Decentralised same day test and treatment of hepatitis C levering existing peer support networks among men who inject drugs: feasibility and effectiveness.

BACKGROUND: Prevalence of hepatitis C virus (HCV) infection among people who inject drugs in the state of Manipur, India, is 43%; however, access to care is poor. We piloted a Community-led and comprehensive hepatitis care model that included same-day HCV treatment at drug treatment centres. METHODS: Screening was conducted through venipuncture samples collected by community peer PWID, using HCV antibody (HCV Ab) rapid screening and hepatitis B virus (HBV) surface antigen (HBsAg) rapid diagnostic tests. Reactive HCV Ab samples were tested for HCV RNA using near point-of-care Truenat® HCV on Truelab® Quattro. Eligible HCV RNA-positive participants were treated on the same day using direct-acting antivirals and followed for sustained virologic response (SVR). HBsAg-negative participants received rapid HBV vaccination regimen while those positive for HBsAg were tested for DNA and referred for treatment. RESULTS: Between November 2021 and August 2022, 643 individuals were approached and 503 consented and were screened. All screened were males with history of injection drug use, and a median age of 27 years (IQR 23-32). Of the 241 (47.9%) HCV Ab reactive all underwent RNA testing and 156 (64.7%) were RNA detectable. Of those with viraemia, 155 (99.4%) were initiated on treatment with 153 (98.1%) on same day, with 2 (1.2%) HBsAg positive and waiting for HBV DNA results. Among those 153, median time from HCV Ab screening to treatment was 6 h 38 min (IQR 5 h 42 min-8 h 23 min). In total 155 (100%) completed HCV treatment, of those 148 (95.5%) completed SVR testing and 130 (87.8%) achieved SVR12. 27 (5%) participants were HBsAg-positive, 3 (11.1%) were also living with HCV viraemia; 443 (97.6%) were eligible for vaccination and 436 (98.4%) received all 3 vaccine doses. CONCLUSION: Community-led hepatitis care incorporating same day "test and treat" for HCV was feasible and effective. HBV screening identified a large proportion who were unvaccinated. Peer support extended resulted in ensuring compliance to care and treatment cascade and completing all the three doses of HBV vaccination. As the screening, diagnostics infrastructure and vaccine are available in most countries with national viral hepatitis programs also in place, our model can be adapted or replicated to progress towards global elimination targets.

The metabolic fingerprint of chronic hepatitis C progression: Metabolome shifts and cutting-edge diagnostic options.

Hepatitis C virus infection causes chronic diseases such as cirrhosis and hepatocellular carcinoma. Metabolomics research has been shown to be linked to pathophysiologic pathways in liver illnesses. The aim of this study was to investigate the serum metabolic profile of patients with chronic hepatitis C (CHC) infection and to identify underlying mechanisms as well as potential biomarkers associated with the disease. Nuclear magnetic resonance (NMR) was used to evaluate the sera of 83 patients with CHC virus and 52 healthy control volunteers (NMR). Then, multivariate statistical analysis was used to find distinguishing metabolites between the two groups. Sixteen out of 40 metabolites including include 3-HB, betaine, carnitine, creatinine, fucose, glutamine, glycerol, isopropanol, lysine, mannose, methanol, methionine, ornithine, proline, serine, and valine-were shown to be significantly different between the CHC and normal control (NC) groups (variable importance in projection >1 and p < 0.05). All the metabolic perturbations in this disease are associated with pathways of Glycine, serine, and threonine metabolism, glycerolipid metabolism, arginine and proline metabolism, aminoacyl-tRNA biosynthesis, cysteine and methionine metabolism, alanine, aspartate, and glutamate metabolism. Multivariate statistical analysis constructed using these expressed metabolites showed CHC patients can be discriminated from NCs with high sensitivity (90%) and specificity (99%). The metabolomics approach may expand the diagnostic armamentarium for patients with CHC while contributing to a comprehensive understanding of disease mechanisms.

Dysregulated metabolites and lipids in serum of patients with acute hepatitis E: A longitudinal study.

