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1.
Liver Int ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32052552

RESUMO

BACKGROUND AND AIMS: Non-O blood-type (BT) is a risk factor for thromboses, which has been attributed to its effects on von Willebrand factor (VWF)/factor VIII (FVIII) levels. Although high VWF/FVIII may be risk factors for portal vein thrombosis (PVT) in patients with advanced chronic liver disease (ACLD), the impact of BT on PVT is unknown. We aimed to assess (I) whether non-O-BT is a risk factor for PVT and (II) whether non-O-BT impacts VWF/factor VIII in patients with ACLD. METHODS: Retrospective analysis comprising two cohorts: (I) 'U.S.' including all adult liver transplantations in the U.S. in the MELD era and (II) 'Vienna' comprising patients with a hepatic venous pressure gradient (HVPG)≥6mmHg. RESULTS: (I) The 'U.S.-cohort' included 84,947 patients (non-O:55.43%). The prevalence of PVT at the time of listing (4.37%vs.4.56%;P=0.1762) and at liver transplantation (9.56%vs.9.33%;P=0.2546) was similar in patients with O- and non-O-BT. (II) 411 patients were included in the 'Vienna-cohort' (non-O:64%). Mean HVPG was 18(9)mmHg and 90% had an HVPG≥10mmHg. Patients with non-O-BT had slightly increased VWF levels (318(164)%vs.309(176)%;P=0.048;increase of 23.8-23.9% in adjusted analyses), but this difference was driven by patients with less advanced disease. However, non-O-BT explained only 1% of the variation in VWF and had no effect on FVIII. CONCLUSIONS: Although non-O-BT impacts VWF in patients with early-stage ACLD, its contribution to VWF variation is considerably smaller than in the general population. Moreover, non-O-BT had no impact on FVIII. These findings may explain the absence of an association between non-O-BT and PVT in patients with advanced cirrhosis.

2.
Liver Int ; 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-32017359

RESUMO

BACKGROUND & AIMS: HIV/HCV coinfection is common in people who inject drugs (PWIDs). Recently, 'high-risk' behavior among men who have sex with men (MSM) has emerged as another main route of HCV transmission. We analyzed temporal trends in HCV epidemiology in a cohort of Viennese HIV+ patients. METHODS: HCV parameters were recorded at HIV diagnosis (baseline, BL) and last visit (follow-up, FU) for all HIV+patients attending the HIV clinic between January-2014 and December-2016. Proportions of HIV+patients with anti-HCV(+) and HCV viremia (HCV-RNA(+)) at BL/FU were assessed and stratified by route of transmission. RESULTS: 1806/1874(96.4%) HIV+patients were tested for HCV at BL. Anti-HCV(+) was detected in 93.2%(276/296) of PWIDs and in 3.7%(31/839) of MSM. After a median follow-up of 6.9 years, 1644(91.0%) patients underwent FU HCV-testing: 167(90.3%) of PWIDs and 49(6.7%) of MSM showed anti-HCV(+). Among 208 viremic (HCV-RNA(+)) patients at BL, 30(14.4%) had spontaneously cleared HCV, 76(36.5%) achieved treatment-induced eradication and 89(42.8%) remained HCV-RNA(+) at FU. Among 1433 initially HCV-naive patients, 45(3.5%) acquired de-novo HCV infection (11.1% PWIDs/80.0% MSM; incident rate (IR) 0.004%; 95%CI 0.0-0.022%)) and 14 had HCV reinfections (85.7% PWIDs/14.3% other; IR 0.001%; 95%CI 0.0-0.018%)) during a median FU of 6.7 years (IQR 7.4). CONCLUSION: HCV testing was succesfully implemented in the Viennese HIV(+) patients. Anti-HCV(+) prevalence remained stable in HIV+PWIDs but almost doubled in HIV+MSM. De-novo HCV infection occurred mostly in MSM, while HCV reinfections were mainly observed in PWIDs. HCV treatment uptake was suboptimal with 42.8% remaining HCV-RNA(+) at FU.

