Liver International
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Hepatitis C virus incidence in <scp>HIV</scp>‐infected and in preexposure prophylaxis (PrEP)‐using men having sex with men Abstract Background & Aims HCV incidence still appears on the rise in HIV ‐infected MSM in France. We assessed the incidence of HCV infection in HIV ‐positive and in preexposure prophylaxis (PrEP )‐using MSM .Methods HIV ‐infected, HCV ‐negative MSM with serological follow‐up in 2016 and HIV ‐negative, HCV ‐negative PrEP ‐using MSM enrolled from January 2016 to May 2017 in the French Dat’AIDS cohort were analysed to assess the incidence of a primary HCV infection. The incidence of HCV reinfection was also determined in patients having cured a previous infection.Results Among 10 049 HIV ‐infected MSM followed in 2016, 681 patients were already HCV ‐infected when entering the study (prevalence 6.8%). Serological follow‐up was available in 2016 for 4151 HCV ‐negative patients. Virological follow‐up was available for 478 patients who had cured a previous infection. Fifty‐seven HCV infections occurred in 2016 (42 primary infections, 15 reinfections). Incidence of primary HCV infection, reinfection and overall HCV infection was, respectively, 1.0, 3.1 and 1.2/100 person‐years (PY ). From January 2016 to May 2017, 930 HIV ‐negative subjects were enrolled for PrEP . Seventeen patients were already HCV ‐infected (prevalence 1.8%). Twelve HCV infections occurred during follow‐up (10 primary infections, 2 reinfections) giving an incidence of primary infection of 1.0/100 PY and an overall incidence of 1.2/100 PY . Conclusions The overall incidence of HCV infection and of a primary HCV infection in HIV ‐positive and in PrEP ‐using MSM appeared similar in France in 2016 to early 2017. HIV ‐positive and PrEP ‐using MSM probably share similar at‐risk practices and both should be targeted for preventative interventions.
Liver International - Tập 38 Số 10 - Trang 1736-1740 - 2018
The value of different CT‐based methods for diagnosing low muscle mass and predicting mortality in patients with cirrhosis Abstract Background & Aims Low muscle mass impacts on morbidity and mortality in cirrhosis. The skeletal‐muscle index (SMI) is a well‐validated tool to diagnose muscle wasting, but requires specialized radiologic software and expertise. Thus, we compared different Computed tomography (CT)‐based evaluation methods for muscle wasting and their prognostic value in cirrhosis. Methods Consecutive cirrhotic patients included in a prospective registry undergoing abdominal CT scans were analysed. SMI, transversal psoas muscle thickness (TPMT), total psoas volume (TPV) and paraspinal muscle index (PSMI) were measured. Sarcopenia was defined using SMI as a reference method by applying sex‐specific cut‐offs (males: <52.4 cm2 /m2 ; females: <38.5 cm2 /m2 ). Results One hundred and nine patients (71.6% male) of age 57 ± 11 years, MELD 16 (8‐26) and alcoholic liver disease (63.3%) as the main aetiology were included. According to established SMI cut‐offs, low muscle mass was present in 69 patients (63.3%) who also presented with higher MELD (17 vs 14 points; P = .025). The following optimal sex‐specific cut‐offs (men/women) for diagnosing low muscle mass were determined: TPMT: <10.7/ <7.8 mm/m, TPV: <194.9/ <99.2 cm3 and PSMI <26.3/ <20.8 cm2 /m2 . Thirty (27.5%) patients died during a follow‐up of 15 (0.3‐45.7) months. Univariate competing risks analyses showed a significant risk for mortality according to SMI (aSHR:2.52, 95% CI: 1.03‐6.21, P = .043), TPMT (aSHR: 3.87, 95% CI: 1.4‐8.09, P = .007) and PSMI (aSHR: 2.7, 95% CI: 1.17‐6.23, P = .02), but not TPV (P = .18) derived low muscle mass cut‐offs. In multivariate analysis only TPMT (aSHR: 2.82, 95% CI: 1.20‐6.67, P = .018) was associated with mortality, SMI (aSHR: 1.93, 95% CI: 0.72‐5.16, P = .19) and PSMI (aSHR: 1.93, 95% CI: 0.79‐4.75, P = .15) were not. Conclusion Low muscle mass was highly prevalent in our cohort of patients with cirrhosis. Gender‐specific TPMT, SMI and PSMI cut‐offs for low muscle mass can help identify patients with an increased risk for mortality. Importantly, only TPMT emerged as an independent risk factor for mortality in patients with cirrhosis.
