Umberto Vespasiani Gentilucci

Liver vitamin D receptor, CYP2R1, and CYP27A1 expression: relationship with liver histology and vitamin D3 levels in patients with nonalcoholic steatohepatitis or hepatitis C virus

Evidence suggests an association between low serum 25‐hydroxy‐vitamin D3 [25(OH)D3] levels and the presence and prognosis of liver disease. Vitamin D receptor (VDR) has been widely detected in the liver, but its expression in the course of liver disease has never been investigated. We evaluated the hepatic expression of VDR along with that of vitamin D 25‐hydroxylases in patients with nonalcoholic steatohepatitis (NASH) or chronic hepatitis C (CHC) and its relationship with hepatic histological features and serum 25(OH)D3 levels. We evaluated 61 patients (25 NASH and 36 CHC) who had undergone liver biopsy for clinical purposes and 20 subjects without liver disease. Serum 25(OH)D3 was measured via colorimetric assay. Expression of VDR, CYP2R1, and CYP27A1 was evaluated via immunohistochemistry in hepatocytes, cholangiocytes, and liver inflammatory cells. Parenchymal and inflammatory cells from liver biopsies of patients with NASH and CHC expressed VDR, CYP2R1, and CYP27A1. In NASH patients, VDR expression on cholangiocytes was inversely correlated with steatosis severity (P < 0.02), lobular inflammation (P < 0.01), and nonalcoholic fatty liver disease score (P < 0.03). Moreover, expression of CYP2R1 in hepatocytes correlated strongly with VDR positivity on liver inflammatory cells. In CHC subjects, fibrosis stage was associated with low hepatic CYP27A1 expression, whereas portal inflammation was significantly higher in patients with VDR‐negative inflammatory cells (P < 0.009) and low VDR expression in hepatocytes (P < 0.03). Conclusion: VDR is widely expressed in the liver and inflammatory cells of chronic liver disease patients and its expression is negatively associated with the severity of liver histology in both NASH and CHC patients. These data suggest that vitamin D/VDR system may play a role in the progression of metabolic and viral chronic liver damage. (HEPATOLOGY 2012;56:2180–2187)

Diabetes in chronic liver disease: from old concepts to new evidence

The liver is one of the principal organs involved in glucose metabolism together with skeletal muscle and adipose tissue. A link between diabetes and chronic liver disease (CLD) was first observed in the early half of the last century, but to date several questions remain unsolved. Altered glucose tolerance has been well described in alcoholic CLD, non‐alcoholic fatty liver disease, chronic hepatitis C and portal hypertension. Moreover, insulin resistance is assuming an ever‐growing importance in CLD; chronic hepatitis C has recently been proposed as a metabolic disease and insulin sensitivity as a predictive factor for liver fibrosis.

Hepatitis C virus-related B cell subtypes in non Hodgkin's lymphoma

AIM To evaluate if indolent B cell-non Hodgkins lymphoma (B-NHL) and diffuse large B-cell lymphoma (DLBCL) in hepatitis C virus (HCV) positive patients could have different biological and clinical characteristics requiring different management strategies. METHODS A group of 24 HCV related B-NHL patients (11 indolent, 13 DLBCL) in whom the biological and clinical characteristics were described and confronted. Patients with DLBCL were managed with the standard of care of treatment. Patients with indolent HCV-related B-NHL were managed with antiviral treatment pegylated interferon plus ribavirin and their course observed. The outcomes of the different approaches were compared. RESULTS Patients with DLBCL had a shorter duration of HCV infection and a higher prevalence of HCV genotype 1 compared to patients with indolent B-NHL in which HCV genotype 2 was the more frequent genotype. Five of the 9 patients with indolent HCV-related B-NHL treated with only antiviral therapy, achieved a complete response of their onco-haematological disease (55%). Seven of the 13 DLBCL patients treated with immunochemotheraphy obtained a complete response (54%). CONCLUSION HCV genotypes and duration of HCV infection differed between B-NHL subtypes. Indolent lymphomas can be managed with antiviral treatment, while DLBCL is not affected by the HCV infection.

TNF-α and growth hormone resistance in patients with chronic liver disease

Liver cirrhosis is characterized by a severe impairment of the growth hormone/insulin-like growth factor-1 (GH-IGF-1) axis, that is, acquired GH resistance. The condition of the GH-IGF-1 axis in the phase of chronic liver disease (CLD) preceding cirrhosis, however, remains uncertain. The origin of GH resistance during CLD is multifactorial, and to date, the liver functional mass is considered to play a major role. Although proinflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-1β, were found to be elevated in patients with CLD and were shown to induce a state of GH resistance in other disease models, their involvement in the pathogenesis of GH resistance during CLD has never been investigated. We characterized the GH-IGF-1 axis by analyzing the individual components of the axis (GH, IGF-1, IGF-binding protein-3 [IGFBP-3], acid-labile subunit [ALS]) and the corresponding ratios (GH/IGF-1, GH/IGFBP-3, and GH/ALS) and verified the links with circulating proinflammatory cytok...

HCV genotype 1a shows a better virological response to antiviral therapy than HCV genotype 1b.

