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1.
Artigo em Inglês | MEDLINE | ID: mdl-32413340

RESUMO

BACKGROUND: Although non-alcoholic fatty liver disease (NAFLD) is commonly associated with obesity, it is increasingly being identified in non-obese individuals. We aimed to characterise the prevalence, incidence, and long-term outcomes of non-obese or lean NAFLD at a global level. METHODS: For this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and the Cochrane Library from inception to May 1, 2019, for relevant original research articles without any language restrictions. The literature search and data extraction were done independently by two investigators. Primary outcomes were the prevalence of non-obese or lean people within the NAFLD group and the prevalence of non-obese or lean NAFLD in the general, non-obese, and lean populations; the incidence of NAFLD among non-obese and lean populations; and long-term outcomes of non-obese people with NAFLD. We also aimed to characterise the demographic, clinical, and histological characteristics of individuals with non-obese NAFLD. FINDINGS: We identified 93 studies (n=10 576 383) from 24 countries or areas: 84 studies (n=10 530 308) were used for the prevalence analysis, five (n=9121) were used for the incidence analysis, and eight (n=36 954) were used for the outcomes analysis. Within the NAFLD population, 19·2% (95% CI 15·9-23·0) of people were lean and 40·8% (36·6-45·1) were non-obese. The prevalence of non-obese NAFLD in the general population varied from 25% or lower in some countries (eg, Malaysia and Pakistan) to higher than 50% in others (eg, Austria, Mexico, and Sweden). In the general population (comprising individuals with and without NAFLD), 12·1% (95% CI 9·3-15·6) of people had non-obese NAFLD and 5·1% (3·7-7·0) had lean NAFLD. The incidence of NAFLD in the non-obese population (without NAFLD at baseline) was 24·6 (95% CI 13·4-39·2) per 1000 person-years. Among people with non-obese or lean NALFD, 39·0% (95% CI 24·1-56·3) had non-alcoholic steatohepatitis, 29·2% (21·9-37·9) had significant fibrosis (stage ≥2), and 3·2% (1·5-5·7) had cirrhosis. Among the non-obese or lean NAFLD population, the incidence of all-cause mortality was 12·1 (95% CI 0·5-38·8) per 1000 person-years, that for liver-related mortality was 4·1 (1·9-7·1) per 1000 person-years, cardiovascular-related mortality was 4·0 (0·1-14·9) per 1000 person-years, new-onset diabetes was 12·6 (8·0-18·3) per 1000 person-years, new-onset cardiovascular disease was 18·7 (9·2-31·2) per 1000 person-years, and new-onset hypertension was 56·1 (38·5-77·0) per 1000 person-years. Most analyses were characterised by high heterogeneity. INTERPRETATION: Overall, around 40% of the global NAFLD population was classified as non-obese and almost a fifth was lean. Both non-obese and lean groups had substantial long-term liver and non-liver comorbidities. These findings suggest that obesity should not be the sole criterion for NAFLD screening. Moreover, clinical trials of treatments for NAFLD should include participants across all body-mass index ranges. FUNDING: None.

2.
JAMA Netw Open ; 3(4): e201844, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32271388

RESUMO

Importance: To achieve the World Health Organization goal of viral hepatitis elimination by 2030, it is important to estimate current rates of chronic hepatitis B (CHB) diagnosis and treatment. Objective: To provide an accurate accounting of the number of patients with CHB aged 6 years or older who have not yet been diagnosed in the United States. Design, Setting, and Participants: This cross-sectional study used the commercial US Truven Health MarketScan Database (138 634 154 privately insured individuals in January 2007 to December 2014) to identify patients with CHB diagnosis and the National Health and Nutrition Examination Survey to estimate the actual number of privately insured persons with CHB. Based on sex and age distribution derived from the US Census Bureau, we calculated the total population with CHB and the proportion of those who remained undiagnosed among the 198 073 302 privately insured individuals. Next, we identified diagnosed CHB patients who received 1 or more prescription for CHB medications to calculate the treatment rate for those with severe disease states, such as cirrhosis and hepatocellular carcinoma, that would warrant treatment. Analyses were performed from October 2017 to January 2020. Main Outcomes and Measures: The rate and number of patients with CHB who remained undiagnosed and treatment rates for patients with CHB who have cirrhosis or hepatocellular carcinoma. Results: Among the 198 073 302 privately insured individuals (48.55% male; 15.52% aged 6-17 years; 84.48% aged ≥18 years), there were 511 029 (95% CI, 317 733-704 325) individuals with CHB, but only 95 075 of these had been diagnosed, yielding a diagnosis rate of only 18.60% (95% CI, 13.50%-29.92%), meaning that 81.40% (95% CI, 70.08%-86.50%) were undiagnosed. The treatment rates were 34.79% (95% CI, 33.31%-36.27%) for those with cirrhosis and 48.64% (95% CI, 45.59%-51.69%) for those with hepatocellular carcinoma. Conclusions and Relevance: In this study, only approximately 1 in 5 privately insured patients with CHB had been diagnosed. Only one-third of patients with CHB who had cirrhosis and one-half who had hepatocellular carcinoma received antiviral therapy. Further efforts are needed to improve the current situation of poor connection to care for patients with CHB, especially for those with advanced liver disease.