Liver International - Tập 39 Số 12 - Trang 2374-2385 - 2019
<i>NOD2</i> gene variants are a risk factor for culture‐positive spontaneous bacterial peritonitis and monomicrobial bacterascites in cirrhosis Abstract
Background: Spontaneous bacterial peritonitis (SBP) is considered as result of bacterial translocation from the gastrointestinal lumen to the mesenteric lymph nodes and subsequent circulation. Variants of the NOD2 gene contribute to bacterial translocation and were associated with SBP in a recent study.
Methods: We determined common NOD2 variants by TaqMan polymerase chain reaction and analysed the ascitic fluid neutrophil count and bacterial culture results in 175 prospectively characterized hospitalized patients with decompensated cirrhosis who underwent diagnostic paracentesis in two German centres.
Results: Ten patients presented with culture‐positive SBP, 19 with culture‐negative SBP and six had bacterascites. Minor allele frequencies for R702W, G908R and 1007fs in subjects with sterile non‐neutrocytic ascites were 3.2, 2.5 and 2.5% respectively. Patients with SBP [odds ratio (OR) 2.7; P =0.036], culture‐positive SBP (OR 6.0; P =0.012) and bacterascites (OR 6.0; P =0.050) were more often carriers of NOD2 variants than patients with sterile non‐neutrocytic ascites. The mutations 1007fs and G908R were associated with culture‐positive SBP (P ≤0.005) and R702W with bacterascites (P =0.014). There was no significant association of NOD2 variants with culture‐negative SBP (OR 1.6; P =0.493). In logistic regression, previous SBP, a higher model for end‐stage liver disease (MELD) score and the presence of a NOD2 variant were independent predictors of ascitic fluid infection. The median survival was insignificantly shorter in patients with NOD2 variants (268 vs. 339 days; P =0.386). In patients without hepatocellular carcinoma at study entry (N =148), NOD2 was a predictor of survival after adjustment for the MELD score and age (hazard ratio 1.89; P =0.045).
Conclusion:
NOD2 variants increase the risk for culture‐positive SBP and bacterascites in cirrhosis and may affect survival.
Liver International - Tập 32 Số 2 - Trang 223-230 - 2012
Cardiac and proinflammatory markers predict prognosis in cirrhosis Abstract Background & Aims Inflammation and cardiac dysfunction plays an important role in the development of complications leading to increased mortality in patients with cirrhosis. Novel cardiac markers such as prohormone of ANP (proANP), copeptin and high‐sensitivity troponin T (hs‐TnT) and proinflammatory markers including soluble urokinase‐type plasminogen activator receptor (suPAR) and high‐sensitive C‐reactive protein (hs‐CRP) are related to these complications. We aimed to investigate if cardiac and proinflammatory markers are related to severity of liver disease, cardiac and haemodynamic changes, and long‐term survival. Methods One hundred and ninety‐three stable cirrhotic patients (Child class: A = 46; B = 97; C = 50) had a full haemodynamic investigation performed with measurement of splanchnic and systemic haemodynamics and measurement of circulating levels of proBNP, proANP, copeptin, hs‐TnT, LBP, IL 6, IL 8, IP 10, VEGF, hs‐CRP and suPAR. Results Soluble urokinase‐type plasminogen activator receptor soluble urokinase‐type plasminogen activator receptor, hs‐CRP, and hs‐TnT were significantly different throughout the Child classes (P < 0.01; P < 0.01; P < 0.02). All markers except copeptin correlated with indicators of disease severity in cirrhosis; ProANP and suPAR correlated with hepatic venous pressure gradient (r = 0.24 and r = 0.34; P < 0.001) and systemic vascular resistance (r = −0.24 and r = −0.33; P < 0.001). Cardiac (proANP, hs‐TnT; P < 0.01) and proinflammatory (hs‐CRP, suPAR; P < 0.05) markers were associated with mortality in a univariate Cox analysis, however, the strongest predictors of mortality in a multivariate Cox analysis were hs‐TnT, ascites and hepatic venous pressure gradient (reg.coeff.: 0.34, P < 0.001; 0.16, P < 0.001; 0.06, P = 0.04). Conclusion Markers of cardiac dysfunction and inflammation are significantly associated with disease severity, degree of portal hypertension and survival in cirrhosis. In particular, hs‐TnT and suPAR seem to contain prognostic information.
