Alessandra Fumagalli

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.

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‐Aminopyrine breath test to evaluate severity of disease in patients with chronic hepatitis C virus infection

There are few data on the use of the 13C‐aminopyrine breath test to evaluate the severity of disease in patients with hepatitis C virus‐related chronic liver disease, although these patients represent one of the most important problems in clinical hepatology.

The 1-year and 3-month prognostic utility of the AST/ALT ratio and model for end-stage liver disease score in patients with viral liver cirrhosis

OBJECTIVE:The AST/ALT ratio has shown good diagnostic accuracy in patients with chronic viral liver disease. However, its prognostic utility has never been tested. Recently, the Model for End-Stage Liver Disease (MELD) has been proposed as a simple and effective tool to predict survival in patients with liver cirrhosis. The aims of this study were to assess the 3-month and 1-yr prognostic ability of the AST/ALT ratio in a series of patients with virus-related liver cirrhosis, and to evaluate the relationship between the AST/ALT ratio and the MELD score and to compare their prognostic ability.METHODS:The AST/ALT ratios and MELD scores of 99 patients with liver cirrhosis of viral etiology (73 patients with hepatitis C virus and 26 with hepatitis B virus) who had been followed-up for at least 1 yr were retrospectively calculated and correlated with the patients’ 3-month and 1-yr prognosis. Receiver operating characteristic curves were used to determine the AST/ALT ratio and the MELD score cut-offs with the best sensitivity (SS) and specificity (SP) in discriminating between patients who survived and those who died. Univariate survival curves were estimated by the Kaplan-Meier method using the cut-offs identified by means of receiver operating characteristic curves.RESULTS:AST/ALT ratios and MELD scores showed a significant correlation (rs= 0.503, p = 0.0001). In all, 8% and 30% of the patients had died after 3 months and 1 yr of follow-up, respectively. AST/ALT ratios and MELD scores were significantly higher among the patients who died during both 3-month and 1-yr follow-up. An AST/ALT ratio cut-off of 1.17 had 87% SS and 52% SP, whereas a MELD cut-off of 9 had 57% SS and 74% SP in discriminating between patients who survived and those who died after 1 yr. The combined assessment of the AST/ALT ratio and/or MELD score had 90% SS and 78% SP. Survival curves of the patients showed that both parameters clearly discriminated between patients who survived and those who died in the short term (AST/ALT ratio, p = 0.0094; MELD score, p = 0.0089) as well as in the long term (AST/ALT ratio, p < 0.0005; MELD score, p = 0.004).CONCLUSIONS:In patients with virus-related cirrhosis, the AST/ALT ratio has prognostic capability that is not significantly different from that of an established prognostic score such as MELD. Combined assessment of the two parameters increases the medium-term prognostic accuracy.

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.

Can inclusion of serum creatinine values improve the Child–Turcotte–Pugh score and challenge the prognostic yield of the model for end‐stage liver disease score in the short‐term prognostic assessment of cirrhotic patients?*

Abstract: Background: The model for end‐stage liver disease (MELD) score is a useful tool to assess prognosis in critically ill cirrhotic patients. However, its short‐term prognostic superiority over the traditional Child–Turcotte–Pugh (CTP) score has not been definitely confirmed. The creatinine serum level is an important predictor of survival in patients with liver cirrhosis.

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.

Influence of 1-week Helicobacter pylori eradication therapy with rabeprazole, clarithromycin, and metronidazole on 13C-aminopyrine breath test

Helicobacter pylori eradication therapy is commonly prescribed in the general population. Treatment consists of drugs that are mainly metabolized by the liver cytochrome P-450 (CYP) enzymatic pool. Most H. pylori-infected patients often take drugs for comorbid illnesses, therefore increasing the potential for drug–drug interactions. We aimed to evaluate the interactions of rabeprazole, clarithromycin, and metronidazole 1-week H. pylori eradication therapy with CYP-dependent liver metabolic function in clinical practice. Ten patients referred to our unit for H. pylori infection underwent 1-week eradication therapy with rabeprazole (20 mg, b.i.d.), clarithromycin (500 mg, b.i.d.), and metronidazole (500 mg, b.i.d.). We chose the 13C-aminopyrine breath test (13C-ABT) to evaluate CYP-dependent liver function since it is noninvasive and nonharmful. All patients underwent 13C-ABT at three time points: before therapy (t0), at the end of therapy (t8), and after 1 month of follow-up (t38). Mean 13C-ABT dose/hr (t0 = 14.0 ± 5.4, t8 = 13.5 ± 4.0, t38 = 16.1 ± 5.6) as well as 13C-ABT cumulative dose (t0 = 2.4 ± 1.1, t8 = 2.4 ± 0.8, t38 = 2.6 ± 1.0) were not statistically different at the three time points of the study. These results did not seem to be influenced by drugs being administered concomitantly. In everyday clinical practice rabeprazole-based H. pylori eradication therapy does not seem to display any significant interactions with CYP-dependent liver function, even in patients on multiple drugs.