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1.
Dig Dis Sci ; 68(9): 3774-3780, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37540389

RESUMO

BACKGROUND: Percutaneous liver biopsy (P-bx) is the gold standard for diagnosing advanced fibrosis. Despite the proven technical feasibility of EUS-guided liver bx (EUS-bx) as a novel alternative way of liver biopsy, the clinical applicability remains to be determined. AIMS: The primary aim of this study is to evaluate if EUS-bx, compared to P-bx, can effectively and safely obtain adequate specimen and accurately predict hepatic fibrosis. METHODS: This is a single center, retrospective chart review among patients with liver diseases at a tertiary endoscopy center from February 2011 to March 2020. We assessed the EUS-bx versus P-bx outcomes by success rate, performance, and safety profile. The primary outcome was the association between EUS-bx clinical variables and the presence of histologic liver fibrosis stage ≥ 3. The secondary outcomes were the associations between EUS-bx and variables indicative of fibrosis. RESULTS: Fifty-nine patients underwent EUS-bx; and 59, P-bx. All EUS-bx procedures were successfully completed. All 56/56 (100%) of EUS-bx vs. 50/52 (96.2%) P-bx were considered adequate samples. Tissue lengths were significantly longer in the EUS-bx cohort (p < 0.0001) with a trend towards a greater number of portal tracts. 46/56 (82.1%) cases of EUS-bx vs. 32/52 (61.5%) of P-bx had > 10 portal tracts; 21/56 (37.5%) cases of EUS-bx vs. 14/52 (26.9%) of P-bx had > 15 portal tracts. There were 6 (10.2%) EUS-bx vs. 1 (1.7%) P-bx related complication leading to a phone call (p = 0.061). CONCLUSIONS: EUS-bx can safely performed and accurately predict liver fibrosis stage as the standard P-bx without being influenced by procedure-related factors.


Assuntos
Endossonografia , Cirrose Hepática , Humanos , Estudos Retrospectivos , Biópsia por Agulha/métodos , Cirrose Hepática/diagnóstico por imagem , Endossonografia/métodos , Ultrassonografia de Intervenção , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico
2.
Dig Dis Sci ; 68(8): 3237-3248, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37338616

RESUMO

Hepatitis D virus (HDV) depends on hepatitis B virus (HBV) to enter and exit hepatocytes and to replicate. Despite this dependency, HDV can cause severe liver disease. HDV accelerates liver fibrosis, increases the risk of hepatocellular carcinoma, and hastens hepatic decompensation compared to chronic HBV monoinfection. The Chronic Liver Disease Foundation (CLDF) formed an expert panel to publish updated guidelines on the testing, diagnosis, and management of hepatitis delta virus. The panel group performed network data review on the transmission, epidemiology, natural history, and disease sequelae of acute and chronic HDV infection. Based on current available evidence, we provide recommendations for screening, testing, diagnosis, and treatment of hepatitis D infection and review upcoming novel agents that may expand treatment options. The CLDF recommends universal HDV screening for all patients who are Hepatitis B surface antigen-positive. Initial screening should be with an assay to detect antibodies generated against HDV (anti-HDV). Patients who are positive for anti-HDV IgG antibodies should then undergo quantitative HDV RNA testing. We also provide an algorithm that describes CLDF recommendations on the screening, diagnosis, testing, and initial management of Hepatitis D infection.


Assuntos
Hepatite D , Vírus Delta da Hepatite , Coinfecção , Humanos , Hepatite D/diagnóstico , Hepatite D/terapia , Hepatite D/transmissão , Superinfecção , Vírus da Hepatite B
3.
J Gastroenterol Hepatol ; 37(7): 1373-1379, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35513894

