Helicobacter pylori attachment-blocking antibodies protect against duodenal ulcer disease.

The majority of the world population carry the gastric pathogen Helicobacter pylori. Fortunately, most individuals experience only low-grade or no symptoms, but in many cases the chronic inflammatory infection develops into severe gastric disease, including duodenal ulcer disease and gastric cancer. Here we report on a protective mechanism where H. pylori attachment and accompanying chronic mucosal inflammation can be reduced by antibodies that are present in a vast majority of H. pylori carriers. These antibodies block binding of the H. pylori attachment protein BabA by mimicking BabA's binding to the ABO blood group glycans in the gastric mucosa. However, many individuals demonstrate low titers of BabA blocking antibodies, which is associated with an increased risk for duodenal ulceration, suggesting a role for these antibodies in preventing gastric disease.

A pattern-recognition-based clustering method for non-invasive diagnosis and classification of various gastric conditions.

Conventional endoscopic biopsy tests are not suitable for early detection of the acute onset and progression of peptic ulcer as well as various gastric complications. This also limits its suitability for widespread population-based screening and consequently, many people with complex gastric phenotypes remain undiagnosed. Here, we demonstrate a new non-invasive methodology for accurate diagnosis and classification of various gastric disorders exploiting a pattern-recognition-based cluster analysis of a breathomics dataset generated from a simple residual gas analyzer-mass spectrometry. The clustering approach recognizes unique breathograms and "breathprints" signatures that clearly reflect the specific gastric condition of an individual person. The method can selectively distinguish the breath of peptic ulcer and other gastric dysfunctions like dyspepsia, gastritis, and gastroesophageal reflux disease patients from the exhaled breath of healthy individuals with high diagnostic sensitivity and specificity. Moreover, the clustering method exhibited a reasonable power to selectively classify the early-stage and high-risk gastric conditions with/without ulceration, thus opening a new non-invasive analytical avenue for early detection, follow-up, and fast population-based robust screening strategy of gastric complications in the real-world clinical domain.

Efficacy and safety of saroglitazar in real-world patients of non-alcoholic fatty liver disease with or without diabetes including compensated cirrhosis: A tertiary care center experience.

Background and Aim: Saroglitazar, a dual PPAR α/γ agonist, is useful in management of NAFLD and diabetic dyslipidemia. Here, we report the safety and efficacy of saroglitazar in NAFLD patients with or without diabetes including compensated cirrhosis. Methods: Patients, started on saroglitazar 4 mg were prospectively evaluated for 52 weeks in a tertiary care center in Eastern India. Effectiveness was measured in terms of anthropometric measurements, fasting blood glucose, LFT, lipid profile, HbA1c, and elastography parameters (LSM and CAP) measured at baseline, 24, and 52 weeks. Adverse drug reactions were monitored. Results: A total of 112 patients were enrolled in the study, of whom 63 patients were taken up for per-protocol analysis. Mean age was 49.11 ± 11.09 years and 46(73%) were male. Thirty-four (54%) were nondiabetic. Eleven patients had compensated cirrhosis. There was significant improvement of LSM from baseline (11.03 ± 7.19 kPa) to 24-week (9.29 ± 6.39 kPa) and 52-week (8.59 ± 6.35 kPa) values respectively (P < 0.001). Significant reduction was also seen in CAP values, ALT, AST, HbA1c, LDL, total cholesterol, and triglyceride values. There was no significant weight change along the study interval. Pruritus occurred in one patient who required treatment discontinuation and another patient had mild symptomatic loose motion. Conclusions: Saroglitazar is effective and safe in improving biochemical parameters and LSM and CAP values irrespective of weight reduction. It may be used in compensated cirrhotics with close monitoring for side effects.

Indian consensus statements on irritable bowel syndrome in adults: A guideline by the Indian Neurogastroenterology and Motility Association and jointly supported by the Indian Society of Gastroenterology.

