Abstract:
BACKGROUND & AIMS:Direct-acting antiviral (DAA) therapy is used in patients with HCV-related decompensated cirrhosis with the expectation of improving hepatic function. However, little is known about the long-term hepatic benefit of successful antiviral treatment. METHODS:Patients with advanced/decompensated cirrhosis (model for end-stage liver disease [MELD] ≥10), in whom NS5A-containing DAA therapy was initiated prior to September 2018, were included (from the HCV-TARGET cohort). Treatment outcomes and the impact of treatment on short-term and long-term hepatic function were examined. RESULTS:A total of 642 patients were analyzed. The mean age was 60 years, 68% were male. The median baseline MELD was 12 (range 10-39) and 64% had prior decompensation. Among patients with available virologic outcomes, 90.5% achieved a sustained virologic response at 12 weeks (SVR12). Eighty (24%) patients achieved a clinically significant decrease in MELD by ≥3 points during short-term follow-up (9-26 weeks after the end of treatment). However, in long-term follow-up (median of 4 years after treatment), mean changes in MELD (-0.30 points), total bilirubin (+0.23 mg/dl) and albumin (+0.36 g/dl) were marginal. Fifty-one patients died and 22 underwent liver transplant. In long-term follow-up, a clinically meaningful decrease in MELD of ≥3 occurred in 29% and a final MELD score of <10 was achieved in 25%. CONCLUSION:In a large real-world experience of patients with advanced/decompensated HCV-related cirrhosis treated with DAAs, there were only marginal improvements in MELD, total bilirubin, or albumin at long-term follow-up (after achieving SVR12). These patients may remain at high risk of decompensation and must continue to be closely monitored. CLINICALTRIALS.GOV: NCT01474811. LAY SUMMARY:Hepatitis C virus infection can now be cured with medications, even in patients who have advanced scarring of the liver (cirrhosis). In this study, we evaluated whether liver function improves or deteriorates in the long-term, following successful treatment of hepatitis C in patients with cirrhosis. We found that overall liver function was relatively stable with only 29% of patients achieving a clinically meaningful improvement in liver function, and we therefore believe that these patients require ongoing monitoring.
journal_name
J Hepatoljournal_title
Journal of hepatologyauthors
Verna EC,Morelli G,Terrault NA,Lok AS,Lim JK,Di Bisceglie AM,Zeuzem S,Landis CS,Kwo P,Hassan M,Manns MP,Vainorius M,Akushevich L,Nelson DR,Fried MW,Reddy KRdoi
10.1016/j.jhep.2020.03.031subject
Has Abstractpub_date
2020-09-01 00:00:00pages
540-548issue
3eissn
0168-8278issn
1600-0641pii
S0168-8278(20)30193-8journal_volume
73pub_type
杂志文章abstract:BACKGROUND/AIMS:ATP stimulation of purinergic P2 receptors (P2YR and P2XR) regulates several hepatic functions. Here we report the involvement of ATP-mediated signals in enhancing hepatocyte tolerance to lethal stress. METHODS:The protection given by purinergic agonists was investigated in rat hepatocytes exposed to h...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2006.02.017
更新日期:2006-08-01 00:00:00
abstract:BACKGROUND/AIMS:This study evaluates the agreement between reported use of interventions for patients with liver diseases and research evidence in Cochrane systematic reviews. METHODS:In July 2002, the Cochrane Hepato-Biliary Group had completed 28 systematic reviews on 36 interventions that were available in Denmark....
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2005.06.017
更新日期:2005-12-01 00:00:00
abstract::This study evaluates systemic and splanchnic haemodynamics and the effect of propranolol in 15 patients with presinusoidal portal hypertension (portal vein obstruction, n = 11; schistosomiasis, n = 4). These patients exhibited a hyperkinetic circulatory syndrome characterized by high cardiac index (4.4 +/- 1.61.min-1....
