HERACLIS-HDV cohort for the factors of underdiagnosis and prevalence of hepatitis D virus infection in HBsAg-positive patients.

BACKGROUND AND AIMS: Hepatitis D virus (HDV) underdiagnosis remains common. We assessed the HDV screening and prevalence rates in HBsAg-positive patients seen at tertiary liver centres throughout Greece as well as factors affecting HDV diagnosis. METHODS: All adult HBsAg-positive patients seen within the last 5 years were included. Non-screened patients who visited or could be recalled to the clinics over a 6-month period were prospectively tested for anti-HDV. RESULTS: Of 5079 HBsAg-positive patients, 53% had anti-HDV screening (41% before and 12% after study initiation). Pre-study (8%-88%) and total screening rates (14%-100%) varied widely among centres. Screening rates were associated with older age, known risk group, elevated ALT, centre location and size and period of first visit. Anti-HDV prevalence was 5.8% without significant difference in patients screened before (6.1%) or after study initiation (4.7%, p = 0.240). Anti-HDV positivity was associated with younger age, parenteral drug use, born abroad, advanced liver disease and centre location. Overall, HDV RNA detectability rate was 71.6% being more frequent in anti-HDV-positive patients with elevated ALT, advanced liver disease and hepatitis B therapy. CONCLUSIONS: Anti-HDV screening rates and recall capabilities vary widely among Greek liver clinics being higher in HBsAg-positive patients of known risk group with active/advanced liver disease seen at smaller centres, while non-medical factors are also important. Anti-HDV prevalence varies throughout Greece being higher in patients born abroad with younger age, parenteral drug use and advanced liver disease. Viremia is more frequently but not exclusively detected in anti-HDV-positive patients with elevated ALT and advanced liver disease.

Ombitasvir/paritaprevir/ritonavir plus ribavirin for 24 weeks in patients with HCV GT4 and compensated cirrhosis (AGATE-I Part II).

BACKGROUND AND AIMS: AGATE-I Part I previously reported high sustained virologic response rates in hepatitis C genotype 4 patients with cirrhosis, with 12 and 16 weeks' treatment with a combination of two direct-acting antivirals, ombitasvir and paritaprevir (codosed with ritonavir), plus ribavirin. Part II, reported here, extended the trial to include a 24-week treatment arm to fully assess treatment duration in patients with chronic hepatitis C genotype 4 infection and compensated cirrhosis. METHODS: Enrollment took place between June and November of 2015. Treatment-naive and interferon-experienced patients with chronic hepatitis C genotype 4 infection and compensated cirrhosis were enrolled into Arm C; patients previously treated with a sofosbuvir-based regimen were enrolled into Arm D. All patients received a 24-week treatment with ombitasvir, paritaprevir, and ritonavir plus ribavirin. The primary outcome was the proportion of patients with a sustained virologic response (hepatitis C virus RNA < 25 IU/mL) at posttreatment week 12 in the intention-to-treat population. The safety population included all patients who received at least one dose of study drug. RESULTS: In total, 64 patients were enrolled into AGATE-I Part II. Sustained virologic response at posttreatment week 12 was achieved in 57 of 61 patients (93.4%; 97.5% confidence interval, 92.6-97.7) in Arm C and 3 of 3 patients (100%) in Arm D. Two patients were missing SVR12 data, and two prematurely discontinued treatment. The most common adverse events for Arm C were fatigue (16 [26%]) and asthenia (15 [25%]). Results were comparable with those reported in Part I. CONCLUSIONS: AGATE-I Part II indicates that extending treatment beyond 12 weeks in genotype 4-infected patients with compensated cirrhosis does not offer additional benefit.

Hybrid therapy as first-line regimen for Helicobacter pylori eradication in a high clarithromycin resistance area: a prospective open-label trial.