Hepatitis E is a disease associated with acute inflammation of the liver. It is related to several dysregulated metabolic pathways and alterations in the concentration of several metabolites. However, longitudinal analysis of the alterations in metabolites and lipids is generally lacking. This study investigated the changes in levels of metabolites and lipids over time in sera from men with acute hepatitis E compared to healthy controls similar in age and gender. Untargeted measurement of levels of various metabolites and lipids was done using mass spectrometry on 65 sera sequentially sampled from 14 patients with acute hepatitis E and 25 serum samples from five controls. Temporal changes in intensities of metabolites and lipids were determined over different times at 3-day periods for the hepatitis E virus (HEV) group. In carbohydrate metabolism, glucose levels, fructose 1-6-bisphosphate and ribulose-5-phosphate were increased in the HEV-infected persons compared to the healthy controls. HEV infection is significantly associated with decreased levels of inosine, guanosine, adenosine and urate in purine metabolism and thymine, uracil and ß-aminoisobutyrate in pyrimidine metabolism. Glutamate, alanine and valine levels were significantly lower in the HEV group than in healthy individuals. Homogentisate of tyrosine metabolism and cystathionine of serine metabolism were increased, whereas kynurenate of tryptophan metabolism decreased in the HEV group. Metabolites of the bile acid biosynthesis, urea cycle (arginine and citrulline) and ammonia recycling (urocanate) were significantly altered. Co-enzymes, pantothenate and pyridoxal, and co-factors, lipoamide and FAD, were elevated in the HEV group. The acylcarnitines, sphingomyelins, phosphatidylcholine (PC), phosphatidylethanolamine (PE), lysoPC and lysoPE tended to be lower in the HEV group. In conclusion, acute hepatitis E is associated with altered metabolite and lipid profiles, significantly increased catabolism of carbohydrates, purines/pyrimidines and amino acids, and decreased levels of several glycerophospholipids.

Impact of body mass index on disease progression and outcomes in patients with nonalcoholic fatty liver disease.

BACKGROUND: The relationship between body mass index (BMI) and outcomes in patients with nonalcoholic fatty liver disease (NAFLD) is not well defined. This study aimed to assess the presentations, outcomes, and development of liver-related events (LREs) and non-LREs in patients with NAFLD stratified by BMI. METHODS: Records of NAFLD patients from 2000-2022 were reviewed. Patients were categorized as lean (18.5-22.9 kg/m2), overweight (23-24.9 kg/m2), and obese (>25 kg/m2) based on BMI. Stage of steatosis, fibrosis, and NAFLD activity score were noted in the patients undergoing liver biopsy in each group. RESULTS: Out of 1051 NAFLD patients, 127 (12.1%) had normal BMI, 177 (16.8%) and 747 (71.1%) were overweight and obese, respectively. Median [interquartile range] BMI was 21.9 [20.6-22.5], 24.2 [23.7-24.6], and 28.3 [26.6-30.6] kg/m2 in each group, respectively. Prevalence of metabolic syndrome and dyslipidemia were significantly higher in the obese. Obese patients had significantly higher median [interquartile range] liver stiffness (6.4 [4.9-9.4] kPa) than overweight and lean subjects. A higher proportion of obese patients had significant and advanced liver fibrosis. At follow-up, there were no significant differences in the progression of liver disease, new LREs, coronary artery disease, or hypertension across the BMI groups. Overweight and obese patients were more likely to develop new-onset diabetes by follow-up. The mortality rates in the three groups were comparable (0.47, 0.68, and 0.49 per 100 person-years, respectively), with similar causes of death (liver-related vs non-liver-related). CONCLUSIONS: Patients with lean NAFLD have similar disease severity and rates of progression as the obese. BMI is not a reliable determinant of outcomes in NAFLD patients.

Eight versus twelve weeks of sofosbuvir-velpatasvir in treatment-naïve non-cirrhotic patients with chronic hepatitis C virus infection: Study protocol for a multicentric, open labelled, randomized, non-inferiority trial (RESOLVE trial).

