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1.
Dig Dis Sci ; 69(6): 2204-2214, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38637454

RESUMEN

BACKGROUND AND AIMS: Terlipressin infusion is effective in hepatorenal syndrome (HRS-AKI). However, its efficacy for HRS-AKI resolution in acute-on-chronic liver failure (ACLF) patients has been suboptimal. Progression of AKI is rapid in ACLF. We investigated whether early initiation of terlipressin(eTerli) can improve response rates. METHODS: Consecutive ACLF patients with stage II/III AKI despite albumin resuscitation (40 g) were randomized to receive terlipressin at 2 mg/24 h plus albumin at 12 h (ET, n = 35) or at 48 h as standard therapy (ST, n = 35). (June 22, 2020 to June 10, 2022). The primary end-point was AKI reversal by day7. RESULTS: Baseline parameters including AKI stage and ACLF-AARC scores in two arms were comparable. Full AKI response at day 7 was higher in ET [24/35 (68.6%)] than ST arm [11/35 (31.4%; P 0.03]. Day3 AKI response was also higher in ET arm [11/35 (31.4%) vs. 4/35 (11.4%), P 0.04]. Using ST compared to ET [HR 4.3; P 0.026] and day 3 serum creatinine > 1.6 mg/dl [HR 9.1; AUROC-0.866; P < 0.001] predicted HRS-AKI non-response at day 7. ET patients showed greater improvement in ACLF grade, mean arterial pressure, and urine output at day 3, and required lower albumin within 7 days than ET arm (149.1 ± 41.8 g vs. 177.5 ± 40.3 g, P 0.006) and had lower 28-day mortality: 40% vs. 65.7%, P 0.031]. Early use of terlipressin than ST [HR 2.079; P 0.038], baseline HE [HR 2.929; P 0.018], and AKI persistence at day 3 [HR 1.369; P 0.011] predicted 28-day mortality. Fifteen (21.4%) patients had treatment related adverse effects, none was life threatening. CONCLUSION: In ACLF patients, early initiation of terlipressin for AKI persisting after 12 h of volume expansion with albumin helps in reduced short-term mortality and early AKI reversal with regression of ACLF stage. These results indicate need for change in current practice for terlipressin usage in HRS-AKI.


Asunto(s)
Lesión Renal Aguda , Insuficiencia Hepática Crónica Agudizada , Terlipresina , Vasoconstrictores , Humanos , Terlipresina/administración & dosificación , Masculino , Lesión Renal Aguda/tratamiento farmacológico , Lesión Renal Aguda/etiología , Lesión Renal Aguda/diagnóstico , Femenino , Persona de Mediana Edad , Vasoconstrictores/administración & dosificación , Insuficiencia Hepática Crónica Agudizada/tratamiento farmacológico , Insuficiencia Hepática Crónica Agudizada/complicaciones , Insuficiencia Hepática Crónica Agudizada/mortalidad , Adulto , Resultado del Tratamiento , Anciano , Factores de Tiempo , Tiempo de Tratamiento
2.
Clin Gastroenterol Hepatol ; 20(4): e831-e854, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-33524593

RESUMEN

BACKGROUND: High volume plasma-exchange (HVPE) improves survival in patients with acute liver failure (ALF), but apprehension regarding volume overload and worsening of cerebral edema remain. METHODS: In an open-label randomized controlled trial, 40 consecutive patients of ALF were randomized 1:1 to either standard medical treatment (SMT) or SMT with standard-volume plasma-exchange (SVPE). SVPE was performed using centrifugal apheresis [target volume of 1.5 to 2.0 plasma volumes per session] until desired response was achieved. Cerebral edema was assessed by brain imaging. Results were analyzed in an intention-to-treat analysis. Primary outcome was 21-day transplant-free survival. The levels of cytokines, damage-associated molecular patterns (DAMPs) and endotoxins were analyzed at baseline and day 5. RESULTS: ALF patients [aged 31.5 ± 12.2 years, 60% male, 78% viral, 83% hyperacute, 70% with SIRS were included. At day 5, SVPE [mean sessions 2.15 ± 1.42, median plasma volume replaced 5.049 L] compared to SMT alone, resulted in higher lactate clearance (p = .02), amelioration of SIRS (84% vs. 26%; P = .02), reduction in ammonia levels [(221.5 ± 96.9) vs.(439 ± 385.6) µg/dl, P = .02) and SOFA scores [9.9(±3.3) vs. 14.6(±4.8); P = .001]. There were no treatment related deaths. SVPE was associated with a higher 21-day transplant free-survival [75% vs. 45%; P = .04, HR 0.30, 95%CI 0.01-0.88]. A significant decrease in levels of pro-inflammatory cytokines and an increase in anti-inflammatory cytokines along with a decrease in endotoxin and DAMPs was seen with SVPE. CONCLUSION: In ALF patients with cerebral edema, SVPE is safe and effective and improves survival possibly by a reduction in cytokine storm and ammonia. CLINICALTRIAL: gov (identifier: NCT02718079).


