Definitions, Etiologies, and Outcomes of Acute on Chronic Liver Failure: A Systematic Review and Meta-analysis.

BACKGROUND & AIMS: Acute-on-chronic liver failure (ACLF) is a major public health concern. We aimed to assess the definitions, etiologic spectrum, organ failure (OF), and outcomes of ACLF globally. METHODS: Three databases were searched for studies on ACLF from 1990 until September 2022. Information regarding definitions, acute precipitants, underlying chronic liver disease (CLD), OF, and mortality were extracted. Meta-analyses were performed for pooled prevalence rates (95% confidence interval [CI]) using random-effects model for each definition of ACLF. RESULTS: Of the 11,451 studies identified, 114 articles (142 cohorts encompassing 210,239 patients) met the eligibility criteria. Most studies (53.2%) used the European Association for the Study of the Liver (EASL) definition, followed by Asia-Pacific Association for the Study of the Liver (APASL) (33.3%). Systemic infection was the major acute precipitant, and alcohol use was the major cause of CLD in EASL-defined studies, whereas alcohol was both the major acute precipitant and cause of CLD in APASL-defined studies. Liver failure was the major OF in APASL-based studies, whereas renal failure was predominant in EASL-based studies. Thirty-day mortality varied across definitions: APASL: 38.9%, 95% CI, 31.2%-46.9%; EASL: 47.9%, 95% CI, 42.2%-53.5%; and NACSELD: 52.2%, 95% CI, 51.9%-52.5%. Diagnostic overlap between definitions ranged from 7.7% to 80.2%. Meta-regression suggested that the World Health Organization region influenced 30-day mortality in studies using EASL definition. CONCLUSIONS: Heterogeneity in the definition of ACLF proposed by different expert societies and regional preferences in its use result in differences in clinical phenotype and outcomes. A uniform definition would enhance the comparability and interpretation of global data.

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.

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.

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.

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.

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.

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.

Comparison between presepsin, procalcitonin, and CRP as biomarkers to diagnose sepsis in critically ill patients.

Background and Aims: Mortality associated with sepsis continues to remain high. Early diagnosis and aggressive management may improve outcomes. Biomarkers may help in early diagnosis, but the search for an ideal biomarker continues. Presepsin has been introduced as a new biomarker, however, it still needs validation before its use becomes routine. In this study, we aimed to compare the efficacy of various biomarkers in patients with suspected sepsis. Material and Methods: A retrospective analysis of 100 patients with suspected infection, admitted in the medical intensive care unit (ICU) was conducted. Diagnosis of sepsis was made on the basis of the current surviving sepsis guidelines criteria. Results: Out of 100 patients, 70 were diagnosed to have sepsis, and overall ICU mortality was 22%. Overall, C-reactive protein (CRP) was positive in 98, procalcitonin in 75, and presepsin in 64 patients. For diagnosis of sepsis the sensitivity, specificity, and AUC, respectively, for CRP was 98.6%, 3.3%, and 0.725. For procalcitonin (>0.5 ng/ml) it was 87.1%, 53.3%, and 0.776, and for procalcitonin (>1 ng/ml) 70%, 70%, and 0.816, respectively. For presepsin sensitivity, specificity, and AUC, respectively, for diagnosis of sepsis was 77.1%, 66.7%, and 0.734. For ICU mortality, sensitivity and specificity for CRP was 95.5% and 1.3%, for procalcitonin (>0.5) 72.7% and 24.4.%, for procalcitonin (>1) 59.1% and 42.3%, and for presepsin 61.5% and 27.3%, respectively. Conclusion: Inflammatory markers may be raised in a large proportion of ICU patients, even in those without sepsis. Procalcitnonin and presepsin had similar efficacy in diagnosing sepsis. However, none of the three biomarkers studied were accurate in predicting ICU mortality.

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.

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.

Short course of low-dose pregabalin is effective for the treatment of restless leg syndrome in patients with cirrhosis: A pilot study.