BackgroundThe impact of viral subtype on the rate of sustained virological response (SVR) to antiviral therapy in patients chronically infected with hepatitis C genotype 1 subtype 1a and 1b has not been extensively investigated. The aim of this study is to determine whether the HCV genotype 1 subtypes 1a and 1b respond differently to treatment with PEGylated interferon (PEG-IFN) plus ribavirin.MethodsFor 48 weeks, 388 “naïve”genotype 1 patients were treated weekly with PEG-IFN α-2a or PEG-INF α-2b combined with daily ribavirin (1000–1200 mg/day). The numbers of patients in whom HCV-RNA was undetectable were compared after 4 (rapid virological response, RVR), 12 (early virological response, EVR), and 48 (end treatment virological response, ETR) weeks of treatment as well as 24 weeks after the last treatment (sustained virological response, SVR).ResultsThe rate of SVR was higher in subtype 1a patients than subtype 1b patients (55% vs. 43%; p < 0.02). Multiple logistic regression analysis showed that infection with genotype 1a (odds ratio(OR) : 1.8; 95% confidence interval (CI): 1.4 to 4.1), age < 50 years (OR:7.0; 95% CI 1.1 to 21.2), alanine aminotransferase level (ALT)<100 IU/ml (OR:2.1; 95% CI: 1.3 to3.5), HCV-RNA < 5.6 log10 IU/ml (OR: 3.2; 95% CI: 2.7 to 6.9) and fibrosis score < S3 (OR: 3.8; 95% CI:3.2 to 7.4), were all independent predictors of SVR.ConclusionDual antiviral therapy is more effective against HCV subtype 1a than against subtype 1b and this difference is independent of other factors that may favour viral clearance.Trial registrationClinicalTrials.gov Identifier: NCT01342003

Westernization of the Filipino population resident in Rome: obesity, diabetes and hypertension

Aims of the present study were to examine the anthropometrical and metabolic characteristics of the Filipino population migrant to the Southern European city of Rome, Italy.

Non-cirrhotic portal hypertension with large regenerative nodules: a diagnostic challenge.

Non-cirrhotic portal hypertension is a poorly understood condition characterized by portal hypertension in the absence of conventional hepatic cirrhosis and described in association with blood coagulation disorders, myeloproliferative and immunological diseases and with exposure to toxic drugs. Very recently, precise classification criteria have been proposed in order to define four distinct subcategories. The present case highlights how the clinical presentation, the confounding results from imaging studies, and the difficulties in the histological evaluation often render cases of non-cirrhotic portal hypertension a real diagnostic challenge. It also underscores the classification problems which can be faced once this diagnosis is performed. Indeed, the different subcategories proposed result from the prevalent subtypes in a spectrum of hepatic regenerative responses to a variety of injuries determining microcirculatory disturbances. More flexibility in classification should derive from this etiopathogenic background.

Deep Vein Thrombosis, Inferior Vena Cava Interruption and Multiple Thrombophilic Gene Mutations

Interruption or hypoplasia of the inferior vena cava, with associated azygos continuation, is an uncommon congenital vascular malformation (Ellis et al, Comput Radiol 1986;10:15-22). Although this anomaly causes venous stasis, few patients present with history of deep vein thrombosis (DVT). The exact role of coexisting thrombophilic gene mutations, also heterozygotic, is far from being completely understood. However, in these cases, because of a probable additive effect, treatment of complications and careful prophylaxis for recurrent DVT are recommended lifelong. The authors report a case of inferior vena cava interruption with azygos continuation in a 30-year-old woman who presented with a history of recurrent lower limb DVT. In addition, heterozygosis for the H1299R polymorphism of the factor V gene (Factor V HR2), for the C677T polymorphism of the methylenetetrahydrofolate reductase gene (MTHFR C677T) and for the 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene (PAI-1 4G/5G) was found in DNA analyses.

Gas exchanges and pulmonary vascular abnormalities at different stages of chronic liver disease.

Background: It is unclear whether and to which extent respiratory function abnormalities may complicate the earliest stages of chronic liver disease (CLD). Aim of this study was to compare pulmonary capillary volumes and gas exchange efficiency of CLD patients with and without cirrhosis.

Case Report: Liver Cirrhosis After Prolonged Therapy with IFN-α plus Interleukin-2 in a Metastatic Renal Cancer Long-Term Survivor

Interleukin-2 (IL-2) therapy is associated with serious toxic effects on the cardiopulmonary system. Less frequent toxicity is described in liver and the gastrointestinal system. A case of severe liver toxicity is described in a patient who underwent long-term immunotherapy with IL-2 (4.5 MU/m2 s.c. daily, 5 days per week for 6 weeks, with 4 weeks of interval) plus interferon-α (IFN-α) (3 MU s.c. t.i.w., also covering the intervals between IL-2 cycles) for a metastatic renal carcinoma. A review of the literature is provided. The patient tolerated well the immunotherapy scheduled with apparently only a World Health Organization (WHO) G3 anemia and a G2 asthenia and is still alive, with a disease-free survival of 28 months. Notwithstanding a complete absence of liver function test abnormality during all scheduled clinical controls, the patient developed portal hypertension due to liver cirrhosis, which was histologically demonstrated. All common etiologic viral and toxic agents were ruled out. Long-term IL-...