Asunto(s)
Fallo Hepático Agudo , Intercambio Plasmático , Adulto , Citocinas , Femenino , Humanos , Fallo Hepático Agudo/terapia , Masculino , Intercambio Plasmático/métodos , Adulto Joven
3.
J Public Health (Oxf) ; 44(2): 286-295, 2022 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-33428747

RESUMEN

BACKGROUND: There is limited evidence on technology addiction among adolescents in low- and middle-income countries where 90% of global adolescents live. We aimed to investigate the prevalence and correlates of technology addiction (Internet, gaming, smartphone, television) among school-going adolescents in India. METHODS: A cross-sectional survey covering the entire district (administrative unit for health) of India was conducted among representative sample of school-going adolescents using stratified cluster sampling. A total of 1729 adolescents completed the survey (age M = 12.58; SD = 0.97) by responding to Internet Addiction Test-Adolescents, Game Addiction Scale, Smartphone Addiction Scale and Television Addiction Scale. Associated factors were analyzed using binomial logistic regression analysis. RESULTS: Almost all the participants (99.59%; 95% confidence interval (CI): 99.28-99.91%) were using technology in one or other form. Prevalence of technology addiction among the users was 10.69% (95% CI: 5.26-16.11%). Phone addiction (8.91%; 95% CI: 3.31-14.52%) was the most common type followed by gaming addiction (2.55%; 95% CI: 1.16-3.95%). Technology addiction among adolescents was significantly associated with several risk factors at individual, family and school levels. CONCLUSION: Technology addiction emerges as an important public health problem among adolescents in India. An integrated socio-ecological framework with multi-level approach that targets risk factors at various levels is required to promote healthy behaviors towards technology.


Asunto(s)
Salud del Adolescente , Adicción a la Tecnología , Adolescente , Estudios Transversales , Humanos , India/epidemiología , Internet , Instituciones Académicas , Encuestas y Cuestionarios
4.
Liver Int ; 41(5): 1083-1096, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33529450

RESUMEN

BACKGROUND AND AIM: Plasma-exchange (PE) has improved survival in acute liver failure by ameliorating systemic inflammatory response syndrome (SIRS). We evaluated PE and compared it to Fractional Plasma Separation and Adsorption (FPSA) and standard medical treatment (SMT) in a large multinational cohort of ACLF patients. METHODS: Data were prospectively collected from the AARC database and analysed. Matching by propensity risk score (PRS) was performed. Competing risk survival analysis was done to identify deaths because of multiorgan failure (MOF). In a subset of 10 patients, we also evaluated the mechanistic basis of response to PE. RESULTS: ACLF patients (n = 1866, mean age 44.3 ± 12.3 yrs, 93% males, 65% alcoholics) received either artificial liver support (ALS) (n = 162); [PE (n = 131), FPSA (n = 31)] or were continued on standard medical therapy (SMT) (n = 1704). In the PRS-matched cohort (n = 208, [ALS-119; PE-94, FPSA-25)], SMT-89). ALS therapies were associated with a significantly higher resolution of SIRS (Odd's ratio 9.23,3.42-24.8), lower and delayed development of MOF (Hazard ratio 7.1, 4.5-11.1), and lower liver-failure-related deaths as compared to FPSA and SMT (P < .05). PE cleared inflammatory cytokines, damage-associated molecular patterns, and endotoxin in all patients. Responders improved monocyte phagocytic function and mitochondrial respiration and increased the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1RA) compared to non-responders. PE was associated with lesser adverse effects as compared to FPSA. CONCLUSIONS: PE improves systemic inflammation and lowers the development of MOF in patients with ACLF. Plasma-exchange provides significant survival benefit over FPSA and could be a preferred modality of liver support for ACLF patients.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Insuficiencia Hepática Crónica Agudizada/terapia , Adulto , Femenino , Humanos , Inflamación/terapia , Masculino , Persona de Mediana Edad , Intercambio Plasmático , Puntaje de Propensión
5.
J Pediatr Gastroenterol Nutr ; 73(5): e109-e114, 2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34310440