Liver International - Tập 34 Số 6 - 2014
Implication of inflammation‐related cytokines in the natural history of liver cirrhosis Abstract: Background/Aims: Increased serum concentrations of pro‐inflammatory cytokines have been detected in patients with liver cirrhosis. However, their role in the natural history of cirrhosis and portal hypertension, in the absence of infection, and the prognostic significance of inflammation‐related cytokines have not been reported. Our objective was the analysis of the prognostic value of inflammation‐related cytokines in cirrhotic patients.Patients and methods: Serum concentrations of tumor necrosis factor (TNF‐α) and its soluble receptors I and II and interleukin 6 (IL‐6), as well as mean blood pressure, plasma renin activity, aldosterone, vasopressin and norepinephrine concentrations were determined in 72 cirrhotic patients (Child–Pugh score: A 50%, B 33.3%, C 16.7%), without any evidence of infection, and in 25 healthy controls. Patients were followed up for a median of 35.9 (range 6–60) months.Results: Increased concentrations of soluble TNF receptors were detected in cirrhotic patients when compared with healthy controls. TNF receptors and IL‐6 concentrations were both significantly more elevated in advanced phases of cirrhosis (Child–Pugh score C vs B and vs A). Sixteen patients died as a related consequence of liver cirrhosis. Multivariant analysis demonstrated that Child–Pugh score, mean blood pressure and serum levels of TNF receptor I were associated with mortality.Conclusions: In addition to the classic factors implicated in mortality (Child–Pugh score and hemodynamic parameters), alterations in inflammation‐related components are of prognostic significance in cirrhotic patients.
Liver International - Tập 24 Số 5 - Trang 437-445 - 2004
Longitudinal monocyte Human leukocyte antigen‐DR expression is a prognostic marker in critically ill patients with decompensated liver cirrhosis Abstract Background: Critical illness in cirrhotic patients is associated with a poor prognosis and increased susceptibility to infections. Monocyte HLA‐DR expression is decreased in cirrhotic patients, but its prognostic value has not been investigated prospectively.Methods: Thirty‐eight critically ill patients with decompensated liver cirrhosis were included in this prospective study. On admission to the intensive care unit (ICU), inflammatory parameters (C‐reactive protein, procalcitonin and lipopolysaccharide‐binding protein), interleukin (IL)‐10, interferon (IFN)‐γ serum levels, tumour necrosis factor (TNF)‐αex vivo stimulation (whole blood assay) and HLA‐DR expression on monocytes (FACS analysis) were determined. Immune parameters were furthermore measured every third day until discharge from the ICU or death of the patients.Results: Intensive care unit mortality of the cirrhotic patients was 34.2%. During admission, TNF ex vivo , IFN‐γ and HLA‐DR expression were lower in non‐survivors (all P <0.05), while IL‐10 levels were increased in non‐survivors compared with survivors (P =0.001). However, individual values clearly overlapped between groups. Prospective analysis revealed that monocyte HLA‐DR expression remained stable or increased in survivors, but decreased in non‐survivors (P =0.002). A decrease in HLA‐DR expression between admission and day 3 was strongly associated with decreased IFN‐γ levels and increased ICU mortality (hazard ratio 3.36, P =0.008), mostly owing to late sepsis. This association was independent of the sequential organ failure assessment and model for end‐stage liver disease score.Conclusions: Here we establish the relative HLA‐DR expression (admission/day 3) as a prognostic marker for ICU mortality in critically ill cirrhotic patients. These results may guide the evaluation of immune‐modulating therapies in these patients.