BACKGROUND: Hybrid therapy is a promising first-line regimen for Helicobacter pylori (H. pylori) eradication. We evaluated a hybrid therapy, assessing the impact of antibiotic resistance on eradication outcome. METHODS: This was a prospective study that included 155 treatment-naïve patients diagnosed with H. pylori infection by positive CLO-test, confirmed with histology and/or culture. The hybrid therapy consisted of 40 mg esomeprazole and 1 g amoxicillin for 14 days, with the addition of 500 mg clarithromycin and 500 mg metronidazole for the final 7 days (all b.i.d.). Eradication was defined by negative 13C-urea breath test or histology. RESULTS: The eradication rates were 85.8% (133/155; 95% confidence interval [CI] 79.4-90.5%) by intention-to-treat and 90.2% (129/143; 95%CI 84.1-94.2%) by per-protocol analysis in a setting of high antibiotic resistance (clarithromycin 25.9%, metronidazole 31.1%, dual resistance 8.9%). Adverse events occurred in 29.7% and 1.3% discontinued treatment because of adverse events. Adherence >90% was achieved in 96.6%. The eradication rate in patients with dual clarithromycin/metronidazole resistance (50%) was markedly lower compared to those with single clarithromycin resistance (91.4%), single metronidazole resistance (90.5%) or dual susceptibility (97.8%). Dual resistance was the only factor to correlate with the failure of hybrid therapy (odds ratio 14.4, 95%CI 3.8-54.9, P=0.0003). CONCLUSIONS: Hybrid therapy is an effective and safe first-line regimen in populations with relatively high rates of antibiotic resistance. However, dual clarithromycin/metronidazole resistance may significantly compromise its efficacy.

Treatment of chronic hepatitis C with direct-acting antivirals in patients with ß-thalassaemia major and advanced liver disease.

Interferon-based regimens for chronic hepatitis C (CHC) were often deferred in patients with ß-thalasaemia major (ß-TM) due to poor efficacy and tolerance. Current guidelines recommend direct-acting antivirals (DAAs) for these patients. The aim of this study was to assess the safety and efficacy of DAAs in patients with ß-TM and advanced liver disease due to CHC. Patients were recruited from eight liver units in Greece. The stage of liver disease was assessed using transient elastography and/or liver histology. Five regimens were used: sofosbuvir (SOF) + ribavirin (RBV); SOF + simeprevir ± RBV; SOF + daclatasvir ± RBV; ledipasvir/SOF ± RBV and ombitasvir/paritaprevir-ritonavir + dasabuvir ± RBV. Sixty-one patients (median age 43 years) were included. The majority of patients was previously treated for hepatitis C (75%) and had cirrhosis (79%). Viral genotype distribution was: G1a: n = 10 (16%); G1b: n = 22 (36%); G2: n = 2 (3%); G3: n = 14 (23%); G4: n = 13 (22%). The predominant chelation therapy was a combination of deferoxamine and deferiprone (35%). Overall sustained virological response rates were 90%. All treatment regimens were well tolerated and no major adverse events or drug-drug interactions were observed. Approximately half of the patients who received RBV (7/16, 44%) had increased needs for blood transfusion. Treatment of CHC with DAAs in patients with ß-TM and advanced liver disease was highly effective and safe.

Helicobacter pylori and colorectal neoplasia: Is there a causal link?

Ever since Helicobacter pylori (H. pylori) was recognized as an infectious cause of gastric cancer, there has been increasing interest in examining its potential role in colorectal carcinogenesis. Data from case-control and cross-sectional studies, mostly relying on hospital-based samples, and several meta-analyses have shown a positive statistical relationship between H. pylori infection and colorectal neoplasia. However, the possibility exists that the results have been influenced by bias, including the improper selection of patients and disparities with respect to potential confounders. While the evidence falls short of a definitive causal link, it appears that infection with H. pylori/H. pylori-related gastritis is associated with an increased, although modest, risk of colorectal adenoma and cancer. The pathogenic mechanisms responsible for this association remain uncertain. H. pylori has been detected in colorectal malignant tissues; however, the possibility that H. pylori is a direct activator of colonic carcinogenesis remains purely hypothetical. On the other hand, experimental data have indicated a series of potential oncogenic interactions between these bacteria and colorectal mucosa, including induction and perpetuation of inflammatory responses, alteration of gut microflora and release of toxins and/or hormonal mediators, such as gastrin, which may contribute to tumor formation.

Elemental mercury mixed with alcohol injected intravenously as a suicide attempt.