RESUMEN

OBJECTIVES: The objectives of the study were to evaluate the indications, feasibility, complications and clinical implications of transjugular liver biopsy (TJLB) in children. METHODS: Data of all TJLB performed in children <18 years old was retrieved from the computerized hospital information system. TJLB was done using a 19 G quick-core needle biopsy system with 20 mm throw length. Hepatic venous pressure gradient was additionally measured in children with portal hypertension. A single pathologist reviewed all the biopsies again and provided structured information. RESULTS: A total of 102 children, including 5 with acute liver failure underwent TJLB with technical success in 101 (99%). A mean of 2.3 ±â€Š0.9 passes (range: 1-5) was taken for the biopsy. The most common indications for TJLB in our cohort were elevated international normalized ratio >1.5 (66, 64.7%), ascites (46, 45.1%) and thrombocytopenia (platelet count < 60,000/mm3) (42, 41.2%). Mean size of the tissue received was 14.5 ±â€Š5.6 mm with an average of 10.2 ±â€Š4.7 portal tracts. Only one child developed major (category D) complication (hemobilia) and 12 (11.8%) developed minor complications post-procedure. Etiological diagnosis could be made in a total of 64 (63.9%) children undergoing TJLB, the most common diagnosis being autoimmune hepatitis (n = 31), non-cirrhotic portal fibrosis (n = 16) and drug-induced liver injury (n = 4). CONCLUSION: TJLB is well tolerated, feasible and helps make a diagnosis in close to 64% children allowing timely medical and/or surgical intervention. It is especially useful for diagnosis of autoimmune liver diseases, drug-induced liver injury and non-cirrhotic portal fibrosis.


Asunto(s)
Hepatopatías , Fallo Hepático Agudo , Adolescente , Biopsia , Biopsia con Aguja Gruesa , Niño , Estudios de Factibilidad , Humanos , Venas Yugulares , Hígado , Pronóstico , Estudios Retrospectivos
6.
Genomics ; 112(2): 1598-1610, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31521711

RESUMEN

Understanding male gametophyte development is essential to augment hybrid production in sorghum. Although small RNAs are known to critically influence anther/pollen development, their roles in sorghum reproduction have not been deciphered yet. Here, we report small RNA profiling and high-confidence annotation of microRNAs (miRNAs) from meiotic and post-meiotic anthers in sorghum. We identified 262 miRNAs (82 known and 180 novel), out of which 58 (35 known and 23 novel) exhibited differential expression between two stages. Out of 35 differentially expressed known miRNAs, 13 are known to regulate anther/pollen development in other plant species. We also demonstrated conserved spatiotemporal patterns of 21- and 24-nt phasiRNAs and their respective triggers, miR2118 and miR2275, in sorghum anthers as evidenced in other monocots. miRNA target identification yielded 5622 modules, of which 46 modules comprising 16 known and 8 novel miRNA families with 38 target genes are prospective candidates for engineering male fertility in grasses.


Asunto(s)
Redes Reguladoras de Genes , Meiosis , MicroARNs/genética , Infertilidad Vegetal/genética , Polen/genética , Sorghum/genética , Gametogénesis en la Planta , Regulación de la Expresión Génica de las Plantas , MicroARNs/metabolismo , Polen/citología , Sorghum/fisiología , Transcriptoma
7.
Hepatology ; 70(3): 802-811, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-30664267

