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Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as nonalcoholic fatty liver disease (NAFLD),1 represents a global public health issue. Fibrosis stage is the most important risk for long-term undesirable outcomes.2,3 From recent meta-analyses, all-cause and liver-related mortalities significantly increased from fibrosis stage 2 (significant fibrosis; F≥2) onward.4,5 In primary care setting, those with F≥2 should be referred to hepatologists; therefore, noninvasive tests to stratify risk of patients with MASLD are crucial. Steatosis-associated fibrosis estimator (SAFE) was recently developed to predict F≥2.6 SAFE has been externally validated and outperformed fibrosis-4 (FIB-4) and NAFLD fibrosis score (NFS).7,8 Recently, international guidelines proposed sequential diagnostic steps, initially using FIB-4 and then transient elastography (TE) in non-low-risk patients.9,10 However, the guidelines focused on identifying advanced fibrosis (F≥3), which might be too late. This study aimed to compare the performance among SAFE, FIB-4, and NFS, and evaluate SAFE-TE sequential approach. We hypothesized that by initially using SAFE, the proportion of patients misclassified as low risk despite already having F≥2 could be diminished.
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BACKGROUND AND AIM: Patients with type 2 diabetes mellitus (T2DM) face a heightened susceptibility to advanced fibrosis, a condition linked to adverse clinical outcomes. However, reported data on liver fibrosis severity among individuals with T2DM vary significantly across studies with diverse characteristics. This meta-analysis aimed to estimate the global prevalence of advanced fibrosis among T2DM patients. METHODS: A comprehensive systematic search of the EMBASE and MEDLINE databases from inception to November 2022 was conducted to identify studies assessing advanced fibrosis in individuals with T2DM. Random-effects models were utilized to calculate point estimates of prevalence, accompanied by 95% confidence interval (CI). Meta-regression with subgroup analysis was employed to address heterogeneity. RESULTS: We identified 113 eligible studies involving 244,858 individuals from 29 countries. Globally, the prevalence of advanced fibrosis among T2DM patients was 19.5% (95% CI 16.8-22.4%). Regionally, the prevalence rates were as follows: 60.5% in West Asia (95% CI 50.3-70.4%), 24.4% in South Asia (95% CI 16.2-33.7%), 20.1% in East Asia (95% CI 14.7-26.1%), 20.0% in Europe (95% CI 15.8-24.6%), 15.8% in North America (95% CI 11.0-21.3%), and 11.3% in South America (95% CI 6.2-17.5%). The prevalence of advanced fibrosis varied notably based on the study setting and diagnostic methodology employed. Meta-regression models highlighted that 45.13% of the observed heterogeneity could be attributed to combined diagnostic modality and study setting. CONCLUSIONS: Globally, approximately one fifth of the T2DM population presents advanced fibrosis, with prevalence differing across geographical regions. Our findings underscore the need for effective strategies to alleviate its global burden.
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BACKGROUND: There is an urgent need for noninvasive tests to identify patients with psoriasis at risk of significant liver fibrosis. OBJECTIVES: To externally validate the ability of the Steatosis-Associated Fibrosis Estimator (SAFE) score to detect significant liver fibrosis in patients with psoriasis using transient elastography (TE) as a reference. METHODS: We analysed data from 75 patients with psoriasis, including TE, SAFE score, Fibrosis-4 Index (FIB-4) and Nonalcoholic Fatty Liver Disease Fibrosis Score (NFS). Significant liver fibrosis was defined as TE values ≥ 7.1 kPa. Diagnostic accuracy was assessed using the area under the receiver operating characteristic curve (AUROC). RESULTS: Fifteen patients (20%) exhibited significant liver fibrosis. The AUROCs for the SAFE and FIB-4 scores were 0.82 [95% confidence interval (CI) 0.67-0.97] and 0.62 (95% CI 0.45-0.79), respectively. The SAFE score outperformed the FIB-4 Index (P = 0.01) but was comparable with the NFS (P = 0.05) in predicting significant fibrosis. Using thresholds of < 0, 0 to < 100 and ≥ 100, the SAFE score categorized 36, 24 and 15 patients into low, intermediate and high-risk groups for significant fibrosis, respectively. The negative predictive value for excluding significant fibrosis with a SAFE score of < 0 was 94.4%, and the positive predictive value for diagnosing significant fibrosis with a SAFE score of > 100 was 53.3%. The duration of psoriasis, joint involvement and methotrexate treatment did not affect the diagnostic ability of the SAFE score whereas age of the patient did. CONCLUSIONS: The SAFE score demonstrated good accuracy in assessing clinically significant fibrosis among patients with psoriasis. This score should prove valuable for risk stratification and patient management in dermatology practice.
