Can Helicobacter pylori eradication regimens be shortened in clinical practice? An open-label, randomized, pilot study of 4 and 7-day triple therapy with rabeprazole, high-dose levofloxacin, and tinidazole.

BACKGROUND: Rabeprazole is a proton pump inhibitor which is particularly suitable for use in short-term Helicobacter pylori eradication treatment. Levofloxacin-based H. pylori eradication regimens have shown good efficacy and very few side effects. Shorter treatment and absence of significant side effects should improve compliance to therapy and increase the Hp H. pylori eradication rate. AIMS: To evaluate the effectiveness of 2 rabeprazole-based H. pylori eradication regimens in an open-label, randomized study carried out in a clinical practice setting. METHODS: One hundred sixty-nine consecutive, treatment-naive patients with H. pylori infection were randomized to receive rabeprazole (20 mg, bid), levofloxacin (500 mg, bid), and tinidazole (500 mg, bid) for either 4 [4-d rabeprazole, levofloxacin, tinidazole (RLT), n=85] or 7 days (7-d RLT, n=84). Before treatment, all patients underwent upper digestive endoscopy. Cure rates were assessed by means of C-urea breath test. and were compared with the eradication rate obtained with standard triple therapy in our Unit (ie, 78%) and average eradication rate reported in the literature (ie, 79%). RESULTS: The intention-to-treat eradication rates were 94% [87% to 98%, 95% confidence interval (CI)] and 95% (88% to 99%, 95% CI) in the 4-day RLT and 7-day RLT regimens, respectively, whereas per-protocol eradication rates were 95% (88% to 99%, 95% CI) in the 4-day RLT and 96% (90% to 99%, 95% CI) in the 7-day RLT. Both treatment regimens obtained significantly higher eradication rates as compared with standard triple therapy. The 4-day RLT showed significantly fewer side effects. CONCLUSIONS: In a clinical practice setting, both 4-day and 7-day rabeprazole, high-dose levofloxacin, tinidazole-based regimens achieved relevant H. pylori eradication rates in treatment-naive patients. The lower number of side effects makes the shorter treatment regimen preferable over the conventional 7-day 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.

A 10-day levofloxacin-based therapy in patients with resistant Helicobacter pylori infection: a controlled trial.

BACKGROUND & AIMS: Antibiotic resistance is a major issue in anti- Helicobacter pylori treatment. This study was aimed at assessing the efficacy of 2 therapies in patients with resistant H pylori infection. METHODS: Patients who had failed 1 or more eradication regimens underwent upper gastrointestinal endoscopy and 2 antral and 2 corpus biopsy specimens were taken for histology and culture. Metronidazole, clarithromycin, and amoxicillin resistance were determined by E-test. Patients were randomly assigned to 2 therapies: 1 group received pantoprazole 40 mg, amoxicillin 1 g, levofloxacin 250 mg, all twice daily for 10 days, and the other group was treated with omeprazole 20 mg twice daily for the first week and omeprazole 20 mg twice daily, tetracycline 250 mg 4 times daily, metronidazole 500 mg twice daily, and bismuth subcitrate 240 mg twice daily for the second week. Therapeutic success was evaluated by 13C urea breath test after 4 weeks of treatment. RESULTS: We enrolled 44 patients in the levofloxacin-based regimen and 46 patients in the quadruple therapy. The former was successful in 31 of 44 (70%; 95% confidence interval: 53-87) and the latter in 17 of 46 (37%; 95% confidence interval: 23-47) patients, using intention-to-treat (ITT) analysis (P < .001). The rates of H pylori resistance to metronidazole, clarithromycin, and amoxicillin were 46%, 12%, and 0%, respectively. Resistance to both metronidazole and clarithromycin was found in 10% of cases. CONCLUSIONS: Triple therapy containing levofloxacin was better than quadruple therapy. The 70% success rate observed indicates that 10 days of pantoprazole, amoxicillin, and levofloxacin should be considered in patients who had failed 1 or more eradication regimens.

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.

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.