RESUMO

BACKGROUND AND AIM: The portal pressure gradient (PPG) is a useful predictor of portal hypertension (PH) related complications. We previously showed the feasibility and safety of endoscopic ultrasound guided PPG measurement (EUS-PPG). Now EUS-guided liver biopsy (EUS-bx) has been shown to be a safe and effective alternative to percutaneous or Interventional Radiology-guided liver biopsy for the diagnosis of chronic liver disease (CLD). We aimed to evaluate the correlation between PPG and clinical markers of PH, and assess the feasibility and safety of concomitant, single session EUS-PPG and EUS-bx. METHODS: This was a retrospective study of patients undergoing EUS-PPG for CLD at a single tertiary endoscopy center between February 2014 and March 2020. EUS-PPG was performed using a 25-gauge needle and compact manometer. Data analysis was performed with SAS version 9.4. RESULTS: Eighty-three patients underwent EUS-PPG with 100% technical success. The mean PPG was 7.06 mmHg (SD 6.09, range 0-27.3). PPG was higher in patients with (vs without) clinical features of cirrhosis (9.46 vs 3.61 mmHg, P < 0.0001), esophageal or gastric varices (13.88 vs 4.34 mmHg, P < 0.0001), and thrombocytopenia (9.25 vs 4.71 mmHg, P = 0.0022). In the 71 patients (85.5%) who underwent EUS-bx, 70 (98.6%) specimens were deemed adequate by the pathologist for histologic diagnosis. There were no early or late major adverse events. CONCLUSION: EUS-PPG correlates well with clinical markers of PH. EUS-bx can be performed safely during the same session as EUS-PPG, providing a comprehensive endoscopic evaluation of the patient with CLD.


Assuntos
Gastroenterologia , Hepatopatias , Biomarcadores , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/efeitos adversos , Endossonografia/efeitos adversos , Humanos , Hepatopatias/diagnóstico por imagem , Hepatopatias/etiologia , Pressão na Veia Porta , Estudos Retrospectivos
4.
Dig Dis Sci ; 67(12): 5685-5692, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35279787

RESUMO

BACKGROUND AND AIMS: Endoscopic ultrasound is a novel diagnostic approach to chronic liver diseases (CLDs), and EUS-guided porto-systemic pressure gradient measurement (EUS-PPG) is an important expansion with a well-developed technique. However, the clinical value and applicability of EUS-PPG measurement in predicting histologically advanced hepatic fibrosis remain unknown. METHODS: This was a single-center retrospective study on patients with various CLDs undergoing EUS-PPG and EUS-guided liver biopsy (EUS-bx) to assess if EUS-PPG measurements correlate with histological fibrosis stage and various surrogate markers for severity of CLDs and its safety. Cases with EUS-PPG were identified at the University of California Irvine, a tertiary endoscopy center, between January 2014 and March 2020. RESULTS: In 64 patients, the mean age was 57.5; 40 (62.5%), males; mean Child-Turcotte-Pugh (CTP) and Model for End-Stage Liver Disease (MELD) scores, 5.9 and 10.4, respectively. The procedure success rate was 100%. Twenty-nine (45.3%) had EUS-PPG ≥ 5 mmHg that was associated with clinical cirrhosis (p < 0.0001), clinical portal hypertension (p = 0.002), hepatic decompensation (p = 0.013), MELD-Na > 10 (p = 0.036), PLTs ≤ 120 × 109/L (p = 0.001), INR ≥ 1.05 (p = 0.007), presence of EV, GV, or PHG (p < 0.0001), biopsy-proven fibrosis stage ≥ 3 (p = 0.002), APRI > 2 (p = 0.001), and FIB-4 > 3.25 (p = 0.001). Multivariable analysis confirmed that EUS-PPG ≥ 5 mmHg was significantly associated with liver biopsy-proven fibrosis stage ≥ 3 (LR 27.0, 95% CI = 1.653-360.597, p = 0.004), independent of C-cirrhosis, C-PHTN, thrombocytopenia, splenomegaly, and APRI score > 2, and FIB-4 score > 3.25. There were no serious complications related to EUS-PPG procedures. CONCLUSIONS: EUS-PPG measurements provide excellent correlation with histological hepatic fibrosis stage and various clinical, laboratory, endoscopic and imaging variables indicative of advanced liver disease without serious adverse events.


Assuntos
Doença Hepática Terminal , Masculino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Doença Hepática Terminal/complicações , Índice de Gravidade de Doença , Cirrose Hepática/complicações , Fibrose , Ultrassonografia de Intervenção/métodos
6.
World J Hepatol ; 13(1): 1-5, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33584985

RESUMO

The World Journal of Hepatology (WJH) was launched in October 2009. It mainly publishes articles reporting research findings in the field of hepatology, covering a wide range of topics, including viral hepatitis B and C, non-alcoholic fatty liver disease, alcoholic liver disease, autoimmune and chronic cholestatic liver disease, drug-induced liver injury, cirrhosis, liver failure, hepatocellular carcinoma, coronavirus disease 2019-related liver conditions, etc. As of December 31, 2020, the WJH has published 1349 articles, among which, the total cites is 18995 and the average cites per article is 14. In celebrating the New Year, we are pleased to share with you special a New Year's greeting from the WJH Editors-in-Chief, along with a detailed overview of the journal's submission, peer review and publishing metrics from 2020. In all, we are appreciative for the substantive support and submissions from authors worldwide, and the dedicated efforts and expertise provided by our invited reviewers and editorial board members.