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Técnicas de Imagem por Elasticidade , Hepatopatia Gordurosa não Alcoólica , Psoríase , Humanos , Biópsia , Cirrose Hepática/diagnóstico , Cirrose Hepática/etiologia , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Psoríase/complicações , FibroseRESUMO
INTRODUCTION AND OBJECTIVES: Cohort studies reported controversial results regarding the long-term prognosis of patients with lean non-alcoholic fatty liver disease (NAFLD) compared to non-lean NAFLD patients. This updated meta-analysis aimed to estimate the magnitude of the association between lean body mass index and all-cause mortality risk in NAFLD patients. MATERIALS AND METHODS: We systematically searched the EMBASE and MEDLINE databases from inception to March 2023 to identify observational studies that reported hazard ratio (HR) for all-cause mortality of patients with lean NAFLD versus those with non-lean, overweight, or obese NAFLD. Multivariable-adjusted hazard ratios (HRs) for all-cause mortality were pooled using a random effects model. RESULTS: Fourteen studies with 94,181 NAFLD patients (11.3 % with lean NAFLD) and 7,443 fatal events over a median follow-up of 8.4 years (IQR, 6.6-17.4 years) were included. Patients with lean NAFLD had a higher risk of all-cause mortality than those with non-lean NAFLD (random-effects HR 1.61, 95 % CI 1.37-1.89; I2=77 %). The magnitude of this risk remained unchanged even after stratified analysis by measures of NAFLD diagnosis, study country, cohort setting, length of follow-up, adjustment with fibrosis stage/cirrhosis, and the Newcastle-Ottawa Scale. The risk was independent of age, sex, and cardiometabolic risk factors. Sensitivity analyses did not alter these findings. The funnel plot and Egger's test revealed no significant publication bias. CONCLUSIONS: This meta-analysis revealed that lean NAFLD is associated with an approximately 1.6-fold increased mortality risk. Further studies are needed to unravel the existing but complex link between lean NAFLD and an increased risk of death.
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Índice de Massa Corporal , Causas de Morte , Hepatopatia Gordurosa não Alcoólica , Hepatopatia Gordurosa não Alcoólica/mortalidade , Hepatopatia Gordurosa não Alcoólica/complicações , Humanos , Fatores de Risco , Magreza/mortalidade , Magreza/complicações , Medição de Risco , PrognósticoRESUMO
BACKGROUND AND AIMS: The heritability of nonalcoholic fatty liver disease (NAFLD) in lean individuals is undetermined. This familial aggregation study aimed to evaluate familial linkage for NAFLD and the risk of NAFLD among first-degree relatives of probands with lean NAFLD. METHODS: This study prospectively recruited cohorts of probands with lean NAFLD, probands with obese NAFLD, and lean probands with non-NAFLD and their respective first-degree relatives. A total of 257 participants were evaluated for liver steatosis, defined by the controlled attenuation parameter ≥288 dB/m2 , metabolic characteristics, and the PNPLA3, TM6SF2, and MBOAT7 polymorphisms. RESULTS: The prevalence of NAFLD in first-degree relatives of lean NAFLD probands (39.9%) was similar to that in the obese NAFLD group (36.9%) and was significantly higher than in lean persons without NAFLD (19.1%). First-degree relatives of probands with NAFLD who were male, and had central obesity, hypertriglyceridaemia, insulin resistance, and the PNPLA3 rs738409C>G allele had a significantly higher prevalence of NAFLD. After multivariable adjustment for gender, metabolic characteristics, and the PNPLA3 rs738409C>G allele, first-degree relatives of probands with lean NAFLD (odds ratio [OR], 5.13; 95% CI, 1.77-14.86) and obese NAFLD (OR, 3.20; 95% CI, 1.14-8.99) exhibited an increased risk of NAFLD compared with those of lean controls without NAFLD. CONCLUSIONS: Our well-phenotype cohorts revealed familial clustering of NAFLD and higher risks of NAFLD in first-degree relatives of probands with lean or obese NAFLD. The findings encourage clinicians caring for NAFLD patients to be more vigilant for NAFLD in their family members.
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Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Humanos , Adulto , Masculino , Feminino , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/genética , Análise por Conglomerados , Fenótipo , Obesidade/epidemiologia , Obesidade/genética , FígadoRESUMO
BACKGROUND: Physical inactivity and sarcopenia are two important predictors associated with increased morbidity and mortality in patients with cirrhosis. At present, the benefit of a home-based exercise training program is not well established in cirrhotic patients. The main objective of this study was to evaluate the effect of a 12-week home-based exercise training program on aerobic capacity in cirrhotic patients. METHODS: This is a randomized controlled study. Patients with compensated cirrhosis were randomized by a block of 4 with concealed allocation to the home-based exercise training (n = 20) or control (n = 20). Both groups received protein supplementation (9 g/day) for 12 weeks. The home-based exercise training program included several aerobic/isotonic moderate-intensity continuous training exercises for 40 min per session, at least four times a week, with a total duration of 12 weeks. The heart rate was continuously monitored using a Garmin® watch. In the control group, patients received exercise instruction without active encouragement and continuous monitoring. The primary outcome was a change in the 6-min walk test from baseline. Secondary outcomes were the difference in thigh muscle thickness, liver stiffness, spleen stiffness, and quality of life. RESULTS: A total of 40 patients were enrolled prospectively. The mean age was 56.3 ± 7.8 years, with a male predominance of 65%. The mean body mass index was 25.23 ± 3.0 kg/m2, and all were Child-Pugh A. Chronic hepatitis B or C was the primary cause of cirrhosis. The baseline values were a 6-min walk test of 475 ± 70 m, liver stiffness of 15.3 ± 9.3 kPa, spleen stiffness of 29.8 ± 21.7 kPa, and thigh muscle thickness (average compression index) of 0.64 ± 0.2 cm/m2. All baseline characteristics between the two groups were not different except the mean muscle mass which was significantly higher in the home-based exercise training group (p = 0.03, 95% CI 0.01 to 0.17). At the end of the study, no significant difference in the 6-min walk test was observed (p = 0.36, 95% CI -15.5 to 41.7). Liver stiffness measurement significantly improved in both groups, but no significant difference between groups was demonstrated (p = 0.77, 95% CI -1.3 to 1.8). Thigh muscle thickness was not different between groups. The fatigue domain of the quality of life index was significantly improved in the home-based exercise training group compared with the control group (p = 0.05, 95% CI 0.00 to 0.67). No adverse events occurred in a home-based exercise training program. CONCLUSIONS: A 12-week moderate-intensity home-based exercise training program in compensated cirrhotic patients significantly improved the fatigue domain of the quality of life index without an increase in adverse events. However, no benefit in terms of aerobic capacity, thigh muscle mass, liver stiffness, and spleen stiffness was demonstrated. TRIAL REGISTRATION: Thai Clinical Trials Registry number TCTR20190926002, 26/09/2019 (Retrospectively registered).