3.
Heart ; 106(13): 985-991, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32245882

RESUMO

OBJECTIVE: The European Society of Cardiology (ESC) 0/1 hour algorithm has been primarily validated in Europe, America and Australasia with less knowledge of its performance outside of these settings. We aim to evaluate the performance of the ESC 0/1 hour algorithm across different contexts. METHODS: We searched PubMed, Embase, Scopus, Web of Science and the Cochrane Central Register of Controlled Trials for relevant studies published between 1 January 2008 and 31 May 2019. The primary outcome was index myocardial infarction and the secondary outcome was major adverse cardiac event or mortality. A bivariate random-effects meta-analysis was used to derive the pooled estimate of each outcome. RESULTS: A total of 11 014 patients from 10 cohorts were analysed for the primary outcome. The algorithm based on high-sensitivity cardiac troponin (hs-cTn)T (Roche), hs-cTnI (Abbott) and hs-cTnI (Siemens) had pooled sensitivity of 98.4% (95% CI=95.1% to 99.5%), 98.1% (95% CI=94.6% to 99.3%) and 98.7% (95% CI=97.3% to 99.3%), respectively. The algorithm based on hs-cTnT (Roche) and hs-cTnI (Siemens) had pooled specificity of 91.2% (95% CI=86.0% to 94.6%) and 95.9% (95% CI=94.1% to 97.2%), respectively. Among patients in the rule-out category, the pooled mortality rate at 30 days and at 1 year was 0.1% (95% CI=0.0% to 0.4%) and 0.8% (95% CI=0.5% to 1.2%), respectively. Among patients in the observation zone, the pooled mortality rate was 0.7% (95% CI=0.3% to 1.2%) at 30 days but increased to 8.1% (95% CI=6.1% to 10.4%) at 1 year, comparable to the mortality rate in the rule-in group. CONCLUSION: The ESC 0/1 hour algorithm has high diagnostic accuracy but may not be sufficiently safe if the 1% miss-rate for myocardial infarction is desired. PROSPERO REGISTRATION NUMBER: CRD42019142280.

4.
Hepatol Int ; 14(2): 259-269, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32130675

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease worldwide. This study aimed to estimate the prevalence, incidence, and outcome of NAFLD in the large and diverse population of Mainland China. METHODS: PubMed, Embase, and the Cochrane Library databases were searched to identify published studies with NAFLD epidemiology data in adult participants (≥ 18 years old) from Mainland China. Random effects models were used to determine pooled estimates. RESULTS: We screened 1,328 studies and included 167 eligible studies (participant n = 1,486,635): 149 studies (n = 1,350,819) for prevalence, 18 studies (n = 147,316) for incidence, 7 studies (n = 5446) for evolution of hepatic steatosis, and 2 studies (n = 647) for mortality analysis. The NAFLD prevalence of the overall populations was 29.88%, with higher rates in males, increasing age and increasing gross regional domestic product (GRDP) per capita (all p ≤ 0.010). The prevalence was the highest in North China (36.41%; higher in Uyghur and Hui Chinese 40.86% and 34.36% vs 28.11% in Han Chinese), higher in diabetics (51.83% vs. 30.76% in non-diabetics) and in obese participants (66.21% vs. 11.72% in lean). The NAFLD incidence was 56.7 (95% CI 47.4-66.8) per 1000 person-years, higher in males and with higher GRDP per capita. The overall mortality was 7.3 (3.3-12.7) per 1000 person-years. CONCLUSIONS: The overall prevalence of NAFLD in Mainland China is about 30%. The highest prevalences were found among regions with higher income, North China, the non-Han ethnic minorities, diabetics, and the obese. China's NAFLD prevalence is on par with Western countries.

