiver operating characteristic (ROC) curve was employed to explore the diagnostic value of LSM.

Results: In CHB patients, LSM value ascended with the increased severity of liver necroinflammation in patients with the same fibrosis stage. Such positive correlation between LSM and liver necroinflammation was also found in non-alcoholic steatohepatitis and autoimmune-related liver diseases populations. Furthermore, the ROC curve exhibited that LSM could identify moderate and severe inflammation in CHB patients (area under the ROC curve as 0.779 and 0.838) and in non-alcoholic steatohepatitis patients (area under the ROC curve as 0.826 and 0.871), respectively. Such moderate diagnostic value was also found in autoimmune-related liver diseases patients. In addition, in the longitudinal entecavir treated CHB cohort, a decline of LSM values was observed in parallel with the control of inflammatory activity in liver.

Conclusions: Our study implicates a diagnostic potential of LSM to evaluate the severity of liver necroinflammation in chronic liver disease patients.

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the developed world, with a global prevalence of around 25%. NAFLD is considered to be the hepatic manifestation of metabolic syndrome and is strongly associated with obesity, insulin resistance and dyslipidemia. Insulin resistance plays a pivotal role in the development of NAFLD-related dyslipidemia, which ultimately increases the risk of premature cardiovascular diseases, a leading cause of morbidity and mortality in patients with NAFLD. Insulin affects hepatic glucose and lipid metabolism by hepatic or extrahepatic pathways. Aside from insulin resistance, several other factors also contribute to the pathogenesis of atherogenic dyslipidemia in patients with NAFLD. These include diet composition, gut microbiota and genetic factors, to name a few. The identification of potentially modifiable risk factors of NAFLD is of importance, so as to target those who may benefit from lifestyle changes and to help develop targeted therapies that decrease the risk of cardiovascular diseases in patients with NAFLD.

Background and Aims: The liver is the first organ affected by toxic copper in the classical and severe hepatic forms of Wilson’s disease (WD). Because their associated chronic liver damage is mostly asymptomatic, an intervention using a special test including serum alanine aminotransferase (ALT) activity is needed for detecting WD.

Methods: Using the modified international criteria for the diagnosis of WD, 45 patients were selected from the collective databases of our institutions, and 7 infants were reviewed from the literature. Two patients had the severe hepatic form, with normoceruloplasminemia and no mutations in ATP7B. The rapid ALT change during hemolytic anemia was adjusted for a baseline. The diagnostic potential of the ALT test was assessed from the age-dependent natural course of the liver damage of WD.

Results: The natural course had three stages. ALTs were still low in some infants younger than 4 years-old. They were high in all children between the ages of 4 and 8 years-old; then, they reduced to low levels in some patients over 9 years of age. The high ALT stage represents chronic active hepatitis, and the subsequent low ALT stage is due to silent cirrhosis. The hepatic copper content is a reliable but invasive test, while urinary copper secretion is an alternative, non-invasive test for copper toxicosis of WD. The serum ceruloplasmin and ATP7B analyses are subtype tests of WD. The response to anti-copper regimens is the final test result.

Conclusions: ALT could be the first parameter to test to detect WD in children between the ages of 4 and 8 years.

Background and Aims: Despite resection being considered the treatment of choice for intrahepatic cholangiocarcinoma (ICC), percutaneous thermal ablation can be an alternative treatment for patients unfit for surgery. Our aim was to compare long-term results of percutaneous sonographically-guided radiofrequency ablation (RFA) with high-powered microwave ablation (MWSA) in treatment of ICC.

Methods: Results of 71 ICC patients with 98 nodules treated with RFA (36 patients) or MWSA (35 patients) between January 2008 and June 2018 in 5 Interventional Ultrasound centers of Southern Italy were retrospectively reviewed. Cumulative overall survival curves were calculated with the Kaplan-Meyer method and differences with the log-rank test. Eleven possible factors affecting survival were analyzed.

Results: Overall survival of the entire series was 88%, 65%, 45% and 34% at 12, 36, 60 and 80 months, respectively. Patients treated with MWSA survived longer than patients treated with RFA (p < 0.005). The MWSA group with ICC nodules ≤3 cm or nodules up to 4 cm survived longer than the RFA group (p < 0.0005). In patients with nodules >4 cm, no significant difference was found. Disease-free survival and progression-free survival were better in the MWSA group compared to the RFA group (p < 0.005). Diameter of nodules and MWSA were independent factors predicting a better survival. No major complications were observed.

Conclusions: MWSA is superior to RFA in treating ICC unfit for surgery, achieving better long-term survival in small (≤3 cm) ICC nodules as well as nodules up to 4 cm of neoplastic tumors and should replace RFA.

Background and Aims: Psychometric hepatic encephalopathy score (PHES) is used widely for diagnosis of minimal hepatic encephalopathy (MHE). This prospective study aimed to determine the utility of the inhibitory control test (ICT) for the diagnosis of MHE. Additionally, the efficacy of rifaximin and lactulose for reversal of MHE was evaluated.