BACKGROUND: Hepatitis C virus (HCV) is a common cause of liver cirrhosis and hepatocellular carcinoma. Globally, nearly 71 million people have chronic HCV infection, and approximately 399,000 dies annually. In patients without cirrhosis, HCV infection is treated with 12 weeks of sofosbuvir/velpatasvir combination. Results from available small, single-centre observational studies suggest that the sofosbuvir/velpatasvir combination given for 8 weeks may be as effective as the standard 12 weeks of treatment. We propose to compare the treatment response of 12 weeks versus 8 weeks of sofosbuvir/velpatasvir in non-cirrhotic people with chronic HCV infection. METHODS: This multicentric, randomized, open-label, non-inferiority trial will include 880 (2 arms x 440) treatment naïve, viraemic (HCV RNA >10,000 IU/mL), non-cirrhotic adults (age >18 years) with chronic hepatitis C. People who are at high-risk for HCV reinfection such as haemophiliacs, people who inject drugs, those on maintenance hemodialysis or having HIV will be excluded. The presence or absence of cirrhosis will be determined with a combination of history, examination, ultrasound, liver stiffness measured with transient elastography, APRI, FIB-4, and esophagogastroduodenoscopy. Participants will be randomized to receive either 8- or 12-week sofosbuvir/velpatasvir treatment. A blood specimen will be collected before starting the treatment (to determine the HCV genotype), after 4 weeks of treatment (for early virological response), and at 12 weeks after treatment discontinuation for SVR12. DISCUSSION: The study will provide data on the efficacy of 8 weeks of treatment as compared to the standard of care (12 weeks) in non-cirrhotic patients with chronic HCV infection. Treatment for a shorter duration may improve treatment compliance, reduce the cost of treatment, and ease the treatment implementation from a public health perspective. TRIAL REGISTRATION: Registered with Clinical Trial Registry of India (http://ctri.nic.in) Registration No. CTRI/2022/03/041368 [Registered on: 24/03/2022]-Trial Registered Prospectively.

Endoscopic ultrasound-guided liver biopsy using a single-pass, slow-pull technique with a 19-G Franseen tip fine-needle biopsy needle: A prospective study.

BACKGROUND AND AIMS: Endoscopic ultrasound-guided liver biopsy (EUS-LB) is considered to be safe and effective. Commonly a 19-G fine-needle aspiration or biopsy needle is used. But, the results vary with different techniques that are used. Herein, we report the results of liver biopsy with a single-pass, three actuations (1:3) using the slow-pull technique. METHODS: In this prospective study, 50 consecutive patients with indications for liver biopsy underwent EUS-LB with a 19-gauge fine-needle biopsy (FNB) needle from both right and left lobes. The primary outcome was the adequacy of the specimen for histological diagnosis. Total specimen length (TSL), longest specimen length (LSL), complete portal tracts (CPTs) and comparison of these outcomes between the left lobe and right lobe specimens were secondary outcomes. Adverse events (AEs) were also measured during this study. RESULTS: Adequate tissue for histological diagnosis was obtained in all 50 patients (100%). The median number of CPTs was 32.5 (range, 11-58), while the median of TSL was 58 mm (range, 35-190) and the median LSL was 15 mm (range, 5-40). There was no significant difference in CPTs, TSL and LSL between left and right lobe biopsies. There was no major complication; one of the patients (2%) had bleed from the duodenal puncture site, which was managed endoscopically without the need for blood transfusion. CONCLUSIONS: Endoscopic ultrasound-guided liver biopsy using a 19-gauge Franseen tip needle with a single pass, three actuation (1:3) and slow-pull technique provides adequate tissue yield and has a good safety profile.

Antibody response to ChAdOx1 nCoV-19 (Covishield®) vaccine in people on maintenance hemodialysis.

INTRODUCTION: People on renal replacement therapy (RRT) have a high risk of COVID-19 infection and subsequent death. COVID-19 vaccination is strongly recommended for those on RRT. Data are limited on the immune response of the ChAdOx1 nCoV-19/AZD1222 (Covishield®) vaccine in patients on RRT. METHODS: A prospective cohort of adult (age > 18 years), on RRT in the form of hemodialysis were included and received two intramuscular doses of Covishield®. A blood specimen of 5.0 mL was collected at two time points, within a few days before administering the first dose of the vaccine and at 4-16 weeks after the second dose. According to their prior COVID-19 infection status, the participants were grouped as (i) prior symptomatic COVID-19 infection, (ii) prior asymptomatic COVID-19 infection, and (iii) no prior COVID-19 infection. RESULTS: A large proportion (81%) of participants had anti-spike antibodies (ASAb) before vaccination, and a reasonable proportion (30%) also had neutralizing antibodies (NAb). The titer of ASAb was relatively low (207 U/mL) before vaccination. The ASAb titer (9405 [1635-25,000] U/mL) and percentage of NAb (96.4% [59.6-98.1%]) were markedly increased following the administration of two doses of the vaccine. The participants' prior COVID-19 exposure status did not influence the rise in ASAb titer and NAb percentage. Further, administering two doses of the Covishield vaccine helps them achieve a high ASAb titer. CONCLUSION: Two doses of ChAdOx1 nCoV-19/AZD1222 (Covishield®) vaccine, given 12 weeks apart, achieve a high titer of ASAb and a high percentage of NAb in people on hemodialysis.