BACKGROUND AND AIM: Restless leg syndrome (RLS) is common in patients with cirrhosis, but its treatment in such patients remains unclear. This pilot study assessed the clinical effectiveness of intravenous iron and a 6-week course of low-dose (75 mg/day) pregabalin for the treatment of RLS in patients with cirrhosis. METHODS: It was a prospective, interventional study that included adult patients with cirrhosis and RLS. The participants underwent serum ferritin measurement. Patients with low serum ferritin (< 75 µg/dL) were treated with intravenous iron. Those with normal ferritin levels and those with low levels whose RLS symptoms failed to respond to iron replacement were treated with oral pregabalin, initially 75 mg/day for 6 weeks, followed by 150 mg/day for 6 weeks if there was no response. Recurrence of symptoms was assessed at 6-12 weeks after stopping pregabalin. RESULTS: Of the 50 patients (male patients 52%; median age 48 [interquartile range: 21-65] years; median Child-Pugh-Turcotte score 8 [5-13] and median Model for End-Stage Liver disease score 17 [12-20]) studied, 29 (58%) had low ferritin; of them, 14 (48%) responded to intravenous iron alone. Eleven of 15 (38%) patients with low ferritin and nonresponse to iron, and 16 of 21 (76%) with normal ferritin levels had a response with low-dose pregabalin. Of the nine nonresponders who received 150 mg/day of pregabalin, four had to discontinue it because of adverse effects. CONCLUSION: A short course of low-dose (75 mg/day) pregabalin was effective (82%) in alleviating RLS in patients with cirrhosis. (CTRI/2019/02/017642).

Acute hepatitis C treatment in advanced renal failure using 8 weeks of pan-genotypic daclatasvir and reduced-dose sofosbuvir.

BACKGROUND: Sofosbuvir is not recommended in persons with estimated glomerular filtration rate (eGFR) <30 mL/min. We report the results of treatment with an off-label 8-week regimen of daclatasvir and half-dose sofosbuvir in patients with acute infection with hepatitis C virus ( HCV) and eGFR <30 mL/min. METHODS: Clinic records were searched to identify treatment-naïve, noncirrhotic adults with acute hepatitis C (HCV viremia and a ≥10-fold elevation of serum alanine aminotransferase activity) and eGFR <30 mL/min, who had been treated with a sofosbuvir-based regimen. Treatment response was assessed using serum HCV RNA testing at 4 weeks of treatment, end of the 8-week treatment and 12 weeks after stopping treatment. RESULTS: Of the 31 patients with acute hepatitis C, 27 [median age (range): 36 (18-74) years; 20 (74%) male] were started on treatment with 200 mg sofosbuvir and 60 mg daclatasvir daily for 8 weeks, irrespective of HCV genotype. All the 27 completed the planned 8-week treatment. One patient died 10 weeks after completing the treatment of an unrelated cause. All the 27 patients had undetectable HCV RNA after 4 weeks of and at the end of treatment. At 12 weeks after completion of treatment, only one tested HCV RNA positive and 25 were negative, with sustained virological response rate of 25/27 (92.6%) and 25/26 (96.2%) on intention-to-treat and per-protocol basis, respectively. CONCLUSION: Eight-week course of daclatasvir and half-dose sofosbuvir is effective for acute hepatitis C in patients with eGFR <30 mL/min and could be a useful alternative to costly, kidney-safe anti-HCV oral drugs in resource-constrained settings.

Temporal profile of HEV RNA concentration in blood and stool from patients with acute uncomplicated hepatitis E in a region with genotype 1 predominance.

Acute hepatitis E virus (HEV) is associated with viremia and faecal excretion of the virus. The information on duration and temporal pattern of viremia and faecal shedding in HEV infection is important, but is not available. Serial serum and stool specimens were collected from patients with acute hepatitis E (typical clinical picture, serum alanine aminotransferase levels > 5-folds the upper limit of normal and presence of IgM anti-HEV), beginning from within 7 days of the onset of symptoms. HEV RNA concentrations were measured in sera and 10% stool suspensions, using a real-time Taqman-based nucleic acid amplification assay. Seventeen patients (median age 25 [range 19-61] years; all men) were enrolled within a median of 5 (range 3-8) days of the onset of the first symptom and provided 113 serum specimens and 71 stool specimens. The median (range) highest levels of serum bilirubin, alanine aminotransferase and aspartate aminotransferase in the patients were 10.3 (5.9-43.4) mg/dL, 1817 (442-4642) IU/L and 1016 (88-4561) IU/L, respectively. All the 17 patients had demonstrable viremia, and 12 of the 13 patients who were tested had faecal excretion at one or more time points. The HEV RNA titres were the highest in the early phase of disease and declined rapidly with time, becoming nondetectable in the serum by day 20 and in the stool by day 21. In most of the patients with acute uncomplicated acute hepatitis E, the degree of viremia and faecal shedding decline quickly after the onset of clinical illness and rapidly disappear in parallel with each other.

Prevalence of hepatitis E viraemia among blood donors: a systematic review.