The Indian Neurogastroenterology and Motility Association (INMA), earlier named the Indian Motility and Functional Diseases Association developed this evidence-based practice guidelines for the management of irritable bowel syndrome (IBS). A modified Delphi process was used to develop this consensus containing 28 statements, which were concerning diagnostic criteria, epidemiology, etiopathogenesis and comorbidities, investigations, lifestyle modifications and treatments. Owing to the Coronavirus disease-19 (COVID-19) pandemic, lockdowns and mobility restrictions, web-based meetings and electronic voting were the major tools used to develop this consensus. A statement was regarded as accepted when the sum of "completely accepted" and "accepted with minor reservation" voted responses were 80% or higher. Finally, the consensus was achieved on all 28 statements. The consensus team members are of the view that this work may find use in teaching, patient care, and research on IBS in India and other nations.

Development and evaluation of a simple PCR assay and nested PCR for rapid detection of clarithromycin-resistant Helicobacter pylori from culture and directly from the biopsy samples in India.

BACKGROUND: Eradication of Helicobacter pylori provides the most effective treatment for gastroduodenal diseases caused by H. pylori infection. Clarithromycin, a member of the macrolide family, still remains the most important antibiotic used in H. pylori eradication treatment. But the increasing prevalence of clarithromycin resistant H. pylori strains due to point mutations in the V region of the 23S rRNA, poses a great threat in treating the ailing patients. So, we aimed for PCR-mediated rapid detection of the point mutation at 2143 position of 23S rRNA gene in H. pylori that is relevant to clarithromycin resistance from culture and simultaneously from biopsy specimens to avoid the empirical treatment. RESULTS: Newly developed PCR assay using DNA of pure culture detected point mutation in 23S rRNA gene in 21 (8.04%) of 261 clinical strains tested. The agar dilution method showed that all these 21 strains were resistant to clarithromycin indicating the perfect match of the PCR based results. Additionally, the sequencing study also identified the A to G mutation at 2143 position in 23S rRNA gene of the resistant strains only. Consequently, the newly developed Nested-ASP-PCR dealing directly with 50 biopsy specimens demonstrated 100% sensitivity and specificity with the findings of agar dilution method taken as Gold standard. Bioinformatics based analysis such as accessibility analysis and dot plot clearly stated that the base pairing probability has increased due to mutation. Computational studies revealed that the point mutation confers more stability in secondary structure due to conversion of loop to stem. Furthermore, interaction studies showed binding affinity of the CLR to the mutant type is weaker than that to the wild type. CONCLUSION: This assay outlines a rapid, sensitive and simple approach to identify point mutation that confers clarithromycin resistance as well as clarithromycin sensitive strains, providing rapid initiation of effective antibiotic treatment. Additionally, it is simple to adopt for hospital based diagnostic laboratories to evaluate the degree of regional clarithromycin resistance from biopsy specimens itself. Furthermore, in silico studies provide evidence or a signal that the prevalence of clarithromycin resistance may rise in the near future as a result of this point mutation.

Region-specific genomic signatures of multidrug-resistant Helicobacter pylori isolated from East and South India.

Helicobacter pylori is a ubiquitous bacterium and contributes significantly to the burden of chronic gastritis, peptic ulcers, and gastric cancer across the world. Adaptive phenotypes and virulence factors in H. pylori are heterogeneous and dynamic. However, limited information is available about the molecular nature of antimicrobial resistance phenotypes and virulence factors of H. pylori strains circulating in India. In the present study, we analyzed the whole genome sequences of 143 H. pylori strains, of which 32 are isolated from two different regions (eastern and southern) of India. Genomic repertoires of individual strains show distinct region-specific signatures. We observed lower resistance phenotypes and genotypes in the East Indian (Kolkata) H. pylori isolates against amoxicillin and furazolidone antibiotics, whereas higher resistance phenotypes to metronidazole and clarithromycin. Also, at molecular level, a greater number of AMR genes were observed in the east Indian H. pylori isolates as compared to the southern Indian isolates. From our findings, we suggest that metronidazole and clarithromycin antibiotics should be used judicially in the eastern India. However, no horizontally acquired antimicrobial resistance gene was observed in the current H. pylori strains. The comparative genome analysis shows that the number of genes involved in virulence, disease and resistance of H. pylori isolated from two different regions of India is significantly different. Single-nucleotide polymorphisms (SNPs) based phylogenetic analysis distinguished H. pylori strains into different clades according to their geographical locations. Conditionally beneficial functions including antibiotic resistance phenotypes that are linked with faster evolution rates in the Indian isolates.