Nasojejunal tube-assisted endoscopic ultrasound-guided gastrojejunostomy for the management of gastric outlet obstruction is safe and effective.

Background and aims: Endoscopic ultrasound-guided gastrojejunostomy (EUS-GJ) is a therapeutic option for patients with gastric outlet obstruction (GOO), which provides long-term luminal patency without the risk of tumor ingrowth and/or overgrowth and avoids surgical morbidity. The goal of this study was to assess technical success, clinical success, and adverse events associated with a nasojejunal tube-assisted EUS- GJ technique. Methods: This was a retrospective study conducted at a single tertiary care center. The nasojejunal tube (14F) was used to perform the EUS-GJ (device-assisted method). During the study period, consecutive GOO patients who underwent EUS-GJ between August 2018 and December 2021 were included. Technical success was defined as adequate positioning and deployment of the stent. The patient's ability to tolerate a normal oral diet without vomiting was defined as clinical success. Results: Thirty patients underwent EUS-GJ during this study period. Twenty-six patients had malignant GOO, while four had a benign obstruction. EUS-GJ was successfully performed in 29 patients, and technical success was 96.67% (29/30). Nasojejunal tube-assisted EUS-GJ technique was used in all patients. Clinical success was achieved in all patients who had technical success (29/29, 100%). The adverse events rate was 6.6%. During the procedure, the median procedure time was 25 min (interquartile range 15-42.5), and the average hospitalization was 4.4 days. Normal meals were tolerated by all patients. After 210 days of median follow-up (range 5-880 days), no recurrence of symptoms was observed. Conclusion: The nasojejunal tube-assisted EUS-GJ is a safe and effective technique to treat GOO symptoms.

Pharmacological inhibition of CFTR attenuates nonalcoholic steatohepatitis (NASH) progression in mice.

Nonalcoholic steatohepatitis (NASH) is considered a pivotal stage in nonalcoholic fatty liver disease (NAFLD) progression and increases the risk of end-stage liver diseases such as fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The etiology of NASH is multifactorial and identifying reliable molecular players has proven difficult. Presently, there are no approved drugs for NASH treatment, which has become a leading cause of liver transplants worldwide. Here, using public human transcriptomic NAFLD dataset, we uncover Cystic fibrosis transmembrane conductance receptor (CFTR) as a differentially expressed gene in the livers of human NASH patients. Similarly, murine Cftr expression was also found to be upregulated in two mouse models of diet-induced NASH. Furthermore, the pharmacological inhibition of CFTR significantly reduced NASH progression in mice and its overexpression aggravated lipotoxicity in human hepatic cells. These results, thus, underscore the involvement of murine Cftr in the pathogenesis of NASH and raise the intriguing possibility of its pharmacological inhibition in human NASH.

A Systematic Review of Risk Factors for Hepatitis C Virus Infection Among Low-Risk Population in India.

Background: Identification of risk factors for hepatitis C virus (HCV) transmission will help in targeted screening of people who are at risk for HCV. Method: Indian studies, published between January 1989 and June 2020, were systematically reviewed to identify the relevant studies. We searched electronic databases including PubMed/Medline, Embase, Scopus, and Google scholar to identify the original data published in English language. The full-text studies, published in any form, which reported data on risk factors for HCV transmission among low-risk population were selected. The studies which exclusively included high-risk groups were excluded. Results: Data were extracted from 31,176 participants included in 25 studies (median [range] 40 [7-20,113). The participants were HCV infected patients who visited the hospital (n = 10), community population (n = 6), pregnant women (n = 5), blood donors (n = 2), people with diabetes mellitus (n = 1), army recruits (n = 1), or slum dwellers (n = 1). These studies provided data on blood transfusion, use of unsafe injections, minor or major surgery, unsafe dental procedures, tattooing, body piercing, obstetrical procedures, unsafe shaving, intravenous drug use, and unsafe sexual practices as risk factors for HCV transmission. Conclusion: Unsafe injections, body piercing, unsafe dental procedure, unsafe shaving, and tattooing were identified as major risk factors for reported by HCV population participants.More data are needed to identify the risk factors for HCV in Indian population. Risk-factor-targeted screening may increase the yield and reduce the cost of HCV screening in India.

Scoring systems in critically ill: Which one to use in cancer patients?