3.
J Hepatol ; 2020 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-32061870

RESUMO

BACKGROUND & AIMS: The occurrence of acute decompensation (AD) worsens the prognosis of advanced chronic liver disease (ACLD). Various insults leading to increased systemic inflammation trigger acute-on-chronic liver failure (ACLF) with dramatically increased short-term mortality. During acute conditions such as sepsis, high-density lipoprotein cholesterol (HDL-C) levels decrease rapidly and HDL particles undergo profound changes in their composition and function. Indices of HDL quantity and quality may therefore associate with progression and survival in patients with advanced liver disease. METHODS: We studied levels of HDL-cholesterol (HDL-C), its subclasses HDL2-C and HDL3-C, and apolipoprotein(apo)A-I as indices of HDL quantity and HDL cholesterol efflux capacity as a metric of HDL functionality in 508 patients with compensated or decompensated cirrhosis including ACLF and 40 age- and gender-matched controls. RESULTS: Baseline levels of HDL-C and apoA-I were significantly lower in stable cirrhosis compared to control and further decreased in AD and ACLF. In stable cirrhosis (n=228), both HDL-C and apoA-I predicted the development of liver-related complications independently of MELD. In patients with AD with or without ACLF (n=280) both HDL-C and apoA-I were MELD-independent predictors of 90-day mortality. On ROC analysis, high diagnostic accuracies for 90-day mortality in AD patients were found for HDL-C (AUROC 0.79) and apoA-I (AUROC 0.80), very similar to that of MELD (AUROC 0.81). On Kaplan-Meier analysis, HDL-C <17 mg/dl and apoA-I <50 mg/dl indicated poor short-term survival. The prognostic accuracy of HDL-C was validated in a large external validation cohort of 985 patients with portal hypertension due to ACLD (AUROCs HDL-C: 0.81 vs. MELD: 0.77). CONCLUSION: HDL-related biomarkers are robust predictors of disease progression and survival in chronic liver failure.

4.
Liver Int ; 40(2): 393-404, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31967400

RESUMO

BACKGROUND & AIMS: The loss-of-function rs72613567 T > TA-variant in the 17ß-hydroxysteroid dehydrogenase 13 (HSD17B13) gene might protect from alcoholic and non-alcoholic fatty liver disease (ALD/NAFLD) and associated fibrosis/cirrhosis. We investigated the impact of the T > TA-variant on hepatic decompensation and mortality and investigated its implications on retinol and sex steroid metabolism in patients who had already developed advanced chronic liver disease (ACLD). METHODS: Retrospective analysis in prospectively characterized patients with viral hepatitis- and ALD/NAFLD-induced portal hypertension (hepatic venous pressure gradient (HVPG) ≥ 6 mmHg) diagnosed at the Medical University of Vienna. RESULTS: Among 487 patients who were followed longitudinally, 166 (34%) were heterozygous and 24 (5%) were homozygous for the 'protective' TA-allele. Patients harbouring at least one TA-allele had a lower MELD (9 (8-12) vs 10 (8-13) points; P = .003) and showed a trend towards lower HVPG (16 ± 6 vs 17 ± 7 mmHg; P = .067). Interestingly, in competing risk analyses adjusted for age, HVPG and MELD, harbouring the TA-allele was associated with numerically increased risks for mortality (adjusted subdistribution hazard ratio (aSHR): 1.3 (95% confidence interval (95% CI): 0.888-1.91); P = .18), liver-related death (aSHR: 1.34 (95% CI: 0.9-1.98); P = .15) and hepatic decompensation (aSHR: 1.29 (95% CI: 0.945-1.77); P = .11). This might be explained by trends towards worse outcomes (eg liver-related death: aSHR: 1.64 (95% CI: 0.95-2.84); P = .076) in patients with viral hepatitis-induced ACLD. In a cross-sectional analysis of 211 additional patients, serum retinol levels were comparable between HSD17B13 genotypes, but in males, serum testosterone levels numerically decreased with an increasing number of TA-alleles. CONCLUSION: In patients with viral hepatitis- and ALD-induced portal hypertension, the T > TA-variant was not protective of hepatic decompensation and mortality. Further studies should investigate the pathophysiological mechanisms underlying the effects of HSD17B13 genotype at different stages of liver disease.