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Qualidade de Vida , Baço , Exercício Físico , Feminino , Humanos , Cirrose Hepática/complicações , Masculino , Pessoa de Meia-Idade , Músculo EsqueléticoRESUMO
BACKGROUND: Aggressive intravenous fluid hydration, by administering 3500 mL of lactated Ringer's solution (LRS) in 9 h with a peri-procedural bolus, reduces post-ERCP pancreatitis (PEP) incidence. A concern of this strategy is adverse events related to volume overload; however, the impact of fluid hydration over an extended period without a bolus on PEP is unknown. AIM: To assess the effect of continuous infusion of high-volume fluid at a constant rate over 24 h on PEP incidence and severity. METHODS: Two-hundred patients were randomly assigned (1:1) to receive either 3600 mL of LRS in 24 h starting 2 h before the ERCP (high-volume group) or maintenance fluid hydration calculated by the Holliday-Segar method (control group). RESULTS: The mean age of the patients was 50.6 ± 11.6 years. The predominant indications were choledocholithiasis (48%) and malignancies (32%). Patient demographics and PEP risk factors were similar in both groups. Patients in the high-volume group received significantly more fluid than the control group (3600 vs. 2413 ml, P < 0.001). PEP incidence was not different between the high-volume and the control group (14% vs. 15%; relative risk 0.93: 95% CI 0.48-1.83, P = 0.84). There were no differences in moderate to severe PEP (3% vs. 4%; relative risk 0.75: 95% CI, 0.17-3.27, P = 1.00). Subgroup analysis did not show a benefit in high-risk patients. Only one patient in the control group developed peripheral edema. CONCLUSIONS: An infusion of high-volume hydration over 24 h is not sufficient to provide optimal hydration for PEP prevention. CLINICAL TRIAL REGISTRY NUMBER: No. NCT02821546.
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Colangiopancreatografia Retrógrada Endoscópica , Pancreatite , Adulto , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Humanos , Incidência , Pessoa de Meia-Idade , Pancreatite/epidemiologia , Pancreatite/etiologia , Pancreatite/prevenção & controle , Lactato de Ringer , Fatores de RiscoRESUMO
BACKGROUND: Gastrointestinal endoscopy is frequently recommended for chronic diarrhea assessment in Western countries, but its benefit in the Southeast Asia region is not well established. METHODS: Medical records of consecutive patients undergoing esophagogastroduodenoscopy (EGD), colonoscopy, and small bowel endoscopy for chronic diarrhea from 2008 to 2018 were reviewed. Small bowel endoscopy included push enteroscopy, balloon-assisted enteroscopy (BAE), and video capsule endoscopy (VCE). The diagnostic yield of each endoscopic modality and predictors for positive small bowel endoscopy were analyzed. RESULTS: A total of 550 patients were included. The mean age was 54 years, and 266 (46.3%) patients were male. The mean hemoglobin and albumin levels were 11.6 g/dL and 3.6 g/dL, respectively. EGD and colonoscopy were performed in 302 and 547 patients, respectively, and the diagnostic yield was 24/302 (7.9%) for EGD and 219/547 (40.0%) for colonoscopy. EGD did not reveal positive findings in any patients with normal colonoscopy. Fifty-one patients with normal EGD and colonoscopy underwent small bowel endoscopy. Push enteroscopy, BAE, and VCE were performed in 28, 21, and 19 patients with a diagnostic yield of 5/28 (17.9%), 14/21 (66.7%), and 8/19 (42.1%), respectively. Significant weight loss, edema, and hypoalbuminemia were independent predictors for the positive yield of small bowel endoscopy. CONCLUSION: Colonoscopy was an essential diagnostic tool in identifying the cause of chronic diarrhea in Thai patients, whereas EGD provided some benefits. Small bowel endoscopy should be performed when colonoscopy and EGD were negative, particularly in patients with significant weight loss, edema, and hypoalbuminemia.
