HOMA, BMI, and Serum Leptin Levels Variations during Antiviral Treatment Suggest Virus-Related Insulin Resistance in Noncirrhotic, Nonobese, and Nondiabetic Chronic Hepatitis C Genotype 1 Patients.

Objective. To investigate the relationship between insulin resistance and viral load decay in nondiabetic and noncirrhotic genotype 1 chronic HCV patients during peginterferon and ribavirin treatment and the possible influence of BMI and leptin as metabolic confounders. Methods. 75 consecutive noncirrhotic, nonobese, and nondiabetic patients with genotype 1 chronic hepatitis C treated with peginterferon alpha 2a plus ribavirin were evaluated. HOMA-IR, serum leptin, and BMI were measured in all patients at baseline and at weeks 12 and 48, whereas viral load was measured at the same time points and then 24 weeks after the end of treatment. Results. HOMA-IR was significantly associated with both BMI and leptin at baseline. During peginterferon plus ribavirin treatment, there was a significant reduction of HOMA-IR at weeks 12 and 48 from baseline (P = 0.033 and 0.048, resp.) in patients who achieved an early viral load decay (EVR), a trend not observed in patients who not achieved EVR. No variations during treatment were observed regarding BMI and leptin irrespective of EVR. Conclusion. The early reduction of HOMA-IR but not of BMI and leptin during antiviral treatment in noncirrhotic, chronic hepatitis C genotype 1 patients who achieved EVR suggests a viral genesis of insulin resistance in patients with nonmetabolic phenotype.

Are metabolic factors still important in the era of direct antiviral agents in patients with chronic hepatitis C?

The high rate of sustained viral response (SVR) to boceprevir or telaprevir-based triple therapy in hepatitis C (HCV)-related, non-cirrhotic naïve patients or relapsers to previous antiviral treatment leads clinicians to believe that the impact of metabolic host factors on SVR is minimal when triple therapy is used, unlike what is observed with the peginterferon and ribavirin schedules. This concept is strongly expressed by some opinion leaders on the basis of the data derived from sub-analyses of registrative trials as well as from a post-hoc analysis of the phase II C208 clinical trial. The perception of unrestrainable therapeutic success with the use of newer, more powerful antivirals is now reinforced by the brilliant results obtained with sofosbuvir, an HCV NS5B polymerase inhibitor, as well as by the data from the phase II and III studies on the various combinations of second-generation NS3/4A inhibitors and NS5A and/or NS5B inhibitors. However, a great deal of concern has emerged from the real world scenario in which patients are often older and have more comorbidities than patients in the "world of trials". Furthermore, many of them have advanced fibrosis and previous failure with peginterferon and ribavirin treatment. Some data from the recent literature suggest that the host metabolic factors may play a minor but non-negligible role in these difficult-to-treat patients, an issue that will hopefully be investigated in further studies. This editorial aims to provide a detailed analysis of the role that host metabolic factors played in the past and what role they may play in the era of direct antiviral agents.

Therapy of chronic hepatitis C with PEG-IFN α-2b plus ribavirin in patients with genotype 2 or 3: 16 versus 24 weeks, clinical outcome and direct cost analyses.

INTRODUCTION: Short antiviral therapy has been proposed for patients with chronic hepatitis C, easy genotypes, low fibrosis score, low viral load at baseline, and rapid virological response (RVR). However, this approach is not completely accepted. OBJECTIVES: The aims of this study were (a) to evaluate the sustained virological response (SVR) in noncirrhotic patients with genotype 2 or 3, achieving an RVR, randomized to receive pegylated-interferon (IFN) α-2b plus ribavirin for either 16 or 24 weeks and (b) to carry out direct cost analysis comparing patients treated for 16 versus 24 weeks. RESULTS: Of the 142 initially evaluated patients, 130 were enrolled according to the selection criteria, but independent of the viral load. According to the intention-to-treat analysis, SVR was achieved in 104 patients (80%). Logistic regression analysis showed that RVR (P<0.001) and genotype 2 (P<0.03) were the most important factors independently associated with SVR. Among patients with RVR, SVR was comparable between patients treated for 16 weeks and those treated for 24 weeks (86.2 vs. 89.7%, P=NS). The mean direct costs were €4003.7 for patients treated for 16 weeks and €5676.7 for those treated for 24 weeks, with a 30% difference between the two arms. CONCLUSION: In patients achieving an RVR, a 16-week treatment with pegylated-interferon plus ribavirin was comparable to a 24-week treatment. Short treatment in patients with RVR allows us to save 30% of the direct costs, independent of the viral load at baseline.

Hepatitis B Reactivation in a HBsAg-Negative, HBcAb-Positive Patient Receiving Fludarabine for the Treatment of Chronic Lymphocytic Leukaemia.

