Paolo Conca

Non-alcoholic fatty liver disease: Further expression of the metabolic syndrome

Non‐alcoholic fatty liver disease has been associated with metabolic disorders, including central obesity, dyslipidema, hypertension and hyperglycemia. Metabolic syndrome, obesity, and insulin resistance are major risk factors in the pathogenesis of non‐alcoholic fatty liver disease. Non‐alcoholic fatty liver disease refers to a wide spectrum of liver damage, ranging from simple steatosis to non‐alcoholic steatohepatitis, advanced fibrosis and cirrhosis.

Could inflammatory markers help diagnose nonalcoholic steatohepatitis

Background Nonalcoholic fatty liver disease describes a set of conditions that range from fatty liver to nonalcoholic steatohepatitis (NASH), and is considered the hepatic manifestation of metabolic syndrome. Obesity and insulin resistance are strongly associated with systemic markers of inflammation. Objective Focusing on this aspect, we have attempted to find a noninvasive method that could likely assess the presence of NASH and help to decide the liver biopsy performance. Methods Using histology as a gold standard to diagnose nonalcoholic fatty liver disease, we consecutively studied 43 patients with NASH and 40 with fatty liver, comparing their data with those of 48 healthy control participants. The outcomes evaluated were ultrasonographic spleen longitudinal diameter coupled with the splenic artery resistive index, serum IL-6 and vascular endothelial growth factor concentrations. Results The NASH group had higher spleen longitudinal diameter values (P=0.0001) as well as significantly higher IL-6 and vascular endothelial growth factor concentrations than the other groups (P=0.0001). The optimal cut-off value for spleen longitudinal diameter that best discriminated NASH from fatty liver patients was 116 mm (specificity 95% and sensitivity 88%); the sensitivity and specificity of this parameter was better than both IL-6 and vascular endothelial growth factor in the same setting (area under the receiver operating characteristic curve 0.920 vs. 0.817 and 0.678). Splenic artery resistive index was similar between patients with NASH and those with fatty liver, but differed when compared with controls, P=0.0001. Conclusions IL-6 was highly specific in confirming the absence of NASH at normal values. In our series, normal values of spleen longitudinal diameter and IL-6 were strongly associated with fatty liver.

A prospective study of acute drug-induced liver injury in patients suffering from non-alcoholic fatty liver disease

Aim:  Liver damage due to facultative hepatotoxins is scarcely foreseeable. We evaluated the prevalence of acute drug‐induced liver injury (DILI) in a specific setting, assessing eventual interactions with pre‐existing hepatic illnesses.

Metabolic factors involved in the therapeutic response of patients with hepatitis C virus-related chronic hepatitis

Background:  The purpose of the present paper was to investigate the factors possibly involved in the failure of pegylated interferon (Peg IFN) plus ribavirin treatment at standard dosage in hepatitis C virus (HCV) 1b patients, with chronic hepatitis.

What are the implications of the spontaneous spleno-renal shunts in liver cirrhosis?

BackgroundAlthough significant advances are expected to be made in the assessment of the portal hypertension-related complications, the prognostic role of spleno-renal shunts has not been fully explored so far. Clarifying this aspect could help tackle the life-treating events occurring in patients suffering from liver cirrhosis. The aim of the study was to analyze the relationships between the spleno-renal shunts presence at doppler ultrasound and the liver cirrhosis complications.MethodsDesign: eighty one patients out of 129 formed the study population (35 females). Chronic liver damage in these patients was caused by HCV (66), HBV (2), alcohol abuse (2) or unknown etiology, likely non-alcoholic steatohepatitis (11). Setting: two Liver Units of university/primary hospitals in Southern Italy. Main outcome measures: grading of esofageal varices; detection of ascites: assessment of hepatic encephalopathy; evaluation of liver cirrhosis severity; tracking hepatocellular carcinoma; doppler features of spleno-renal shunts and splenic flow velocity; spleen longitudinal diameter at sonography.ResultsThe prevalence of spleno-renal shunts was 18.5%, without no difference concerning the etiology (HCV versus non-HCV, p = 0.870); the prevalence of hepatocellular carcinoma in patients with spleno-renal shunts was superior to that of patients without them (Pearson Chi-square, p = 0.006, power of sample size 74%), also after adjustment for liver decompensation (p = 0.024). The median score of hepatic encephalopathy in patients with and without spleno-renal shunts was similar, i.e., 0 (range, 0-2) versus 0 (0 - 3), p = 0.67. The median splenic vein flow velocity in patients with spleno-renal shunts was significantly inferior to that of patients without them, i.e., 13 cm/sec (95% confidence intervals, 6-18) versus 21 cm/sec (17-24), p < 0.0001. By far the largest percentage of large esophageal varices was in patients without spleno-renal shunts (p = 0.005). In contrast, the frequency of ascites and hepatic encephalopathy severity was overlapping in the two groups. BMI values but not Child-Pughs classification predicted spleno-renal shunts (Ors = 1.84, 95% confidence intervals = 1.28-2.64, p = 0.001 and 1.145, 95% confidence intervals = 0.77-1.51, p = 0.66).ConclusionTaking into consideration the relatively small sample size, patients with spleno-renal shunts are burdened by an increased incidence of hepatocellular carcinoma. BMI predicted the spleno-renal shunts presence.

Serum concentrations of the tissue polypeptide specific antigen in patients suffering from non-alcoholic steatohepatitis

Background  Liver histology is the gold standard for diagnosis of non‐alcoholic fatty liver disease. Ethical considerations and patient choice often preclude performing a liver biopsy, especially considering the rare but potential risk. Searching for a good serological marker substitute for the invasive procedure was the aim of our study. Keratins, mainly 8 and 18, play not only a mere structural role providing mechanical stability to hepatocytes, but also represent a target via toxic stress ultimately inducing apoptosis/necrosis. Tissue polypeptide‐specific antigen (TPS), a serological mirror of keratin 18, is widely used as a marker for various cancers. This antigen was assessed in three different groups who were overweight or obese.