A 22-year-old woman was admitted to the emergency department with symptoms of chest discomfort after a suicide attempt by injecting intravenously the amount of mercury extracted from 3 thermometers mixed with alcohol. At presentation, the patient was well oriented with normal vital signs, but a few hours later she presented an abrupt deterioration of her mental status, with confusion, disorientation, tremor and finally stupor. She was transferred to the intensive care unit for monitoring and therapy. A nasogastric tube was immediately placed and the patient received treatment with a chelating agent dimercaptosuccinic acid (DMSA)/succimer 800 mg orally three times a day, a dosage decided on the basis of her body weight, plus phenytoin 125 mg intravenously three times a day. Two hours after treatment initiation, the patient reported a remarkable improvement of her symptoms. However, she experienced seizures during a 6-month period after her discharge.

Treatment of Helicobacter Pylori infection: optimization strategies in a high resistance era.

INTRODUCTION: Treatment of Helicobacter pylori (H. pylori) infection is paramount for the management of prevalent gastrointestinal disorders and in the prevention of gastric cancer. Due to increasing antimicrobial resistance, performance of standard triple therapies has now declined to unacceptably low levels. AREAS COVERED: In this article: i) we critically revise optimization tools aiming to improve the outcome of standard treatments; ii) we provide updated evidence on the efficacy and rationale for the use of several non-bismuth quadruple regimens in clinical practice, recommended as preferred empirical therapies in areas of high clarithromycin resistance. EXPERT OPINION: Prolonged (14-day) treatment duration may boost the efficacy of standard triple therapy by approximately 5%. Use of a high-dose PPI and/or new-generation PPIs, rabeprazole and esomeprazole, might improve eradication rates, particularly in regions where the CYP2C19 rapid metabolizer phenotype is prevalent. Adjunctive probiotics may be considered to improve treatment tolerability, though more data are required to better define their role in H. pylori eradication. Among non-bismuth quadruple regimens, both concomitant and sequential therapies are appropriate options for high-resistance settings; however, concomitant therapy appears to be less impaired by dual clarithromycin/metronidazole resistance. Hybrid therapy is a promising new alternative which seems not to be inferior to concomitant therapy.

Current status and emerging challenges in the treatment of hepatitis C virus genotypes 4 to 6.

Hepatitis C virus (HCV) genotypes 4, 5 and 6 are mainly present in Africa, the Middle East and Asia and they have been less extensively studied with respect to epidemiology, natural disease history and therapeutic endpoints. Response rates to a 48-wk combined peginterferon/ribavirin treatment range to 40%-69% for HCV 4, 55%-60% for HCV 5 and 60%-90% for HCV 6. Response-guided schedules are recommended to optimize the outcomes of peginterferon/ribavirin treatment in HCV 4 and, in form of preliminary data, for HCV 6, but no data are yet available to support such an individualization of therapy for HCV 5. Recently, the direct-acting antivirals (DAAs) with pan-genotypic activities simeprevir, sofosbuvir and daclatasvir have been recommended in triple regimens with peginterferon/ribavirin for the treatment of HCV genotypes 4 to 6 infections. In the future, DAA-based interferon-free therapies are awaited to drastically improve treatment outcomes in HCV. However, efforts to improve treatment outcomes with peginterferon/ribavirin should continue, as the HCV 4-6 infected population is mainly based in resource-limited settings with restricted access to the costly DAAs.

The impact of newer nucleos(t)ide analogues on patients with hepatitis B decompensated cirrhosis.