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Endoscopia por Cápsula , Endoscopia Gastrointestinal , Adulto , Colonoscopia , Diarreia/etiologia , Endoscopia do Sistema Digestório , Hemorragia Gastrointestinal , Humanos , Masculino , Pessoa de Meia-Idade , TailândiaRESUMO
BACKGROUND: Non-alcoholic steatohepatitis (NASH) has been recognised as a significant form of chronic liver disease and a common cause of cirrhosis and hepatocellular carcinoma, resulting in a considerable financial burden on healthcare resources. Currently, there is no information regarding the economic burden of NASH in low- and middle-income countries (LMICs). The aim of this study was to estimate the economic burden of NASH in Thailand as a lesson learned for LMICs. METHODS: To estimate the healthcare costs and prevalence of NASH with significant fibrosis (fibrosis stage ≥ 2) in the general Thai population, an eleven-state lifetime horizon Markov model with 1-year cycle length was performed. The model comprised Thai population aged 18 years and older. The cohort size was based on Thailand Official Statistic Registration Systems. The incidence of NASH, transitional probabilities, and costs-of-illness were based on previously published literature, including systematic reviews and meta-analyses. The age-specific prevalence of NASH was based on Thai NASH registry data. Costs were expressed in 2019 US Dollars ($). As we undertook analysis from the payer perspective, only direct medical costs were included. All future costs were discounted at an annual rate of 3%. A series of sensitivity analyses were performed. RESULTS: The estimated total number of patients with significant NASH was 2.9 million cases in 2019, based on a NASH prevalence of 5.74%. The total lifetime cost of significant NASH was $15.2 billion ($5,147 per case), representing approximately 3% of the 2019 GDP of Thailand. The probabilistic sensitivity analysis showed that the lifetime costs of significant NASH varied from $11.4 billion to $18.2 billion. CONCLUSIONS: The economic burden associated with NASH is substantial in Thailand. This prompts clinicians and policy makers to consider strategies for NASH prevention and management.
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Neoplasias Hepáticas , Hepatopatia Gordurosa não Alcoólica , Adolescente , Efeitos Psicossociais da Doença , Custos de Cuidados de Saúde , Humanos , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Tailândia/epidemiologiaRESUMO
BACKGROUND & AIMS: Seroclearance of hepatitis B surface antigen (HBsAg) is a marker for clearance of chronic hepatitis B virus (HBV) infection, but reported annual incidence rates of HBsAg seroclearance vary. We performed a systematic review and meta-analysis to provide more precise estimates of HBsAg seroclearance rates among subgroups and populations. METHODS: We searched PubMed, Embase, and the Cochrane library for cohort studies that reported HBsAg seroclearance in adults with chronic HBV infection with more than 1 year of follow-up and at least 1 repeat test for HBsAg. Annual and 5-, 10-, and 15-year cumulative incidence rates were pooled using a random effects model. RESULTS: We analyzed 34 published studies (with 42,588 patients, 303,754 person-years of follow-up, and 3194 HBsAg seroclearance events), including additional and updated aggregated data from 19 studies. The pooled annual rate of HBsAg seroclearance was 1.02% (95% CI, 0.79-1.27). Cumulative incidence rates were 4.03% at 5 years (95% CI, 2.49-5.93), 8.16% at 10 years (95% CI, 5.24-11.72), and 17.99% at 15 years (95% CI, 6.18-23.24). There were no significant differences between the sexes. A higher proportion of patients who tested negative for HBeAg at baseline had seroclearance (1.33%; 95% CI, 0.76-2.05) than those who tested positive for HBeAg (0.40%; 95% CI, 0.25-0.59) (P < .01). Having HBsAg seroclearance was also associated with a lower baseline HBV DNA level (6.61 log10 IU/mL; 95% CI, 5.94-7.27) vs not having HBsAg seroclearance (7.71 log10 IU/mL; 95% CI, 7.41-8.02) (P < .01) and with a lower level of HBsAg at baseline (2.74 log10 IU/mL; 95% CI, 1.88-3.60) vs not having HBsAg seroclearance (3.90 log10 IU/mL, 95% CI, 3.73-4.06) (P < .01). HBsAg seroclearance was not associated with HBV genotype or treatment history. Heterogeneity was substantial across the studies (I2 = 97.49%). CONCLUSION: In a systematic review and meta-analysis, we found a low rate of HBsAg seroclearance in untreated and treated patients (pooled annual rate, approximately 1%). Seroclearance occurred mainly in patients with less active disease. Patients with chronic HBV infection should therefore be counseled on the need for lifelong treatment, and curative therapies are needed.
