Progressive visceral leishmaniasis misdiagnosed as cirrhosis of the liver: a case report

<p>Abstract</p> <p>Introduction</p> <p>Visceral leishmaniasis is a potentially life-threatening infectious disease which is caused by parasites of the genus <it>Leishmania</it> and characterized in most cases by the presence of fever as well as signs and symptoms similar to those found in liver cirrhosis.</p> <p>Case presentation</p> <p>In this case report we describe the history of a 50-year-old Caucasian man incorrectly diagnosed as having hepatitis C virus-associated liver cirrhosis, with a massive weight loss of around 100 kg during the previous 2 years. However, suspecting a lymphoproliferative disorder, we were able to make a correct diagnosis of visceral leishmaniasis by bone marrow examination. After a course of therapy with Liposomal Amphotericin-B the patient recovered and now, 20 months post-treatment, he is well and has regained a good part of the lost weight.</p> <p>Conclusions</p> <p>This case taught us that patients with massive splenomegaly, even with a diagnosis of liver cirrhosis, should be investigated for infectious or lymphoproliferative diseases.</p

Oxidative Stress as a Target for Non-Pharmacological Intervention in MAFLD: Could There Be a Role for EVOO?

: Oxidative stress plays a central role in most chronic liver diseases and, in particular, in metabolic dysfunction-associated fatty liver disease (MAFLD), the new definition of an old condition known as non-alcoholic fatty liver disease (NAFLD). The mechanisms leading to hepatocellular fat accumulation in genetically predisposed individuals who adopt a sedentary lifestyle and consume an obesogenic diet progress through mitochondrial and endoplasmic reticulum dysfunction, which amplifies reactive oxygen species (ROS) production, lipid peroxidation, malondialdehyde (MDA) formation, and influence the release of chronic inflammation and liver damage biomarkers, such as pro-inflammatory cytokines. This close pathogenetic link has been a key stimulus in the search for therapeutic approaches targeting oxidative stress to treat steatosis, and a number of clinical trials have been conducted to date on subjects with NAFLD using drugs as well as supplements or nutraceutical products. Vitamin E, Vitamin D, and Silybin are the most studied substances, but several non-pharmacological approaches have also been explored, especially lifestyle and diet modifications. Among the dietary approaches, the Mediterranean Diet (MD) seems to be the most reliable for affecting liver steatosis, probably with the added value of the presence of extra virgin olive oil (EVOO), a healthy food with a high content of monounsaturated fatty acids, especially oleic acid, and variable concentrations of phenols (oleocanthal) and phenolic alcohols, such as hydroxytyrosol (HT) and tyrosol (Tyr). In this review, we focus on non-pharmacological interventions in MAFLD treatment that target oxidative stress and, in particular, on the role of EVOO as one of the main antioxidant components of the MD

Clinical course and management of acute and chronic viral hepatitis during pregnancy.

Pregnancy is a para-physiologic condition, which usually evolves without any complications in the majority of women, even if in some circumstances moderate or severe clinical problems can also occur. Among complications occurring during the second and the third trimester very important are those considered as concurrent to pregnancy such as hyperemesis gravidarum, intrahepatic cholestasis of pregnancy, HELLP syndrome and acute fatty liver of pregnancy. The liver diseases concurrent to pregnancy typically occur at specific times during the gestation and they may lead to significant maternal and foetal morbidity and mortality. Commonly, delivery of the foetus, even preterm, usually terminates the progression of these disorders. All chronic liver diseases, such as chronic viral hepatitis, autoimmune hepatitis, Wilson's disease, and cirrhosis of different aetiologies may cause liver damage, independently from pregnancy. In this review we will also comment the clinical implications of pregnancies occurring in women who received a orthotopic liver transplantation (OLT) Therefore, the management of immunosuppressive therapy before and after the delivery in women who received liver transplant is becoming a relevant clinical issue. Finally, we will focus on acute and chronic viral hepatitis occurring during pregnancy, on management of advanced liver disease and we will review the literature on the challenging issue regarding pregnancy and OLT