Emerging inflammatory bowel disease demographics, phenotype, and treatment in South Asia, South-East Asia, and Middle East: Preliminary findings from the Inflammatory Bowel Disease-Emerging Nations' Consortium.

BACKGROUND AND AIM: Inflammatory bowel disease (IBD) is emerging in the newly industrialized countries of South Asia, South-East Asia, and the Middle East, yet epidemiological data are scarce. METHODS: We performed a cross-sectional study of IBD demographics, disease phenotype, and treatment across 38 centers in 15 countries of South Asia, South-East Asia, and Middle East. Intergroup comparisons included gross national income (GNI) per capita. RESULTS: Among 10 400 patients, ulcerative colitis (UC) was twice as common as Crohn's disease (CD), with a male predominance (UC 6678, CD 3495, IBD unclassified 227, and 58% male). Peak age of onset was in the third decade, with a low proportion of elderly-onset IBD (5% age > 60). Familial IBD was rare (5%). The extent of UC was predominantly distal (proctitis/left sided 67%), with most being treated with mesalamine (94%), steroids (54%), or immunomodulators (31%). Ileocolic CD (43%) was the commonest, with low rates of perianal disease (8%) and only 6% smokers. Diagnostic delay for CD was common (median 12 months; interquartile range 5-30). Treatment of CD included mesalamine, steroids, and immunomodulators (61%, 51%, and 56%, respectively), but a fifth received empirical antitubercular therapy. Treatment with biologics was uncommon (4% UC and 13% CD), which increased in countries with higher GNI per capita. Surgery rates were 0.1 (UC) and 2 (CD) per 100 patients per year. CONCLUSIONS: The IBD-ENC cohort provides insight into IBD in South-East Asia and the Middle East, but is not yet population based. UC is twice as common as CD, familial disease is uncommon, and rates of surgery are low. Biologic use correlates with per capita GNI.

Current therapeutics against HCV.

Hepatitis C is a positive stranded enveloped RNA virus belonging to the Flaviviridae family. HCV infection leads to severe liver diseases, cirrhosis and hepatocellular carcinoma worldwide. Although treatments have been available for a while, due to its complexity and genetic diversity, only few are reported to be effective against all HCV genotypes. Here, we review the HCV life cycle and its immunogenic potential and various mechanisms via which the virus interferes in the signalling process. A comprehensive overview of current anti-HCV therapeutics, such as, Direct Acting Antiviral (DAA) as well as Host Targeting Agents (HTA), along with their scope, known mechanism of action and limitations are presented. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13337-021-00697-0.

Exploring Triple-Isotopic Signatures of Water in Human Exhaled Breath, Gastric Fluid, and Drinking Water Using Integrated Cavity Output Spectroscopy.