Acute coronary syndrome and severe haemophilia: An unusual association with challenging treatment

Acute coronary syndrome and severe haemophilia: An unusual association with challenging treatment -

Does spleen volume play a role in patients with HCV-related chronic hepatitis?

As the lymphotropism of hepatitis C virus (HCV) has already been ascertained, and in the light of the fact that the immune defense system is an organized network composed of functionally interrelated tissues, this study was carried out to verify the possible involvement of spleen in HCV-related chronic hepatitis. In this cross-sectional study we measured spleen longitudinal diameter by ultrasound, beta2-microglobulin serum levels and splenic artery resistivity index (SARI) by Doppler in 51 patients treated with standard combined (Peg-Interferon plus Ribavirin) antiviral therapy. Thirty-three patients (17 females) completed the regimen and were compared to 31 controls (16 females). The mean basal values of spleen longitudinal diameter were higher in patients with chronic hepatitis than in controls, i.e., 116 mm (9.4) versus 102.7 mm (9.3), P = 0.0001. In the same patients a significant trend towards increased spleen longitudinal diameter was found after antiviral therapy, independently of the stage of HCV-related chronic hepatitis. The median values of the beta2-microglobulin concentrations were not significantly higher in the patients with HCV-related chronic hepatitis compared to controls, i.e., 1.3 (0.5 – 2.6) versus 1 (0.6 – 1.4), P = 0.16, although during the course of therapy they were significantly increased. SARI values of HCV-related chronic hepatitis patients were different from those of controls, but were unvaried compared to values at the end of treatment. Neither spleen measurements nor serum beta2-microglobulin levels were able to predict therapeutic response to antiviral therapy. A stimulation/ expansion of lymphoid tissue was found in patients with HCV-related chronic hepatitis. Such evidence raises the question whether physicians should continue to prescribe antiviral therapy in non-responders and supports the use of a new scheme (SLD plus β2-MG) to diagnose this ongoing, apparently reversible but nevertheless dangerous immunologic process.

Can serum TGF-beta 1 be used to evaluate the response to antiviral therapy of haemophilic patients with HCV-related chronic hepatitis?

Congenital coagulation disorders limit the use of liver biopsy, especially when repeated assessment is needed. TGF-beta 1 plays a pivotal role in inducing fibrosis and has been proposed as its surrogate marker. Aiming at validating the clinical utility of this cytokine, fifteen haemophilic patients suffering from HCV-related chronic hepatitis were treated with Peg-IFN alpha2β plus Ribavirin. Serum TGF-beta 1, viral load and liver enzymes were analyzed at baseline and at six, twelve, and eighteen months. As expected, patients initially showed significantly higher TGF-beta 1 levels than age-matched controls (43.8 ng/mL, 28.7–46.4 vs. 26.9 ng/mL, 23.0–34.0, median and 95% CI; p=0.004). The end of therapy response rate was 67%. The main finding was a significant drop in TGF-beta 1 at six months compared to baseline values; this drop de facto predicted the levels reached in the following six months, which were fixed at lower concentrations (37.0 ng/mL, 21.9–43.8 and 27.0 ng/mL, 24.1–44.0 respectively; p<0.009), independently of treatment outcome (three patients were breakthrough, twelve were sustained virological responders (SVRs). During the treatment period none had clinical or biochemical signs of inflammation in other areas. Treatment was followed by a six-month follow-up, at the end of which TGF-beta 1 was increased compared to the previous values, reaching the initial levels in ten SVRs (45 ng/mL, 24.5–52.9). Interestingly, at a longer follow-up, two out of ten SVRs, who displayed the highest values of TGF-beta 1, relapsed. Serum TGF-beta 1 could be used to assess therapeutic outcome and short-term prognosis of HCV-related chronic hepatitis.

Could High Levels of Tissue Polypeptide Specific Antigen, a Marker of Apoptosis Detected in Nonalcoholic Steatohepatitis, Improve after Weight Loss?

Background: Tissue Polypeptide Specific antigen has recently been proposed as diagnostic marker of apoptosis in NonAlcoholic SteatoHepatitis. The aim of this study was to validate in patients suffering from NonAlcoholic SteatoHepatitis the clinical utility of this marker after different programs of weight reduction. Methods: Overweight/obese patients with visceral adiposity and liver histology compatible were assigned to a Calorically-Restricted diet (n = 22), a Calorically-Restricted diet plus EXercise (n = 19) or No Healthy Life Style (control group, n = 21) for six months. The presence of Body-Weight loss was assessed by a Body Mass Index decrease of at least three points. Serum ALanine aminoTransferase, HOmeostasis Model Assessment method value and Tissue Polypeptide Specific antigen concentrations were determined at time 0, after 3 and 6 months in both the Intervention groups and in the controls’ one. Results: In NonAlcoholic SteatoHepatitis patients who obtained Body-Weight reduction, a significant decrease of the serum Tissue Polypeptide Specific antigen values was showed with a clear linear trend across time, P = 0.0001. Decrement of Tissue Polypeptide Specific antigen concentrations best differentiated the Body-Weight loss from the body-weight maintenance in respect to Tissue Polypeptide Specific antigen and HOmeostasis Model Assessment method values. Conclusion: This study support the clinical utility of serum Tissue Polypeptide Specific antigen antigen levels in the follow-up of overweight/obese patients with NonAlcoholic SteatoHepatitis on weight reduction programs.