BACKGROUND: Scoring systems have not been evaluated in oncology patients. We aimed to assess the performance of Acute Physiology and Chronic Health Evaluation (APACHE) II, APACHE III, APACHE IV, Simplified Acute Physiology Score (SAPS) II, SAPS III, Mortality Probability Model (MPM) II0 and Sequential Organ Failure Assessment (SOFA) score in critically ill oncology patients. AIM: To compare the efficacy of seven commonly employed scoring systems to predict outcomes of critically ill cancer patients. METHODS: We conducted a retrospective analysis of 400 consecutive cancer patients admitted in the medical intensive care unit over a two-year period. Primary outcome was hospital mortality and the secondary outcome measure was comparison of various scoring systems in predicting hospital mortality. RESULTS: In our study, the overall intensive care unit and hospital mortality was 43.5% and 57.8%, respectively. All of the seven tested scores underestimated mortality. The mortality as predicted by MPM II0 predicted death rate (PDR) was nearest to the actual mortality followed by that predicted by APACHE II, with a standardized mortality rate (SMR) of 1.305 and 1.547, respectively. The best calibration was shown by the APACHE III score (χ 2 = 4.704, P = 0.788). On the other hand, SOFA score (χ 2 = 15.966, P = 0.025) had the worst calibration, although the difference was not statistically significant. All of the seven scores had acceptable discrimination with good efficacy however, SAPS III PDR and MPM II0 PDR (AUROC = 0.762), had a better performance as compared to others. The correlation between the different scoring systems was significant (P < 0.001). CONCLUSION: All the severity scores were tested under-predicted mortality in the present study. As the difference in efficacy and performance was not statistically significant, the choice of scoring system used may depend on the ease of use and local preferences.

Exosome-associated microRNA-375 induces cell proliferation by regulating IGFBP4 upon hepatitis C virus infection.

Hepatitis C virus (HCV) infection is one of the most common causes of liver cancer. HCV infection causes chronic disease followed by cirrhosis, which often leads to hepatocellular carcinoma (HCC). In this study, we investigated the roles of exosome-associated miRNAs in HCV-induced disease pathology. Small RNA sequencing was performed to identify miRNAs that are differentially regulated in exosomes isolated from patient sera at two different stages of HCV infection: cirrhosis and hepatocellular carcinoma. Among the differentially expressed miRNAs, miR-375 was found to be significantly upregulated in exosomes isolated from patients with cirrhosis and HCC. A similar upregulation was observed in intracellular and extracellular/exosomal levels of miR-375 in HCV-JFH1 infected Huh7.5 cells. The depletion of miR-375 in infected cells inhibited HCV-induced cell migration and proliferation, suggesting a supportive role for miR-375 in HCV pathogenesis. miR-375, secreted through exosomes derived from HCV-infected cells, could also be transferred to naïve Huh7.5 cells, resulting in an increase in cell proliferation and migration in the recipient cells. Furthermore, we identified Insulin growth factor binding protein 4 (IGFBP4), a gene involved in cell growth and malignancy, as a novel target of miR-375. Our results demonstrate the critical involvement of exosome-associated miR-375 in HCV-induced disease progression.

Multifocal Small Bowel Angioectasias: Managed with Innovative, Nonresectional Surgical Procedure.

Gastrointestinal (GI) angioectasias/angiodysplasias are the most frequent vascular lesions of GI tract, responsible for ∼5 to 6% of GI bleedings. It commonly involves the small bowel, making it difficult to diagnose and manage endoscopically. Though medical management has been used to prevent bleeding, it has only a limited role in acute severe hemorrhage. In such cases, surgical resection remains the only practical option. However, multiple lesions pose a unique challenge, as resection may not be advisable for long length of bowel involvement. Here, we report a case of recurrent GI bleeding due to multifocal small bowel angioectasias who was managed by a novel technique of full-thickness transmural sutures under intraoperative enteroscopic guidance. At 6 months follow-up, no new bleeding episodes were observed.

Prevalence of Non-alcoholic Fatty Liver Disease in India: A Systematic Review and Meta-analysis.