BACKGROUND: Hepatitis E virus (HEV) is usually transmitted by faecal-oral route. Recent reports have documented HEV viraemia in donated blood units and HEV transmission through blood transfusion. This systematic review summarizes the available data on prevalence of HEV viraemia in blood donors. METHODS: Electronic databases were searched on 17 December 2018 to identify full-text English papers reporting original data on prevalence of HEV RNA in donated blood units. Two authors independently extracted the relevant data, which were pooled using simple aggregation as well as a random-effects meta-analysis; heterogeneity was assessed using the I2 method. RESULTS: In all, 59 data sets from 28 countries were identified. The available data showed marked heterogeneity. Of a total of 2 127 832 units studied, 561 (263·6 [95% confidence intervals = 242·7-286·4] per million units) tested positive for HEV RNA. On random-effects meta-analysis, the pooled prevalence was 60·9 [6·7-155·4] per million units. In the viraemic units, HEV RNA titre varied by nearly one million-fold, and most had genotype 3 HEV. The prevalence was higher in blood units with anti-HEV antibodies or elevated alanine aminotransferase. Only nearly one-fourth of viraemic units had anti-HEV antibodies. CONCLUSIONS: The prevalence of HEV viraemia among healthy blood donors is low, though the available data had limited geographical representation and marked heterogeneity. There is a need for further data on HEV viraemia in blood donors from areas with non-3 HEV genotype preponderance.

Burden of hepatitis C virus infection in India: A systematic review and meta-analysis.

BACKGROUND AND AIM: Burden of hepatitis C in India is not known. We therefore conducted a systematic review of the available data on anti-hepatitis C virus (HCV) seroprevalence in the Indian population. METHODS: We searched several publication databases for English language papers that reported data on anti-HCV seroprevalence from India and also identified other unpublished sources of such data. Data on groups likely to represent seroprevalence in general population and in selected high-risk groups were extracted and subjected to meta-analysis. RESULTS: Of the 3995 published papers and 94 additional data sources identified, 327 were selected; these provided 414 anti-HCV seroprevalence data points. Pooled anti-HCV seroprevalence rates in community-based studies, blood donors, and pregnant women were 0.85% (95% confidence interval: 0.00-3.98%), 0.44% (0.40-0.49), and 0.88% (0.21-1.90), respectively. Among groups considered at high risk of HCV, pooled anti-HCV seroprevalence rates were as follows: people living with HIV (40 studies from 17 states: 3.51% [2.43-4.76]), persons on maintenance hemodialysis (37, 13; 19.23% [13.52-25.65]), people who inject drugs (46, 14; 44.71% [37.50-52.03]), multi-transfused persons (38, 12; 24.06% [20.00-28.36]), persons with sexually transmitted diseases (7, 5; 4.10% [0.98-9.04]), and those with high-risk sex behavior (6, 5; 4.06% [1.79-7.10]). CONCLUSIONS: Community-based data on HCV seroprevalence in India were limited. Large amount of data on blood donors and pregnant women were identified, with pooled anti-HCV seroprevalence rates of 0.44% and 0.88%, respectively. Among high-risk groups, anti-HCV prevalence was higher among people living with HIV, those with sexually transmitted diseases, high-risk sex behavior or injection drug use, and those receiving hemodialysis or frequent transfusions.

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.

Daclatasvir and reduced-dose sofosbuvir: An effective and pangenotypic treatment for hepatitis C in patients with estimated glomerular filtration rate <30 mL/min.

AIM: Sofosbuvir is a key agent for HCV treatment. It is not recommended for patients with chronic kidney disease (CKD) and estimated glomerular filtration rate (eGFR) <30 mL/min. We report real-life experience of treating a cohort of CKD patients with eGFR <30 mL/min using daclatasvir and half-daily dose of sofosbuvir. METHODS: Adults patients who (i) had eGFR<30 mL/min and detectable HCV RNA and (ii) were treated with interferon and ribavirin free, DAA based regimens were included. All patients were treated with daily doses of daclatasvir 60 mg and sofosbuvir 200 mg. The planned duration of treatment was 12 weeks, except for 24 weeks in those with either clinical evidence of cirrhosis or on immunosuppressive drugs. The end-points of the study were: (i) 12 weeks of follow-up after treatment completion, (ii) treatment discontinuation, or (iii) death or loss to follow-up. RESULTS: Thirty-six (88%) among 41 included patients (median [range] age: 48 [19-75] years; 25 [61%] male; genotype 1/3/4 were 17/ 22/2; cirrhosis 5) completed the treatment, two discontinued and three died during treatment. On an intention-to-treat basis, HCV RNA were undetectable at 4 weeks of treatment, treatment completion and after 12 weeks of follow-up in 40/41 (97.6%), 37/41 (90.2%) and 37/41 (90.2%), respectively. None of the patients had a relapse. CONCLUSIONS: Daclatasvir and half-daily dose of sofosbuvir was effective against genotype 1 and 3 HCV infection in patients with eGFR <30 mL/min. This combination could be a pangenotypic treatment option for such patients.