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(89)90139-6
更新日期:1989-11-01 00:00:00
abstract:BACKGROUND/AIMS:To examine the extent and mechanisms of apoptosis in cholestatic liver injury and to explore the role of the transcription factor nuclear factor-kappa B in protection against bile acid-induced apoptosis. METHODS:Cholestatic liver injury was induced by bile duct ligation in Wistar rats. Furthermore, pri...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(03)00214-9
更新日期:2003-08-01 00:00:00
abstract:BACKGROUND/AIMS:The electroencephalogram (EEG) is frequently altered in cirrhotic patients. We, therefore, performed a study to ascertain the features and the prognosis of cirrhotic patients without current overt hepatic encephalopathy (OHE) who have EEG alterations. METHODS:A series of 296 consecutive cirrhotic patie...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(01)00129-5
更新日期:2001-07-01 00:00:00
abstract:BACKGROUND/AIMS:Oxidative DNA damage, identifiable in the formation of 8-hydroxydeoxyguanosine (8-OHdG), is relevant in the mutagenesis/carcinogenesis process. The aim of this study was to assess 8-OHdG levels in patients with hepatitis C virus (HCV) infection in relation to extent of liver damage and HCV genotype. ME...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)00098-2
更新日期:2001-04-01 00:00:00
abstract:BACKGROUND/AIMS:Primary sclerosing cholangitis (PSC) is associated with a high risk of cholangiocarcinoma. Our aim was to evaluate the diagnostic value of trypsinogen-1, trypsinogen-2, tumour-associated trypsin inhibitor, human chorionic gonadotropin beta and trypsin-2-alpha(1)-antitrypsin for cholangiocarcinoma and to...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2007.05.017
更新日期:2007-11-01 00:00:00
abstract:BACKGROUND/AIMS:The number of perisinusoidal myofibroblasts has been shown to be increased in hepatocellular carcinoma, as compared to cirrhosis. This increase might suggest a cooperative relationship between tumour cells and myofibroblasts. To assess this relationship, we undertook: (a) an immunohistochemical study to...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(98)80186-4
更新日期:1998-07-01 00:00:00
abstract:BACKGROUND/AIMS:Immune mechanisms may modulate disease severity in chronic hepatitis C and the DR human leukocyte antigens may affect these mechanisms. Our aims were to evaluate the association between the DR antigens and disease severity at presentation and to seek correlation between these antigens, disease severity ...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(96)80261-3
更新日期:1996-06-01 00:00:00
abstract:BACKGROUND & AIMS:Non-alcoholic fatty liver disease (NAFLD) affects up to 30% of the population and signifies increased risk of liver fibrosis and cirrhosis, type 2 diabetes, and cardiovascular disease. Therapies are limited. Weight loss is of benefit but is difficult to maintain. We aimed at examining the effect of th...
journal_title:Journal of hepatology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1016/j.jhep.2013.02.012
更新日期:2013-07-01 00:00:00
abstract::Design and endpoints of clinical trials in hepatocellular carcinoma. Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, Sherman M, Schwartz M, Lotze M, Talwalkar J, Gores GJ; for the Panel of Experts in HCC-Design Clinical Trials. The design of clinical trials in hepatocellular carcinoma (HCC) is comp...
journal_title:Journal of hepatology
pub_type: 评论,杂志文章
doi:10.1016/j.jhep.2008.07.012
更新日期:2008-10-01 00:00:00
abstract:BACKGROUND & AIMS:Low levels of toll-like receptor 3 (TLR3) in patients with hepatocellular carcinoma (HCC) are associated with poor prognosis, primarily owing to the loss of inflammatory signaling and subsequent lack of immune cell recruitment to the liver. Herein, we explore the role of TLR3-triggered apoptosis in HC...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2019.05.031
更新日期:2019-10-01 00:00:00
abstract:BACKGROUND & AIMS:To develop an in situ molecular signature to predict postsurgical recurrence in hepatocellular carcinoma (HCC) patients. METHODS:Immunohistochemistry was performed using tissue microarrays containing both tumoral and peri-tumoral regions of the advancing tumor edge from 336 HCC patients (289 were pos...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2012.03.027
更新日期:2012-08-01 00:00:00
abstract:BACKGROUND & AIMS:Cerebral oxidative stress plays an important role in the pathogenesis of hepatic encephalopathy (HE), but the underlying mechanisms are incompletely understood. Herein, we analyzed a role of heme oxygenase (HO)1, iron and NADPH oxidase 4 (Nox4) for the induction of oxidative stress and senescence in H...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2019.06.020
更新日期:2019-11-01 00:00:00
abstract:BACKGROUND & AIMS:Weak hepatitis C virus (HCV) specific immunity in peripheral blood has been shown to be partially controlled by regulatory T cells (Treg). However, little is known about Treg present in livers of HCV-infected patients, their association with clinical parameters, and immunopathology resulting in diseas...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2009.12.013
更新日期:2010-03-01 00:00:00
abstract:BACKGROUND AND AIMS:Primary sclerosing cholangitis (PSC) is an idiopathic, chronic cholestatic liver disorder characterized by biliary inflammation and fibrosis. Increased numbers of intrahepatic interferon-γ- (IFNγ) producing lymphocytes have been documented in patients with PSC, yet their functional role remains to b...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2019.05.023
更新日期:2019-10-01 00:00:00