ALLELIC VARIANTS OF CYP2E1 GENE IN HEPATOCARCINOMA PATIENTS AND IN HEPATIC TUMOR CELL LINES

Background and Aims: Hepatic enzyme CYP2E1 is involved in the metabolism of a number of exogenous and endogenous substances (i.e. ethanol, drugs and chemical carcinogens). Being polymorphic, CYP2E1 gene can give different xeno-metabolic capabilities in a population and it is well known that inadequate or no enzymatic deactivation of xenobiotics could induce an increased susceptibility to disease and cancer. In particular, one of the 5 -flanking region polymorphisms, able to differentiate CYP2E1 gene transcriptional activity, is caused by the appearance/disappearance of RsaI and PstI restriction sites, which generates two different alleles, namely *C1(Rsa+/Pst−) and *C2(Rsa−/Pst+) respectively, reported to be in complete linkage disequilibrium. Methods: To confirm the existence of a correlation between some particular CYP2E1 genotypes/haplotypes and hepatocarcinoma, we determined CYP2E1 PstI/RsaI genotypes/haplotypes by RFLP-PCR in a cohort of central western Sicily hepatocarcinoma patients and in a population of healthy students from the same geographic area. Results: In hepatocarcinoma patients, modal genotype association was Rsa++/Pst−−, corresponding to CYP2E1 *C1/*C1 haplotype, whereas the Rsa+−/Pst−+ association, equivalent to CYP2E1 *C1/*C2 haplotype, resulted to have the lowest frequency both in patients and in controls. Moreover, both in patients and in controls, noncanonical genotype associations were frequent and arose from a no-linkage disequilibrium between the two polymorphic sites. Other authors reported this finding as a rare occurrence. Thus, from analysis of only one restriction site, Rsa++ genotype was approximately 1.5-fold more frequent in patients than in controls, and the non-canonical Rsa+− genotype was found relatively frequent in patients. Moreover, HuH7 and HA22T transformed hepatocarcinoma cell lines also showed the Rsa+− genotype. Conclusions: These results suggest that the presence in CYP2E1 genotype of at least one allele with an Rsa I restriction site is correlated with hepatocarcinoma. As this site is known a consensus sequence for some specific CYP gene transcription factors, like HNF-1, it may be supposed that a single nucleotide polymorphism can alter the possibility of HNF-1 to bind CYP2E1 promoter. This could determine a marked change in the transcriptional activity of the gene, incompetence in xenobiotic metabolism or in toxic substance deactivation and an increased susceptibility to neoplastic diseases, such as hepatocarcinoma

long term follow up of hepatitis c virus positive patients with persistently normal serum transaminases

Material and methods. This study prospectively evaluated the progression of liver disease in a group of anti-HCV-positive patients with persistently normal ALT levels (PNALT) who were HCV-RNA positive. Patients selected for this study were those who presented with PNALT according to the Italian Association for the Study of the Liver (AISF) criteria in the year 1995/96 and underwent liver biopsy. They were divided into two groups according to their ALT evolution. Forty-five patients were included in this study. Results. After a median follow-up time of 180 months twenty-five of them maintained PNALT, but two of these developed liver cirrhosis (LC) in a mean time of 174 and 202 months, respectively. Twenty patients had flares of ALT and three of them developed LC in a mean time of 162-178 months. Twelve of these patients underwent current antiviral treatment; six patients were SVR. At baseline, the 5 patients who progressed to LC had age and BMI significantly higher than patients without LC (P < 0.005 and P < 0.01, respectively). Grading (P < 0.006) and staging (P < 0.003) were also more severe at histology, while serum HDL-C levels were statistically lower (P < 0.002). Comparing patients with flares of transaminases with and without LC, we found a significant difference at baseline for age, BMI, HDL-C, grading and staging (P < 0.05; P < 0.01 and P < 0.003, respectively). Conclusion. In HCV-RNA positive patients associated with PNALT the grade of disease activity increased over the years in only half of patients and a higher degree of liver fibrosis at baseline was the major relevant factor for progression

Effectiveness of a Food Supplement Based on Glucomannan, D-Chiro-Inositol, Cinnamomum zeylanicum Blume and Inulin in Patients with Metabolic Syndrome

