Efficacy and safety of sorafenib in patients with advanced hepatocellular carcinoma according to baseline status: Subset analyses of the phase III Sorafenib Asia–Pacific trial

Signal transducer and activator of transcription 3 (STAT3) is a transcription factor that is activated by many cytokines and growth factors and plays a key role in cell survival, proliferation, and differentiation. STAT3 activation is detected virtually in all rodent models of liver injury and in human liver diseases. In this review, we highlight recent advances of STAT3 signaling in liver injury, steatosis, inflammation, regeneration, fibrosis, and hepatocarcinogenesis. The cytokines and small molecules that activate STAT3 in hepatocytes may have therapeutic benefits to treat acute liver injury, fatty liver disease, and alcoholic hepatitis, while blockage of STAT3 may have a therapeutic potential to prevent and treat liver cancer.

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Signal Transducer and Activator of Transcription 3 in Liver Diseases: A Novel Therapeutic Target

Bifidobacteria are members of the intestinal microbiota of mammals and other animals, and some strains are able to exert health-promoting effects. The genus Bifidobacterium belongs to the Actinobacteria phylum. Firmicutes, Bacteroidetes, and Actinobacteria constitute the most abundant phyla in the human intestinal microbiota, Firmicutes and Bacteroidetes being predominant in adults, and Actinobacteria in breast-fed infants, where bifidobacteria can reach levels higher than 90% of the total bacterial population. They are among the first microbial colonizers of the intestines of newborns, and play key roles in the development of their physiology, including maturation of the immune system and use of dietary components. Indeed, some nutrients, such as human milk oligosaccharides, are important drivers of bifidobacterial development. Some Bifidobacterium strains are considered probiotic microorganisms because of their beneficial effects, and they have been included as bioactive ingredients in functional foods, mainly dairy products, as well as in food supplements and pharma products, alone, or together with, other microbes or microbial substrates. Well-documented scientific evidence of their activities is currently available for bifidobacteria-containing preparations in some intestinal and extraintestinal pathologies. In this review, we focus on the role of bifidobacteria as members of the human intestinal microbiota and their use as probiotics in the prevention and treatment of disease.

Bifidobacteria and Their Health-Promoting Effects.

Background
The optimal duration for Helicobacter pylori (H. pylori) eradication therapy is controversial, with recommendations ranging from 7 to 14 days. Several systematic reviews have attempted to address this issue but have given conflicting results and limited their analysis to proton pump inhibitor (PPI), two antibiotics (PPI triple) therapy. We performed a systematic review and meta-analysis to investigate the optimal duration of multiple H. pylori eradication regimens.

Objectives
The primary objective was to assess the relative effectiveness of different durations (7, 10 or 14 days) of a variety of regimens for eradicating H. pylori. The primary outcome was H. pylori persistence. The secondary outcome was adverse events.

Search methods
The Cochrane Library, MEDLINE, EMBASE, and CINAHL were searched up to December 2011 to identify eligible randomised controlled trials (RCTs). We also searched the proceedings of six conferences from 1995 to 2011, dissertations and theses, and grey literature. There were no language restrictions applied to any search. 

Selection criteria
Only parallel group RCTs assessing the efficacy of one to two weeks duration of first line H. pylori eradication regimens in adults were eligible. Within each regimen, the same combinations of drugs at the same dose were compared over different durations. Studies with at least two arms comparing 7, 10, or 14 days were eligible. Enrolled participants needed to be diagnosed with at least one positive test for H. pylori on the basis of a rapid urease test (RUT), histology, culture, urea breath test (UBT), or a stool antigen test (HpSA) before treatment. Eligible trials needed to confirm eradication of H. pylori as their primary outcome at least 28 days after completion of eradication treatment. Trials using only serology or a polymerase chain reaction (PCR) to determine H. pylori infection or eradication were excluded.

Data collection and analysis
Study eligibility and data extraction were performed by two independent review authors. Data analyses were performed within each type of intervention, for both primary and secondary outcomes. The relative risk (RR) and number needed to treat (NNT)/number needed to harm (NNTH) according to duration of therapy were calculated using the outcomes of H. pylori persistence and adverse events. A random-effects model was used. Subgroup analyses and sensitivity analyses were planned a priori.