Water, the major body fluid in humans, has four main naturally occurring isotopologues, H216O, H217O, H218O, and H2H16O (i.e., HD16O) with different masses. The underlying mechanisms of the isotope-specific water-metabolism in the human gastrointestinal (GI) tract and respiratory system are largely unknown and remained illusive for several decades. Here, a new strategy has been demonstrated that provides direct quantitative experimental evidence of triple-isotopic signatures of water-metabolism in the human body in response to the individual's water intake habit. The distribution of water isotopes has been monitored in drinking water (DW; δD = -36.59 ± 10.64‰ (SD), δ18O = -5.41 ± 1.47‰ (SD), and δ17O = -2.92 ± 0.79‰ (SD)), GI fluid (GF; δD = -35.91 ± 7.30‰ (SD), δ18O = -3.98 ± 1.29‰ (SD), and δ17O = -2.37 ± 0.57‰ (SD)), and human exhaled breath (EB; δD = -119.63 ± 7.27‰ (SD), δ18O = -13.69 ± 1.23‰ (SD), and δ17O = -8.77 ± 0.98‰ (SD)) using a laser-based off-axis integrated cavity output spectroscopy (OA-ICOS) technique. This study explored a new analytical method to disentangle the competing effects of isotopic fractionations of water during respiration in humans. In addition, our findings revealed that deuterium-enriched exhaled semiheavy water, i.e., HD16O is a new marker of the noninvasive assessment of the ulcer-causing H. pylori gastric pathogen. We also clearly showed that the water-metabolism-derived triple-isotopic compositions due to impaired water absorption in the GI tract can be used as unique tracers to track the onset of various GI dysfunctions. These findings are thus bringing a new analytical methodology to better understand the isotope-selective water-metabolism that will have enormous applications for clinical testing purposes.

Exploring the physiological link of breath N2O through nitrification and denitrification processes in human gastric juice.

Over the past several decades, it has been generally believed that microbial nitrification and denitrification are not significant processes in the human gastrointestinal tract. Moreover, the underlying physiological link between exhaled nitrous oxide (N2O) and aerobic denitrification in the gastric environment is still largely unknown. In this report, we provide direct experimental evidence of the aerobic denitrification process in the human gastrointestinal tract by evaluating concentrations of dissolved N2O and its precursor nitrite ([Formula: see text]) ion in the gastric juice along with exhaled N2O concentration using a high-precision laser spectroscopy technique. Moreover, in vitro studies of gastric fluid in patients reveal a new mechanism of nitrification of ammonium ion ([Formula: see text]) followed by denitrification of [Formula: see text] leading to the formation of N2O in the gastric environment, which is eventually excreted in exhaled breath. This observation was subsequently validated under in vivo physiological conditions exploiting the urease activity of the gastric pathogen Helicobacter pylori. Consequently, our findings established a strong physiological link between exhaled N2O and bacterial infection in the stomach. This deepens our understanding of the unusual microbial denitrification in the gastric environment, providing new insight into the activities of human-associated microorganisms, which eventually affect the human physiology and health.

Non-invasive diagnosis of type 2 diabetes in Helicobacter pylori infected patients using isotope-specific infrared absorption measurements.

Helicobacter pylori causes several gastrointestinal diseases and may also contribute to the development of type 2 diabetes (T2D). Several studies suggest that there might be a potential link between H. pylori infection and T2D, but it still remains the subject of debate. Here, we first report the cumulative effect of H. pylori infection and T2D by exploiting the excretion kinetics of 13C/12C and 18O/16O isotope ratios of exhaled breath CO2 in response to an oral dose of 13C-enriched glucose in individuals with T2D and non-diabetic controls (NDC) harbouring the H. pylori infection. Using a high-resolution integrated cavity output spectroscopy (ICOS) technique in the infrared region, we observed that the isotopic fractionations of 13C and 18O in breath CO2 are distinctly altered in H. pylori infected T2D patients as well as in H. pylori infected NDC. Several optimal diagnostic cut-off points of 13C and 18O isotopes of breath CO2 were also determined which exhibited the diagnostic sensitivity and specificity of ∼97 % and thus suggesting that breath 13C and 18O isotopes might be considered as potential biomarkers for the non-invasive assessment of the gastric pathogen prior to the onset of T2D. This may open a new diagnostic strategy for treating these common diseases in an alternative way.

Indian consensus on chronic constipation in adults: A joint position statement of the Indian Motility and Functional Diseases Association and the Indian Society of Gastroenterology.

The Indian Motility and Functional Diseases Association and the Indian Society of Gastroenterology developed this evidence-based practice guideline for management of chronic constipation. A modified Delphi process was used to develop this consensus containing 29 statements, which were generated by electronic voting iteration as well as face to face meeting and review of the supporting literature primarily from India. These statements include 9 on epidemiology, clinical presentation, and diagnostic criteria; 8 on pathophysiology; and the remaining 12 on investigations and treatment. When the proportion of those who voted either to accept completely or with minor reservation was 80% or higher, the statement was regarded as accepted. The members of the consensus team believe that this would be useful for teaching, clinical practice, and research on chronic constipation in India and in other countries with similar spectrum of the disorders.