Liver International - Tập 29 Số 4 - Trang 536-543 - 2009
Hepatic dysfunction in patients with extrahepatic portal venous obstruction Abstract: Background: Extrahepatic portal venous obstruction (EHPVO) developing due to thrombotic occlusion of the portal vein in children is generally considered a benign disease. Whether hepatic dysfunction develops in these patients in the absence of a gastrointestinal bleed has not been well studied.Materials and methods: Forty‐three patients with EHPVO who had not bled in the last 3 months were studied. Patients were divided into those with (group I) or without ascites (group II). Matched cirrhotic patients with ascites (group III) served as controls. Clinical, biochemical, ultrasonographic, and histopathological evaluation was carried out. Portal biliopathy was assessed in five patients in group I and in 12 patients in group II by cholangiography.Results: Of 43 EHPVO patients, ascites was seen in nine (21%) patients (group I). Thirty‐four patients had no ascites (group II). Serum ALT (54±24 vs. 34±10 IU/l, P <0.01), albumin (3.2±0.3 vs. 3.7±0.4 g/dl, P <0.01), and prothrombin time difference (9.0±4.5 vs. 2.4±1.9 s, P <0.05) were deranged in patients in group I compared with group II. Patients in group I were 4 years older, and the duration of portal hypertension was longer than in group II (11.5 vs. 5.6 year, P <0.05). Portal biliopathy changes were significantly more severe in group I than in group II patients. Ascites was high gradient in all the patients in group I and the serum‐ascitic albumin gradient was comparable between groups I and III. None of the EHPVO patients, but four cirrhotic patients, developed spontaneous bacterial peritonitis during a follow‐up of 11±4 months.Conclusions: Hepatic dysfunction in the form of ascites and deranged liver functions is not uncommon in patients with EHPVO, more so in patients with prolonged portal hypertension. Based on our data it would be worthwhile to study whether prolonged portal vein thrombosis in EHPVO patients could lead to progressive liver disease.
Liver International - Tập 23 Số 6 - Trang 434-439 - 2003
Analysis of factors associated with discrepancies between predicted and observed liver weight in liver transplantation Abstract Background Even using predictive formulas based on anthropometrics in about 30% of subjects, liver weight (LW) cannot be predicted with a ≤20% margin of error. We aimed to identify factors associated with discrepancies between predicted and observed LW. Methods In 500 consecutive liver grafts, we tested LW predictive performance using 17 formulas based on anthropometric characteristics. Hashimoto's formula (961.3 × BSA_D‐404.8) was associated with the lowest mean absolute error and used to predict LW for the entire cohort. Clinical factors associated with a ≥20% margin of error were identified in a multivariable analysis after propensity score matching (PSM) of donors with similar anthropometric characteristics. Results The total LW was underestimated with a ≥20% margin of error in 53/500 (10.6%) donors and overestimated in 62/500 (12%) donors. After PSM analysis, ages ≥ 65, (OR = 3.21; CI95% = 1.63‐6.31; P = .0007), age ≤ 30 years, (OR = 2.92; CI95% = 1.15‐7.40; P = .02), and elevated gamma‐glutamyltransferase (GGT) levels (OR = 0.98; CI95% = 0.97‐0.99; P = .006), influenced the risk of LW overestimation. Age ≥ 65 years, (OR = 5.98; CI95% = 2.28‐15.6; P = .0002), intensive care unit (ICU) stay with ventilation > 7 days, (OR = 0.32; CI95% = 0.12‐0.85; P = .02) and waist circumference increase (OR = 1.02; CI95% = 1.00‐1.04; P = .04) were factors associated with LW underestimation. Conclusions Increased waist circumference, age, prolonged ICU stay with ventilation, elevated GGT were associated with an increase in the margin of error in LW prediction. These factors and anthropometric characteristics could help transplant surgeons during the donor–recipient matching process.