Hepatitis B virus (HBV) reactivation is an increasingly recognized cause of morbidity and mortality in patients undergoing chemotherapy. In haematology, the risk of reactivation of B hepatitis among HBsAg-positive patients has been documented; therefore, use of lamivudine prophylaxis is recommended before starting chemotherapy. Differently, for HBsAg-negative patients with markers of previous HBV infection (i.e., presence of isolated anti-HBc positivity) (anticore patients) management strategies are not univocal. We describe a rare case of HBV reactivation in an anticore patient after fludarabine therapy for chronic lymphocytic leukaemia. The patient fully recovered after a 6-month course of lamivudine with persistent HBV-DNA clearance and loss of HBsAg. The most important feature of this case is that fludarabine alone infrequently determines HBV reactivation, especially in anticore patients. Therefore, we suggest that patients candidates to receive fludarabine therapy should be considered for lamivudine prophylaxis, not only if HBsAg-positive, but even if anticore-positive only.

Insulin resistance predicts rapid virological response in non-diabetic, non-cirrhotic genotype 1 HCV patients treated with peginterferon alpha-2b plus ribavirin.

BACKGROUND/AIMS: The rapid decline in hepatitis C virus RNA is crucial for determining the outcome of therapy in patients with genotype 1 chronic hepatitis C. However, the variables influencing the early phase of viral decay are still largely unexplored. We aimed to assess which pre-treatment variable may predict rapid virologic response (RVR) and sustained virologic response (SVR). METHODS: We evaluated 90 consecutive non-diabetic patients with genotype 1 chronic hepatitis C without cirrhosis, treated with peginterferon alpha-2b plus ribavirin. Viral load (COBAS Amplicore, Roche) was measured at 1, 4 and 12 weeks after starting treatment, and then 24 weeks after the end of treatment. RESULTS: The overall SVR was 47%. The SVR in patients with RVR was 100%. Age, GGT levels, viral load, steatosis, fibrosis and HOMA-IR were significantly associated with RVR in univariate analysis. After logistic regression, HOMA-IR proved to be the strongest independent predictor of RVR (OR 0.37, 95% CI: 0.16-0.89; p=0.027), whereas fibrosis had a weaker independent association with RVR (OR 0.32, 95% CI: 0.1-1.04; p=0.057). Among the eight pre-treatment variables, both BMI and steatosis were significantly associated with HOMA-IR, either in univariate or in multivariate analyses. CONCLUSIONS: Our data suggest that insulin resistance is strongly associated with RVR, thus reflecting the important role played by metabolic factors in the early phase of viral kinetics. HOMA-IR would appear to be a useful tool in predicting RVR and should be evaluated at baseline in all chronic hepatitis C patients before initiating antiviral treatment.

Hyaluronic acid and aspartate aminotransferase levels normalized by liver function can reflect sinusoidal impairment in chronic liver disease.

BACKGROUND/AIM: To evaluate the relationship between hyaluronic acid/aminopyrine breath test (HA/ABT) ratio and fibrosis score in chronic hepatitis, and between HA/ABT and clinical staging (child-turcotte-pugh'score, CTP; and model for end stage liver disease, MELD) in cirrhosis, as well as to evaluate the aspartate aminotransferase (AST)/ABT in relation to the HA/ABT. METHODS: We studied 48 patients with histologically proven chronic hepatitis C (CHC) and 35 patients with compensated cirrhosis (CIR). RESULTS: HA/ABT and AST/ABT showed a more significant correlation with the fibrosis score than HA or ABT or AST alone in the 48 CHC patients: r=0.568 (P<0.0001), r=0.610 (P<0.0001), r=0.450 (P=0.0021), r=-0.449 (P=0.0021), and r=0.472(P=0.0012), respectively. Progressive liver damage (fibrosis 1-2 vs fibrosis 3-6 vs cirrhosis) was significantly (P<0.05) reflected by both HA/ABT (mean+/-SEM: 4.0+/-0.9 vs 18.1+/-4.2 vs 149.9+/-33.1) and AST/ABT (6.3+/-1.8 vs 12.7+/-1.6 vs 42.1+/-14.6). A strong relationship was found between HA/ABT and AST/ABT (r=0.755 P<0.0001). In cirrhotic patients, the most significant relationship was observed between HA/ABT and CTP r=0.483 and P=0.0049, and MELD r=0.523 and P=0.0023. CONCLUSION: Considering that HA levels in chronic hepatitis depend on the progressive impairment of sinusoidal endothelial cells (SEC), related to progressive fibrosis, HA/ABT ratio would seem to be the most specific reflection of progressive impairment of the SEC. AST/ABT could be used as a possible surrogate of HA in identifying SEC impairment in chronic hepatitis.