RESUMEN

Severe alcoholic hepatitis (SAH) is often a progressive disease with high mortality and limited steroid responsiveness. Management options of steroid nonresponsive SAH (day 7 Lille score > 0.45) are limited. We assessed the efficacy and safety of granulocyte colony-stimulating factor (G-CSF) in steroid nonresponders. A randomized, double-blind, single-center trial (NCT01820208) was conducted between March 2013 and June 2016 in patients with histologically proven SAH, nonresponsive to 40 mg/day of prednisolone were randomized to G-CSF (12 doses, 300 µg each in 28 days) or placebo. Responders were continued with prednisolone. Of the 430 patients with SAH, 132 received steroid therapy. Of these, 33 (25%) were nonresponders and were randomized to G-CSF or placebo (14 in each group after exclusions). The baseline characteristics of both groups were comparable. The 28-day mortality was comparable between the groups (21.4%, G-CSF; 28.6%, placebo; P = 0.69). At 90 days, in the G-CSF but not in the placebo group, the Model for End-Stage Liver Disease reduced from 24.6 ± 3.9 to 19.4 ± 3.7 (P = 0.002) and Maddrey's discriminant function from 74.8 ± 22.8 to 57.4 ± 31 (P = 0.26). Infections were less common (28% versus 71%; P < 0.001) with lower 90-day mortality (35.7% versus 71.4%; P = 0.04) in the G-CSF than in the placebo group. On Cox regression analysis, receiving G-CSF (hazard ratio, 0.37; SD, 0.14-0.98; P = 0.04), and high baseline serum creatinine (hazard ratio, 4.12; SD, 1.7-10.3; P = 0.002) predicted day-90 outcomes in steroid nonresponsive SAH. Patients tolerated G-CSF without any major adverse events. Conclusion: Approximately one-quarter of patients with SAH do not respond to corticosteroid therapy. Administration of G-CSF is safe and helps to reduce the disease severity and 90-day mortality in these patients.


Asunto(s)
Progresión de la Enfermedad , Resistencia a Medicamentos , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Hepatitis Alcohólica/tratamiento farmacológico , Prednisolona/administración & dosificación , Adulto , Análisis de Varianza , Biopsia con Aguja , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Esquema de Medicación , Femenino , Hepatitis Alcohólica/diagnóstico , Hepatitis Alcohólica/mortalidad , Humanos , Inmunohistoquímica , India , Inyecciones Subcutáneas , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Valores de Referencia , Retratamiento , Medición de Riesgo , Índice de Severidad de la Enfermedad , Tasa de Supervivencia , Resultado del Tratamiento , Adulto Joven
8.
Am J Gastroenterol ; 114(6): 929-937, 2019 06.
Artículo en Inglés | MEDLINE | ID: mdl-31021832

RESUMEN

OBJECTIVES: Acute insults from viruses, infections, or alcohol are established causes of decompensation leading to acute-on-chronic liver failure (ACLF). Information regarding drugs as triggers of ACLF is lacking. We examined data regarding drugs producing ACLF and analyzed clinical features, laboratory characteristics, outcome, and predictors of mortality in patients with drug-induced ACLF. METHODS: We identified drugs as precipitants of ACLF among prospective cohort of patients with ACLF from the Asian Pacific Association of Study of Liver (APASL) ACLF Research Consortium (AARC) database. Drugs were considered precipitants after exclusion of known causes together with a temporal association between exposure and decompensation. Outcome was defined as death from decompensation. RESULTS: Of the 3,132 patients with ACLF, drugs were implicated as a cause in 329 (10.5%, mean age 47 years, 65% men) and other nondrug causes in 2,803 (89.5%) (group B). Complementary and alternative medications (71.7%) were the commonest insult, followed by combination antituberculosis therapy drugs (27.3%). Alcoholic liver disease (28.6%), cryptogenic liver disease (25.5%), and non-alcoholic steatohepatitis (NASH) (16.7%) were common causes of underlying liver diseases. Patients with drug-induced ACLF had jaundice (100%), ascites (88%), encephalopathy (46.5%), high Model for End-Stage Liver Disease (MELD) (30.2), and Child-Turcotte-Pugh score (12.1). The overall 90-day mortality was higher in drug-induced (46.5%) than in non-drug-induced ACLF (38.8%) (P = 0.007). The Cox regression model identified arterial lactate (P < 0.001) and total bilirubin (P = 0.008) as predictors of mortality. DISCUSSION: Drugs are important identifiable causes of ACLF in Asia-Pacific countries, predominantly from complementary and alternative medications, followed by antituberculosis drugs. Encephalopathy, bilirubin, blood urea, lactate, and international normalized ratio (INR) predict mortality in drug-induced ACLF.