5.
Wien Klin Wochenschr ; 132(1-2): 1-11, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31912289

RESUMO

BACKGROUND AND AIMS: Portal hypertensive gastropathy (PHG) is common in patients with cirrhosis and may cause bleeding. This study systematically explored the independent impact of patient characteristics, portal hypertension and hepatic dysfunction on PHG severity and associated anemia. METHODS: Patients with cirrhosis undergoing endoscopy were included in this retrospective analysis and PHG was endoscopically graded as absent, mild or severe. Clinical and laboratory parameters and hepatic venous pressure gradient (HVPG) were assessed with respect to an association with severity of PHG. RESULTS: A total of 110 patients (mean age: 57 years, 69% male) with mostly alcoholic liver disease (49%) or viral hepatitis (30%) were included: 15 (13.6%) patients had no PHG, 59 (53.6%) had mild PHG, and 36 (32.7%) had severe PHG. Severe PHG was significantly associated with male sex (83.3% vs. 62.2% in no or mild PHG; p = 0.024) and higher Child-Turcotte-Pugh (CTP) stage (CTP-C: 38.9% vs. 27.0% in no or mild PHG; p = 0.030), while MELD was similar (p = 0.253). Patients with severe PHG had significantly lower hemoglobin values (11.2 ± 0.4 g/dL vs. 12.4 ± 0.2 g/dL; p = 0.008) and a higher prevalence of iron-deficiency anemia (IDA: 48.5% vs. 26.9%; p = 0.032). Interestingly, HVPG was not significantly higher in severe PHG (median 20 mm Hg) vs. mild PHG (19 mm Hg) and no PHG (18 mm Hg; p = 0.252). On multivariate analysis, CTP score (odds ratio, OR: 1.25, 95% confidence interval, CI 1.02-1.53; p = 0.033) was independently associated with severe PHG, while only a trend towards an independent association with IDA was observed (OR: 2.28, 95% CI 0.91-5.72; p = 0.078). CONCLUSION: The CTP score but not HVPG or MELD were risk factors for severe PHG. Importantly, anemia and especially IDA are significantly more common in patients with severe PHG.


Assuntos
Anemia Ferropriva , Varizes Esofágicas e Gástricas , Hipertensão Portal , Gastropatias , Anemia Ferropriva/complicações , Varizes Esofágicas e Gástricas/complicações , Feminino , Hemorragia Gastrointestinal , Humanos , Hipertensão Portal/complicações , Cirrose Hepática , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Gastropatias/complicações
6.
Artigo em Inglês | MEDLINE | ID: mdl-31972057

RESUMO

BACKGROUND & AIMS: Iron deficiency anemia (IDA)is the leading cause of anemia worldwide. Data on prevalence and clinical impact of anemia in cirrhosis is scarce. Aim was to report on(i)prevalence of anemia and IDA in cirrhosis and (ii)its possible impact on clinical outcomes. AIMS & METHODS: Consecutive cirrhotic patients from a prospective registry study were included. Anemia was defined as hemoglobin-concentration≤12g/dl. IDA was defined as Hb≤12g/dl+transferrin-saturation<20%.Follow-up for hepatic decompensation and mortality started with study inclusion and terminated in December 2017.A retrospective validation cohort of 1.244 patients was used to validate our findings. RESULTS: 242 patients with compensated[n=53(21.9%)] and decompensated[n=189(78.1%)] cirrhosis were included. Anemia was present in 128 patients(52.9%), of those 63(49.2%) had IDA. Prevalence of anemia increased with CPS(A:26.5%,B:59.2%,C:69%;p<0.001) and with decompensated cirrhosis(62.4% vs. 18.8%,p<0.001). Within anemic patients, a higher proportion of patients in CPS A/B vs. C(73% vs. 35%;p=0.025) and in compensated cirrhosis(80% vs. 46.6%;p=0.043)were found with IDA.MELD scores were significantly lower in patients with IDA(14.4 vs. 17.9 non-ID-anemia;p=0.005). Similar results were found in the validation cohort: median MELD[16(8-28)non-ID anemia vs. 12(7-23)IDA;p<0.001] and within anemic patients IDA was more common in patients with MELD<15(58%) vs. >15(24%,p<0.001). Anemia was associated with a significant risk for hepatic decompensation and/or mortality both in the validation (aSHR:1.65,p=0.008) and derivation cohort (aSHR: 2.11,p<0.001) and an independent risk factor for hepatic decompensation and/or mortality in compensated patients (aHR:4.91,p=0.004). CONCLUSION: Anemia is highly prevalent in cirrhosis. In compensated cirrhosis, CPS A/B and low MELD, IDA seems to be the most likely reason for anemia. Furthermore anemia is associated with a significant risk for hepatic decompensation or mortality during long-term follow-up.

