Gianluca Abbati

Hyperhomocysteinaemia in chronic liver diseases: role of disease stage, vitamin status and methylenetetrahydrofolate reductase genetics

Abstract: Background/Aims: The liver plays a key role in sulphur aminoacid metabolism hence, homocysteine metabolism may be impaired in chronic liver diseases. The aim of this study was to investigate, in patients affected by chronic liver diseases, (1) the prevalence of hyperhomocysteinaemia and (2) the role of its determinants such as the stage and the aetiology of disease, vitamin status, genetic documented alterations (methylenetetrahydrofolate reductase deficiency) and presence/absence of documented malignant evolution (hepatocellular carcinoma).

Serum Ferritin as a Predictor of Treatment Outcome in Patients With Chronic Hepatitis C

OBJECTIVES:Antiviral treatment in chronic hepatitis C (CHC) involves ribavirin, a hemolytic agent. We planned a prospective study to evaluate whether drug-induced iron perturbation is clinically relevant as it relates to therapeutic outcome.METHODS:Iron variables were sequentially assessed in 206 CHC patients undergoing antiviral therapy and were correlated with pretreatment iron status and histology, hemolysis, and therapeutic outcome.RESULTS:At week 1 of therapy, serum iron (SI), transferrin saturation (TS), and serum ferritin (SF) increased markedly in all patients. All iron parameters correlated with hemolysis up to week 4; this correlation was lost for SF at later time points. SF rise during treatment was inversely related to baseline SF and iron deposits in hepatic mesenchymal/Kupffer cells. Both baseline SF and mesenchymal iron significantly correlated with fibrosis at multivariate analysis (P=0.015 and 0.008, respectively). Interestingly, baseline SF, despite good specificity (89%), had low sensitivity in predicting siderosis (25%). During therapy, SI, TS, and hemolysis parameters did not correlate with sustained virological response (SVR), whereas SF rise became an independent predictor of therapeutic response: a 2.5-fold increase of SF at week 12 associated with higher likelihood of SVR (odds ratio 1.91, P=0.032). Accordingly, lack of mesenchymal iron deposits at the baseline biopsy correlated with SVR (odds ratio 3.02, P=0.043).CONCLUSIONS:In CHC, SF is a useful marker for assessing disease duration and progression before starting treatment and for predicting therapeutic response while on therapy. SF rise during antiviral therapy is largely independent of hemolysis and likely indicates activation of macrophages in response to antivirals.

Urinary and Plasma Homocysteine and Cysteine Levels during Prolonged Oral N-Acetylcysteine Therapy

Acute administration of N-acetylcysteine (NAC) may induce alterations in plasma and urinary levels of homocysteine (Hcy) and cysteine (Cys). We studied the effects of continuous oral NAC therapy on different Hcy and Cys plasma and urinary forms in 40 healthy subjects assigned to three groups (groups A: n = 13, no therapy; group B: n = 14, NAC 600 mg/day, and group C: n = 14, NAC 1,800 mg/day) for 1 month (T1). After a 1-month washout period without therapy (T2), all subjects were treated with oral NAC (1,800 mg/day) for 2 months and (T3 and T4) reassessed monthly for plasma and urinary thiols. The treated subjects showed a significant decrease in plasma total Hcy and a slight increase in total Cys levels; the alterations of different forms of plasma thiols suggested an NAC-induced increase in disulfide forms and an increase in urinary Hcy and Cys excretion as disulfide forms. The effects appeared to be dose dependent, being more marked in subjects treated with higher dosages. This approach may be important, as an association or alternative therapy in hyperhomocysteinemic conditions of poor responses to vitamins.

Duplex‐Doppler assessment of cirrhosis in patients with chronic compensated liver disease

Portal venous flow velocity (PFV) was measured with duplex‐Doppler equipment in 50 normal subjects and in 117 patients with suspected chronic liver disease who showed no evidence of decompensation such as ascites, hepatic encephalopathy, jaundice or oesophageal bleeding. All the patients underwent percutaneous liver biopsy which demonstrated non‐cirrhotic liver disease in 58 cases (CH‐patients: steatosis 8, persistent chronic hepatitis 8, active chronic hepatitis 42) and liver cirrhosis in the other 59 cases (LC‐patients).

Duplex Doppler ultrasonographic comparison of the effects of propranolol and isosorbide-5-mononitrate on portal hemodynamics.

Eighteen cirrhotic patients with esophageal varices at risk for bleeding took part in a double‐blind study. The variations in PFV induced by either 40 mg of propranolol or 60 mg of sustained‐release isosorbide‐5‐mononitrate on two consecutive days were evaluated with a duplex Doppler device. Both drugs caused a significant decrease in maximum (propranolol, P = 0.002; isosorbide‐5‐mononitrate, P = 0.021). Four patients responded to propranolol, three to isosorbide‐5‐mononitrate, and eight to both drugs; three did not show any change. Duplex Doppler sonography may be of use in the selection of the right pharmacologic treatment for the individual patient for the prevention of a bleeding esophageal varix.

Missed treatment in an Italian HBV infected patients cohort: HBV RER

BACKGROUND AND AIMS Very little is known about the access to treatment for Chronic Hepatitis B in the real clinical practice and the characteristics of the patients who do not receive antiviral therapy. METHODS HBV-RER is an observational multicenter network that collected data of patients with HBV infection during a 3 years observational period (2009-2012). RESULTS Among 2527 HBsAg positive patients, 1099 were never treated (NT); only 280 were included in the analysis due to different exclusion causes A minority was HBeAg-positive. The median age was 42. At liver biopsy most patients had Metavir score of F0-F1. Univariate analysis between 280 NT patients and the 290 naïve to treatment showed that NT patients were mostly female (P=0.002), not Italian (P=0.044), younger (P<0.001). Metavir score was lower in NT (P0.002), such as the Fib4 score (P<0.001). HBV DNA level was significantly higher in NT. At multivariate analysis, independent variables associated with no-treatment were younger age, female gender, Metavir score F0-F1, Fib4 lower than 1.6 and lower blood level of HBV-DNA. CONCLUSIONS There is a large number of patients eligible to treatment who do not receive it. A younger age and a less severe disease seem to be associated to deferral of treatment.