Asunto(s)
Insuficiencia Hepática Crónica Agudizada/inducido químicamente , Enfermedad Hepática Inducida por Sustancias y Drogas/complicaciones , Hígado/patología , Insuficiencia Hepática Crónica Agudizada/diagnóstico , Insuficiencia Hepática Crónica Agudizada/epidemiología , Adolescente , Adulto , Anciano , Asia/epidemiología , Biopsia , Enfermedad Hepática Inducida por Sustancias y Drogas/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Hígado/efectos de los fármacos , Masculino , Persona de Mediana Edad , Morbilidad/tendencias , Pronóstico , Estudios Prospectivos , Tasa de Supervivencia/tendencias , Factores de Tiempo , Adulto Joven
9.
Liver Int ; 39(1): 168-176, 2019 01.
Artículo en Inglés | MEDLINE | ID: mdl-30188604

RESUMEN

BACKGROUND & AIMS: Familial aggregation of metabolic traits in NAFLD is well documented. However, relevance of these traits in alcoholic cirrhosis is not well studied. We aimed to explore the association of family history of metabolic traits with age at diagnosis, severity and complications of alcoholic cirrhosis. METHODS: In a cross-sectional study, all consecutive patients with alcoholic cirrhosis presenting to our tertiary care centre were included. Family and personal history, demographic characteristics, medical history, anthropometric measurements and laboratory data were recorded. The amount and duration of alcohol consumption were also carefully recorded. RESULTS: Out of 1084 alcoholic cirrhotics (age 48.5 ± 10.1 years, all males), family history for metabolic traits was documented in 688 (63.5%) patients. These patients had younger age at diagnosis, increased incidence of jaundice, ascites, variceal bleed and hepatic encephalopathy with consequently higher MELD and CTP score. These patients developed cirrhosis despite shorter median duration (13 years, IQR 7-20 vs 21, IQR 18-25) and lesser amount of alcohol consumption (74 g/d, IQR 24-96 vs 144, IQR 100-148). Patients with both family and personal history of metabolic traits had a higher risk by 3.3 times (95% CI 2.2-4.8) of an early age at diagnosis, 13.2 times (95% CI 8.7-20.1) of progression to cirrhosis with lesser amount of alcohol consumption and 4.6 times (95% CI 3.1-6.9) with lesser duration of alcohol consumption. CONCLUSIONS: Positive family and personal history of metabolic traits predispose to alcoholic cirrhosis with an earlier age at onset and more severity despite lesser exposure to alcohol.


Asunto(s)
Cirrosis Hepática Alcohólica/complicaciones , Anamnesis , Síndrome Metabólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Adulto , Consumo de Bebidas Alcohólicas/efectos adversos , Ascitis/etiología , Estudios Transversales , Progresión de la Enfermedad , Femenino , Predisposición Genética a la Enfermedad , Encefalopatía Hepática/complicaciones , Humanos , Cirrosis Hepática Alcohólica/diagnóstico , Cirrosis Hepática Alcohólica/patología , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Pronóstico , Índice de Severidad de la Enfermedad , Centros de Atención Terciaria
10.
Natl Med J India ; 32(5): 282-284, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-32985442

RESUMEN

Background: Internet use has increased access to online sexually explicit material. We explored the use of pornography in a community sample. Methods: In a house-to-house survey, 2525 individuals (1239 men; 1286 women) in the age group of 18-40 years were administered a schedule which included a screening tool for pornographic addiction along with a General Health Questionnaire. Results: Around 8.3% (229; 152 men [10.9%]; 77 women [5.6%]; p<0.001) acknowledged the use of pornography. It was more common among single and single parenting group samples. Pornographic addiction was 0.2% (5/2525; 0.3% men; 0.1% women). Sex had a significant association with age and pornography addiction. Conclusion: Our study documents the use of pornography in India. It suggests the need for in-depth studies.


Asunto(s)
Conducta Adictiva/epidemiología , Literatura Erótica , Internet , Conducta Sexual/estadística & datos numéricos , Adolescente , Adulto , Factores de Edad , Femenino , Humanos , India/epidemiología , Masculino , Factores Sexuales , Encuestas y Cuestionarios , Adulto Joven
12.
Inorg Chem ; 57(17): 10984-10992, 2018 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-30102531