Metabolic syndrome (MetS) is associated with cardiovascular risk factors, such as insulin resistance, dyslipidaemia, hypertension and abdominal obesity. Given the growing need to investigate food supplements with positive health effects, this study was aimed at testing the benefits of a specific supplement for people with MetS. Fifty-eight subjects with MetS and T2DM or impaired glucose tolerance assuming metformin, were randomly assigned to take a food supplement of glucomannan, D-chiro-inositol, Cinnamomum zeylanicum blume and inulin at a daily fixed dose of 4 g orally for four months. Body weight, waist circumference, plasma lipid profile (total cholesterol, LDL, HDL and triglyc-erides), plasma glycaemic profile and visceral adiposity index (VAI) were measured at baseline and after four months of supplementation. After 16 weeks, in subjects with T2DM or insulin resistance who took the supplement (+ metformin), there was a significant reduction in body weight and BMI (p &lt; 0.0001), serum insulin (p &lt; 0.05) and the HOMA index (p &lt; 0.01), as well as in the lipaemic pattern, with a significant improvement in total serum cholesterol (p &lt; 0.005), triglycerides (p &lt; 0.03) and LDL (p &lt; 0.02). Our study shows that the food supplement tested is a valid and safe alternative therapeutic approach in the management of MetS and all its resulting risk factors, as its efficacy has been demonstrated across anthropometric, glucose, lipid and hepatic parameters

Prospective evaluation of hepatic steatosis in HIV-infected patients with or without hepatitis C virus co-infection

SummaryBackgroundLimited data are available on hepatic steatosis (HS) in HIV patients who are not infected with hepatitis C virus (HCV). The aims of this study were to assess the prevalence of HS and its risk factors in HIV patients with and without HCV infection, and to evaluate whether HS correlates with advanced liver fibrosis and/or cardiovascular disease risk.MethodsFifty-seven HIV mono-infected and 61 HIV/HCV co-infected patients were enrolled consecutively. All patients underwent liver ultrasound and transient elastography. The main parameters of liver function, HIV and HCV viral loads, CD4+ cell counts, and data on highly active antiretroviral therapy (HAART) were recorded. Cardiovascular disease risk was evaluated using the 10-year Framingham risk score.ResultsHS prevalence in the whole HIV population was 53% (54% in mono-infected patients and 51% in co-infected patients). HS was associated with lipodystrophy and triglyceride values (p1 year (p<0.01). By multivariate analysis, only triglyceride levels (p<0.02) and Framingham risk score (p<0.05) were independently associated with HS in both HIV groups. No correlation was observed between HS and advanced liver fibrosis, measured by transient elastography.ConclusionsHS was common in HIV patients, occurring in about half of the population. HS was found to be linked with the Framingham risk score, but was not correlated with advanced liver fibrosis. We suggest that in our HIV population with HS, the burden of cardiovascular disease risk is greater than that of liver disease progression

Changes in the ultrasound presentation of hepatocellular carcinoma: a center's three decades of experience

Purpose: Ultrasound (US) surveillance is a cornerstone for early diagnosis of HCC, anyway US presentation has undergone significant changes. With the aim of evaluating the effects of US surveillance program in the real-world clinical practice, we wanted to evaluate US presentation of HCCs over the last 30 years and the differences of HCCs presentation according to etiology. Methods: 174 patients diagnosed between 1993 and 98 (G1), 96 between 2003 and 08 (G2), 102 between 2013 and 18 (G3), were compared. US patterns were: single, multiple or diffuse nodules. The echo-patterns: iso-, hypo-, hyper-echoic, or mixed. In G1, the HCC diagnosis was mainly histologic; in G2 by EASL 2001 and AASLD 2005, in G3 AASLD 2011, EASL 2012, and AISF 2013 guidelines. Results: HCV was the most frequent etiology, dropping between G1 (81%) and G3 (66%) (P &lt; 0.01), metabolic increased between G1 (5%) and G3 (14%) (P &lt; 0.01). Single HCC was more prevalent in G3 vs G1 (65.6% vs 40%) (P &lt; 0.0001), multiple nodules in G1 (50%) vs G3 (33.3%) (P &lt; 0.02) and diffuse in G1 (16%) vs G2 (2%) and vs G3 (1%) (P &lt; 0.001). The most frequent echo-pattern was hypo-echoic G1 (50%) vs G2 (79%) and G1 vs G3 (65%) (P &lt; 0.01). Iso-echoic pattern was the least frequent (7-12%). Mixed pattern decreased from G1 (28%) to G3 (12%) (P &lt; 0.002). In G3 there were more multiple or diffuse HCCs in metabolic (P &lt; 0.03). Conclusion: US presentation became less severe due to surveillance programs. HCV remains the most frequent cause, an increase in metabolic etiology has been shown throughout the decades