7.
Radiology ; 294(1): 98-107, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31743083

RESUMO

Background Gadoxetic acid-enhanced MRI enables estimation of liver function in patients with chronic liver disease (CLD). The functional liver imaging score (FLIS), derived from gadoxetic acid-enhanced MRI, has been shown to predict transplant-free survival in liver transplant patients. Purpose To investigate the accuracy of the FLIS for predicting hepatic decompensation and transplant-free survival in patients with CLD. Materials and Methods Patients with CLD who had undergone gadoxetic acid-enhanced liver MRI, including T1-weighted volume-interpolated breath-hold examination sequences with fat suppression, performed between 2011 and 2015 were included. FLIS was assigned on the basis of the sum of three hepatobiliary phase features, each scored on an ordinal 0-2 scale: hepatic enhancement, biliary excretion, and the signal intensity in the portal vein. Patients were stratified into the following three groups according to fibrosis stage and a presence or history of hepatic decompensation: nonadvanced CLD, compensated advanced CLD (CACLD), and decompensated advanced CLD (DACLD). The predictive value of FLIS for first and/or further hepatic decompensation and for transplant-free survival was investigated by using Kaplan-Meier analysis, log-rank tests, and Cox regression analysis. Results This study evaluated 265 patients (53 years ± 14 [standard deviation]; 164 men). Intraobserver (κ = 0.98; 95% confidence interval: 0.97, 0.99) and interobserver (κ = 0.93; 95% confidence interval: 0.90, 0.95) agreement for FLIS were excellent. In patients with CACLD, the FLIS was independently predictive of a first hepatic decompensation (adjusted hazard ratio, 3.7; 95% confidence interval: 1.1, 12.6; P = .04), but not for further hepatic decompensations in patients with DACLD (adjusted hazard ratio, 1.4; 95% confidence interval: 0.9, 1.9; P = .17). The FLIS was an independent risk factor for mortality in both patients with CACLD (adjusted hazard ratio, 7.4; 95% confidence interval: 2.7, 20.2; P < .001) and those with DACLD (adjusted hazard ratio, 3.8; 95% confidence interval: 1.7, 9.5; P = .004). Conclusion The functional liver imaging score derived from gadoxetic acid-enhanced MRI identified patients with advanced chronic liver disease who are at increased risk for a first hepatic decompensation and for mortality. © RSNA, 2019 Online supplemental material is available for this article.

8.
Liver Int ; 40(1): 194-204, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31444993

RESUMO

BACKGROUND: Anaemia is common in advanced chronic liver disease (ACLD) as a result of various risk factors. AIMS & METHODS: We evaluated the prevalence and severity of anaemia as well as the impact of anaemia on clinical outcomes in consecutive patients with ACLD and portal hypertension. RESULTS: Among 494 patients, 324 (66%) patients had anaemia. Anaemic patients showed higher MELD (12 ± 4 vs 9 ± 3; P < .001), lower albumin (34 ± 6 vs 39 ± 5 g/dL; P < .001) and more often Child-Pugh B/C stage (56% vs 17%; P < .001). The prevalence of moderate-severe anaemia (haemoglobin <10 g/dL) increased with the degree of portal hypertension (HVPG: 6-9 mm Hg: 22% vs HVPG: 10-19 mm Hg: 24% vs HVPG ≥ 20 mm Hg: 36%; P = .031). The most common aetiologies of anaemia were gastrointestinal bleeding (25%) and iron deficiency (9%), while reason for anaemia remained unclear in 53% of cases. Male gender (odds ratio [OR]: 1.94 [95% CI: 1.09-3.47]; P = .025), MELD (OR: 1.20 [95% CI: 1.09-1.32]; P < .001), hepatic decompensation (OR: 4.40 [95% CI: 2.48-7.82]; P < .001) and HVPG (OR per mm Hg: 1.07 [95% CI: 1.02-1.13]; P = .004) were independent risk factors for anaemia. Anaemia was associated with hepatic decompensation (1 year: 25.1% vs 8.1%; 5 years: 60.3% vs 32.9%; P < .0001), hospitalization (73% vs 57%; P < .001) and a higher incidence rate of acute-on-chronic liver failure (0.05 [95% CI: 0.04-0.07] vs 0.03 [95% CI: 0.01-0.04]). Anaemic patients had worse overall survival (1 year: 87.1% vs 93.7%, 5 year survival: 50.5% vs 68.6%; P < .0001) and increased liver-related mortality (1 year mortality: 9.7% vs 5.7%, 5 year mortality: 38.0% vs 26.9%; P = .003). CONCLUSION: Two-thirds of patients with ACLD suffer from anaemia. The degree of hepatic dysfunction and of portal hypertension correlate with severity of anaemia. Anaemia is associated with decompensation, ACLF and increased mortality in patients with ACLD.