RESUMEN

Separation of uranium (U) from interfering lanthanide ions (Ln3+) in aqueous medium is important in view of sustainable nuclear power production and remediation of radioactive waste. Separation of U in aqueous medium by electrochemical means is still unexplored. Herein, we report electrochemical separation of U from interfering lanthanides ions in 0.1 M KCl on poly(3,4-ethylenedioxythiophene) poly(styrenesulfonate) modified platinum (PEDOT:PSS/Pt) electrode. U in solution commonly exists as uranyl (UO22+). U separation is achieved in a two step process: (i) UO22+ reduction to insoluble urania (UO2) which gets deposited on PEDOT:PSS/Pt in the presence of Ln3+ (La3+, Ce3+, and Sm3+) ions and (ii) oxidation of electrodeposited UO2 to UO22+ in fresh 0.1 M KCl (pH = 2) solution. Electrodeposition of UO2 is confirmed by X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Although, the presence of Ln3+ ions in UO22+solution hinders electrodeposition of UO2, but application of more negative reduction potential (-0.6 V vs Ag/AgCl) for longer duration (8 h) results in quantitative electrodeposition of UO2. Inductively coupled plasma mass spectrometry (ICP-MS) shows that 94% (±10%) recovery of UO22+ is possible from mixed solution of UO22+and Ln3+ ions on PEDOT:PSS/Pt electrode.

13.
Hepatol Res ; 48(6): 451-458, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29314573

RESUMEN

AIM: Monotherapy with pegylated interferon-α (Peg-IFNα) or the nucleos(t)ide analogs (NA) currently approved for treating chronic hepatitis B (CHB) has limited efficacy. Studies on the combination of Peg-IFNα/NA have shown conflicting results. We investigated whether sequentially adding on Peg-IFNα to tenofovir enhances serological response rates. METHODS: Treatment-naïve, hepatitis B envelope antigen (HBeAg)-positive CHB patients with moderately elevated alanine aminotransferase (ALT; 48-200 IU/mL) were started on tenofovir (300 mg/day) and enrolled at week 12 in a 1:1 ratio to either receive Peg-IFNα2b add-on (1.5 µg/kg/week) from week 12 to 36 (n = 53) or continue tenofovir monotherapy (n = 53). Both treatment arms received tenofovir consolidation therapy until week 72. The primary end-point was HBeAg loss at week 72. RESULTS: At week 72, the rate of HBeAg loss was higher in the Peg-IFNα2b add-on group (35.8%) compared to the tenofovir monotherapy group (17%) (P = 0.028; odds ratio, 2.73, 95% confidence interval, 1.09-6.79), and considerably higher in patients with a baseline hepatitis B virus (HBV)-DNA level >6 log IU/mL (32.6% vs 11.4%; P = 0.021). Rates of HBV-DNA loss (77.4% vs 71.7%; P = 0.51), ALT normalization (62.3% vs 52.8%; P = 0.32), and sustained virologic response (20.8% vs 11.3%; P = 0.18) at week 72 were comparable between the two groups. Significantly more patients in the add-on group had >3 log HBV-DNA reduction at week 36 (92.5% vs 66%; P = 0.001). Four patients treated with Peg-IFNα2b add-on achieved hepatitis B surface antigen (HBsAg) loss compared with one patient receiving tenofovir monotherapy. Decline of HBV-DNA of >2 log at week 4 led to higher HBeAg loss at week 72, independent of treatment arm. No patient had treatment-related adverse effects requiring treatment discontinuation. CONCLUSIONS: Twenty-four weeks of Peg-IFNα2b as an add-on sequential regimen to tenofovir is safe and resulted in greater loss of HBeAg and HBsAg compared to tenofovir monotherapy in selected HBeAg-positive patients. Viral load reduction followed by immune modulation is a potentially useful approach.

14.
Dig Dis Sci ; 63(2): 493-501, 2018 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28780608

RESUMEN

BACKGROUND AND AIMS: Almost 10% of bleeding episodes are refractory to combination of vasoactive agent and endotherapy, and are associated with a mortality up to 50%. Severity of liver disease and high portal pressure are mainly responsible for it. TIPS cannot be used in these patients due to high MELD score. We aimed to evaluate the efficacy of self-expandable DE stents for control of refractory variceal bleeds in patients with ACLF. METHODS: Acute-on-chronic liver failure patients (n = 88, mean age 47.3 ± 10.9 years) with refractory variceal bleeds received either DE stent (Gr. A, n = 35) or continued with repeat endotherapy and vasoactive drug (Gr.B, n = 53). Matching by propensity risk score (PRS) was done to avoid selection bias. Competing risk Cox regression analysis was done to identify event-specific, i.e., gastrointestinal bleed-related death. RESULTS: Majority (78.4%) of patients were alcoholic with MELD score of 45.9 ± 20.1. Control of initial bleeding was significantly more in the DE stent group as compared to controls in both pre-match (89 vs. 37%; p < 0.001) and PRS-matched cohorts (73 vs. 32%; 0.007). Further, bleed-related death was also significantly lower in DE group as compared to controls in both pre-match (14 vs. 64%; p = 0.001) and PRS-matched cohorts (6 vs. 56%; p = 0.001). In a multivariate competing risk Cox model, patients who underwent DE stenting had reduced mortality in both pre-match (p = 0.04, HR 0.36, 95% CI 0.13-0.96) and PRS-matched cohorts (p < 0.001, HR 0.21, 95% CI 0.08-0.51). CONCLUSIONS: Self-expandable DE stents are very effective in control of refractory variceal bleeding and reduced mortality in patients with severe liver failure.


