Paolo Borro

Serum thrombopoietin levels are linked to liver function in untreated patients with hepatitis C virus-related chronic hepatitis

BACKGROUND Thrombocytopenia can be found in patients with chronic hepatitis related to hepatitis C virus (HCV). Both hypersplenism and decreased liver production of thrombopoietin (TPO) have been hypothesized as mechanisms responsible for thrombocytopenia. AIMS To assess the presence of relationships among platelet count, spleen size, TPO serum levels, liver histology, and liver function in a group of patients with HCV-related chronic hepatitis. METHODS Platelet count, TPO serum levels, and spleen size were assessed in 25 untreated HCV positive chronic hepatitis patients undergoing liver biopsy. These parameters were correlated to liver histology and liver function as evaluated by means of [(13)C]aminopyrine breath test (ABT). RESULTS Both platelet counts (146 +/- 48 vs. 202 +/- 56 x 10(9)/1, P < 0.03) and TPO serum levels (103 +/- 24 vs. 158 +/- 7 1 pg/ml, P < 0.02) were lower among patients with high fibrosis scores as compared to patients with low fibrosis scores. Patients with thrombocytopenia as well as patients with high fibrosis scores had lower ABT results as compared to patients with normal platelet counts and patients with no or mild fibrosis, respectively. TPO serum levels were correlated to platelet count (r(s) = 0.493, P = 0.016), and negatively correlated to fibrosis stage (r(s) = -0.545, P = 0.008). Lastly, low TPO serum levels were associated to a decrease in liver function. CONCLUSIONS Our study showed that in patients with chronic hepatitis related to HCV infection serum TPO levels are correlated to liver functional impairment and to the degree of liver fibrosis.

Comparative effects of levosulpiride and cisapride on gastric emptying and symptoms in patients with functional dyspepsia and gastroparesis

The efficacy of several prokinetic drugs on dyspeptic symptoms and on gastric emptying rates are well‐established in patients with functional dyspepsia, but formal studies comparing different prokinetic drugs are lacking.

Relationship between thrombopoietin serum levels and liver function in patients with chronic liver disease related to hepatitis C virus infection

OBJECTIVES:Thrombopoietin (Tpo) is an important regulator of megakaryocyte maturation and platelet production, and is mainly produced by the liver. A decrease in Tpo production is partly responsible for the thrombocytopenia observed in patients with chronic liver disease (CLD). The aim of this study was to evaluate the relationship between Tpo serum levels and liver function in patients with CLD related to hepatitis C virus (HCV) infection.METHODS:We studied 37 patients with various degrees of HCV-related CLD. Of the patients, 17 had chronic hepatitis and 20 liver cirrhosis. Liver function was evaluated in all patients by the following hepatic blood flow dependent and independent tests that explore various hepatic metabolic functions: carbon-13 (13C)–aminopyrine breath test (13C-ABT), 13C-galactose breath test (13C-GBT), and monoethylglycinexylidide (MEGX) test. Liver function tests results were correlated with Tpo serum levels.RESULTS:Tpo serum levels were significantly lower in patients with liver cirrhosis (88 ± 23 pg/ml) as compared to those in patients with chronic hepatitis (128 ± 55 pg/ml, p = 0.0031). However, they did not correlate with serum albumin, bilirubin, or prothrombin activity. Tpo serum levels showed a significant positive correlation with 13C-ABT results (hourly dose at 30 min, rs= 0.489, p = 0.002; cumulative dose at 120 min, rs= 0.425, p = 0.008). Moreover, they showed a fair, positive correlation with 13C-GBT hourly dose at 30 min (rs= 0.366, p = 0.028), and a trend toward a positive correlation with the various MEGX test sampling times (MEGX15, rs= 0.314, p = 0.059; MEGX30, rs= 0.284, p = 0.088; and MEGX60, rs= 0.320, p = 0.059).CONCLUSIONS:In this study we have shown that a progressive decline in liver function in patients with HCV-related CLD is paralleled by a decrease in Tpo production. The different correlations observed between Tpo and the various liver function tests suggests that this finding is mainly the result of a decrease in hepatic functional mass rather than dependent on alteration in splanchnic hemodynamic.