Exhaled nitric oxide as a potential marker for detecting non-ulcer dyspepsia and peptic ulcer disease.

Nitric oxide (NO) plays a key role in the development of peptic ulcer disease (PUD). Conversely, the gastric pathogen Helicobacter pylori colonizes the human stomach and contributes to the development of non-ulcer dyspepsia (NUD) and PUD. However, the underlying relation between molecular NO in exhaled breath and H. pylori-associated NUD and PUD remains largely unknown. Here, we found that the excretion kinetics of NO profiles in exhaled breath are altered markedly in H. pylori-infected NUD and PUD subjects. In our observations, PUD led to considerably higher enrichments of NO in exhaled breath compared to NUD, thus revealing a potential link between exhaled NO and ulcer and non-ulcer complications. Our findings therefore suggest that molecular NO in exhaled breath could be used as a potential biomarker for non-invasive diagnosis and selective differentiation of NUD from PUD. Our observations also highlight that alterations of NO in the gastric environment can play an important role in the pathogenesis of peptic ulcers and thus may provide a new strategy for precise evolution of the actual disease state without the need for endoscopic biopsy, even after the eradication of H. pylori infection.

Natural 18O and 13C-urea in gastric juice: a new route for non-invasive detection of ulcers.

The 13C-urea breath test (13C-UBT), developed a few decades ago, is widely used as a non-invasive diagnostic method to detect only the presence of the gastric pathogen Helicobacter pylori infection; however, the actual disease state, i.e. whether the person harbouring H. pylori has peptic ulcer disease (PUD) or non-ulcerous dyspepsia (NUD), is still poorly understood. Nevertheless, the present 13C-UBT has numerous limitations, drawbacks and pitfalls owing to the ingestion of 13C-labelled external urea. Here, we show that H. pylori is able to utilize the natural 13C and 18O-urea inherently present in the gastric juice in humans for its urease activity which has never been explored before. In vitro measurements of isotopic fractionations of gastric juice urea provide new insights into the actual state of the infection of PUD or NUD. We also provide evidence of the unusual 13C and 18O-isotopic fractionations of breath CO2 that are distinctively altered in individuals with PUD encompassing both gastric and duodenal ulcers as well as with NUD by the enzymatic activity of H. pylori in the gastric niche without oral administration of any 13C-enriched external urea. This deepens our understanding of the UBT exploiting the natural 13C and 18O-gastric juice urea in the pathogenesis of H. pylori infection, reveals the actual disease state of PUD or NUD and thus offers novel opportunities for a simple, robust, cost-effective and non-toxic global strategy devoid of any 13C-enriched urea for treating these common diseases by a single breath test. Graphical Abstract Urea breath test without any external urea.

Molecular hydrogen in human breath: a new strategy for selectively diagnosing peptic ulcer disease, non-ulcerous dyspepsia and Helicobacter pylori infection.

The gastric pathogen Helicobacter pylori utilizes molecular hydrogen (H2) as a respiratory substrate during colonization in the gastric mucosa. However, the link between molecular H2 and the pathogenesis of peptic-ulcer disease (PUD) and non-ulcerous dyspepsia (NUD) by the enzymatic activity of H. pylori still remains mostly unknown. Here we provide evidence that breath H2 excretion profiles are distinctly altered by the enzymatic activity of H. pylori for individuals with NUD and PUD. We subsequently unravelled the potential molecular mechanisms responsible for the alteration of H2 in exhaled breath in association with peptic ulcers, encompassing both gastric and duodenal ulcers, along with NUD. We also established that carbon-isotopic fractionations in the acid-mediated bacterial environment regulated by bacterial urease activity cannot discriminate the actual disease state i.e. whether it is peptic ulcer or NUD. However, our findings illuminate the unusual molecular H2 in breath that can track the precise evolution of PUD and NUD, even after the eradication of H. pylori infection. This deepens our understanding of the pathophysiology of PUD and NUD, reveals non-invasively the actual disease state in real-time and thus offers a novel and robust new-generation strategy for treating peptic-ulcer disease together with non-ulcer related complications even when the existing (13)C-urea breath test ((13)C-UBT) fails to diagnose.