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 (to), 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.

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.

Effects of the association of lansoprazole, clarithromycin and metronidazole for helicobacter Pylori eradication therapy, measured by the 13C Aminopyrine breath test.

BACKGROUND: Lansoprazole (LAN) is a proton pump inhibitor drug (PPI) metabolized by the P-450 liver cytochrome (CYP-450) system. LAN is used in association with antimicrobial agents in Helicobacter pylori (HP) eradication therapy. The 13C-Aminopyrine breath test (ABT) is a non-invasive tool exploring liver CYP-450 metabolic activity. Since pharmacological interactions may occur during PPI administration, we attempted to evaluate possible interference with liver CYP-450 activity during HP eradication therapy. MATERIAL/METHODS: Fourteen HP positive patients received LAN (30 mg b.i.d.), clarithromycin (500 mg b.i.d.) and metronidazole (500 mg b.i.d.) for one week. Prior to therapy, and at day 8, each patient underwent 13C-ABT. The 13CO2 concentration in breath samples was measured every 15 minutes from t0 to t120. Results are expressed as cumulative percentage of the administered dose of 13C recovered over time (% 13C dose cum), and as a percentage of the administered dose of 13C recovered per hour (% l3C dose/h). Comparisons were carried out by the Wilcoxon test. Data are presented as mean +/- SD. RESULTS: At day 8, mean ABT was no different from baseline values, both considering % 13C dose cum and% 13C dose/h at each sampling time (e.g.,% 13C dose cum120 which is the most expressive value of the parameters taken into consideration, baseline vs day 8: 10.88 +/- 3.81 vs 10.13 +/- 3.57). CONCLUSIONS: These results show that LAN administration and the concomitant use of antimicrobial drugs during HP eradication therapy do not seem to be associated with significant modifications in liver CYP-450 activity.

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?

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. AIMS: To evaluate and compare the short-term prognostic accuracy of the CTP, the creatinine-modified CTP, and the MELD scores in patients with liver cirrhosis. METHODS: CTP, creatinine-modified CTP, and MELD scores were calculated in a cohort of 145 cirrhotic patients. The creatinine-modified CTP was calculated as follows: we assessed the mean creatinine serum level and standard deviation (SD) of the 145 study patients, then assigned a score of 1 to patients with creatinine serum levels < or = to the mean, a score of 2 to patients with creatinine levels between the mean and the mean+1 SD, and a score of 3 to patients with creatinine levels above the mean+1 SD. The creatinine-modified CTP was then calculated by simply adding each patients' creatinine score to their traditional CTP scores. We calculated and compared the accuracy (c-index) of the three parameters in predicting 3-month survival. RESULTS: The creatinine-modified CTP score showed better prognostic accuracy as compared with the traditional CTP (P=0.049). However, the MELD score proved to be better at defining patients' prognosis in the short-term as compared with both the traditional CTP score (P=0.012) and the creatinine-modified CTP (P=0.047). The excellent short-term prognostic accuracy of the MELD score was confirmed even when patients with abnormal creatinine serum levels were excluded from the analysis (c-index=0.935). CONCLUSIONS: Adding creatinine values to the CTP slightly improves the prognostic usefulness of the traditional CTP score alone. The MELD score has a short-term prognostic yield that is better than what is provided by both the CTP and CTP creatinine-modified scores, even in cirrhotic patients who are not critically ill. The positive results obtained by using the MELD score were confirmed even after excluding patients with impaired renal function.

High ascitic fluid leptin levels in patients with decompensated liver cirrhosis and sterile ascites: relationship with TNF-alpha levels.

Leptin is an adipocyte-derived hormone involved in the homeostasis of body composition. An imbalance in leptin regulation has been observed in patients with liver cirrhosis. We aimed to assess serum and ascitic leptin levels in a group of patients with decompensated liver cirrhosis and to evaluate the relationship of these levels with tumor necrosis factor alpha (TNF-alpha). We assessed both serum and ascitic fluid leptin levels in a series of 16 consecutive patients with liver cirrhosis. We calculated the body mass index (BMI) and assessed body fat (BF) of all patients by means of bioelectric impedence analysis. Leptin levels were analyzed in relationship to biochemical indexes, TNF-alpha levels, and body composition. None of the patients had spontaneous bacterial peritonitis. Both serum and ascites leptin levels were correlated with BMI and BF. On average, ascitic fluid leptin levels (13.1 +/- 10.9 ng/ml) were twice as high as serum levels (7.0 +/- 6.4 ng/ml), and the ascitic fluid/serum ratio of leptin was > 1 in all patients. Serum and ascites leptin levels were positively correlated (rS = 0.675, P = 0.009), while no correlation was observed between leptin and TNF-alpha levels, both in serum and in ascites. Serum and ascites TNF-alpha were not correlated. The ascitic fluid leptin levels of cirrhotic patients with sterile ascites are on average two times higher than circulating levels of this hormone. Noteworthily, they correlate significantly with body composition. These findings seem to suggest that in patients with decompensated liver cirrhosis, intraabdominal production of leptin may contribute to the metabolic picture.