Asunto(s)
Hemorragia/cirugía , Fallo Hepático/complicaciones , Hígado/irrigación sanguínea , Stents , Várices/cirugía , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Fallo Hepático/cirugía , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
16.
Liver Int ; 37(10): 1497-1507, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28393476

RESUMEN

BACKGROUND AND AIM: There is limited data on predictors of acute kidney injury in acute on chronic liver failure. We developed a PIRO model (Predisposition, Injury, Response, Organ failure) for predicting acute kidney injury in a multicentric cohort of acute on chronic liver failure patients. PATIENTS AND METHODS: Data of 2360 patients from APASL-ACLF Research Consortium (AARC) was analysed. Multivariate logistic regression model (PIRO score) was developed from a derivation cohort (n=1363) which was validated in another prospective multicentric cohort of acute on chronic liver failure patients (n=997). RESULTS: Factors significant for P component were serum creatinine[(≥2 mg/dL)OR 4.52, 95% CI (3.67-5.30)], bilirubin [(<12 mg/dL,OR 1) vs (12-30 mg/dL,OR 1.45, 95% 1.1-2.63) vs (≥30 mg/dL,OR 2.6, 95% CI 1.3-5.2)], serum potassium [(<3 mmol/LOR-1) vs (3-4.9 mmol/L,OR 2.7, 95% CI 1.05-1.97) vs (≥5 mmol/L,OR 4.34, 95% CI 1.67-11.3)] and blood urea (OR 3.73, 95% CI 2.5-5.5); for I component nephrotoxic medications (OR-9.86, 95% CI 3.2-30.8); for R component,Systemic Inflammatory Response Syndrome,(OR-2.14, 95% CI 1.4-3.3); for O component, Circulatory failure (OR-3.5, 95% CI 2.2-5.5). The PIRO score predicted acute kidney injury with C-index of 0.95 and 0.96 in the derivation and validation cohort. The increasing PIRO score was also associated with mortality (P<.001) in both the derivation and validation cohorts. CONCLUSIONS: The PIRO model identifies and stratifies acute on chronic liver failure patients at risk of developing acute kidney injury. It reliably predicts mortality in these patients, underscoring the prognostic significance of acute kidney injury in patients with acute on chronic liver failure.


Asunto(s)
Lesión Renal Aguda/etiología , Insuficiencia Hepática Crónica Agudizada/complicaciones , Técnicas de Apoyo para la Decisión , Lesión Renal Aguda/sangre , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/mortalidad , Insuficiencia Hepática Crónica Agudizada/sangre , Insuficiencia Hepática Crónica Agudizada/diagnóstico , Insuficiencia Hepática Crónica Agudizada/mortalidad , Adulto , Asia , Biomarcadores/sangre , Femenino , Humanos , Estimación de Kaplan-Meier , Modelos Lineales , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Nomogramas , Oportunidad Relativa , Valor Predictivo de las Pruebas , Pronóstico , Estudios Prospectivos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo
18.
J Gastroenterol Hepatol ; 31(5): 988-94, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-26598065