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Antígenos de Superfície da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/imunologia , Adulto , Biomarcadores/sangue , DNA Viral/análise , Feminino , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Valores de Referência , Fatores de Risco , Estudos Soroepidemiológicos , Testes SorológicosRESUMO
Ultrasound-based elastography and serum indexes have been individually validated as noninvasive methods for staging liver fibrosis in chronic viral hepatitis. We aimed to compare the accuracy of transient elastography (TE), shear wave elastography (SWE), aspartate aminotransferase to platelet index (APRI) and Fibrosis-4 index (FIB-4) with the METAVIR liver fibrosis staging in viral hepatitis patients. We enrolled 121 treatment-naïve chronic hepatitis B and C monoinfected patients. All underwent liver biopsy had biochemistry tests and liver stiffness measurements by TE using M and XL probes followed by point SWE performed on the same day. The accuracy of each method for predicting different fibrosis stages was demonstrated as an area under the receiver operating characteristic (AUROC) curves. The AUROCs of TE using M and XL probes, SWE, APRI and FIB-4 were 0.771, 0.761, 0.700, 0.698 and 0.697, respectively, for significant fibrosis; 0.974, 0.973, 0.929, 0.738 and 0.859, respectively, for advanced fibrosis; and 0.954, 0.949, 0.962, 0.765 and 0.962, respectively, for cirrhosis. TE using the M probe was comparable to the XL probe in detecting all fibrosis stages. TE was superior to SWE for assessing significant fibrosis and advanced fibrosis. For cirrhosis, the performances of TE, SWE and FIB-4 were similar. APRI was least accurate in liver fibrosis staging. To conclude, for patients with viral hepatitis, TE using either M or XL probe is an effective noninvasive test for assessing liver fibrosis, particularly advanced fibrosis and cirrhosis, while SWE and FIB-4 possess an excellent accuracy in predicting cirrhosis.
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Técnicas de Imagem por Elasticidade , Hepatite B Crônica , Cirrose Hepática/diagnóstico , Aspartato Aminotransferases , Hepatite B Crônica/patologia , Humanos , Fígado/patologia , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Estudos Prospectivos , Curva ROCRESUMO
BACKGROUND: Gastrointestinal (GI) cytomegaloviral (CMV) infection is common among patients with immunocompromised status; however, data specific to GI-CMV infection in immunocompetent patients are comparatively limited. METHODS: This retrospective study included patients diagnosed with GI-CMV infection at Siriraj Hospital (Bangkok, Thailand) during 2008-2017. Baseline characteristics, presentations, comorbid conditions, endoscopic findings, treatments, and outcomes were compared between immunocompetent and immunocompromised. RESULTS: One hundred and seventy-three patients (56 immunocompetent, 117 immunocompromised) were included. Immunocompetent patients were significantly older than immunocompromised patients (73 vs. 48.6 years, p < 0.0001). Significantly more immunocompetent patients were in the ICU at the time of diagnosis (21.0% vs. 8.6%, p = 0.024). GI bleeding was the leading presentation in immunocompetent, while diarrhea and abdominal pain were more common in immunocompromised. Blood CMV viral load was negative in significantly more immunocompetent than immunocompromised (40.7% vs. 12.9%, p = 0.002). Ganciclovir was the main treatment in both groups. Significantly more immunocompetent than immunocompromised did not receive any specific therapy (25.5% vs. 4.4%, p ≤ 0.01). Six-month mortality was significantly higher among immunocompetent patients (39.0% vs. 22.0%, p = 0.047). Independent predictors of death were old age and inpatient or ICU clinical setting. Treatment with antiviral agents was the only independent protective factor. CONCLUSION: GI-CMV infection was frequently observed among immunocompetent elderly patients with comorbidities or severe concomitant illnesses. GI bleeding was the most common presentation. Blood CMV viral load was not diagnostically helpful. Significantly higher mortality was observed in immunocompetent than in immunocompromised patients, but this could be due to more severe concomitant illnesses in the immunocompetent group.
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Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/imunologia , Gastroenteropatias/diagnóstico , Gastroenteropatias/virologia , Imunocompetência , Dor Abdominal/diagnóstico , Corticosteroides/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antivirais/uso terapêutico , Citomegalovirus/isolamento & purificação , Infecções por Citomegalovirus/tratamento farmacológico , Diarreia/diagnóstico , Feminino , Ganciclovir/uso terapêutico , Gastroenteropatias/tratamento farmacológico , Hemorragia Gastrointestinal/diagnóstico , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Prognóstico , Carga ViralRESUMO
BACKGROUND: We investigated real-world effectiveness and safety of sofosbuvir and the nonstructural protein 5A inhibitors in the treatment of patients infected with hepatitis C virus (HCV) genotypes 1, 2, 3, 4, or 6. METHODS: We analyzed data from 1021 patients with HCV infection (506 with genotype 1; 16 with genotype 2; 314 with genotype 3; 13 with genotype 4; 166 with genotype 6) who received 12 to 24 weeks of daclatasvir plus sofosbuvir (n = 767), ledipasvir/sofosbuvir (n = 197), or sofosbuvir/velpatasvir (n = 57), with or without ribavirin in 12 centers across Thailand to estimate sustained virologic response at post-treatment week 12 (SVR12). RESULTS: Overall, SVR12 rate was 98.0% (95% confidence interval [CI], 96.7-98.8%) with daclatasvir plus sofosbuvir, 97.9% (95% CI, 94.8-99.2%) with ledipasvir/sofosbuvir, and 96.5% (95% CI, 88.1-99.0%) with sofosbuvir/velpatasvir. SVR12 was achieved by 99.2% (95% CI, 97.9-99.7%) of subjects with genotype 1 infection, 100% (95% CI, 78.5-100%) of those with genotype 2 infection, 96.7% (95% CI, 94.0-98.2%) of those with genotype 3 infection, 90.9% (95% CI, 62.3-98.4%) of those with genotype 4 infection, and 96.7% (95% CI 92.5-98.6%) of those with genotype 6 infection. Patients with advanced liver disease were at risk of treatment failure. Only four patients discontinued treatment before week 4 due to non-hepatic adverse events. CONCLUSIONS: In this large cohort of patients with various HCV genotypes managed in the real-world practice setting, daclatasvir plus sofosbuvir, ledipasvir/sofosbuvir, and sofosbuvir/velpatasvir achieved high SVR rates with good safety profile, comparable to those observed in clinical trials.