5.
Hepatology ; 71(2): 431-443, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31228279

RESUMO

Hepatitis B virus (HBV) infection remains a major global health problem, exacerbated by poor linkage to care. We aimed to determine the prevalence of HBV infection, exposure, self-reported vaccination, vaccine-induced immunity, disease awareness, and treatment in the United States by birthplace and race/ethnicity during 1999-2016. A total of 47,628 adult participants in the National Health and Nutrition Examination Survey who completed HBV core antibody (anti-HBc) and surface antigen (HBsAg) tests and 47,618 adults who completed HBV surface antibody (anti-HBs) and anti-HBc tests were included in the analysis. HBV infection was defined by positive HBsAg and past exposure by positive anti-HBc. Vaccine-mediated immunity was defined by positive anti-HBs and negative anti-HBc. No significant change in the prevalence of HBV infection was observed between 1999 and 2016 (P = 0.442), affecting 0.35% (95% confidence interval [CI], 0.28-0.45) or 0.84 million adults. In contrast, a significant decrease in HBV exposure and increase in vaccine-mediated immunity was observed. U.S.-born persons had significantly lower prevalence of HBV infection and exposure as well as higher prevalence of vaccine-mediated immunity and self-reported vaccination than foreign-born persons. Prevalence of HBV infection was highest in non-Hispanic Asians in both foreign- (3.85%; 95% CI, 2.97-4.97) and U.S.-born (0.79%; 95% CI, 0.17-3.59) persons during 2011-2016. Among infected persons, liver disease awareness was only 15.19%, and treatment rate was only 4.60%. Conclusion: This study revealed disparities of HBV infection among ethnic/racial groups and between U.S.-born and foreign-born persons. Awareness of liver disease and treatment rate among infected persons was dismal.

6.
Dig Dis Sci ; 65(5): 1520-1528, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31598919

RESUMO

BACKGROUND AND AIMS: Liver cirrhosis is a substantial health burden in the USA, but population-based data regarding the trend and medical expenditure are limited and outdated. We investigated the trends of inpatient admissions, costs, and inpatient mortality from 2005 to 2015 among cirrhotic patients. METHODS: A retrospective analysis was conducted using the National Inpatient Sample database. We adjusted the costs to 2015 US dollars using a 3% inflation rate. National estimates of admissions were determined using discharge weights. RESULTS: We identified 1,627,348 admissions in cirrhotic patients between 2005 and 2015. From 2005 to 2015, the number of weighted admissions in cirrhotic patients almost doubled (from 505,032 to 961,650) and the total annual hospitalization cost in this population increased three times (from 5.8 to 16.3 billion US dollars). Notably, admission rates varied by liver disease etiology, decreasing from 2005 to 2015 among patients with hepatitis C virus (HCV)-related cirrhosis while increasing (almost tripled) among patients with nonalcoholic fatty liver disease (NAFLD)-related cirrhosis. The annual inpatient mortality rate per 1000 admissions overall decreased from 63.8 to 58.2 between 2005 and 2015 except for NAFLD (27.2 to 35.8) (P < 0.001). CONCLUSIONS: Rates and costs of admissions in cirrhotic patients have increased substantially between 2005 and 2015 in the USA, but varied by liver disease etiology, with decreasing rate for HCV-associated cirrhosis and for HBV-associated cirrhosis but increasing for NAFLD-associated cirrhosis. Inpatient mortality also increased by one-third for NAFLD, while it decreased for other diseases. Cost also varied by etiology and lower for HCV-associated cirrhosis.