9.
J Gastroenterol ; 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31832759

RESUMO

BACKGROUND: The ratio of von Willebrand Factor to platelets (VITRO) reflects the severity of fibrosis and portal hypertension and might thus hold prognostic value. METHODS: Patients with compensated cirrhosis were recruited. VITRO, Child-Pugh score (CPS) and MELD were determined at study entry. Hepatic decompensation was defined as variceal bleeding, ascites or hepatic encephalopathy. Liver transplantation and death were recorded. RESULTS: One hundred and ninety-four patients with compensated cirrhosis (CPS-A 89%, B 11%; 56% male; median age 56 years; 50% with varices) were included. During a median follow-up of 45 months (IQR 29-61), decompensation occurred in 35 (18%) patients and 14 (7%) patients deceased. The risk of hepatic decompensation was significantly increased in the n = 88 (45%) patients with a VITRO ≥ 2.5 (p < 0.001). Patients with a VITRO ≥ 2.5 had a higher probability of decompensation at 1-year 9% (95% CI 3-16) vs. 0% (95% CI 0-0) and at 2-years 18% (95% CI 10-27%), vs. 4% (95% CI 0-8%) as compared to patients with VITRO < 2.5. Patients with VITRO ≥ 2.5, the estimated 1-year/2-year survival rates were at 98% (95% CI 95-100%) and 94% (95% CI 88-99%) as compared to 100% (95% CI 100-100%) both in the patients with a VITRO < 2.5 (p < 0.001). After adjusting for age, albumin and MELD, VITRO ≥ 2.5 remained as significant predictor of transplant-free mortality (HR 1.38, CI 1.09-1.76; p = 0.007). Patients with compensated cirrhosis and VITRO > 2.1 after hepatitis C eradication remained at significantly increased risk for decompensation (p = 0.033). CONCLUSIONS: VITRO is a valuable prognostic tool for estimating the risk of decompensation and mortality in patients with compensated cirrhosis-including the setting after hepatitis C eradication.

10.
Dig Dis Sci ; 2019 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-31875288

RESUMO

BACKGROUND: The prognostic impact of liver steatosis in obese patients is well established. Limited data on the risk factors for and impact of hepatic steatosis in lean patients are available. AIMS: Assess risk factors for liver steatosis in lean patients and investigate its impact on survival. METHODS: Patients without viral hepatitis and with a BMI ≤ 25 kg/m2 undergoing liver stiffness measurement (LSM) and controlled attenuation parameter (CAP) by transient elastography were retrospectively identified. Clinical characteristics and laboratory test results were obtained at the time of LSM/CAP measurement. National death registry data were obtained in order to assess survival. RESULTS: Among n = 218 lean patients, n = 97 (34.5%) showed significant liver steatosis (CAP ≥ 268 dB/m), while n = 184 (65.5%) had no or just mild steatosis (CAP < 268 dB/m). Patients with steatosis had higher GGT (238.0(± 450.3) vs. 112.1(± 180.0) IU/mL; p = 0.013), AST (63(± 67.4) vs. 38.5(± 32.9) IU/mL; p = 0.001), ALT (59.1(± 58.8) vs. 44.3(± 52.7) IU/mL; p = 0.048) and triglyceride levels (120.1(± 80.3) vs. 96.1(± 58.2) mg/dL; p = 0.014), and showed a trend toward more severe fibrosis (LSM 15.6(± 19.5) vs. 12.0(± 15.7) kPa; p = 0.115). In multivariate binary logistic regression analysis, only serum uric acid levels were independently associated with liver steatosis (odds ratio 1.43 per unit mg/dL; 95% CI 1.001-2.054; p = 0.049). During a mean follow-up of 38.9(± 10.6) months, n = 14 patients (5.0%) died. In the absence of advanced fibrosis, survival after 1 year was similar in patients without (98.7%) and with (98.6%) significant steatosis. Patients with advanced fibrosis had worse 1-year survival without concomitant significant steatosis (84.8%) than patients with steatosis (95.8%; log-rank p < 0.001). CONCLUSIONS: High serum uric acid levels increase the risk of liver steatosis in lean patients. Liver fibrosis but not hepatic steatosis is a risk factor for impaired survival in lean patients.