7.
Clin Transl Gastroenterol ; 11(12): e00271, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33512798

RESUMO

INTRODUCTION: Liver cancer-secreted serine protease inhibitor Kazal (LC-SPIK) is a protein that is specifically elevated in cases of hepatocellular carcinoma (HCC). We assessed the performance of LC-SPIK in detecting HCC, including its early stages, in patients with cirrhosis, hepatitis B virus (HBV), and hepatitis C virus (HCV). METHODS: We enrolled 488 patients, including 164 HCC patients (81 early HCC) and 324 controls in a blinded, prospective, case-control study. Serum LC-SPIK levels were determined by an enzyme-linked immunosorbent assay-based assay. The performance of serum LC-SPIK and α-fetoprotein (AFP), including area under the curve (AUC), sensitivity, and specificity, are compared. The performance of LC-SPIK was evaluated in an independent validation cohort with 102 patients. RESULTS: In distinguishing all HCC patients from those with cirrhosis and chronic HBV/HCV, LC-SPIK had an AUC of 0.87, with 80% sensitivity and 90% specificity using a cutoff of 21.5 ng/mL. This is significantly higher than AFP, which had an AUC of 0.70 and 52% sensitivity and 86% specificity using a standard cutoff value of 20.0 ng/mL. For early-stage HCC (Barcelona Clinic Liver Cancer stage 0 and A), LC-SPIK had an AUC of 0.85, with 72% sensitivity and 90% specificity, compared with AFP, which had an AUC of 0.61, with 42% sensitivity and 86% specificity. In addition, LC-SPIK accurately detected the presence of HCC in more than 70% of HCC patients with false-negative AFP results. DISCUSSION: The study provided strong evidence that LC-SPIK detects HCC, including early-stage HCC, with high sensitivity and specificity, and might be useful for surveillance in cirrhotic and chronic HBV/HCV patients, who are at an elevated risk of developing HCC.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/diagnóstico , Detecção Precoce de Câncer/métodos , Neoplasias Hepáticas/diagnóstico , Inibidor da Tripsina Pancreática de Kazal/sangue , Adulto , Biópsia , Carcinoma Hepatocelular/sangue , Estudos de Casos e Controles , Feminino , Humanos , Fígado/diagnóstico por imagem , Fígado/patologia , Neoplasias Hepáticas/sangue , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Isoformas de Proteínas , Curva ROC , Tomografia Computadorizada por Raios X
8.
Front Med ; 13(6): 658-666, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31655955

RESUMO

Direct acting antiviral (DAA) treatments may reduce the elevated α fetoprotein (AFP), but data on how these treatments affect elevated AFP in patients with chronic hepatitis C (CHC) remain insufficient. In the present study, the frequency of baseline AFP elevations and their related factors, AFP dynamics during and after DAA treatment, and factors associated with AFP reduction was assessed. This retrospective study included 141 patients with CHC without hepatocellular carcinoma who received DAA and achieved sustained virological response. The details are as follows: mean post-treatment follow-up was 99 weeks (12-213); mean age, 57.8 years old; 52%, males; 79%, genotype (GT) 1; and 47%, cirrhosis. Pre-treatment AFP elevation (> 5.5 ng/mL) was seen in 48.2% patients. On multivariate analysis, baseline AFP > 5.5 was associated with the presence of cirrhosis (P =0.001), coexisting non-alcoholic steatohepatitis (NASH) (P = 0.035), and GT 1 (P = 0.029). AFP normalization was seen in 28.2% patients at treatment week 2, in 52% at the end of treatment, and in 73.4% at the end of follow-up. Post-treatment week 24 AFP normalization was associated with the absence of cirrhosis (P = 0.003), Child-Pugh score < 6 (P = 0.015), and baseline AFP < 10 (P = 0.015). AFP elevation is common in patients with CHC and independently associated with NASH, cirrhosis, and GT 1. DAA treatment resulted in AFP normalization as early as treatment week 2. Post-treatment week 24 AFP normalization is independently associated with the absence of cirrhosis, Child-Pugh score < 6, and baseline AFP < 10.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/sangue , Hepatite C Crônica/tratamento farmacológico , Neoplasias Hepáticas/sangue , alfa-Fetoproteínas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , California , Carcinoma Hepatocelular/virologia , Feminino , Hepacivirus/efeitos dos fármacos , Hepacivirus/genética , Hepatite C Crônica/sangue , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/patologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Resposta Viral Sustentada , Adulto Jovem
9.
Clin Transl Gastroenterol ; 10(5): 1-12, 2019 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-31033506