RESUMEN

BACKGROUND: The prevalence and clinical significance of hyponatremia in cirrhotics have been well studied; however, there are limited data on hyperkalemia in cirrhotics. AIM: We evaluated the prevalence and prognostic significance of hyperkalemia in hospitalized patients with cirrhosis and developed a prognostic model incorporating potassium for prediction of liver-related death in these patients. METHODS: The training derivative cohort of patients was used for development of prognostic scores (Group A, n = 1160), which were validated in a large prospective cohort of cirrhotic patients. (Group B, n = 2681) of cirrhosis. RESULTS: Hyperkalemia was seen in 189 (14.1%) and 336 (12%) in Group A and Group B, respectively. Potassium showed a significant association that was direct with creatinine (P < 0.001) and urea (P < 0.001) and inverse with sodium (P < 0.001). Mortality was also significantly higher in patients with hyperkalemia (P = 0.0015, Hazard Ratio (HR) 1.3, 95% confidence interval 1.11-1.57). Combination of all these parameters into a single value predictor, that is, renal dysfunction index predicted mortality better than the individual components. Combining renal dysfunction index with other known prognostic markers (i.e. serum bilirubin, INR, albumin, hepatic encephalopathy, and ascites) in the "K" model predicted both short-term and long-term mortality with an excellent accuracy (Concordance-index 0.78 and 0.80 in training and validation cohorts, respectively). This was also superior to Model for End-stage Liver Disease, Model for End-stage liver disease sodium (MELDNa), and Child-Turcott-Pugh scores. CONCLUSIONS: Cirrhotics frequently have impaired potassium homeostasis, which has a prognostic significance. Serum potassium correlates directly with serum creatinine and urea and inversely with serum sodium. The model incorporating serum potassium developed from this study ("K"model) can predict death in advanced cirrhotics with an excellent accuracy.


Asunto(s)
Técnicas de Apoyo para la Decisión , Indicadores de Salud , Hospitalización , Hiperpotasemia/epidemiología , Cirrosis Hepática/epidemiología , Potasio/sangre , Adulto , Biomarcadores/sangre , Causas de Muerte , Femenino , Humanos , Hiperpotasemia/sangre , Hiperpotasemia/diagnóstico , Hiperpotasemia/mortalidad , India/epidemiología , Riñón/fisiopatología , Cirrosis Hepática/sangre , Cirrosis Hepática/diagnóstico , Cirrosis Hepática/mortalidad , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Prevalencia , Pronóstico , Estudios Prospectivos , Reproducibilidad de los Resultados , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Factores de Tiempo
19.
Opt Express ; 23(24): 30904-16, 2015 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-26698723

RESUMEN

In both lensless Fourier transform holography (FTH) and coherent diffraction imaging (CDI), a beamstop is used to block strong intensities which exceed the limited dynamic range of the sensor, causing a loss in low-frequency information, making high quality reconstructions difficult or even impossible. In this paper, we show that an image can be recovered from high-frequencies alone, thereby overcoming the beamstop problem in both FTH and CDI. The only requirement is that the object is sparse in a known basis, a common property of most natural and manmade signals. The reconstruction method relies on compressed sensing (CS) techniques, which ensure signal recovery from incomplete measurements. Specifically, in FTH, we perform compressed sensing (CS) reconstruction of captured holograms and show that this method is applicable not only to standard FTH, but also multiple or extended reference FTH. For CDI, we propose a new phase retrieval procedure, which combines Fienup's hybrid input-output (HIO) method and CS. Both numerical simulations and proof-of-principle experiments are shown to demonstrate the effectiveness and robustness of the proposed CS-based reconstructions in dealing with missing data in both FTH and CDI.


Asunto(s)
Algoritmos , Compresión de Datos/métodos , Holografía/métodos , Interpretación de Imagen Asistida por Computador/métodos , Refractometría/métodos , Tomografía de Coherencia Óptica/métodos , Aumento de la Imagen/métodos , Imagenología Tridimensional/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Procesamiento de Señales Asistido por Computador
20.
Arch Virol ; 160(1): 329-33, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25193070

RESUMEN

This report presents a molecular characterization of the complete genome of a rare hepatitis C virus (HCV) genotype (GT5a) from India. Sequence homology of full genome revealed that the strain belonged to HCV GT5a. To trace the origin of this virus and to understand its evolutionary pattern, a phylogenetic reconstruction was carried out on full HCV genome sequences using Bayesian coalescent methods. The phylogenetic tree reconstruction revealed genotypic divergence, with formation of distinct clades. This analysis revealed that HCV genotype 5 might have originated from HCV genotype 3, as they have a recent common ancestor.


Asunto(s)
Genotipo , Hepacivirus/clasificación , Hepacivirus/genética , Hepatitis C/epidemiología , Hepatitis C/virología , Adulto , Genoma Viral , Humanos , India/epidemiología , Masculino , Filogenia
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