13C-galactose breath test and 13C-aminopyrine breath test for the study of liver function in chronic liver disease

BACKGROUND AND AIMS Liver biopsy examination is the gold standard to diagnose the presence of cirrhosis. The aim of this study was to evaluate the accuracy of both 13 C-aminopyrine breath test ( 13 C-ABT) and 13 C-galactose breath test ( 13 C-GBT) in the noninvasive assessment of the presence of cirrhosis in patients with chronic liver disease. METHODS We evaluated 61 patients with chronic liver disease of diverse etiologies (21 compensated cirrhosis). All patients underwent 13 C-GBT and 13 C-ABT, and the results were expressed as a percentage of the administered dose of 13 C recovered per hour (%dose/h) and as the cumulative percentage of administered dose of 13 C recovered over time (%dose cumulative). Results were analyzed according to absence vs presence of cirrhosis. RESULTS On average, 13 C-GBT %dose/h and %dose cumulative were decreased significantly in patients with compensated cirrhosis, and the same finding was observed for 13 C-ABT results from 30 to 120 minutes. 13 C-GBT %dose/h at 120 minutes had 71.4% sensitivity, 85.0% specificity, and 83.7% accuracy, whereas 13 C-ABT %dose cumulative at 30 minutes had 85.7% sensitivity, 67.5% specificity, and 77.1% accuracy for distinguishing between the 2 subgroups of patients. Combined assessment of 13 C-GBT and 13 C-ABT increased the diagnostic accuracy (80% positive predictive value) of either test alone and reached 92.5% specificity and 100% sensitivity for the diagnosis of cirrhosis. CONCLUSIONS In patients with chronic liver disease, both 13 C-GBT and 13 C-ABT are useful for the diagnosis of cirrhosis. Combination of the tests increases the diagnostic yield of each test alone.

Stool antigen assay (HpSA) is less reliable than urea breath test for post-treatment diagnosis of Helicobacter pylori infection

Background : The diagnostic yield of the stool antigen test (HpSA) in evaluating the results of Helicobacter pylori eradication therapy is controversial, but many studies have used only the 13C‐urea breath test (13C‐UBT) as a gold standard which has greatly reduced their relevance.

Alcohol and hepatocellular carcinoma:A review and a point of view

It is well recognized that one cause of chronic liver disease and hepatocellular carcinoma (HCC) is alcohol consumption. Research in Italy and the United States concludes that the most common cause of HCC (responsible for 32% to 45% of HCC) is alcohol. It has recently been shown that a significant relationship between alcohol intake, metabolic changes, and hepatitis virus infection does exist. Alcohol may be a factor in the development of HCC via direct (genotoxic) and indirect mechanisms (cirrhosis). There is only one way of diagnosing HCC, which is early identification through surveillance, when curative treatments become possible. After stopping alcohol intake the risk of liver cancer decreases by 6% to 7% a year, and an estimated time period of 23 years is also needed. Therefore, surveillance is also important in former drinkers and, in our opinion, independently from the presence of compensated cirrhosis. In cases of very early stage (VES) and early stage with portal hypertension, liver transplantation is the optimal option; and in cases of associated disease, percutaneous ethanol injections, radiofrequency and microwave ablation are the ideal treatments. Despite the possibility of detecting microvascular invasion with HR, several studies and some randomized controlled trials revealed that overall survival and DSF rates in patients with VES HCC are much the same after ablation and HR. Therefore, ablation can be regarded as a first-line choice for patients with VES HCC. It is important to emphasize that the choice of treatment should be weighed carefully in the context of a multidisciplinary cancer team.

Altered oxidative stress/antioxidant status in blood of alcoholic subjects is associated with alcoholic liver disease