RESUMO

OBJECTIVES: Chronic hepatitis B (CHB) can progress into liver fibrosis and cirrhosis with poor outcomes. Early and accurate diagnosis of liver fibrosis/cirrhosis is important to guide the preventive strategy of their related complications. METHODS: A Chinese multicenter cross-sectional study was conducted to develop and validate a novel noninvasive program for staging liver fibrosis in untreated patients with CHB. Liver histology was evaluated independently by 2 pathologists. The alanine aminotransferase ratio, Hepascore, and aspartate aminotransferase to platelet index values were calculated. Liver stiffness measurement (LSM) and diameter of the spleen were measured. Logistic regression with ℓ1 penalty of regression coefficients was used to select the optimal predictors. The diagnostic accuracy for the stage of liver fibrosis was assessed by the area under the receiver operator characteristic curve with 95% confidence interval (CI). RESULTS: A total of 1,200 patients with CHB were included, of whom 800 and 400 were in training and validation sets, respectively. LSM, platelets, age, hyaluronic acid, and diameter of the spleen were the top 5 predictors associated with any stage of liver fibrosis and integrated into a novel noninvasive program, named as the Chin-CHB score. The area under the receiver operator characteristic curve of the Chin-CHB score was 0.893 (95% CI: 0.77-0.92) for diagnosing significant fibrosis, 0.897 (95% CI: 0.85-0.95) for advanced fibrosis, and 0.909 (95% CI: 0.87-0.95) for cirrhosis. The diagnostic performance of the Chin-CHB score was similar between training and validation sets. The Chin-CHB score had better diagnostic performance than aspartate aminotransferase to platelet index, alanine aminotransferase ratio, LSM alone, and Hepascore for diagnosing any stage of liver fibrosis. CONCLUSIONS: The Chin-CHB score had good diagnostic performance for any stage of liver fibrosis.


Assuntos
Hepatite B Crônica/patologia , Cirrose Hepática/diagnóstico , Fígado/patologia , Índice de Gravidade de Doença , Adulto , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Biópsia , Estudos Transversais , Progressão da Doença , Técnicas de Imagem por Elasticidade , Feminino , Hepatite B Crônica/sangue , Humanos , Fígado/diagnóstico por imagem , Cirrose Hepática/sangue , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Curva ROC
10.
Dig Dis Sci ; 63(5): 1237-1242, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29516328

RESUMO

BACKGROUND: Our recent study indicated the possible presence of detectable hepatitis C virus antigens (HCV-Ags) after denaturation of sera with resolved HCV (R-HCV) infection. The present study determined and characterized persistent HCV-Ags-specific immune complexes (ICs) in these patients. METHODS: Sixty-eight sera with R-HCV and 34 with viremic HCV (V-HCV) infection were tested for free and IC-bound HCV-Ags using HCV-Ags enzyme immunoassay (EIA), the presence of HCV-Ags-specific ICs by immunoprecipitation and Western blot (IP-WB), HCV ICs containing HCV virions using IP and HCV RNA RT-PCR, and correlation of HCV ICs with clinical presentation in these patients. RESULTS: Using HCV-Ags EIA, we found 57.4% of sera with R-HCV infection were tested positive for bound, but not free HCV-Ags. Using pooled or individual anti-HCV E1/E2, cAg, NS3, NS4b, and/or NS5a to precipitate HCV-specific-Ags, we confirmed persistent HCV-Ags ICs specific to various HCV structural and non-structural proteins not only in V-HCV infection, but also in R-HCV infection. Using IP and HCV RNA PCR, we then confirmed the presence of HCV virions within circulating ICs in V-HCV, but not in R-HCV sera. Multivariable analysis indicated significant and independent associations of persistent circulating HCV-Ags-specific ICs with both age and the presence of cirrhosis in patients with R-HCV infection. CONCLUSIONS: Various HCV-Ag-specific ICs, but not virions, persist in 57.4% of patients who had spontaneous or treatment-induced HCV clearance for 6 months to 20 years. These findings enriched our knowledge on HCV pathogenesis and support further study on its long-term clinical relevance, such as extrahepatic manifestation, transfusion medicine, and hepatocarcinogenesis.