7.
Eur J Gastroenterol Hepatol ; 32(3): 406-419, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31490419

RESUMO

BACKGROUND/OBJECTS: Early hepatocellular carcinoma diagnosis is associated with better long-term survival. Studies of at-risk patients who are monitored in routine practice have reported an overall adherence rate to hepatocellular carcinoma screening/surveillance of approximately 60% and suboptimal diagnostic efficacy of the current screening/surveillance tools. However, it is unclear how many hepatocellular carcinoma patients were actually diagnosed via screening/surveillance given these obstacles. Therefore, via a systematic review of PubMed and Scopus databases from 2000 to 2019, we aimed to identify the proportion of patients with hepatocellular carcinoma diagnosed via screening/surveillance in routine practice. METHODS: We included original research articles of studies of patients already diagnosed with hepatocellular carcinoma that reported the proportion of hepatocellular carcinoma diagnosed via screening/surveillance. RESULTS: The study included 60 studies and 50 554 hepatocellular carcinoma cases. The pooled proportion of hepatocellular carcinoma diagnosed by screening/surveillance was 37% (95% confidence interval: 31%-44%) and differed by geographic region (North America/Asia/Europe/Oceania/Africa/South America, 31%/42%/41%/30%/29%/47%, P = 0.017, respectively) and by surveillance interval (<12 months 39% vs. 12 months 19%, P < 0.01) but not by disease etiology, cirrhosis status, clinical setting, practice setting, hepatocellular carcinoma diagnosis period, or surveillance method. CONCLUSION: Globally, hepatocellular carcinoma was diagnosed via screening/surveillance in less than half of the patients (37%) regardless of healthcare setting or liver disease etiology and without improvement over time despite several recent guideline updates. Research is needed to understand the barriers to screening/surveillance to include medical as well as social and cultural influences.

8.
J Infect Dis ; 221(3): 408-418, 2020 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-31560391

RESUMO

BACKGROUND: Athough curative therapy is now available for hepatitis C virus (HCV) infection in the United States, it is not clear whether all affected persons have been diagnosed and/or linked to care. METHODS: This cross-sectional study utilized data from the National Health and Nutrition Examination Survey (1999-2016) and included 46 465 nonincarcerated and noninstitutionalized participants. RESULTS: Viremic HCV prevalence decreased from 1.32% in 1999-2004 to 0.80% in 2011-2016, although most of the decrease occurred in US-born whites and blacks but not the foreign-born or those born after 1985. In 2011-2016, approximately 1.90 million US adults remained viremic with HCV, and 0.33 million were at higher risk for advanced fibrosis, but only 49.8% were aware of their HCV infection, with higher disease awareness in those with health insurance coverage and US-born persons. CONCLUSIONS: The prevalence of viremic HCV has decreased in recent years among US born whites and blacks but not in other race/ethnicities and foreign-born persons and birth cohort born after 1985. Less than half of the viremic population was aware of having HCV infection. Improved HCV screening and linkage to care are needed, especially for the uninsured, foreign-born, birth cohort after 1985 and certain ethnic minorities.

9.
Clin Infect Dis ; 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31777940

RESUMO

BACKGROUND: The cure rate of hepatitis C virus (HCV) treatment with direct-acting antivirals (DAAs) for patients with active and inactive hepatocellular carcinoma (HCC) may differ, but well-controlled studies are limited. We aimed to evaluate DAA outcomes in a large East Asian HCV/HCC population compared to HCV/non-HCC patients. METHODS: Using data from the REAL-C registry (Hong Kong, Japan, South Korea, and Taiwan), we used propensity score matching (PSM) to match HCC and non-HCC (1:1) groups for age, sex, cirrhosis, prior treatment, HCV genotype, treatment regimen, baseline platelet count, HCV RNA, total bilirubin, alanine aminotransferase, and albumin level to evaluate DAA treatment outcomes in a large population of HCV/HCC compared to HCV/non-HCC patients. RESULTS: We included 6,081 patients (HCC, n=465; non-HCC, n=5,616) treated with interferon-free DAAs. PSM of the entire study population yielded 436 matched pairs with similar baseline characteristics. There was no statistically significant difference in the overall SVR rate of the HCC (92.7%) and non-HCC (95.0%) groups. Rates of treatment discontinuation, adverse effects, and death were also similar between the HCC and non-HCC groups. Among patients with HCC, those with active HCC had a lower SVR than inactive HCC cases (85.5% vs. 93.7%, P=0.03). On multivariable analysis, active HCC, but not inactive HCC, was significantly associated with lower SVR (OR 0.28, P=0.01) when compared to non-HCC. CONCLUSIONS: Active HCC but not inactive HCC was independently associated with lower SVR compared to non-HCC patients undergoing DAA therapy, though cure rate was still relatively high (85%) in active HCC patients.