BACKGROUND/AIM: Patients with HBV-related decompensated cirrhosis (HBV-DeCi) should be treated with potent nucleos(t)ide analogues (NA)[entecavir (ETV) or tenofovir (TDF)]. The aim was the evaluation of safety and efficacy in terms of changes in liver disease course in HBV-DeCi patients treated with ETV or TDF. METHODS: In 52 HBV-DeCi patients clinical and laboratory data, including glomerular filtration rates (GFR), were recorded. The changes in MELD (DMELD) and Child-Pugh (DCTP) scores between baseline and after 6 months of treatment were evaluated. The independent factors associated with survival were evaluated. RESULTS: 31 patients under TDF and 21 under ETV were evaluated. During a median follow-up of 22.5 months (range: 6-68), there were no differences between the two groups in GFR and serum phosphate levels. At the end of follow up, in the TDF group, 2 patients died and 3 received liver transplantations (LT), while in the ETV group, 1 patient died and 3 received LT. In multivariable Cox regression analysis, DMELD was independently associated with the outcome in the total cohort (HR: 1.78, 95%C.I.:1.12-2.79, P=0.013) as well as in the subgroup of naïve (n=37) patients (HR: 1.8, 95%C.I.:1.19-4.5, P=0.03). Finally, in the non-hepatocellular carcinoma patients, the DCTP score was independently associated with the outcome in the total cohort (HR: 2.64, 95%C.I.: 1.21-7.29, P=0.015). CONCLUSIONS: TDF and ETV appear to have similar renal safety profile in HBV-DeCi patients. DMELD score in the total cohort and DCTP score in non-HCC patients were independently associated with the outcome; these findings need confirmation in larger studies.

On-treatment prediction of sustained response to peginterferon alfa-2a for HBeAg-negative chronic hepatitis B patients.

BACKGROUND & AIMS: We assessed predictors of response in HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a in routine clinical practice. METHODS: Ninety-five HBeAg-negative patients received peginterferonalfa-2a for 48 weeks and were followed-up for 48 weeks post-treatment. Serum HBsAg and HBV DNA levels were monitored during and after therapy with valid commercial assays. Sustained response (SR) was defined as HBV DNA <2000 IU/ml at study week 96. RESULTS: Twenty-two patients (23%) achieved SR and nine (9.5%) lost HBsAg. HBsAg decline was more profound in patients with SR. HBsAg decline ≥10% from baseline to week 24 was significantly associated with SR [81% (17/21) vs 37% (21/57); Odds ratio: 7.286 (2.162-24.552), P = 0.001]. The PARC rule (no decrease in HBsAg and <2 log drop in HBV DNA at week 12) was evaluated in a subset of 47 patients. Among eight patients who fulfilled the PARC rule, none achieved SR. Of the 39 patients who did not fulfil the PARC rule, 24 (62%) had HBsAg decline of ≥10% at week 24 (12 achieved SR) and 15 (38%) had HBsAg decline of <10% (1 achieved SR; negative predictive value: 93%). CONCLUSIONS: In HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a, HBsAg decline >10% at 24 weeks is significantly associated with SR. The combination of the PARC rule and week 24 decline in HBsAg can identify almost two-thirds of patients who are unlikely to achieve SR. Clinicaltrials.gov identifier: NCT01283074.

Treatment of Helicobacter pylori infection: Past, present and future.

Helicobacter pylori (H. pylori) is a major human pathogen associated with significant morbidity and mortality. However, after decades of efforts, treatment of H. pylori remains a challenge for physicians, as there is no universally effective regimen. Due to the rising prevalence of antimicrobial resistance, mainly to clarithromycin, efficacy of standard triple therapies has declined to unacceptably low levels in most parts of the world. Novel regimens, specifically experimented to improve the therapeutic outcome against antibiotic-resistant H. pylori strains, are now recommended as first-line empirical treatment options providing high efficacy (reportedly > 90% in intention to treat analysis) even in high clarithromycin resistance settings. These include the bismuth quadruple, concomitant, sequential and hybrid therapies. Due to the rapid development of quinolone resistance, levofloxacin-based regimens should be reserved as second-line/rescue options. Adjunct use of probiotics has been proposed in order to boost eradication rates and decrease occurrence of treatment-related side effects. Molecular testing methods are currently available for the characterization of H. pylori therapeutic susceptibility, including genotypic detection of macrolide resistance and evaluation of the cytochrome P450 2C19 status known to affect the metabolism of proton pump inhibitors. In the future, use of these techniques may allow for culture-free, non-invasive tailoring of therapy for H. pylori infection.

Treatment of Helicobacter pylori infection: meeting the challenge of antimicrobial resistance.