Assuntos
Complexo Antígeno-Anticorpo/sangue , Antígenos da Hepatite C/imunologia , Hepatite C/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Western Blotting , Estudos de Casos e Controles , Feminino , Hepatite C/sangue , Hepatite C/virologia , Antígenos da Hepatite C/sangue , Humanos , Técnicas Imunoenzimáticas , Imunoprecipitação , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada
11.
N Am J Med Sci (Boston) ; 9(2): 47-54, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27293521

RESUMO

Chronic Hepatitis C virus (HCV) infection carries a significant clinical burden in the United States, affecting more than 4.6 million Americans. Untreated chronic HCV infection can result in cirrhosis, portal hypertension, and hepatocellular carcinoma. Previous interferon based treatment carried low rates of success and significant adverse effects. The advent of new generation oral antiviral therapy has led to major improvements in efficacy and tolerability but has also resulted in an explosion of data with increased treatment choice complexity. Treatment guidelines are constantly evolving due to emerging regimens and real world treatment data. There also still remain subpopulations for whom current treatments are lacking or unclearly defined. Thus, the race for development of HCV treatment regimens still continues. This review of the current literature will discuss the current recommended treatment strategies and briefly overview next generation agents.

12.
Hepatology ; 64(2): 415-24, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27273268

RESUMO

UNLABELLED: The current standard in diagnosing hepatitis C virus (HCV) infection requires two sequential steps: anti-HCV test to screen, followed by HCV RNA reverse-transcription polymerase chain reaction to confirm viremic HCV (V-HCV) infection. HCV core antigen tests provided potential for possible one-step diagnosis. However, low sensitivity and specificity limit their clinical utility. The present study developed a novel HCV antigens enzyme immunoassay (HCV-Ags EIA) and assessed its sensitivity, specificity, and utility for one-step diagnosis of V-HCV infection using 365 serum specimens, including 176 without and 189 with V-HCV infection. First, we confirmed the presence of HCV nonstructural proteins 3, 4b, and 5a besides HCV core antigen during HCV infection and developed a novel HCV-Ags EIA through simultaneous detection of all four HCV proteins. For the first time, the present study demonstrated that serum sample denaturation decreases the test specificity due to release of HCV-Ags sequestered in HCV immune complexes and should not be used in any HCV-Ags, including all the current HCV core antigen assays. On the other hand, using sample nondenaturation, the HCV-Ags EIA results showed 98.9% specificity and 100% sensitivity compared to serum anti-HCV and HCV RNA reverse-transcription polymerase chain reaction results. Using serum sample dilution, and nondenaturation, the lowest limits of detection of the HCV-Ags EIA were equivalent to serum HCV RNA levels of approximate 150-250 IU/mL. CONCLUSIONS: The highly specific and sensitive HCV-Ags EIA developed in the present study has the lowest limit of detection equivalent to serum HCV RNA levels of 150-250 IU/mL; using nondenaturation of serum samples, our HCV-Ags EIA reliably differentiated V-HCV infection from resolved HCV infection, accomplishing screening and diagnosis of V-HCV infection in one step. (Hepatology 2016;64:415-424).