11.
PLoS One ; 14(11): e0224506, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31693695

RESUMO

BACKGROUND AND AIMS: Studies in animal models have suggested that hepatic steatosis impacts on portal pressure, potentially by inducing liver sinusoidal endothelial dysfunction and thereby increasing intrahepatic resistance. Thus, we aimed to evaluate the impact of hepatic steatosis on hepatic venous pressure gradient (HVPG) in patients with chronic liver disease. METHOD: 261 patients undergoing simultaneous HVPG measurements and controlled attenuation parameter (CAP)-based steatosis assessment were included in this retrospective study. RESULTS: The majority of patients had cirrhosis (n = 205; 78.5%) and n = 191 (73.2%) had clinically significant portal hypertension (CSPH; HVPG≥10mmHg). Hepatic steatosis (S1/2/3; CAP ≥248dB/m) was present in n = 102 (39.1%). Overall, HVPG was comparable between patients with vs. without hepatic steatosis (15.5±7.5 vs. 14.8±7.7mmHg; p = 0.465). Neither in patients with HVPG (<6mmHg; p = 0.371) nor in patients with mild portal hypertension (HVPG 6-9mmHg; p = 0.716) or CSPH (HVPG≥10mmHg; p = 0.311) any correlation between CAP and HVPG was found. Interestingly, in patients with liver fibrosis F2/3, there was a negative correlation between CAP and HVPG (Pearson's ρ:-0.522; p≤0.001). In multivariate analysis, higher CAP was an independent 'protective' factor for the presence of CSPH (odds ratio [OR] per 10dB/m: 0.92, 95% confidence interval [CI]:0.85-1.00; p = 0.045), while liver stiffness was associated with the presence of CSPH (OR per kPa: 1.26, 95%CI: 1.17-1.36; p≤0.001). In 78 patients, in whom liver biopsy was performed, HVPG was neither correlated with percentage of histological steatosis (p = 0.714) nor with histological steatosis grade (p = 0.957). CONCLUSION: Hepatic steatosis, as assessed by CAP and liver histology, did not impact on HVPG in our cohort comprising a high proportion of patients with advanced chronic liver disease. However, high CAP values (i.e. pronounced hepatic steatosis) might lead to overestimation of liver fibrosis by 'artificially' increasing transient elastography-based liver stiffness measurements.

13.
World J Gastroenterol ; 25(39): 5897-5917, 2019 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-31660028

RESUMO

Portal hypertension (PHT) in advanced chronic liver disease (ACLD) results from increased intrahepatic resistance caused by pathologic changes of liver tissue composition (structural component) and intrahepatic vasoconstriction (functional component). PHT is an important driver of hepatic decompensation such as development of ascites or variceal bleeding. Dysbiosis and an impaired intestinal barrier in ACLD facilitate translocation of bacteria and pathogen-associated molecular patterns (PAMPs) that promote disease progression via immune system activation with subsequent induction of proinflammatory and profibrogenic pathways. Congestive portal venous blood flow represents a critical pathophysiological mechanism linking PHT to increased intestinal permeability: The intestinal barrier function is affected by impaired microcirculation, neoangiogenesis, and abnormal vascular and mucosal permeability. The close bidirectional relationship between the gut and the liver has been termed "gut-liver axis". Treatment strategies targeting the gut-liver axis by modulation of microbiota composition and function, intestinal barrier integrity, as well as amelioration of liver fibrosis and PHT are supposed to exert beneficial effects. The activation of the farnesoid X receptor in the liver and the gut was associated with beneficial effects in animal experiments, however, further studies regarding efficacy and safety of pharmacological FXR modulation in patients with ACLD are needed. In this review, we summarize the clinical impact of PHT on the course of liver disease, discuss the underlying pathophysiological link of PHT to gut-liver axis signaling, and provide insight into molecular mechanisms that may represent novel therapeutic targets.