Main results
In total, 75 studies met the inclusion criteria. Eight types of regimens were reported with at least two comparative eligible durations. They included: PPI + two antibiotics triple therapy (n = 59), PPI bismuth-based quadruple therapy (n = 6), PPI + three antibiotics quadruple therapy (n = 1), PPI dual therapy (n = 2), histamine H2-receptor antagonist (H2RA) bismuth quadruple therapy (n = 3), H2RA bismuth-based triple therapy (n = 2), H2RA + two antibiotics triple therapy (n = 3), and bismuth + two antibiotics triple therapy (n = 2). Some studies provided data for more than one regimen or more than two durations.

For the PPI triple therapy, 59 studies with five regimens were reported: PPI + clarithromycin + amoxicillin (PCA); PPI + clarithromycin + a nitroimidazole (PCN); PPI + amoxicillin + nitroimidazole (PAN); PPI + amoxicillin + a quinolone (PAQ); and PPI + amoxicillin + a nitrofuran (PANi). Regardless of type and dose of antibiotics, increased duration of PPI triple therapy from 7 to 14 days significantly increased the H. pylori eradication rate (45 studies, 72.9% versus 81.9%), the RR for H. pylori persistence was 0.66 (95% CI 0.60 to 0.74), NNT was 11 (95% CI 9 to 14). Significant effects were seen in the subgroup of PCA (34 studies, RR 0.65, 95% CI 0.57 to 0.75; NNT 12, 95% CI 9 to 16); PAN (10 studies, RR 0.67, 95% CI 0.52 to 0.86; NNT = 11, 95% CI 8 to 25); and in PAQ (2 studies, RR 0.37, 95% CI 0.16 to 0.83; NNT 3, 95% CI 2 to 10); but not in PCN triple therapy (4 studies, RR 0.87, 95% CI 0.71 to 1.07). Significantly increased eradication rates were also seen for PPI triple therapy with 10 versus 7 days (24 studies, 79.9% versus 75.7%; RR 0.80, 95% CI 0.72 to 0.89; NNT 21, 95% CI 15 to 38) and 14 versus 10 days (12 studies, 84.4% versus 78.5%; RR 0.72, 95% CI 0.58 to 0.90; NNT 17, 95% CI 11 to 46); especially in the subgroup of PAC for 10 versus 7 days (17 studies, RR 0.80, 95% CI 0.70 to 0.91) and for 14 versus 10 days (10 studies, RR 0.69, 95% CI 0.52 to 0.91). A trend towards increased H. pylori eradication rates was seen with increased duration of PCN for 10 versus 7 days, and of PAN for 10 versus 7 days and 14 versus 10 days, though this was not statistical significant. The proportion of patients with adverse events, defined by authors, was marginally significantly increased only between 7 days and 14 days (15.5% versus 19.4%; RR 1.21, 95% CI 1.06 to 1.37; NNTH 31, 95% CI 18 to 104) but not for other duration comparisons. The proportion of patients discontinuing treatment due to adverse events was not significantly different between treatment durations.

Only limited data were reported for different durations of regimens other than PPI triple therapy. No significant difference of the eradication rate was seen for all regimens according to different durations except for H2RA bismuth quadruple therapy, where a significantly higher eradication rate was seen for 14 days versus 7 days, however only one study reported outcome data.

Authors' conclusions
Increasing the duration of PPI-based triple therapy increases H. pylori eradication rates. For PCA, prolonging treatment duration from 7 to 10 or from 10 to 14 days is associated with a significantly higher eradication rate. The optimal duration of therapy for PCA and PAN is at least 14 days. More data are needed to confirm if there is any benefit of increasing the duration of therapy for PCN therapy. Information is limited for regimens other than PPI triple therapy; more studies are needed to draw meaningful conclusions for optimal duration of other H. pylori eradication regimens.

Optimum duration of regimens for Helicobacter pylori eradication

Recurrent TERT promoter mutations identified in a large-scale study of multiple tumour types are associated with increased TERT expression and telomerase activation

PROBIOTICS—THE CONCEPTHistory and DefinitionsA century ago, Elie Metchnikoff (a Russian scientist, Nobel laureate, and professor at the Pasteur Institute in Paris) postulated that lactic acid bacteria (LAB) offered health benefits capable of promoting longevity. He suggested that “intestinal autoint

Raj Vaidya

Papers

World Gastroenterology Organisation Global Guidelines: GERD Global Perspective on Gastroesophageal Reflux Disease.