Assuntos
Antígenos da Hepatite C/sangue , Hepatite C/diagnóstico , Técnicas Imunoenzimáticas/métodos , Hepatite C/sangue , Hepatite C/imunologia , Humanos , Sensibilidade e Especificidade
13.
Cancer Prev Res (Phila) ; 8(9): 864-72, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26130251

RESUMO

In animal models of hepatocellular carcinoma (HCC), deficiency of S-adenosylmethionine (SAMe) increased the risk of HCC whereas administration of SAMe reduced HCC. The aim of this trial was to determine whether oral SAMe administration to patients with hepatitis C cirrhosis would decrease serum α-fetoprotein (AFP) level, a biomarker of HCC risk in hepatitis C. This was a prospective, randomized, placebo-controlled, double-blind trial of SAMe, up to 2.4 g/d, for 24 weeks as compared with placebo among subjects with hepatitis C cirrhosis and a mildly elevated serum AFP. Primary outcome was change in AFP between baseline and week 24. Secondary outcomes included changes in routine tests of liver function and injury, other biomarkers of HCC risk, SAMe metabolites, markers of oxidative stress, and quality of life. One hundred ten subjects were randomized and 87 (44 SAMe and 43 placebo) completed treatment. There was no difference in the change in AFP during 24 weeks among subjects receiving SAMe as compared with placebo. Changes in markers of liver function, liver injury, and hepatitis C viral level were not significantly different between groups. Similarly, SAMe did not change markers of oxidative stress or serum glutathione level. SAMe blood level increased significantly among subjects receiving SAMe. Changes in quality of life did not differ between groups. Overall, this trial did not find that SAMe treatment improved serum AFP in subjects with advanced hepatitis C cirrhosis and a mildly elevated AFP. SAMe did not improve tests of liver function or injury or markers of oxidative stress or antioxidant potential.


Assuntos
Hepatite C/sangue , Cirrose Hepática/sangue , S-Adenosilmetionina/administração & dosagem , alfa-Fetoproteínas/metabolismo , Antioxidantes/metabolismo , Biomarcadores/metabolismo , Método Duplo-Cego , Feminino , Hepatite C/complicações , Hepatite C/tratamento farmacológico , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/tratamento farmacológico , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Estudos Prospectivos , Qualidade de Vida , S-Adenosilmetionina/efeitos adversos , S-Adenosilmetionina/sangue
14.
J Med Virol ; 87(12): 1989-99, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25989114

RESUMO

Chronic hepatitis B virus (HBV) infection affects approximately 375 million people worldwide. Current antiviral treatment effectively controls, but rarely clears chronic HBV infection. In addition, a significant portion of chronic HBV infected patients are not suitable for currently available antiviral therapy, and still face higher risk for cirrhosis and hepatocellular carcinoma. The poorly understood pathogenesis of HBV infection is the main barrier for developing more effective treatment strategies. HBV has long been viewed as non-cytopathic and the central hypothesis for HBV pathogenesis lies in the belief that hepatitis B is a host specific immunity-mediated liver disease. However, this view has been challenged by the accumulating experimental and clinical data that support a model of cytopathic HBV replication. In this article we systematically review the pathogenic role of HBV replication in hepatitis B and suggest possible HBV replication related mechanisms for HBV-mediated liver injury. We propose that a full understanding of HBV pathogenesis should consider the following elements. I. Liver injury can be caused by high levels of HBV replication and accumulation of viral products in the infected hepatocytes. II. HBV infection can be either directly cytopathic, non-cytopathic, or a mix of both in an individual patient depending upon accumulation levels of viral products that are usually associated with HBV replication activity in individual infected hepatocytes.


Assuntos
Efeito Citopatogênico Viral , Vírus da Hepatite B/fisiologia , Vírus da Hepatite B/patogenicidade , Hepatite B Crônica/patologia , Hepatite B Crônica/fisiopatologia , Fígado/patologia , Replicação Viral , Hepatite B Crônica/virologia , Humanos , Fígado/virologia
15.
PLoS One ; 10(4): e0123065, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25849963

RESUMO

BACKGROUND: Accumulating evidences have suggested that percutaneous cryoablation could be a valuable alternative ablation therapy for HCC but there has been no large cohort-based analysis on its long-term outcomes. METHODS: A series of 866 patients with Child-Pugh class A-B cirrhosis and HCC within Milan criteria who underwent percutaneous cryoablation was long-term followed. The safety, efficacy, 5-year survival, and prognostic factors of percutaneous cryoablation in the treatment of HCC were analyzed. RESULTS: A total of 1197 HCC lesions were ablated with 1401 cryoablation sessions. Complete response (CR) was achieved in 1163 (97.2%) lesions and 832 (96.1%) patients with 34 (2.8%) major complications, but no treatment-related mortality. After a median of 30.9 months follow-up, 502 (60.3%) patients who achieved CR developed different types of recurrence. The cumulative local tumor recurrence rate was 24.2% at 5-years. Multiple tumor lesions, tumor size > 3 cm, and repeated ablation of same lesion were independent risk factors associated with local recurrence. The 5-year overall survival (OS) rates were 59.5%. Age < 36 years, HCC family history, baseline hepatitis B virus DNA >106 copies/ml, and three HCC lesions were independently and significantly negative predictors to the post-cryoablation OS. CONCLUSIONS: Percutaneous cryoablation is an effective therapy for patients with HCC within Milan criteria, with comparable efficacy, safety and long-term survival to the reported outcomes of radiofrequency ablation.


