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.

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.

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.

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.

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.

Predictors of sustained virological response in Greek and Egyptian patients with hepatitis C genotype 4: does ethnicity matter?

Hepatitis C virus genotype 4 (HCV-4) is spreading beyond Africa and the Middle East but data regarding treatment with pegylated interferon alpha and ribavirin of European populations infected with HCV-4 remains limited. Interestingly, European (vs. Egyptian) origin has been associated with lower sustained virological response rates. Hence the aim of this study was to investigate the treatment outcomes of Greek (vs. Egyptian), treatment-naïve patients infected with HCV-4 (subtype a) and to identify factors influencing response rates. One hundred seventy-seven consecutive patients (mean age: 44.6 ± 10.2, males: 143/177; 80.8%, Egyptians: 76/177; 42.9%) treated over a 7-year period at the Hepatology clinics of three tertiary care hospitals in Greece were retrospectively evaluated. Overall, sustained virological response was achieved in 75/177 (42.4%) of the cohort without a significant difference between the two ethnic groups [Greek: 44/101 (43.6%); Egyptian 31/76 (40.8%), P = 0.7598]. In multivariate analysis, it was found that ethnicity was not associated with an impaired response but age ≥45 years [odds ratio (OR): 0.4225, 95% confidence interval (CI): 0.2135-0.8133; P = 0.0134], diabetes (OR: 0.2346, 95% CI: 0.0816-0.0674; P = 0.0071), advanced liver fibrosis (OR: 0.3964, 95% CI: 0.1933-0.8133; P = 0.0116), and treatment suspension (OR: 0.1738, 95% CI: 0.0482-0.6262; P = 0.0075) showed an independent negative association with response to antiviral treatment. In contrast to previous European data suggesting Egyptian ethnicity to be a positive predictor for a sustained virological response, there was no influence of Greek versus Egyptian ethnicity on treatment outcomes. Higher age, advanced liver fibrosis, and diabetes have been shown to reduce significantly response rates in patients infected with HCV-4.

Hepatitis C virus genotyping in Greece: unexpected high prevalence of genotype 5a in a Greek island.

Hepatitis C virus (HCV) genotype 5 (G5) is a rare genotype reported mainly in South Africa. However, increasing data suggest the sporadic presence of this genotype in different European countries. To assess the epidemiology of HCV-G5 in Greece, genotyping was performed in 973 consecutive patients infected with HCV, referred to 7 hepatology centers throughout Greece, from January 2005 to December 2009. Genotype 5a (19 patients, 1.9%) was the fifth most prevalent genotype after genotype 1 (408 patients, 41.9%), genotype 3 (318 patients, 32.7%), genotype 4 (158 patients, 16.2%), and genotype 2 (70 patients, 7.2%). The majority of patients infected with G5 (16/19,84.2%) were referred to the General Hospital of Rhodes, an island in south-east Greece. The HCV genotype distribution in that particular island, indicates a particularly high G5 prevalence of 12.8%, after genotype 1 (40%), genotype 3 (28%), and genotype 4 (15%). Among the patients from Rhodes infected with G5 (n = 16), 13 (81.2%) were females. The mean age was 62.3 ± 6.5 years, significantly older than the patients infected with other HCV genotypes (mean age 40.6 ± 7.2, P < 0.0001). Nine out of the 16 cases (56.2%) presented features of high pre-treatment viral loads. Advanced liver fibrosis (Metavir F3-F4) was found in four out of five performed liver biopsies. Ten patients received treatment with pegylated interferon plus ribavirin and a sustained viral response were achieved in six cases. The source of infection is unknown but parenteral iatrogenic routes of transmission seem to have contributed significantly to the spread of genotype 5a in this region.

Evaluation of a four-drug, three-antibiotic, nonbismuth-containing "concomitant" therapy as first-line Helicobacter pylori eradication regimen in Greece.

BACKGROUND: The eradication rates of Helicobacter pylori (H. pylori) with standard treatments are decreasing worldwide as in Greece. Studies with new antibiotic combinations are needed to find better methods of eradication. Therefore, the aim of this study was to evaluate efficacy and tolerability of a 10-day, four-drug, three-antibiotic, nonbismuth-containing concomitant regimen. MATERIALS AND METHODS: This is a prospective, open-label, multicenter study that included 131 patients infected with H. pylori. All patients were diagnosed with peptic ulcer disease or nonulcer dyspepsia by endoscopy. H. pylori infection was established by at least two positive tests among rapid urease test, gastric histology, and (13) C-urea breath test. For 10 days, all patients received esomeprazole 40mg, amoxycillin 1000mg, clarithromycin 500mg, and metronidazole 500mg, all b.d. eradication was assessed with (13) C urea breath test 8weeks after the start of treatment. Intention-to-treat and per-protocol eradication rates were determined. RESULTS: One hundred and twenty-seven of the 131 patients completed the study. At intention-to-treat analysis, the eradication rate was 91.6% (95% confidence interval (CI), 85.5-95.7%). For the per-protocol analysis, the eradication rate was 94.5% (95% CI, 89-97.8%). Adverse events were noted in 42 of 131 (32.1%); drug compliance was excellent with 96.9% of the patients taking more than 90% of the prescribed medication. CONCLUSION: A 10-day concomitant regimen appears to be an effective, safe, and well-tolerated treatment option for first-line H. pylori eradication in Greece.

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.

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.

Multiple myeloma emerging after chemotherapy for non-small-cell lung cancer.

A 67-year-old man underwent total resection of the left lung because of adenocarcinoma, with no evidence of extra-thoracic spread of the cancer. On follow-up, metastatic bone disease was documented and chemotherapy (CMT) which included cisplatin, docetaxel, vinorelbine, and topotecan was administered. Six months after completion of CMT, a rise in total serum protein was noted. Bone marrow biopsy revealed the diagnosis of an IgG lambda myeloma. We report a case of a man with adenocarcinoma of the lung who presented multiple myeloma after completion of chemotherapy.

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.

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.

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.

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.

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.

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.