Background: Non-alcoholic fatty liver disease (NAFLD) contributes to a large proportion of liver disease burden in the world. Several groups have studied the prevalence of NAFLD in the Indian population. Aim: A systematic review of the published literature and meta-analysis was carried out to estimate the prevalence of NAFLD in the Indian population. Methods: English language literature published until April 2021 was searched from electronic databases. Original data published in any form which had reported NAFLD prevalence in the Indian population were included. The subgroup analysis of prevalence was done based on the age (adults or children) and risk category, i.e., average-risk group (community population, participants of control arm, unselected participants, hypothyroidic individuals, athletes, aviation crew, and army personnel) and high-risk group (obesity or overweight, diabetes mellitus, coronary artery disease, etc.). The prevalence estimates were pooled using the random-effects model. Heterogeneity was assessed with I2. Results: Sixty-two datasets (children 8 and adults 54) from 50 studies were included. The pooled prevalence of NAFLD was estimated from 2903 children and 23,581 adult participants. Among adults, the estimated pooled prevalence was 38.6% (95% CI 32-45.5). The NAFLD prevalence in average-risk and high-risk subgroups was estimated to be 28.1% (95% CI 20.8-36) and 52.8% (95% CI 46.5-59.1), respectively. The estimated NAFLD prevalence was higher in hospital-based data (40.8% [95% CI 32.6-49.3%]) than community-based data (28.2% [95% CI 16.9-41%]). Among children, the estimated pooled prevalence was 35.4% (95% CI 18.2-54.7). The prevalence among non-obese and obese children was 12.4 (95% CI 4.4-23.5) and 63.4 (95% CI 59.4-67.3), respectively. Conclusion: Available data suggest that approximately one in three adults or children have NAFLD in India.

Seroprevalence and burden of hepatitis C virus infection in WHO South-East Asia Region: A systematic review.

BACKGROUND: This systematic review was aimed to estimate hepatitis C virus (HCV) seroprevalence and burden in disease in WHO South East Asia Region (SEAR). METHODS: Electronic databases (PubMed, Scopus, Embase, and Google Scholar) and websites of non-indexed national medical journals, government and international health agencies were searched to identify English language literature published between 1991 and June 2020. We selected the studies reporting HCV seroprevalence in asymptomatic general (low-risk) and high-risk adult populations, that is, persons living with HIV (PLHIV), persons who inject drugs (PWID), sex workers, persons on maintenance hemodialysis (MHD), people in prison, and men sex with men (MSM). Seroprevalence data were combined to estimate weighted pooled prevalence (95% confidence interval) in each group and in each country, using the random-effects model. Estimated pooled seroprevalences were multiplied with estimated populations at risk to estimate the overall HCV burden. RESULTS: The analysis included 538 studies (35 Bangladesh, 6 Bhutan, 2 DPR Korea, 323 India, 43 Indonesia, 2 Maldives, 18 Myanmar, 29 Nepal, 11 Sri Lanka, 67 Thailand, and 2 Timor-Leste). In SEAR, the weighted pooled anti-HCV seroprevalence was estimated as 0.84% (0.56-1.12) in low-risk population and 13.67% (10.95-16.40) in PLHIV, 51.44% (43.67-59.20) in PWID, 25.80% (20.34-32.09) in MHD, 8.39% (5.84-11.51) in prison inmates, 2.69% (1.43-4.13) in people with high-risk sex behavior, and 11.43% (8.61-14.74) in MSM. The total HCV burden in low-risk and high-risk populations in SEAR countries was estimated as 12.45 million and 1.65 million, respectively. CONCLUSION: Our estimates of HCV seroprevalence and burden should help the respective countries in planning their HCV elimination strategies.

LncRNA NEAT1 regulates HCV-induced Hepatocellular carcinoma by modulating the miR-9-BGH3 axis.

Chronic hepatitis C virus (HCV) infection is a leading cause of end-stage liver diseases, such as fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Several cellular entities, including paraspeckles and their related components, are involved in viral pathogenesis and cancer progression. NEAT1 lncRNA is a major component of paraspeckles that has been linked to several malignancies. In this study, analysis of the Cancer Genome Atlas (TCGA) database and validation in HCV-induced HCC tissue and serum samples showed significantly high expression of NEAT1 in patients with liver cancer. Moreover, we found that NEAT1 levels increased upon HCV infection. To further understand the mechanism of NEAT1-induced HCC progression, we selected one of its targets, miR-9-5 p, which regulates BGH3 mRNA levels. Interestingly, miR-9-5 p levels were downregulated upon HCV infection, whereas BGH3 levels were upregulated. Additionally, partial NEAT1 knockdown increased miR-9-5 p levels and decreased BGH3 levels, corroborating our initial results. BGH3 levels were also upregulated in HCV-induced HCC and TCGA tissue samples, which could be directly correlated with NEAT1 levels. As a known oncogene, BGH3 is directly linked to HCC progression mediated by NEAT1. We also found that NEAT1 levels remained upregulated in serum samples from patients treated with direct-acting antivirals (DAA), indicating that NEAT1 might be a molecular trigger that promotes HCC development. Collectively, these findings provide molecular insights into HCV-induced HCC progression via the NEAT1-miR-9-BGH3 axis.