Assuntos
Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Criocirurgia/métodos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Criocirurgia/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
17.
Hepatology ; 61(5): 1579-90, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25284802

RESUMO

UNLABELLED: Radiofrequency ablation (RFA) is considered a curative treatment option for hepatocellular carcinoma (HCC). Growing data have demonstrated that cryoablation represents a safe and effective alternative therapy for HCC, but no randomized controlled trial (RCT) has been reported to compare cryoablation with RFA in HCC treatment. The present study was a multicenter RCT aimed to compare the outcomes of percutaneous cryoablation with RFA for the treatment of HCC. In all, 360 patients with Child-Pugh class A or B cirrhosis and one or two HCC lesions ≤ 4 cm, treatment-naïve, without metastasis were randomly assigned to cryoablation (n = 180) or RFA (n = 180). The primary endpoints were local tumor progression at 3 years after treatment and safety. Local tumor progression rates at 1, 2, and 3 years were 3%, 7%, and 7% for cryoablation and 9%, 11%, and 11% for RFA, respectively (P = 0.043). For lesions >3 cm in diameter, the local tumor progression rate was significantly lower in the cryoablation group versus the RFA group (7.7% versus 18.2%, P = 0.041). The 1-, 3-, and 5-year overall survival rates were 97%, 67%, and 40% for cryoablation and 97%, 66%, and 38% for RFA, respectively (P = 0.747). The 1-, 3-, and 5-year tumor-free survival rates were 89%, 54%, and 35% in the cryoablation group and 84%, 50%, and 34% in the RFA group, respectively (P = 0.628). Multivariate analyses demonstrated that Child-Pugh class B and distant intrahepatic recurrence were significant negative predictors for overall survival. Major complications occurred in seven patients (3.9%) following cryoablation and in six patients (3.3%) following RFA (P = 0.776). CONCLUSION: Cryoablation resulted in a significantly lower local tumor progression than RFA, although both cryoablation and RFA were equally safe and effective, with similar 5-year survival rates.


Assuntos
Carcinoma Hepatocelular/cirurgia , Ablação por Cateter , Criocirurgia , Neoplasias Hepáticas/cirurgia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Criocirurgia/métodos , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida
18.
J Immigr Minor Health ; 17(1): 13-20, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24474437

RESUMO

The prevalence of hepatitis B virus (HBV) infection is reportedly high in Vietnamese Americans (VAs), but most previous studies did not assess full HBV serology, and not the prevalence of HBV and hepatitis C virus (HCV) infection simultaneously. The aim of the study is to assess the prevalence of different HBV serologies and HCV infection in VAs. This study was based on the data collected by testing for Hepatitis B surface antigen (HBsAg), anti-hepatitis B core antibody (HBcAb IgG), anti-HBs antibody (HBsAb), and anti-HCV antibody (anti-HCV) in a series of community screening in VAs in Orange County, California. In 1,405 VA participants, the mean age was 51 (17-87) years, 45.1% were males; 68.2%, married; 97.2%, born in Vietnam. Most of the participants were non-US born with their primary language being non-English and with limited access to health care. Of the 1,405 cases, 124 (8.8%) were confirmed HBV infection by HBsAg+; 81 (5.8%), HCV infection by anti-HCV+; including four (0.3%) with HBV/HCV coinfection. Twelve percent of the participants with confirmed HBV infection thought they were previously tested negative, while 29.7% of the participants with confirmed HCV infection thought they were previously tested negative. In this cohort, 15.4% were HBsAg-/HBsAb-/HBcAb IgG-, i.e. being susceptible to HBV infection. In HCV infected participants, 65.4% were born between 1945 and 1965. This large serial survey and screening in the Vietnamese American community confirmed the rates of HBV and HCV infection to be as high as 8.8% and 5.8%, respectively. We have also identified factors related to HBV and HCV infection in this high-risk population.