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.

Helicobacter pylori infection is associated with greater impairment of cytochrome P-450 liver metabolic activity in anti-HCV positive cirrhotic patients.

Helicobacter pylori gastric infection has been associated with various digestive and extradigestive diseases. In liver disease bacterial infections have been associated with impairment of cytochrome P-450 liver metabolic activity. Moreover, infection by Helicobacter spp. seems to be linked with the development of hepatocellular carcinoma (HCC) in mice. Our aims were to evaluate the influence of H. pylori infection on cytochrome P-450 liver metabolic activity as assessed by means of monoethylglycinexylidide (MEGX) test and to assess the prevalence of H. pylori infection in patients with HCC. Ninety-six hepatitis C virus (HCV) -positive cirrhotic patients, 36 of whom had HCC, were tested for H. pylori infection by means of anti-H. pylori IgG. Patients underwent the MEGX test. Characteristics of the patients were then analyzed on the basis of the presence of H. pylori infection. Seroprevalence of H. pylori infection was similar between cirrhotic patients without (68%) or with (63.8%) HCC. Mean MEGX values were significantly (P < 0.0001) lower in H. pylori infected patients (18.2 +/- 13.9 ng/ml) as compared to the noninfected ones (46.9 +/- 17.1 ng/ml), independently of Child-Pugh's classification. These differences persisted even after subdividing patients according to the presence of HCC. In conclusion, in anti-HCV positive cirrhotic patients H. pylori infection is associated to an impairment of cytochrome P-450 liver metabolic activity. Seroprevalence of H. pylori infection in HCC patients is similar to that observed in tumor-free cirrhotics.

Validity and clinical utility of the aspartate aminotransferase-alanine aminotransferase ratio in assessing disease severity and prognosis in patients with hepatitis C virus-related chronic liver disease.

BACKGROUND: The aspartate aminotransferase-alanine aminotransferase ratio (AST/ALT ratio) has been used to noninvasively assess the severity of disease in patients with chronic liver disease (CLD). We previously demonstrated that progressive liver functional impairment is associated with an increase in the AST/ALT ratio. OBJECTIVES: To evaluate the reproducibility and transportability of the AST/ALT ratio in a large cohort of patients with different degrees of hepatitis C virus (HCV)-related CLD, to confirm the correlation between progressive impairment of liver function and increase in the AST/ALT ratio, to evaluate whether diagnostic accuracy of the ALT/AST ratio can be improved by using it with other biochemical variables, and to assess the 1-year prognostic capability of the AST/ALT ratio in patients with liver cirrhosis. PATIENTS AND METHODS: We retrospectively evaluated 252 patients with HCV-related CLD. The AST/ALT ratio was correlated with the degree of liver fibrosis in patients with chronic hepatitis and with the Child-Pugh score in patients with cirrhosis. All patients had undergone monoethylglycinexylidide (MEGX) testing to evaluate liver function. We assessed the prognostic ability of the AST/ALT ratio in a subset of 63 cirrhotic patients who were followed up for at least 1 year. RESULTS: The AST/ALT ratio was more frequently 1 or higher in cirrhotic patients (P<.001). There was a significant correlation between MEGX values and the AST/ALT ratio (r(s) = -0.621, P<.001). Multivariate stepwise logistic analysis showed that AST/ALT ratio, platelet count (PLT), MEGX values, and prothrombin activity were independently associated with the presence of cirrhosis. Combined assessment of the AST/ALT ratio and/or PLT obtained 97.0% positive predictive value and 97.9% negative predictive value for the diagnosis of cirrhosis. The AST/ALT ratio had 81.3% sensitivity and 55.3% specificity in identifying cirrhotic patients who died within 1-year of follow-up. CONCLUSIONS: The AST/ALT ratio is both reproducible and transportable in patients with HCV-related CLD. The AST/ALT ratio is correlated with both histologic stage and clinical evaluation. Progressive liver functional impairment is reflected by an increase in the AST/ALT ratio. Noninvasive evaluation by means of the combined AST/ALT ratio and PLT assessment misclassifies only a few cirrhotic patients. In cirrhotic patients, the AST/ALT ratio provides medium-term prognostic information that is no different from that provided by established prognostic scores.

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.

OBJECTIVES: 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 (r(s) = 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 I 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.

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.