Liver International - Tập 41 Số 6 - Trang 1379-1388 - 2021
Telmisartan attenuates progression of steatohepatitis in mice: role of hepatic macrophage infiltration and effects on adipose tissue Abstract Background/Aims: Non‐alcoholic fatty liver disease and non‐alcoholic steatohepatitis (NASH) are the hepatic manifestation of metabolic syndrome. However, its therapeutic strategy has not been established. Recently, an angiotensin II type 1 receptor blocker, telmisartan (Tel), has received a great deal of attention as a therapeutic tool for metabolic syndrome. The aim of this study was to investigate the efficacy and mechanisms of Tel on a murine NASH model.Methods: C57BL/6 mice were fed a methionine‐ and choline‐deficient high‐fat diet (MCDHF) or a standard diet with/without the administration of Tel (10 mg/kg/day) for 8 weeks.Results: MCDHF feeding induced marked steatohepatitis with macrophage infiltration. Tel attenuated liver steatosis with decreased hepatic triglycerides (P<0.05) and fibrogenesis with decreased type I collagen and transforming growth factor‐β1 mRNA expressions (P<0.05). Tel also suppressed the infiltration of macrophages into the liver and decreased hepatic monocyte chemoattractant protein‐1 and its receptor (CC‐chemokine receptor 2; CCR2) mRNA expressions, especially CCR2. In vitro , Tel suppressed CCR2 expression, which was induced by low‐density lipoprotein. The size of adipocyte in visceral fat tissue was reduced with an increased serum adiponectin concentration in the Tel group.Conclusions: In this study, we revealed that Tel attenuated steatohepatitis progression by suppressing the macrophage infiltration into the liver. Tel also affected the reduction of adipocyte size and elevation of serum adiponectin. Tel might serve as a new therapeutic strategy for NASH.
Liver International - Tập 29 Số 7 - Trang 988-996 - 2009
Natural history, spectrum and outcome of stage 3 <scp>AKI</scp> in patients with acute‐on‐chronic liver failure Abstract Background and Aim There is limited data on natural course and interventions in stage‐3 acute kidney injury (AKI‐3) in patients with acute‐on‐chronic liver failure (ACLF). We studied the factors of AKI‐3 reversal and outcomes of dialysis in ACLF patients. Methods Consecutive patients with ACLF were prospectively enrolled (n = 1022) and variables determining AKI and its outcomes were analysed. Results At 1 month, 337 (33%) patients had AKI‐3, of which, 131 had AKI‐3 at enrolment and 206 developed AKI‐3 during hospital stay. Of patients with AKI‐3 at enrolment, 18% showed terlipressin response, 21% had AKI resolution and 59% required dialysis. High MELD (≥35) (model 1), serum bilirubin (≥23 mg/dL) (model 2) and AARC score (≥11) (model 3) were independent risk factors for dialysis. Dialysis was associated with worse survival in all AKI patients but improved outcomes in patients with AKI‐3 (p = .022, HR 0.69 [0.50–0.95]). Post‐mortem kidney biopsies (n = 61) revealed cholemic nephropathy (CN) in 54%, acute tubular necrosis (ATN) in 31%, and a combination (CN and ATN) in 15%. Serum bilirubin was significantly higher in patients with CN, CN and ATN compared with ATN respectively ([30.8 ± 12.2] vs. [26.7 ± 12.0] vs. [18.5 ± 9.8]; p = .002). Conclusion AKI‐3 rapidly increases from 13% to 33% within 30 days in ACLF patients. Histopathological data suggested cholemic nephropathy as the predominant cause which correlated with high bilirubin levels. AKI‐3 resolves in only one in five patients. Patients with AARC grade 3 and MELD >35 demand need for early dialysis in AKI‐3 for improved outcomes.
Liver International - Tập 42 Số 12 - Trang 2800-2814 - 2022
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