Hydrogen sulphide in exhaled breath: a potential biomarker for small intestinal bacterial overgrowth in IBS.

There is a pressing need to develop a novel early-detection strategy for the precise evolution of small intestinal bacterial overgrowth (SIBO) in irritable bowel syndrome (IBS) patients. The current method based on a hydrogen breath test (HBT) for the detection of SIBO is highly controversial. HBT has many limitations and drawbacks. It often fails to indentify SIBO when IBS individuals have 'non-hydrogen-producing' colonic bacteria. Here, we show that hydrogen sulphide (H2S) in exhaled breath is distinctly altered for diarrhea-predominant IBS individuals with positive and negative SIBO by the activity of intestinal sulphate-reducing bacteria. Subsequently, by analyzing the excretion kinetics of breath H2S, we found a missing link between breath H2S and SIBO when HBT often fails to diagnose SIBO. Moreover, breath H2S can track the precise evolution of SIBO, even after the eradication of bacterial overgrowth. Our findings suggest that the changes in H2S in the bacterial environment may contribute to the pathogenesis of SIBO and the breath H2S as a potential biomarker for non-invasive, rapid and precise assessment of SIBO without the endoscopy-based microbial culture of jejunal aspirates, and thus may open new perspectives into the pathophysiology of SIBO in IBS subjects.

Mechanisms linking metabolism of Helicobacter pylori to (18)O and (13)C-isotopes of human breath CO2.

The gastric pathogen Helicobacter pylori utilize glucose during metabolism, but the underlying mechanisms linking to oxygen-18 ((18)O) and carbon-13 ((13)C)-isotopic fractionations of breath CO2 during glucose metabolism are poorly understood. Using the excretion dynamics of (18)O/(16)O and (13)C/(12)C-isotope ratios of breath CO2, we found that individuals with Helicobacter pylori infections exhibited significantly higher isotopic enrichments of (18)O in breath CO2 during the 2h-glucose metabolism regardless of the isotopic nature of the substrate, while no significant enrichments of (18)O in breath CO2 were manifested in individuals without the infections. In contrast, the (13)C-isotopic enrichments of breath CO2 were significantly higher in individuals with Helicobacter pylori compared to individuals without infections in response to (13)C-enriched glucose uptake, whereas a distinguishable change of breath (13)C/(12)C-isotope ratios was also evident when Helicobacter pylori utilize natural glucose. Moreover, monitoring the (18)O and (13)C-isotopic exchange in breath CO2 successfully diagnosed the eradications of Helicobacter pylori infections following a standard therapy. Our findings suggest that breath (12)C(18)O(16)O and (13)C(16)O(16)O can be used as potential molecular biomarkers to distinctively track the pathogenesis of Helicobacter pylori and also for eradication purposes and thus may open new perspectives into the pathogen's physiology along with isotope-specific non-invasive diagnosis of the infection.

Modulation of TLR 3, 7 and 8 expressions in HCV genotype 3 infected individuals: potential correlations of pathogenesis and spontaneous clearance.