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Benzimidazóis/uso terapêutico , Carbamatos/uso terapêutico , Fluorenos/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Imidazóis/uso terapêutico , Sofosbuvir/uso terapêutico , Proteínas não Estruturais Virais/antagonistas & inibidores , Adiponectina/sangue , Idoso , Alanina Transaminase/sangue , Glicemia/análise , Colesterol/sangue , Combinação de Medicamentos , Quimioterapia Combinada , Feminino , Genótipo , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Pirrolidinas , Estudos Retrospectivos , Ribavirina/uso terapêutico , Resposta Viral Sustentada , Valina/análogos & derivadosRESUMO
BACKGROUND & AIMS: Measuring liver stiffness only in patients with indeterminate or high nonalcoholic fatty liver disease (NAFLD) fibrosis scores (called a 2-step approach) was reported to reduce indeterminate or discordant results while maintaining the accuracy to identify patients with advanced fibrosis. We aimed to validate this approach using data collected from the Gut and Obesity in Asia Workgroup. METHODS: We performed a retrospective analysis of data from 759 patients with biopsy-proven NAFLD (24% with advanced fibrosis), seen at 10 centers in 9 countries in Asia, from 2006 through 2018. By using liver biopsies as the reference standard, we calculated percentages of misclassifications and indeterminate or discordant results from assessments made based on fibrosis scores (NAFLD fibrosis score [NFS] or Fibrosis-4 score) and liver stiffness measurements (LSMs), alone or in combination. The analysis was repeated using randomly selected subgroups with a different prevalence of advanced fibrosis (histologic fibrosis stage ≥F3). RESULTS: In groups in which 3.7% and 10% of patients had advanced fibrosis, a 2-step approach (using the NFS followed by LSM only for patients with indeterminate or high NFS) and using a gray zone of 10 to 15 kPa for LSM, produced indeterminate or discordant results for 6.9% of patients and misclassified 2.7% of patients; only 25.6% of patients required LSM. In the group in which 10% of patients had advanced fibrosis, the same approach produced indeterminate or discordant results for 7.9% of patients and misclassified 6.6% of patients; only 27.4% of patients required LSM. In groups in which 24% and 50% of patients had advanced fibrosis, using LSM ≥10 kPa alone for the diagnosis of advanced fibrosis had the highest accuracy and misclassified 18.1% and 18.3% of patients, respectively. These results were similar when the Fibrosis-4 score was used in place of NFS. CONCLUSIONS: In a retrospective analysis, we found that a 2-step approach using fibrosis scores followed by LSM most accurately detects advanced fibrosis in populations with a low prevalence of advanced fibrosis. However, LSM ≥10 kPa identifies patients with advanced fibrosis with the highest level of accuracy in populations with a high prevalence of advanced fibrosis.
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Técnicas de Imagem por Elasticidade , Cirrose Hepática/diagnóstico , Fígado/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/complicações , Índice de Gravidade de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
BACKGROUND & AIMS: The clinical significance of steatohepatitis in chronic hepatitis B remains unclear. This study aimed to determine the prevalence and risk factors for steatohepatitis in chronic hepatitis B, and to determine its correlation with liver fibrosis and response to antiviral therapy. METHODS: Liver histopathology of 256 consecutive chronic hepatitis B patients with serum hepatitis B virus DNA >2000 IU/mL were analysed with clinical and laboratory characteristics. Virological and biochemical responses were prospectively assessed in the 112 patients treated with antiviral monotherapy. RESULTS: Hepatic steatosis was observed in 38% of the entire cohort, and steatohepatitis was diagnosed in 18% of patients with hepatic steatosis according to Brunt's classification. The presence of steatohepatitis was associated with overweight/obese (odds ratio, 5.99; 95% CI, 1.32-27.2) and hypertriglyceridaemia (odds ratio, 2.95; 95% CI, 1.07-8.15). None of the viral characteristics including HBeAg status, genotypes and viraemia levels was associated with the presence of steatohepatitis. Steatohepatitis was an independent predictor of significant fibrosis (odds ratio, 10.0; 95% CI, 2.08-48.5) and advanced fibrosis (odds ratio, 3.45; 95% CI, 1.11-10.7) after adjusting for viraemia levels and features of the metabolic syndrome. The rates of suppression of serum hepatitis B virus DNA <20 IU/mL combined with aminotransferase normalization at week 48 of antiviral therapy were not different between the steatohepatitis and non-steatohepatitis groups (43% vs 53%; P=.475). CONCLUSIONS: Steatohepatitis is not uncommon in chronic hepatitis B patients. It is associated with metabolic syndrome but not viral factor. This study demonstrates that steatohepatitis is related to the severity of liver fibrosis but it does not affect response to antiviral therapy.