10.
Hepatol Commun ; 3(10): 1334-1346, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31592492

RESUMO

There is growing evidence that links nonalcoholic fatty liver disease (NAFLD) with impairment of renal function. As such, we aimed to demonstrate the trend of NAFLD, NAFLD with renal insufficiency (RI), disease awareness, and mortality over time. Patient data were extracted from the National Health and Nutrition Examination Survey (NHANES) 1999-2016. A total of 14,255 adult study participants without competing liver disease or heavy drinking and with complete laboratory data were included. NAFLD was defined using the U.S. Fatty Liver Index (USFLI) and RI was defined using the Chronic Kidney Disease Epidemiology Collaboration equation and urine albumin:creatinine ratio. Death data were obtained from the National Death Index (up to December 31, 2015). Prevalence of NAFLD in participants was 31.2% (95% confidence interval [CI], 30.01-32.46); of these participants, 22.05% (95% CI, 20.34-23.85) had RI. From 1999 to 2016, prevalence of both NAFLD without RI (P = 0.048) and NAFLD-RI (P = 0.006) increased significantly. Among those with NAFLD-RI, awareness of kidney disease was 8.56% (95% CI, 6.69-10.89), while awareness of liver disease among all NAFLD was 4.49% (95% CI, 3.17-6.33). Among those with NAFLD, mortality incidence per 1,000 person years was highest among those with severe RI in all-cause mortality (104.4; 95% CI, 83.65-130.39) and other residual causes of mortality (mean, 50.88; 95% CI, 37.02-69.93). Conclusion: Prevalence of NAFLD and NAFLD-RI has increased over the past 2 decades in the United States. Low kidney disease and liver disease awareness are major public health issues as those with NAFLD-RI have significantly higher mortality than those with only NAFLD.

11.
Hepatology ; 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31610027

RESUMO

BACKGROUND AND AIMS: Survival data among patients with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) after achieving sustained virologic response (SVR) with interferon-free direct-acting antivirals (DAAs) in both Asian and western countries are limited. Survival rates were compared between patients with HCV-related HCC who were untreated for HCV and those who achieved SVR. APPROACH AND RESULTS: Using data from two U.S. and six Asian centers from 2005 to 2017, we categorized 1,676 patients who were mono-infected with HCV-related HCC into patients untreated for HCV (untreated group) and DAA-treated patients with SVR (SVR group) and matched by propensity score matching (PSM); multivariable Cox regression with HCV treatment status as a time-varying covariate was used to determine mortality risk and landmark analysis to avoid immortal time bias. There were 1,239 untreated patients and 437 patients with SVR. After PSM, background risks of the 321 pairs of matched patients were balanced (all P > 0.05). After time-varying adjustment for HCV treatment initiation compared with untreated patients, patients with SVR had significantly higher 5-year overall survival (87.78% vs. 66.05%, P < 0.001). Multivariable Cox regression showed that SVR was independently associated with a 63% lower risk of 5-year all-cause mortality (hazard ratio [HR], 0.37; 95% confidence interval [CI], 0.16-0.83; P = 0.016) and 66% lower risk of 5-year liver-related mortality (HR, 0.34; 95% CI, 0.13-0.88; P = 0.026) with similar trends after removing patients with liver transplants. Landmark analysis at 90, 180, and 360 days showed consistent results (HRs ranged 0.22 to 0.44, all P < 0.05). CONCLUSION: In this multinational consortium, patients with HCV-related HCC who obtained SVR achieved a 60%-70% improvement in 5-year survival (both all-cause and liver related) compared with patients untreated for HCV. Patients eligible for HCC therapy should also be considered for DAA therapy.

12.
J Clin Med ; 8(9)2019 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-31514449

RESUMO

BACKGROUND AND AIM: Recent practice guidelines suggest healthy normal alanine aminotransferase (ALT) levels should be less than 30 U/L for males and 19 U/L for females. We tried to validate the prediction power of the "low cut off" for liver related outcomes in the general population. METHODS: A total of 426,013 subjects were followed up for 10 years using the National Health Screening Cohort database. Prediction ability of long term mortality and liver related outcomes between conventional (<40 U/L in men and women) and low (<30 U/L in men and <19 U/L in women) ALT cut-off values were compared. RESULTS: Both conventional and low ALT cut-offs predicted liver related unfavorable outcomes in Kaplan-Meier analysis. Following adjustment for age, body mass index, smoking, exercise, alcohol consumption, fasting blood glucose, and cholesterol via multivariate Cox regression, abnormal ALT using new 'low ALT cut off' was a significant independent predictor for liver-related mortality, HCC, and decompensated liver events. When the low cut-off criteria were added to the prediction model, the ability to predetect liver-related hard outcomes significantly increased in both men and women (p-values < 0.0001). The C-index values for predicting liver-related adverse events were the same in both ALT cut-offs, after adjusting confounding factors (C index value: 0.73~0.88). CONCLUSIONS: New low ALT cut-off showed good prediction power for liver related unfavorable outcomes.