15.
Clin Infect Dis ; 2019 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-31562817

RESUMO

BACKGROUND: Increasing numbers of hepatitis C virus (HCV) infections among men who have sex with men (MSM) are being observed in the Western world. The actual routes of HCV transmission during high-risk sex-practices and associated drug use remain poorly understood. METHODS: 47 HCV patients were prospectively enrolled. Rectal and nasal swabs were collected to quantify HCV-RNA levels within rectal and nasal fluids. Contamination by occult rectal bleeding was ruled out by guaiac paper test. Risk-behaviour was assessed by standardized questionnaires. RESULTS: Median age was 41.9 years, 89% were HIV+ (42/47) and of 85% (40/47) male, 58% (23/40) were MSM. Acute HCV infection was diagnosed in 32% (15/47) with all patients being HIV+MSM and 93% (14/15) having a documented history of sexually transmitted disease. Thirty-three (70%) patients had at least one HCV-positive swab sample (HCV+SS; 48%, 22/46 rectal; 62%, 29/47 nasal) and contamination with blood was ruled out in all patients. Individuals with HCV+SS had significantly higher serum HCV-RNA levels than patients with HCV-negative SS (6.28 IQR 0.85 logU/mL vs. 4.08 IQR 2.45 logU/mL; p<0.001). Using ROC-curve analysis, serum HCV-RNA cut-offs for ruling in-/out any HCV+SS were established at 6.02log IU/mL and 4.02log IU/mL, respectively. CONCLUSIONS: HCV-RNA is commonly detectable in rectal and nasal fluids of both HIV+ and HIV-negative HCV patients with high serum HCV-RNA, independently of the suspected route of HCV transmission. Accordingly, high-risk sex-practices and sharing of nasal drug-sniffing 'tools' might be important HCV transmission routes, especially in patients with high serum HCV-RNA.

16.
Wien Klin Wochenschr ; 131(17-18): 395-403, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31493100

RESUMO

BACKGROUND: Liver disease impacts on hepatic synthesis of lipoproteins and lipogenesis but data on dyslipidemia during disease progression are limited. We assessed the patterns of dyslipidemia in (i) different liver disease etiologies and discriminated (ii) non-advanced (non-ACLD) from advanced chronic liver disease (ACLD) as it is unclear how progression to ACLD impacts on dyslipidemia-associated cardiovascular risk. METHODS: Patients with alcoholic liver disease (n = 121), hepatitis C (n = 1438), hepatitis B (n = 384), metabolic/fatty liver disease (n = 532), cholestatic liver disease (n = 119), and autoimmune hepatitis (n = 114) were included. Liver stiffness ≥15 kPa defined ACLD. Dyslipidemia was defined as total cholesterol >200 mg/dL, low-density lipoprotein (LDL)-cholesterol >130 mg/dL and triglycerides >200 mg/dL. RESULTS: Across all etiologies, total cholesterol levels were significantly lower in ACLD, when compared to non-ACLD. Accordingly, LDL-cholesterol levels were significantly lower in ACLD due to hepatitis C, hepatitis B, metabolic/fatty liver disease and autoimmune hepatitis. Triglyceride levels did not differ due to disease severity in any etiology. Despite lower total and LDL cholesterol levels in ACLD, etiology-specific dyslipidemia patterns remained similar to non-ACLD. Contrary to this "improved" lipid status in ACLD, cardiovascular comorbidities were more prevalent in ACLD: arterial hypertension was present in 26.6% of non-ACLD and in 55.4% of ACLD patients (p < 0.001), and diabetes was present in 8.1% of non-ACLD and 25.6% of ACLD patients (p < 0.001). CONCLUSION: Liver disease etiology is a major determinant of dyslipidemia patterns and prevalence. Progression to ACLD "improves" serum lipid levels while arterial hypertension and diabetes mellitus are more prevalent. Future studies should evaluate cardiovascular events after ACLD-induced "improvement" of dyslipidemia.