EUS-guided drainage of pancreatic fluid collection, using a modified technique of cystotome alone without a FNA needle.

BACKGROUND: Endoscopic ultrasound (EUS)-guided drainage for pancreatic fluid collection (PFC) involves puncture with a fine-needle aspiration (FNA) needle, followed by tract dilation involving exchange of multiple accessories, and finally deployment of stent. The procedure is time consuming and carries a risk of loss of wire access and hence technical failure. We used a modified technique with a 10-F cystotome alone instead of a FNA needle and dilators. METHODS: We retrospectively analysed records of consecutive patients who had undergone EUS-guided drainage of PFC using a modified technique, with puncture of PFC using a 10-Fcystotome, followed by passage of a guidewire through it into the PFC cavity and deployment of a biflanged, 2-cm-long, fully covered self-expanding metal stent over it. Technical and clinical success rates and procedure time were assessed. RESULTS: Forty-five patients underwent PFC drainage, median age was 35 (12-76), and 35 (77.8%) were males. The median (range) duration of symptoms was 125 (38-1080) days, while the median PFC size was 11.8 × 11 × 11 cm, and the follow-up period after stent removal was 111 ± 72 (18-251) weeks. The procedure took 10 (8-12) min and had technical and clinical success rates of 100 and 97.8%, respectively. Minor complications occurred in six (13.3%) patients, while recurrence occurred in one. CONCLUSION: EUS-guided drainage of PFC using a cystotome is a quick, effective and safe procedure. It may also be less expensive since it obviates the use of FNA needles and dilators, and is likely to be a useful alternative to the conventional technique.

Blood transfusion is unlikely to be a source for hepatitis E virus transmission in India.

INTRODUCTION: Transmission of hepatitis E virus (HEV) through transfusion has been reported from countries where genotype 3 virus is predominant. Data from countries with predominantly genotype 1 HEV, such as India, are limited. We studied the risk of HEV transmission following transfusion of blood or blood components in India. METHODS: Adult patients undergoing cardiac surgery who received transfusion of blood or blood products in the peri-operative period and who lacked history of any transfusion or surgery in the preceding 1 year were studied. A pre-transfusion blood specimen was collected for IgG anti-HEV antibody test. For the participants who were seronegative for anti-HEV, follow up specimens were collected at every 2-3-month intervals for up to 6 months after surgery and were tested for IgM and IgG anti-HEV antibodies. RESULTS: Of the 335 participants originally enrolled, 191 (57%) could be followed up. Of them, 103 (53.9%) were seropositive for HEV IgG at baseline and were excluded. Of the remaining 88 participants (age 42 ± 14.1 years; 55 [63%] male), none reported hepatitis-like illness during the follow up period of 81 ± 23 days. Also, none of these 88 participants was found to have seroconversion to anti-HEV IgM or IgG positivity in the follow up specimens. CONCLUSION: Transfusion-mediated transmission of HEV was not observed in our cohort and may be infrequent in the Indian population, where genotype 1 is the predominant HEV type.

Gut microbiota abnormalities, small intestinal bacterial overgrowth, and non-alcoholic fatty liver disease: An emerging paradigm.

Evidence accumulates to implicate a role for the gut microbiota in non-alcoholic fatty liver disease (NAFLD)-a disorder that has reached almost epidemic proportions around the globe. For some time a disturbance in the gut microbiome, small intestinal bacterial overgrowth (SIBO), has been described among patients with liver disease, in general, and in the development and progression of NAFLD to nonalcoholic steatohepatitis (NASH), decompensated liver disease and hepatocellular cancer (HCC), in particular. More recently and permitted by the advent of high-throughput sequencing and allied molecular techniques, a much more detailed analysis of gut microbiota in NAFLD and NASH has become possible. In animal models, several mechanisms have been delineated which reveal how gut bacteria and their products could promote steatosis, hepatic inflammation, fibrosis, cirrhosis, and carcinogenesis. For understandable reasons evidence from human studies is less complete, but here again a plausible case is beginning to emerge to incriminate microbiota in NAFLD and NASH pathogenesis. Therapeutic interventions based on the modulation of the microbiome have been explored to some extent, but their application to everyday medical practice is still in the future.

Positional therapy for obstructive sleep apnoea.