14.
World J Gastroenterol ; 25(23): 2961-2972, 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31249453

RESUMO

BACKGROUND: Recently, the American Association for the Study of Liver Disease suggested no preference between tenofovir (TDF) and entecavir (ETV) regarding potential long-term risks of renal complications. Over the years, renal safety has become a critical concern in nucleos(t)ide analog-treated patients due to the long-term use of these drugs. However, existing studies do not show significant differences in renal dysfunction between these two drugs. Further, there is a paucity of studies comparing the long-term renal effects of TDF and ETV. AIM: To investigate the effects of TDF and ETV on renal function, we performed systematic review and meta-analysis. METHODS: Two investigators independently searched the Cochrane Library, MEDLINE, and Embase databases for randomized controlled trials and nonrandomized studies (NRSs) using the keywords "CHB", "Tenofovir", and "Entecavir", and additional references were obtained from the bibliographies of relevant articles published through December 2017. The quality of each study was assessed using the Newcastle-Ottawa scale and the Grading of Recommendations Assessment, Development and Evaluation criteria. The primary outcome was the change in serum creatinine level in the TDF and ETV groups at baseline, 6 mo, 12 mo and 24 mo. RESULTS: Nine NRSs comprising 2263 participants met the inclusion criteria. Changes in creatinine levels were higher in the TDF group than in the ETV group at 6 mo [mean difference (MD) = 0.03 mg/dL; 95%CI: 0.02-0.04; I 2 = 0%], 12 mo (MD = 0.05 mg/dL; 95%CI: 0.02-0.08; I 2 = 78%), and 24 mo (MD = 0.07 mg/dL; 95%CI: 0.01-0.13; I 2 = 93%). The change in estimated glomerular filtration rate (eGFR) was significantly higher in the TDF group than in the ETV group at 6 mo [standardized mean difference (SMD), -0.22; 95%Cl: -0.36--0.08; I 2 = 0%], 12 mo (SMD = -0.24; 95%Cl: -0.43--0.05; I 2 = 50%), and 24 mo (-0.35; 95%Cl: -0.61- -0.09; I 2 = 67%). CONCLUSION: TDF statistically significantly increased serum creatinine levels and decreased the eGFR in 6-24 mo compared to ETV, with moderate to low quality of evidence. However, the differences are negligible.


Assuntos
Antivirais/efeitos adversos , Guanina/análogos & derivados , Hepatite B Crônica/tratamento farmacológico , Nefropatias/epidemiologia , Tenofovir/efeitos adversos , Creatinina/sangue , Taxa de Filtração Glomerular , Guanina/efeitos adversos , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Nefropatias/sangue , Nefropatias/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
Gastroenterology ; 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31150598
16.
Gastroenterology ; 2019 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-31150608
17.
J Hepatol ; 71(3): 473-485, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31096005

RESUMO

BACKGROUND & AIMS: The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC) infection remains unclear. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response (SVR) among patients with CHC and either active, inactive or no HCC. METHODS: PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from 1/1/2013 to 9/24/2018. The pooled SVR rates were computed using DerSimonian-Laird random-effects models. RESULTS: We included 49 studies from 15 countries, comprised of 3,341 patients with HCC and 35,701 without HCC. Overall, the pooled SVR was lower in patients with HCC than in those without HCC (89.6%, 95% CI 86.8-92.1%, I2 = 79.1% vs. 93.3%, 95% CI 91.9-94.7%, I2 = 95.0%, p = 0.0012), translating to a 4.8% (95% CI 0.2-7.4%) SVR reduction by meta-regression analysis. The largest SVR reduction (18.8%) occurred in patients with active/residual HCC vs. inactive/ablated HCC (SVR 73.1% vs. 92.6%, p = 0.002). Meanwhile, patients with HCC who received a prior liver transplant had higher SVR rates than those who did not (p <0.001). Regarding specific DAA regimens, patients with HCC treated with ledipasvir/sofosbuvir had lower SVR rates than patients without HCC (92.6%, n = 884 vs. 97.8%, n = 13,141, p = 0.026), but heterogeneity was high (I2 = 84.7%, p <0.001). The SVR rate was similar in patients with/without HCC who were treated with ombitasvir/paritaprevir/ritonavir ±â€¯dasabuvir (n = 101) (97.2% vs. 94.8%, p = 0.79), or daclatasvir/asunaprevir (91.7% vs. 89.8%, p = 0.66). CONCLUSION: Overall, SVR rates were lower in patients with HCC, especially with active HCC, compared to those without HCC, though heterogeneity was high. Continued efforts are needed to aggressively screen, diagnose, and treat HCC to ensure higher CHC cure rates. LAY SUMMARY: There are now medications (direct-acting antivirals or "DAAs") that can "cure" hepatitis C virus, but patients with hepatitis C and liver cancer may be less likely to achieve cure than those without liver cancer. However, patients with liver cancer are also more likely to have advanced liver disease and risk factors that can decrease cure rates, so better controlled studies are needed to confirm these findings.