abstract::Extracellular vesicles are membrane-bound vesicles containing proteins, lipids, RNAs and microRNAs. They can originate from both healthy and stressed cells, and provide a snapshot of the cell of origin in physiological and pathological circumstances. Various processes that may give rise to the release of extracellular...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2020.07.014
更新日期:2020-12-01 00:00:00
abstract:BACKGROUND & AIMS:In the Netherlands, transmission of hepatitis B virus occurs mainly within behavioural high-risk groups, such as in men who have sex with men. Therefore, a vaccination programme has targeted these high-risk groups. This study evaluates the impact of the vaccination programme targeting Amsterdam's larg...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2013.08.002
更新日期:2013-12-01 00:00:00
abstract:BACKGROUND/AIMS:In primary biliary cirrhosis (PBC), pathogenesis is influenced by genetic factors that remain poorly elucidated up to now. We investigated the impact of sequence diversity in candidate genes involved in immunity (CTLA-4 and TNFalpha), in bile formation (10 hepatobiliary transporter genes) and in the ada...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2008.07.027
更新日期:2008-12-01 00:00:00
abstract:BACKGROUND/AIMS:Central nervous system abnormalities such as fatigue and depression occur more frequently in chronic hepatitis C virus (HCV) infection than in many other causes of chronic liver disease. The finding that fatigue is unrelated to activity of hepatitis or mode of infection could indicate an independent eff...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(02)00172-1
更新日期:2002-09-01 00:00:00
abstract::In order to evaluate age at menopause and serum sex hormone profiles in postmenopausal women with stable chronic liver disease, six non-cirrhotic alcoholics, 13 with alcoholic cirrhosis, eight with non-alcoholic cirrhosis, and 46 healthy controls were studied. In all three groups, patients were significantly (p less t...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/0168-8278(91)90859-a
更新日期:1991-07-01 00:00:00
abstract:BACKGROUND AIMS:In hepatitis C there is controversy over the linearity of the rate of progression and the significance of gender, mode of infection and viral factors. METHODS:2313 untreated patients with a reliable estimated duration of infection and liver fibrosis were included. Fibrosis progression was calculated us...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)00097-0
更新日期:2001-05-01 00:00:00
abstract:BACKGROUND/AIMS:To elucidate the mechanisms of action of interferon (IFN) against hepatitis C virus (HCV), we studied the serum HCV dynamics of free-virions (FV) and immune-complexes (IC) in patients treated with IFN. METHODS:FV and IC were separated by immunoprecipitation using anti-human immunoglobulin and quantifie...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(03)00472-0
更新日期:2003-12-01 00:00:00
abstract:BACKGROUND/AIMS:The purpose of this study was to compare the epidemiological, biochemical, virological and histological characteristics of patients with chronic hepatitis B and C with those of patients suffering from chronic hepatitis C alone. METHODS:Twenty-three patients with chronic hepatitis C, who were anti-HCV p...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(98)80198-0
更新日期:1998-01-01 00:00:00
abstract:BACKGROUND & AIMS:Acute-on-chronic liver failure (ACLF) is characterised by the presence of organ failure in patients with decompensated cirrhosis and is associated with high short-term mortality. However, there are limited data on the prevalence and short-term outcomes of ACLF in patients with cirrhosis seen in the US...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/j.jhep.2018.12.018
更新日期:2019-04-01 00:00:00
abstract:BACKGROUND/AIMS:The development of cholesterol gallstones, in some patients, has been associated with increased proportions of deoxycholic acid in the bile acid pool. Deoxycholic acid is a microbial product of cholic acid 7alpha-dehydroxylation in the intestines. The levels and activities of bile acid 7alpha-dehydroxyl...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(00)80183-x
更新日期:2000-01-01 00:00:00
abstract::In situ hybridization with oligonucleotide probes has been used to localise hepatitis A virus RNA genomic sequences in formalin-fixed and routinely processed human liver biopsies from three patients. Using radiolabelled Sulphur-35 antisense probes, viral genomic sequences were found in all three cases, but signal inte...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(94)80012-x
更新日期:1994-03-01 00:00:00
abstract::Recent progress in basic research has enhanced our understanding of the molecular mechanisms of normal bile secretion and their alterations in cholestasis. Genetic transporter variants contribute to an entire spectrum of cholestatic liver diseases and can cause hereditary cholestatic syndromes or determine susceptibil...
journal_title:Journal of hepatology
pub_type: 杂志文章,评审
doi:10.1016/j.jhep.2009.05.012
更新日期:2009-09-01 00:00:00
abstract:BACKGROUND/AIMS:While combination of peginterferon-alpha (PEG-IFN) and ribavirin (RBV) therapy is the current standard of care for chronic hepatitis C (CHC), only 44-51% of genotype-1 patients achieve a sustained virological response (SVR), and both agents produce treatment-limiting toxicities. In the hepatitis C virus...
journal_title:Journal of hepatology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.jhep.2007.03.028
更新日期:2007-10-01 00:00:00
abstract::The multidrug resistance genes encode plasma membrane glycoproteins named P-glycoproteins, that act as an ATP-dependent drug efflux pump and decrease the cytosolic concentration of chemotherapeutic agents. It has been hypothesized that in rat liver, this protein may have a physiological role as a biliary transporter o...
journal_title:Journal of hepatology
pub_type: 杂志文章
doi:10.1016/s0168-8278(94)80235-1
更新日期:1994-11-01 00:00:00