Assuntos
Antivirais/uso terapêutico , Fígado Gorduroso/epidemiologia , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Adulto , DNA Viral/sangue , Fígado Gorduroso/etiologia , Feminino , Hepacivirus , Humanos , Fígado/patologia , Cirrose Hepática/etiologia , Modelos Logísticos , Masculino , Síndrome Metabólica/complicações , Pessoa de Meia-Idade , Obesidade/complicações , Estudos Prospectivos , Fatores de Risco , Resposta Viral Sustentada , Tailândia/epidemiologiaRESUMO
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) can progress from simple steatosis to hepatocellular carcinoma. None of tools have been developed specifically for high-risk patients. This study aimed to develop a simple risk scoring to predict NAFLD in patients with metabolic syndrome (MetS). METHODS: A total of 509 patients with MetS were recruited. All were diagnosed by clinicians with ultrasonography-confirmed whether they were patients with NAFLD. Patients were randomly divided into derivation (n=400) and validation (n=109) cohort. To develop the risk score, clinical risk indicators measured at the time of recruitment were built by logistic regression. Regression coefficients were transformed into item scores and added up to a total score. A risk scoring scheme was developed from clinical predictors: BMI ≥25, AST/ALT ≥1, ALT ≥40, type 2 diabetes mellitus and central obesity. The scoring scheme was applied in validation cohort to test the performance. RESULTS: The scheme explained, by area under the receiver operating characteristic curve (AuROC), 76.8% of being NAFLD with good calibration (Hosmer-Lemeshow χ2 =4.35; P=.629). The positive likelihood ratio of NAFLD in patients with low risk (scores below 3) and high risk (scores 5 and over) were 2.32 (95% CI: 1.90-2.82) and 7.77 (95% CI: 2.47-24.47) respectively. When applied in validation cohort, the score showed good performance with AuROC 76.7%, and illustrated 84%, and 100% certainty in low- and high-risk groups respectively. CONCLUSIONS: A simple and non-invasive scoring scheme of five predictors provides good prediction indices for NAFLD in MetS patients. This scheme may help clinicians in order to take further appropriate action.
Assuntos
Técnicas de Apoio para a Decisão , Síndrome Metabólica/complicações , Hepatopatia Gordurosa não Alcoólica/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Alanina Transaminase/sangue , Área Sob a Curva , Aspartato Aminotransferases/sangue , Biomarcadores/sangue , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Humanos , Modelos Logísticos , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Análise Multivariada , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Obesidade Abdominal/complicações , Obesidade Abdominal/diagnóstico , Razão de Chances , Valor Preditivo dos Testes , Curva ROC , Reprodutibilidade dos Testes , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND & AIMS: Histologic analysis of liver biopsy specimens allows for grading and staging of nonalcoholic fatty liver disease (NAFLD). We performed a longitudinal study to investigate the long-term prognostic relevance of histologic features for patients with NAFLD. METHODS: We performed a retrospective analysis of 619 patients diagnosed with NAFLD from 1975 through 2005 at medical centers in the United States, Europe, and Thailand. Patients underwent laboratory and biopsy analyses, and were examined every 3-12 months after their diagnosis. Outcomes analyzed were overall mortality, liver transplantation, and liver-related events. Cumulative outcomes were compared by log-rank analysis. Cox proportional-hazards regression was used to estimate adjusted hazard ratios (HRs). Time at risk was determined from the date of liver biopsy to the date of outcome or last follow-up examination. RESULTS: Over a median follow-up period of 12.6 years (range, 0.3-35.1 y), 193 of the patients (33.2%) died or underwent liver transplantation. Features of liver biopsies significantly associated with death or liver transplantation included fibrosis stage 1 (HR, 1.88; 95% confidence interval [CI], 1.28-2.77), stage 2 (HR, 2.89; 95% CI, 1.93-4.33), stage 3 (HR, 3.76; 95% CI, 2.40-5.89), and stage 4 (HR, 10.9; 95% CI, 6.06-19.62) compared with stage 0, as well as age (HR, 1.07; 95% CI, 1.05-1.08), diabetes (HR, 1.61; 95% CI, 1.13-2.30), current smoking (HR, 2.62; 95% CI, 1.67-4.10), and statin use (HR, 0.32; 95% CI, 0.14-0.70). Twenty-six patients (4.2%) developed liver-related events; fibrosis stage 3 (HR, 14.2; 95% CI, 3.38-59.68) and stage 4 (HR, 51.5; 95% CI, 9.87-269.2) compared with stage 0, were associated significantly with the events. Patients with fibrosis, regardless of steatohepatitis or NAFLD activity score, had shorter survival times than patients without fibrosis. CONCLUSIONS: In a longitudinal study of patients with NAFLD, fibrosis stage, but no other histologic features of steatohepatitis, were associated independently with long-term overall mortality, liver transplantation, and liver-related events.