19.
Lancet Gastroenterol Hepatol ; 4(5): 389-398, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30902670

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Asia is a large, heterogeneous area with substantial variation in socioeconomic status and prevalence of obesity. We estimated the prevalence, incidence, and outcomes of NAFLD in the Asian population to assist stakeholders in understanding NAFLD disease burden. METHODS: We searched PubMed, EMBASE, and the Cochrane Library from database inception to Jan 17, 2019, for studies reporting NAFLD prevalence, incidence, or outcome in Asia. We included only cross-sectional and longitudinal observational studies of patients with NAFLD diagnosed by imaging, serum-based indices, or liver biopsy. Studies that included patients with overlapping liver disease or that did not screen for excess alcohol consumption were excluded. Two investigators independently screened and extracted data. The main outcomes were pooled NAFLD prevalence, incidence, and hepatocellular carcinoma incidence and overall mortality in patients with NAFLD. Summary estimates were calculated using a random-effects model. This study is registered with PROSPERO, number CRD42018088468. FINDINGS: Of 4995 records identified, 237 studies (13 044 518 participants) were included for analysis. The overall prevalence of NAFLD regardless of diagnostic method was 29·62% (95% CI 28·13-31·15). NAFLD prevalence increased significantly over time (25·28% [22·42-28·37] between 1999 and 2005, 28·46% [26·70-30·29] between 2006 and 2011, and 33·90% [31·74-36·12] between 2012 and 2017; p<0·0001). The pooled annual NAFLD incidence rate was 50·9 cases per 1000 person-years (95% CI 44·8-57·4). In patients with NAFLD, the annual incidence of hepatocellular carcinoma was 1·8 cases per 1000 person-years (0·8-3·1) and overall mortality rate was 5·3 deaths per 1000 person-years (1·5-11·4). INTERPRETATION: NAFLD prevalence in Asia is increasing and is associated with poor outcomes including hepatocellular carcinoma and death. Targeted public health strategies must be developed in Asia to target the drivers of this rising epidemic and its associated complications, especially in high-risk groups, such as older obese men. FUNDING: None.

20.
J Enzyme Inhib Med Chem ; 34(1): 692-702, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30777474

RESUMO

Matriptase is ectopically expressed in neoplastic B-cells, in which matriptase activity is enhanced by negligible expression of its endogenous inhibitor, hepatocyte growth factor activator inhibitor (HAI)-1. HAI-1, however, is also involved in matriptase synthesis and intracellular trafficking. The lack of HAI-1 indicates that other related inhibitor, such as HAI-2, might be expressed. Here, we show that HAI-2 is commonly co-expressed in matriptase-expressing neoplastic B-cells. The level of active matriptase shed after induction of matriptase zymogen activation in 7 different neoplastic B-cells was next determined and characterised. Our data reveal that active matriptase can only be generated and shed by those cells able to activate matriptase and in a rough correlation with the levels of matriptase protein. While HAI-2 can potently inhibit matriptase, the levels of active matriptase are not proportionally suppressed in those cells with high HAI-2. Our survey suggests that matriptase proteolysis might aberrantly remain high in neoplastic B-cells regardless of the levels of HAI-2.


Assuntos
Linfócitos B/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Glicoproteínas de Membrana/biossíntese , Proteólise/efeitos dos fármacos , Serina Endopeptidases/metabolismo , Linfócitos B/metabolismo , Linhagem Celular Tumoral , Humanos , Glicoproteínas de Membrana/metabolismo , Serina Endopeptidases/biossíntese
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