Treatment of Helicobacter pylori (H. pylori) infection is paramount for the management of prevalent gastrointestinal disorders including peptic ulcer disease and gastric cancer. Due to the wide increase in prevalence of H. pylori resistance to antibiotics, clarithromycin-based triple therapies are not any more suitable for unconditional empiric use, and should not be recommended, unless local resistance to this antibiotic is low (< 20%). Alternative strategies have been proposed to overcome the issue of increasing clarithromycin resistance, and some of them are already implemented in clinical practice. These comprise: (1) adoption of novel, more effective, empirical treatments: bismuth quadruple, sequential, non-bismuth quadruple (concomitant), dual-concomitant (hybrid), and levofloxacin-based regimens, the latter mainly designated as second-line/rescue options; (2) perspectives for a susceptibility-guided (tailored) therapeutic approach based on culture-free molecular testing methods; and (3) adjunct use of probiotics to improve eradication rates. The present article is aimed to provide a comprehensive overview of current and emerging strategies in the treatment of H. pylori infection, focusing on the challenge of antimicrobial resistance.

Current and future insights in H. pylori eradication regimens: the need of tailoring therapy.

Treatment of Helicobacter pylori (H. pylori) infection is crucial for the management of prevalent digestive and more recently also extra-digestive disorders. Rising prevalence of clarithromycin resistance worldwide has accounted for a dramatic decline in the efficacy of standard triple therapies, which should not be prescribed, unless local clarithromycin-resistance is low (<20%) or culture confirms susceptibility to this antibiotic (i,e,; as tailored treatments). Bismuth-quadruple, sequential, non-bismuth quadruple (concomitant), dual-concomitant (hybrid), and levofloxacin-based regimens have been shown to overcome clarithromycin resistance and are now preferred empirical treatments achieving improved eradication rates (>90% in per protocol analysis). In the future, empiric use of both clarithromycin and levofloxacin is likely to become steadily more challenging as even these novel eradication therapies may be prone to the effect of increasing antibiotic resistance. Tailored treatment based on the individual characterization of H. pylori therapeutic susceptibility appears to be a reasonable future alternative, currently limited by the shortcomings of systematically performing H. pylori culture (invasive, expensive, time-consuming). However, recent advances in the genotypic detection of H. pylori susceptibility to antibiotics, and in pharmacogenomics, may represent a breakthrough in our future approach to tailored therapy. Until then, efforts to optimize empirical treatments should continue.

Hepatitis C virus genotype 5: prospective evaluation of peginterferon/ribavirin treatment efficacy and predictive value of on-treatment virological responses for sustained virological response.

GOALS: To examine the treatment efficacy of a combination of pegylated interferon α (PegIFNa) plus ribavirin in patients chronically infected with hepatitis C virus genotype 5 (HCV-5) and to assess the on-treatment virological responses as predictors of sustained virological response (SVR). BACKGROUND: HCV-5 is uncommonly reported, and little therapeutic data is available regarding previous retrospective studies yielding contradictory results. STUDY: In a prospective, open-label, single-center study, 27 treatment-naive HCV-5 patients, treated for 48 weeks with PegIFNa-2a/ribavirin, were evaluated. Rapid viral response (RVR), early viral response (EVR), 24-week viral response (24-wVR), end-of-treatment response (ETR), and SVR were assessed, defined as negative viral load at weeks 4, 12, 24, 48, and 72 after treatment initiation, respectively. RESULTS: Attainment of SVR was observed in 17 of the 27 (63%) patients. RVR, EVR, and 24-wVR occurred in 16 (59.3%), 25 (92.6%), and 24 (88.9%) patients, respectively. All but 1 patient achieving 24-wVR went on to achieve ETR (rate: 85.2%), but 6 patients subsequently relapsed (relapse rate: 26.1%). The positive/negative predictive values on SVR were: 93.8%/81.8% for RVR, 68%/100% for EVR, and 66.7%/66.7% for 24-wVR. CONCLUSIONS: Patients with HCV-5 showed an overall good response to a 48-week combined antiviral treatment (SVR: 63%). Albeit the ETR was high (85.2%), attainment of SVR remained affected by a substantial relapse rate, in our setting 26.1%. The predictive value of early viral dynamics on SVR merits adequate consideration in larger clinical trials targeting to optimize treatment for patients infected with HCV-5.