BACKGROUND: The modalities of therapy for obstructive sleep apnoea (OSA) include behavioural and lifestyle modifications, positional therapy, oral appliances, surgery and continuous positive airway pressure therapy (CPAP). Though CPAP has proven efficacy in treating OSA, adherence with CPAP therapy is suboptimal. Positional therapy (to keep people sleeping on their side) is less invasive and therefore expected to have better adherence. This review considered the efficacy of positional therapy compared to CPAP as well as positional therapy against no positional therapy. Devices designed for positional therapy include lumbar or abdominal binders, semi-rigid backpacks, full-length pillows, a tennis ball attached to the back of nightwear, and electrical sensors with alarms that indicate change in position. OBJECTIVES: To compare the efficacy of positional therapy versus CPAP and positional therapy versus inactive control (sham intervention or no positional therapy intervention) in people with OSA. SEARCH METHODS: We identified studies from the Cochrane Airways' Specialised Register (including CENTRAL, MEDLINE, Embase, CINAHL, AHMED and PsycINFO), ClinicalTrials.gov, and the World Health Organization trials portal (ICTRP). It also contains results derived from handsearching of respiratory journals and abstract books of major annual meetings. We searched all databases from their inception to September 2018, with no restrictions on language of publication or publication type. SELECTION CRITERIA: We included randomised controlled trials comparing positional therapy with CPAP and positional therapy with inactive control. DATA COLLECTION AND ANALYSIS: Two review authors independently selected studies and extracted the data. We used a random-effects model in the meta-analysis to estimate mean differences and confidence intervals. We assessed certainty of evidence using the GRADE approach. MAIN RESULTS: We included eight studies. The studies randomised 323 participants into two types of interventions. The comparison between positional therapy and CPAP included 72 participants, while the comparison between positional therapy and inactive control included 251 participants. Three studies used supine vibration alarm devices, while five studies used physical positioning like specially designed pillows or semirigid backpacks.Positional therapy versus CPAPThe three studies included for this comparison were randomised cross-over trials. Two studies found that there was no difference in Epworth Sleepiness Scale (ESS) scores between CPAP and positional therapy. Two studies showed that CPAP produced a greater reduction in Apnoea-Hypopnoea Index (AHI) with a mean difference (MD) of 6.4 events per hour (95% CI 3.00 to 9.79; low-certainty evidence) compared to positional therapy. Subjective adherence, evaluated in one study, was found to be significantly greater with positional therapy (MD 2.5 hours per night, 95% CI 1.41 to 3.59; moderate-certainty evidence).In terms of secondary outcomes, one study each reported quality-of-life indices and quality-of-sleep indices with no significant difference between the two groups. One study reported cognitive outcomes using multiple parameters and found no difference between the groups. There were insufficient data to comment on other secondary outcomes like respiratory disturbance index (RDI), and frequency and duration of nocturnal desaturation. None of the studies clearly reported adverse effects.Positional therapy versus inactive controlThree studies of positional therapy versus no intervention were randomised cross-over trials, while two studies were parallel-arm studies. Data from two studies showed that positional therapy significantly improved ESS scores (MD -1.58, 95% CI -2.89 to -0.29; moderate-certainty evidence). Positional therapy showed a reduction in AHI compared with control (MD -7.38 events per hour, 95% CI -10.06 to -4.7; low-certainty evidence). One study reported adherence. The number of participants who continued to use the device at two months was no different between the two groups (odds ratio (OR) 0.80, 95% CI 0.33 to 1.94; low-certainty evidence). The same study reported adverse effects, the most common being pain in the back and chest, and sleep disturbance but there was no significant difference between the two groups in terms of device discontinuation (OR 1.25, 95% CI 0.5 to 3.03; low-certainty evidence). One study each reported quality-of-life indices and quality-of-sleep indices, with no significant difference between the two groups. One study reported cognitive outcome, and found no difference between the groups. There was insufficient evidence to comment on other secondary outcomes (RDI, frequency and duration of nocturnal desaturation). AUTHORS' CONCLUSIONS: The review found that CPAP has a greater effect on improving AHI compared with positional therapy in positional OSA, while positional therapy was better than inactive control for improving ESS and AHI. Positional therapy may have better adherence than CPAP. There were no significant differences for other clinically relevant outcomes such as quality of life or cognitive function. All the studies were of short duration. We are unable to comment on the long-term effects of the therapies. This is important, as most of the quality-of-life outcomes will be evident only when the therapies are given over a longer period of time. The certainty of evidence was low to moderate.