BACKGROUND: Hepatitis C virus is the major cause of chronic hepatitis worldwide which finally leads to the development of hepatocellular carcinoma. Toll like receptors (TLRs) play an important role in the course of many viral infections, but the role of TLRs in HCV pathogenesis has not been well elucidated so far. OBJECTIVE: The aim of this study was to analyse the mRNA expression of TLRs 3, 7, and 8 in different stages of HCV infection including chronic, cirrhosis, interferon treated resolved, and relapsed cases. METHODOLOGY: Total RNA from whole blood was extracted and mRNA expression of TLRs 3, 7, and 8 genes was analyzed by quantitative real-time RT-PCR using ß-Actin gene as an internal control. RESULTS: This study consisted of 100 HCV infected individuals and twenty healthy controls. TLR 3 expression was found to be significantly elevated in individuals who had spontaneously cleared the virus (p < 0.001), whereas TLR 7 was found to be 3.26 times more elevated in patients with cirrhosis of liver. In IFN induced individuals, TLR 8 expression levels were found to be 2.28-fold elevated as compared to control population. CONCLUSION: TLRs 3, 7, and 8 are prime biomarker candidates for HCV infection mRNA expression analysis which might improve current therapeutic approaches.

Impact of host IL28B rs12979860, rs8099917 in interferon responsiveness and advanced liver disease in chronic genotype 3 hepatitis C patients.

BACKGROUND AND AIMS: Genetic polymorphisms near interleukin 28B gene are associated with spontaneous and treatment induced clearance of hepatitis C virus (HCV). Our objective was to evaluate the impact of interleukin 28B single nucleotide polymorphism (rs12979860, rs8099917) variability in HCV genotype 3 infected populations. METHODS: 400 hepatitis C seroreactive patients from different population groups in Eastern and North Eastern part of India were assessed for host and viral genotypic analysis. 83 HCV genotype 3 infected patients were administered pegylated interferon- ribavirin therapy. Viral genotyping was performed using nested reverse transcriptase-PCR followed by direct sequencing methods. Host interleukin 28B genotyping was performed using real-time PCR based single nucleotide polymorphism analysis. RESULTS: Out of 400 hepatitis C seroreactive individuals, 73.25% were found to be RNA positive. HCV genotype 3 (65.87%) was found to be the major circulating strain in this region followed by genotype 1 (32.08%). rs12979860 CC genotype was significantly associated with sustained virological response in HCV genotype 3 infected population. In patients achieving rapid virological response, favourable CC/TT allele at rs12979860, rs8099917 was found to be predominant at both the alleles at 77%, 73.2% respectively; whereas in case of patients with relapsed HCV infection CT, TG alleles were found to be predominant. Additionally, CC genotypes at rs12979860 were found to be associated with sustained virological response in patients with high viral load (OR = 6.75, 0.05

Excretion kinetics of 13C-urea breath test: influences of endogenous CO2 production and dose recovery on the diagnostic accuracy of Helicobacter pylori infection.

We report for the first time the excretion kinetics of the percentage dose of (13)C recovered/h ((13)C-PDR %/h) and cumulative PDR, i.e. c-PDR (%) to accomplish the highest diagnostic accuracy of the (13)C-urea breath test ((13)C-UBT) for the detection of Helicobacter pylori infection without any risk of diagnostic errors using an optical cavity-enhanced integrated cavity output spectroscopy (ICOS) method. An optimal diagnostic cut-off point for the presence of H. pylori infection was determined to be c-PDR (%) = 1.47 % at 60 min, using the receiver operating characteristic curve (ROC) analysis to overcome the "grey zone" containing false-positive and false-negative results of the (13)C-UBT. The present (13)C-UBT exhibited 100 % diagnostic sensitivity (true-positive rate) and 100 % specificity (true-negative rate) with an accuracy of 100 % compared with invasive endoscopy and biopsy tests. Our c-PDR (%) methodology also manifested both diagnostic positive and negative predictive values of 100 %, demonstrating excellent diagnostic accuracy. We also observed that the effect of endogenous CO2 production related to basal metabolic rates in individuals was statistically insignificant (p = 0.78) on the diagnostic accuracy. However, the presence of H. pylori infection was indicated by the profound effect of urea hydrolysis rate (UHR). Our findings suggest that the current c-PDR (%) is a valid and sufficiently robust novel approach for an accurate, specific, fast and noninvasive diagnosis of H. pylori infection, which could routinely be used for large-scale screening purposes and diagnostic assessment, i.e. for early detection and follow-up of patients.