Methods: A total of 180 eligible cirrhotic patients underwent testing for MHE. When PHES was ≤ −5 and ICT lures were ≥ 14, MHE was diagnosed. The 108 patients with MHE were randomized to three groups for treatment with either lactulose, rifaximin, or placebo. Treatment outcomes were measured at the end of 3 months.

Results: The 108 patients with MHE diagnosed by PHES and/or ICT accounted for 60%. The diagnosis of MHE was made by both ICT and PHES positivity in 56 patients, by abnormal ICT and normal PHES in 37 patients, and by abnormal PHES and normal ICT in 15 patients. For diagnosis of MHE, ICT had sensitivity of 78.87%, specificity of 66.06% with 60.22% positive predictive value and 82.76% negative predictive value. An area under the curve value of 0.724 (95% CI: 0.653–0.788) was obtained for diagnosis of MHE. Reversal of MHE was seen in 71.42%, 70.27% and 11.11% of patients in the rifaximin, lactulose and placebo arms (p < 0.001). Rifaximin showed better tolerability compared to lactulose.

Conclusions: For the diagnosis of MHE, ICT is a simple tool but has lower sensitivity and better specificity than PHES. Rifaximin is as efficacious as lactulose in the treatment of MHE and better tolerated.

Background and Aims: We aimed to study clinical outcomes and liver biopsy features of alcoholic hepatitis (AH) patients on complementary and alternative medicines (CAMs) and to analyze the retrieved drugs for chemical and toxic components linked to drug-induced liver injury.

Methods: We retrospectively assessed clinical, biochemical and liver biopsy features of AH patients on CAM with drug-induced liver injury (AH-CAM, n = 27) and compared them to a control group (classical AH, n = 29) on standard of care. Patients without liver biopsy evaluation and other causes for liver disease were excluded. Samples of the CAMs (n = 42) from patients were retrieved and assessed for chemical and toxins.

Results: All were males, and significantly worse clinical presentation, biochemical severity, and liver disease scores were notable in patients with AH-CAM. Traditional Ayurvedic-polyherbal formulations were the most commonly used CAM. On liver histology, varying grades of severe-necrosis, severe hepatocellular, canalicular, cholangiolar cholestasis with predominant lymphocytic-portal-inflammation and varying grades of interface-hepatitis were noted in AH-CAM. Analysis of CAMs revealed presence of heavy metals up to 100,000 times above detectable range and adulterants, such as antibiotics, chemotherapy agents, nonsteroidal anti-inflammatory drugs, alcohols, antidepressants, anxiolytics, and recreational drugs. On follow up, a significantly higher number of patients with AH on CAM died at end of 1, 3- and-6-months compared to controls (37% vs. 83%, 29% vs. 62%, 18% vs. 52% respectively; p < 0.001).

Conclusions: Patients with AH and CAM-related drug-induced liver injury have extremely poor short-term survival in the absence of liver transplantation compared to those patients with AH on evidence-based management. Early transplant referral and educating on and curbing of CAM use in severe liver disease through strict monitoring of unregulated traditional health practices can help ease the burden of liver-related death.

Acute liver failure is a unique clinical phenomenon characterized by abrupt deterioration in liver function and altered mentation. The development of high-grade encephalopathy and multisystem organ dysfunction herald poor prognosis. Etiologic-specific treatments and supportive measures are routinely employed; however, liver transplantation remains the only chance for cure in those who do not spontaneously recover. The utility of artificial and bioartificial assist therapies as supportive care—to allow time for hepatic recovery or as a bridge to liver transplantation—has been examined but studies have been small, with mixed results. Given the severity of derangements, intensive critical care is needed to successfully bridge patients to transplant, and evaluation of candidates occurs rapidly in parallel with serial reassessments of operative fitness. Psychosocial assessment is often suboptimal and relative contraindications to transplant, such as ventilator-dependence may be overlooked. While often employed to guide evaluation, no single prognostic model discriminates those who will spontaneously recover and those who will require transplant. The purpose of this review will be to summarize approaches in critical care, prognostic modeling, and medical evaluation of the acute liver failure transplant candidate.

Hepatic encephalopathy is a neurological complication resulting from loss of hepatic function and is associated with poor clinical outcomes. During acute liver failure over 20% of mortality can be associated with the development of hepatic encephalopathy. In patients with liver cirrhosis, 1-year survival for those that develop overt hepatic encephalopathy is under 50%. The pathogenesis of hepatic encephalopathy is complicated due to the multiple disruptions in homeostasis that occur following a reduction in liver function. Of these, elevations of ammonia and neuroinflammation have been shown to play a significant contributing role to the development of hepatic encephalopathy. Disruption of the urea cycle following liver dysfunction leads to elevations of circulating ammonia, which enter the brain and disrupt the functioning of astrocytes. This results in dysregulation of metabolic pathways in astrocytes, oxidative stress and cerebral edema. Besides ammonia, circulating chemokines and cytokines are increased following liver injury, leading to activation of microglia and a subsequent neuroinflammatory response. The combination of astrocyte dysfunction and microglia activation are significant contributing factors to the pathogenesis of hepatic encephalopathy.