Comparing Outcomes of Robotic and Open Inguinal Lymph Node Dissection in Patients with Carcinoma of the Penis.

PURPOSE: We compared outcomes between robot-assisted video endoscopic inguinal lymphadenectomy and open inguinal lymph node dissection in patients without bulky nodal metastasis in a tandem contemporary cohort. MATERIALS AND METHODS: We retrospectively analyzed a prospectively maintained hospital registry of 51 patients who underwent robot-assisted video endoscopic inguinal lymphadenectomy and 100 treated with open inguinal lymph node dissection from 2012 to 2016 for groins without bulky nodal metastasis and who had a minimum 9-month followup. Complications were graded by the Clavien-Dindo classification, and nodal yield and disease recurrence during followup were assessed. Elastic net regression was used to select variables associated with major complications (Clavien 3a or greater) for multivariable analysis of plausible factors, including patient age, diabetes, body mass index, smoking, nodal stage, surgery type, sartorius transposition, saphenous vein transection and adjuvant radiotherapy. Penalized likelihood logistic regression methods were used for multivariate analysis to ascertain final effect sizes while accounting for sparse data bias. RESULTS: Robot-assisted video endoscopic inguinal lymphadenectomy and open inguinal lymph node dissection had comparable median lymph node yields (13 vs 12.5). No patient experienced recurrence during the median followup of 40 months. Robot-assisted video endoscopic inguinal lymphadenectomy was associated with significantly lower hospital stay, days needing a drain in situ, incidence of major complications, edge necrosis, flap necrosis and severe limb edema. On multivariable analysis pathological nodal stage (OR 2.8, 95% CI 1.1-6.8, p = 0.027) and open inguinal lymph node dissection (OR 7.5, 95% CI 1.3-43, p = 0.024) emerged as independent risk factors associated with an increased risk of major complications. CONCLUSIONS: Robot-assisted video endoscopic inguinal lymphadenectomy is a feasible technique which allows for a similar nodal yield while being associated with lower morbidity than open inguinal lymph node dissection in patients without bulky groin adenopathy.

Effect of administration of a probiotic preparation on gut microbiota and immune response in healthy women in India: an open-label, single-arm pilot study.

BACKGROUND: Probiotics have been shown to be useful for the treatment of many disease conditions. These beneficial effects are believed to be mediated by change in the composition of gut microbiota and modulation of the host immune responses. However, the available data on the effect of probiotics on these parameters are quite limited. METHODS: We studied the composition of fecal microbiota, using 16S rRNA sequencing, and host immune responses in peripheral blood (plasma cytokine levels, T cell subsets and in vitro cytokine production after stimulation with anti-CD3/CD28 antibody or lipopolysaccharide) in a group of 14 healthy women at three time-points - before and after administration of a probiotic preparation (a capsule of VSL#3, each containing 112.5 billion freeze-dried bacterial cells belonging to 8 species, twice a day for 4 weeks), and 4-weeks after discontinuation of the probiotic administration. RESULTS: There was no change in the abundance of various bacterial taxa as well as in the alpha diversity of gut microbiota following administration of the probiotic, or following its discontinuation. Probiotic administration led to a reduction in the relative frequency of circulating Th17 cells, and in vitro production of cytokines in whole-blood cultures in response to lipopolysaccharide stimulation. However, it had no effect on the relative frequencies of Th1, Th2 and T regulatory cells among circulating peripheral blood mononuclear cells, on plasma cytokine levels and on in vitro production of cytokines by T cells. CONCLUSIONS: We found that VSL#3 administration did not lead to any changes in gut flora, but led to a reduction in the frequency of Th17 cells and in the production of pro-inflammatory cytokine on lipopolysaccharide stimulation. These findings suggest that the beneficial anti-inflammatory effect of this preparation in patients with autoimmune and allergic disorders may be related to reduced production of monocyte-derived cytokines rather than to changes in the composition of gut microbiota. TRIAL REGISTRATION: NCT03330678 , Date of registration 30th October 2017. Retrospectively registered.