Assuntos
Cirrose Hepática/epidemiologia , Cirrose Hepática/patologia , Transplante de Fígado/mortalidade , Fígado/patologia , Hepatopatia Gordurosa não Alcoólica , Adulto , Fatores Etários , Biópsia , Diabetes Mellitus/epidemiologia , Europa (Continente) , Feminino , Seguimentos , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/patologia , Hepatopatia Gordurosa não Alcoólica/fisiopatologia , Hepatopatia Gordurosa não Alcoólica/terapia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Fumar/epidemiologia , Tailândia , Fatores de Tempo , Estados UnidosRESUMO
OBJECTIVES: Tricyclic antidepressants could be effective in the treatment of symptoms related to hypersensitive esophagus through their pain-modulating effect. We therefore assessed the benefit of imipramine in patients with esophageal hypersensitivity and functional heartburn. METHODS: Patients with normal endoscopy findings and typical reflux symptoms despite standard-dose proton-pump inhibitor therapy underwent 24-h pH-impedance monitoring. Patients with established esophageal hypersensitivity or functional heartburn were randomly assigned to receive 8 weeks of either once-daily imipramine 25 mg (n=43) or placebo (n=40). The primary end point was satisfactory relief of reflux symptoms, defined as a >50% reduction in the gastroesophageal reflux disease score. The secondary end point was improvement in quality-of-life (QoL) as assessed by the 36-Item Short Form Health Survey score. RESULTS: Patients receiving imipramine did not achieve a higher rate of satisfactory relief of reflux symptoms than did patients receiving placebo (intention-to-treat (ITT) analysis: 37.2 vs. 37.5%, respectively; odds ratio (OR), 0.99; 95% confidence interval (CI), 0.41-2.41; per-protocol (PP) analysis: 45.5 vs. 41.2%, respectively; OR, 1.19; 95% CI, 0.45-3.13). Subgroup analysis to assess the efficacy of imipramine for either esophageal hypersensitivity or functional heartburn yielded similar results. Treatment with imipramine provided significant improvement of QoL by PP analysis (72±17 and 61±19, respectively; P=0.048), but ITT analysis did not reveal any differences between imipramine and placebo (68±19 and 61±19, respectively; P=0.26). Adverse events were similar in both groups; however, constipation was more common with imipramine than placebo (51.2 vs. 22.5%, respectively; P=0.01). CONCLUSIONS: Although low-dose imipramine shows potential QoL benefits, it does not relieve symptoms more effectively than does placebo in patients with either esophageal hypersensitivity or functional heartburn.
Assuntos
Antidepressivos Tricíclicos/uso terapêutico , Refluxo Gastroesofágico/tratamento farmacológico , Azia/tratamento farmacológico , Hiperestesia/tratamento farmacológico , Imipramina/uso terapêutico , Adulto , Idoso , Método Duplo-Cego , Monitoramento do pH Esofágico , Feminino , Refluxo Gastroesofágico/complicações , Azia/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Qualidade de Vida , Resultado do TratamentoRESUMO
AIM: To evaluate the utility of the combination of alanine aminotransferase (ALT) course, hepatitis B virus (HBV) DNA level, and liver stiffness measurement (LSM) for determining significant liver disease in hepatitis B e antigen (HBeAg)-negative patients. METHODS: Three hundred and ninety nine consecutive HBeAg-negative patients with HBV DNA >2000 IU/mL and documented serial measurements of ALT were enrolled to undergo LSM followed by liver biopsy. RESULTS: Using ALT <40 IU/L as a normal value, 142 patients had persistently normal ALT (PNALT), whereas 257 had persistently or intermittently elevated ALT (PIEALT) in the prior year. Among patients with HBV DNA of 2000-19 999, 20 000-199 999, and ≥200 000 IU/mL, significant pathological lesions defined as the presence of moderate to severe necroinflammation and/or significant fibrosis by METAVIR scoring was present in 40%, 45%, and 71% of the PIEALT group, and 15%, 31%, and 36% of the PNALT group, respectively. In PNALT patients with HBV DNA <20 000 IU/mL, liver biopsy could be avoided in 88% when LSM <7 kPa is used as an indicator of non-significant liver histology but 12% of those who indeed had significant pathological lesions would be missed. In PIEALT patients with HBV DNA ≥20 000 IU/mL, the need for liver biopsy could be reduced by 53% with a false positive rate of 14% when LSM ≥7 kPa is used as a predictor of significant pathological lesions. CONCLUSION: The combination of serial ALT, viral load, and LSM appears to be a promising non-invasive tool. A management algorithm for HBeAg-negative patients comprising these non-invasive measures is proposed with liver biopsy being pursued in selected cases.