Assuntos
Asiático , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Programas de Rastreamento , Testes Sorológicos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , California/epidemiologia , Demografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Estados Unidos/epidemiologia , Vietnã/etnologia
19.
J Clin Gastroenterol ; 48(10): 830-6, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25148553

RESUMO

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. Although surgical resection and liver transplantation are the curative treatments, many of HCC patients do not qualify for these curative therapies at the presentation. Thus, ablation therapies are currently important modalities in HCC treatment. Among currently available ablation therapies, cryoablation (ie, cryotherapy) is a novel local therapeutic modality. However, cryoablation has not been widely used as one of ablation therapies for HCC, because of historical concerns about risk of bleeding when cryotherapy is delivered by early generation of the argon-helium device. Nevertheless, with technological advances and increased clinical experience in the past decade, clinical application of cryoablation for HCC management has significantly increased. Accumulating data have demonstrated that cryoablation is highly effective in local tumor control with well-acceptable safety profile, and the overall survival is comparable with that of radiofrequency ablation in patients with tumors <5 cm. Compared with radiofrequency ablation and other thermal-based modalities, cryoablation has several advantages, such as the ability to produce larger and precise zones of ablation. This article systemically reviews the advances in clinical application of cryoablation therapy for HCC, including the related mechanisms and technology, clinical indications, efficacy and safety profiles, and future research directions.


Assuntos
Carcinoma Hepatocelular/cirurgia , Criocirurgia , Neoplasias Hepáticas/cirurgia , Carcinoma Hepatocelular/patologia , Criocirurgia/efeitos adversos , Criocirurgia/história , Criocirurgia/instrumentação , Criocirurgia/métodos , Desenho de Equipamento , História do Século XX , História do Século XXI , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Complicações Pós-Operatórias/etiologia , Resultado do Tratamento
20.
Dig Dis Sci ; 59(4): 865-71, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24519522

RESUMO

BACKGROUND AND AIM: The modified normal alanine aminotransferase (ALT) value (i.e., males <30 and females <19 IU/L) is a better criteria associated with histological activity in chronic hepatitis B (CHB). This study was aimed to assess if the modified ALT criteria could be better associated with disease phases in a cohort of Asian Americans (AsAm) with CHB. METHODS: This two-center retrospective study evaluated 198 non-treated AsAm with CHB and a mean follow-up of 21 months. Both conventional and modified ALT criteria were used to determine the differences and clinical value using modified ALT criteria in classifying CHB phases. RESULTS: Among HBeAg (+) patients (29.3 %), HBV pre-core (PC) and basal core promoter (BCP) mutations were detected in 24.4 % and 31.3 %, respectively. Using baseline conventional ALT criteria, 97/153 (63.4 %) patients could be categorized into CHB phases 1 to 4, whereas 56/153 (36.6 %) were indeterminate. Using the modified ALT criteria, 43 (28.1 %) patients had phase changes of which 31/43 (72.1 %) were moved from phase 1 and indeterminate to phases 2 and 4, more active CHB phases. In 13/31 of these patients with liver biopsy, 6 (19.4 %) reported stage 2-4 fibrosis and 10 (32.3 %) reported grade 1-2 inflammation. Using modified ALT criteria to evaluate 48/153 patients with full data at baseline and the end of 1-year follow-up, we observed that 19/48 (39.6 %) changed their CHB phases; 5/48 (10.4 %) moved from phases 1 and 3 to phases 2 and 4; 2/48 (4.2 %) remained in the active phases; 10/48 (20.8 %) became indeterminate. CONCLUSIONS: HBV PC and BCP mutations were detectable in 24.4 % and 31.3 % of HBeAg (+) AsAm patients, respectively. Compared with conventional ALT criteria, modified ALT criteria is more sensitive in identifying CHB patients in active phases.


Assuntos
Alanina Transaminase/sangue , Asiático , Hepatite B Crônica/diagnóstico , Adulto , Feminino , Vírus da Hepatite B , Hepatite B Crônica/sangue , Hepatite B Crônica/etnologia , Hepatite B Crônica/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Carga Viral
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