Durability of a sustained virological response, late clinical sequelae, and long-term changes in aspartate aminotransferase to the platelet ratio index after successful treatment with peginterferon/ribavirin for chronic hepatitis C: a prospective study.

OBJECTIVES: Previous studies, mostly retrospective using conventional interferon, have suggested a favorable prognosis for patients with chronic hepatitis C and a sustained virological response (SVR). However, long-term outcome, including changes in the degree of hepatic fibrosis, of SVR patients in the era of pegylated interferon (PegIFN) remains underdefined. We prospectively evaluated the long-term virological, clinical, and biochemical outcomes, including aspartate aminotransferase-to-platelet ratio index (APRI), in chronic hepatitis C patients with an SVR. PATIENTS AND METHODS: We included 145 consecutive, treatment-naive chronic hepatitis C patients (mean age 47.3±9.1 years; 87 men; 42.1% genotype 1; 36.6% genotype 2/3) who achieved an SVR after combination therapy with PegIFN-α/ribavirin. RESULTS: The mean follow-up time was 68.8±35 months. The overall incidence of hepatocellular carcinoma (HCC) and liver-related death was 1.4 and 0.7%, respectively. Among nine (7.6%) patients with pretreatment cirrhosis, two (22.2%) developed HCC and one of them (11.1%) died. No patient had conclusive evidence of late virological relapse. All patients retained normal liver biochemistry, except for five of 145 (3.5%), who had persistently elevated transaminase levels, all of whom were diagnosed with new liver disease. APRI values improved significantly with treatment (0.95±1.09 vs. 0.66±0.64, P<0.001) and continued to improve after a mean of 61.4±45.5 months from an SVR in patients (n=54; 37.2%) with significant (Metavir ≥F2) pretreatment fibrosis (1.13±0.66 vs. 0.67±0.45, P<0.001). CONCLUSION: The long-term outcome, including APRI, of chronic hepatitis C patients treated successfully with PegIFN/ribavirin and followed for a mean of 5.7 years is favorable. However, a high risk of progression to HCC and liver-related death remains for patients with pretreatment cirrhosis, in our setting, as high as 22.2 and 11.1%, respectively.

Current options for the treatment of Helicobacter pylori.

INTRODUCTION: Treatment of Helicobacter pylori (H. pylori) infection is crucial for prevalent disease's management, including gastritis, peptic ulcer and gastric cancer, whereas novel extradigestive causal associations are increasingly being recognized. Despite long-standing efforts, there is not as yet an optimal empirical therapy to eradicate H. pylori. AREAS COVERED: In the present article the authors review current options for H. pylori eradication. Advantages and disadvantages of each of the recommended regimens, and the perspectives for their rational use in clinical practice, are critically discussed. EXPERT OPINION: The continuous rising of antimicrobial resistance has accounted for the declined efficiency of standard triple therapies, yielding < 70% eradication in most countries. Alternative first-line strategies have been proposed and largely validated and are now replacing standard-of-care therapies in areas with a high incidence of clarithromycin-resistance (> 20%). Such treatments include the bismuth-containing quadruple therapy, concomitant, sequential and levofloxacin-based regimens, the later mainly designated, together with rifabutin-based therapies as second-line/rescue options. Clinicians should be aware of the local resistance pattern and maintain first-line eradication to levels > 90% (per-protocol efficacy). This will prevent both exposing the patient to repeated treatments and spreading of secondary antimicrobial resistance. In the future, perspectives of tailored therapy and a prophylactic vaccine will obviate any treatment concern.

Nonbismuth quadruple "concomitant" therapy versus standard triple therapy, both of the duration of 10 days, for first-line H. pylori eradication: a randomized trial.