BACKGROUND Oxidative stress is implicated in pathogenesis of alcoholic liver disease (ALD). This study investigated the possible correlation among the erythrocyte indices of oxidative stress, the leukocyte panels of antioxidant proteins (metallothioneins), the serum biochemical parameters and the liver steatosis grade. METHODS A total of 118 cases including 60 alcoholic subjects and 58 controls were enrolled. All the alcoholic subjects were screened for body mass index (BMI), liver steatosis, and blood chemistry and serology. The level of oxidative stress and oxidative stress-related parameters were measured in the blood and correlated with clinical findings. RESULTS Alcoholic subjects showed higher BMI, moderate/severe hepatic steatosis, increase in the levels of triglycerides, cholesterol, glucose, γ-glutamyl-transpeptidase (GGT), alanine aminotransferase (ALT), bilirubin, alpha 1 and beta 2 globulins, iron and a decrease in the levels of aspartate aminotransferase (AST) and beta 1 globulin with respect to the reference values. Moreover, alcoholic subjects showed: (i) an increase in Thiobarbituric Acid Reactive Substance (TBARS) content representing a good estimation of global oxidative stress; (ii) a stimulation of the activities of the antioxidant enzymes catalase and SOD; (iii) a modulation of expression of metallothioneins, with a down-regulation of MT-1A and an up-regulation of MT-1E isoforms. CONCLUSIONS Our data suggest that alcoholism is strongly associated with altered pattern of blood metallothioneins; this parameter combined with the score calculated by an ad hoc implemented algorithm (HePaTest) could offer a non-invasive alternative approach for evaluating alcohol-related damages and could be used in follow-up of alcoholic patients.

Clinical and virological survey of patients with hepatitis B surface antigen in an Italian region: clinical considerations and disease burden.

The aim of this study was to determine the prevalence of hepatitis B virus (HBV) infection in an Italian region, Liguria (1,572,000 inhabitants), by means of a network of 12 referral centers for liver diseases. All patients with HBV surface antigen followed throughout 2006 were included. Personal data, infectious status with risk factors, other non‐infectious risk factors for liver disease, clinical status, and treatment were the questionnaire. Four hundred forty‐five patients (71% male) were evaluated. Their median age was 48 years (range 5–84), and 83.4% were of Italian origin. Community‐acquired infection was the principal mode of HBV transmission (82.5%), followed by previous intravenous drug use (9.4%), perinatal transmission (6.3%), and transfusion‐associated transmission (1.8%). Hepatitis B e‐antigen was present in 20.4% of the patients, while co‐infections with hepatitis D virus and/or hepatitis C virus and/or human immunodeficiency virus (HIV) were observed in 18.7% of the patients. Chronic active hepatitis was present in 62.5% of the patients, cirrhosis in 13.5%, hepatocellular carcinoma in 2.2%, and 21.8% of the patients were inactive carriers of HBV. In all, 42.5% of the patients were treated with interferon or lamivudine and/or adefovir‐dipivoxil. Forty‐nine patients were co‐infected with HIV (86% on highly active antiviral therapy). Nevertheless, this study identified only 2.2% of the expected patients with HBV. Hence, it has to be reasoned that few potential infectious or treatable patients are referred to liver disease centers. HBV infection is still an underestimated health problem, and few potential infectious or treatable patients are referred to tertiary centers. J. Med. Virol. 81:1882–1886, 2009.

Impairment of cytochrome P-450-dependent liver activity in cirrhotic patients with Helicobacter pylori infection

Helicobacter pylori gastric infection has been associated with various digestive and extra‐digestive diseases. The systemic influence of gastric H. pylori infection seems to be mediated by the release of various cytokines. In liver disease, bacterial infections have been associated with the impairment of liver metabolic function.

Liver Disease and Hepatocellular Carcinoma in Alcoholics: The Role of Anticraving Therapy.

Alcohol is the main risk factor for death and disability. The treatment of alcohol dependence (AD) is a complex activity as the variables are numerous; however, those which must necessarily be taken into account are the type of AD, the internal comorbidities and the presence of any psychiatric comorbidity. Liver problems are one of the most common causes of alcohol-related liver damage. 45% of deaths from cirrhosis are alcohol-related. Thus, the treatment of AD must often deal with a more or less severe liver disease, which influences the choice of anticraving drug. As chronic liver disease is often present, and as in a substantial proportion of cases, because there is a correlation with viral infections or with hepatocellular carcinoma (HCC), it is clear that hepatologists should make use of nonhepatotoxic molecules. In cases of mild liver disease, all available drugs might be used, but we recommend caution because the liver is usually fragile due to the harmful abuse of alcohol. In the advanced liver disease, the choice of treatment is reduced. A psychosocial approach such as attending support groups could be the first choice. In cases of compensated cirrhosis with or without HCC, or in cases of HCC without cirrhosis, metadoxine, acamprosate and baclofen can be used. In decompensated forms the only drug tested to date has been baclofen. In alcohol-related liver disease a professional team with hepato-alcohologists is also necessary, especially for liver transplantation programs.