GOALS: To compare the efficacy, compliance, and tolerability of a quadruple, nonbismuth-containing concomitant therapy with standard triple therapy, both of the duration of 10 days, for Helicobacter pylori eradication. BACKGROUND: Eradication rates obtained with standard therapies are declining as antibiotic resistance becomes more prevalent worldwide. New first-line treatment strategies are needed. STUDY: Two hundred fifty-seven patients with H. pylori infection were included in the study. Patients were randomized to receive 10-day concomitant therapy comprising esomeprazole 40 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and metronidazole 500 mg, all bid, or 10-day standard triple therapy comprising of esomeprazole 40 mg, amoxicillin 1000 mg, and clarithromycin 500 mg, all bid. Cure rates were defined as a negative 13C urea breath test 8 weeks after the start of treatment. RESULTS: Two hundred forty-six patients completed the study. The intention-to-treat cure rates were 90.5% [95% confidence interval (CI): 84.1%-95%] and 73.8% (95%CI, 65.6%-80.7%), whereas the per protocol cure rates were 93.3% (95%CI, 87.2% -97.1%) and 78.5% (95%CI, 70.3%-84.9%), respectively. The eradication rate was significantly higher in the concomitant group compared with the triple therapy group in both the intention-to-treat (P=0.0006) and per protocol (P=0.0014) populations. Adverse events were generally of mild/moderate intensity and did not interfere significantly with compliance, which was excellent for both treatment groups (96.6% and 98.5%, respectively, P=0.44). CONCLUSIONS: Performance of a 10-day conventional triple regimen is suboptimal. A 10-day concomitant regimen achieved a significantly higher eradication rate and seems to be an effective, safe, and well-tolerated treatment option for H. pylori eradication.

Ultrasonographic prevalence and factors predicting left ventricular diastolic dysfunction in patients with liver cirrhosis: is there a correlation between the grade of diastolic dysfunction and the grade of liver disease?

Presence of cardiac dysfunction has been associated with an unfavorable prognosis in patients with liver cirrhosis. In the present study, 92 consecutive, newly-diagnosed patients with liver cirrhosis were prospectively evaluated. Liver disease was graded according to the modified Child-Turcotte-Pugh (CTP) score whereas left ventricular diastolic function was assessed by Doppler-echocardiography and graded (Stage 0 to 4) according to current guidelines. Overall, DD was diagnosed in 55/92 (59.8%) patients [DD-stage-1: 36/92 (39.1%), DD-stage-2: 19/92 (20.6%)]. Prevalence of DD-stage-1 among the different stages of liver cirrhosis was: CTP-class A: 11/29 (37.9%), B: 15/39 (38.5%), C: 10/24 (41.6%), (P > 0.05 in all comparisons), whereas for DD-stage-2 the corresponding proportions were CTP-class A: 3/29 (10.3%), B: 5/39 (12.8%), C: 11/24 (45.8%), (P = 0.0009 between CTP-class C versus A and B). Age > 53 years (Odd's Ratio [OR]: 4.2; 95% confidence interval [CI]: 1.5-12.1) and CTP-class C (OR: 4.6; 95% CI: 1.1-20) could independently predict DD. No relation between presence of DD and the etiology of the liver disease was found. We conclude that DD is a common feature in liver cirrhosis. DD-stage-1 is fairly prevalent among all CTP-classes whereas DD-stage-2 seems to be characteristic of the advanced liver disease (CTP-class C). A high level of awareness for the presence of the syndrome is required, especially if cirrhotic patients are CTP-class C and/or of older age.

Helicobacter pylori Eradication Therapies in the Era of Increasing Antibiotic Resistance: A Paradigm Shift to Improved Efficacy.

With the rising prevalence of antimicrobial resistance, the eradication rates of Helicobacter pylori (H. pylori) with standard treatments are decreasing to unacceptable levels (i.e., ≤80%) in most countries. After these disappointing results, several authorities have proposed that infection with H. pylori should be approached and treated as any other bacterial infectious disease. This implicates that clinicians should prescribe empirical treatments yielding a per protocol eradication of at least 90%. In recent years several treatments producing ≥90% cure rates have been proposed including sequential therapy, concomitant quadruple therapy, hybrid (dual-concomitant) therapy, and bismuth-containing quadruple therapy. These treatments are likely to represent the recommended first-line treatments in the near future. In the present paper, we are considering a series of critical issues regarding currently available means and approaches for the management of H. pylori infection. Clinical needs and realistic endpoints are taken into account. Furthermore, emerging strategies for the eradication of H. pylori and the existing evidence of their clinical validation and widespread applicability are discussed.