Assuntos
Dislipidemias , Hepatopatias , Adulto , LDL-Colesterol/sangue , Dislipidemias/epidemiologia , Feminino , Humanos , Hepatopatias/epidemiologia , Hepatopatias/etiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Triglicerídeos/sangue
17.
Sci Rep ; 9(1): 11674, 2019 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-31406146

RESUMO

Statins reduce cardiovascular risk. However, "real-life" data on statin use in patients with chronic liver disease and its impact on overall and liver-related survival are limited. Therefore, we assessed 1265 CLD patients stratified as advanced (ACLD) or non-advanced (non-ACLD) stage. Statin indication was evaluated according to the 2013 ACC/AHA guidelines and survival-status was verified by national death registry data. Overall, 122 (9.6%) patients had an indication for statin therapy but did not receive statins, 178 (14.1%) patients were on statins and 965 (76.3%) patients had no indication for statins. Statin underutilization was 34.2% in non-ACLD and 48.2% in ACLD patients. In non-ACLD patients, survival was worse without a statin despite indication as compared to patients on statin or without indication (log-rank p = 0.018). In ACLD patients, statin use did not significantly impact on survival (log-rank p = 0.264). Multivariate cox regression analysis confirmed improved overall survival in patients with statin as compared to patients with indication but no statin (HR 0.225; 95%CI 0.053-0.959; p = 0.044) and a trend towards reduced liver-related mortality (HR 0.088; 95%CI 0.006-1.200; p = 0.068). This was not observed in ACLD patients. In conclusion, guideline-confirm statin use is often withhold from  patients with liver disease and this underutilization is associated with impaired survival in non-ACLD patients.

18.
Liver Int ; 39(12): 2374-2385, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31421002

RESUMO

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.

19.
Hepatology ; 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31365764

RESUMO

BACKGROUND AND AIMS: Sustained virologic response (SVR) to interferon (IFN)-free therapies ameliorates portal hypertension (PH); however, it remains unclear whether a decrease in hepatic venous pressure gradient (HVPG) after cure of hepatitis C translates into a clinical benefit. We assessed the impact of pretreatment HVPG, changes in HVPG, and posttreatment HVPG on the development of hepatic decompensation in patients with PH who achieved SVR to IFN-free therapy. Moreover, we evaluated transient elastography (TE) and von Willebrand factor to platelet count ratio (VITRO) as noninvasive methods for monitoring the evolution of PH. APPROACH AND RESULTS: The study comprised 90 patients with HVPG ≥ 6 mm Hg who underwent paired HVPG, TE, and VITRO assessments before (baseline [BL]) and after (follow-up [FU]) IFN-free therapy. FU HVPG but not BL HVPG predicted hepatic decompensation (per mm Hg, hazard ratio, 1.18; 95% confidence interval, 1.08-1.28; P < 0.001). Patients with BL HVPG ≤ 9 mm Hg or patients who resolved clinically significant PH (CSPH) were protected from hepatic decompensation. In patients with CSPH, an HVPG decrease ≥ 10% was similarly protective (36 months, 2.5% vs. 40.5%; P < 0.001) but was observed in a substantially higher proportion of patients (60% vs. 24%; P < 0.001). Importantly, the performance of noninvasive methods such as TE/VITRO for diagnosing an HVPG reduction ≥ 10% was inadequate for clinical use (area under the receiver operating characteristic curve [AUROC],  < 0.8), emphasizing the need for HVPG measurements. However, TE/VITRO were able to rule in or rule out FU CSPH (AUROC, 0.86-0.92) in most patients, especially if assessed in a sequential manner. CONCLUSIONS: Reassessment of HVPG after SVR improved prognostication in patients with pretreatment CSPH. An "immediate" HVPG decrease ≥ 10% was observed in the majority of these patients and was associated with a clinical benefit, as it prevented hepatic decompensation. These results support the use of HVPG as a surrogate endpoint for interventions that lower portal pressure by decreasing intrahepatic resistance.

20.
United European Gastroenterol J ; 7(6): 850-858, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31316789

RESUMO

Background: Transarterial chemoembolization (TACE) affects hepatic perfusion, and might have an impact on portal pressure in patients with hepatocellular carcinoma (HCC). Objective: The objective of this article is to report the secondary outcome "hepatic hemodynamics" from the AVATACE trial, a prospective randomized, placebo-controlled trial on the efficacy of conventional TACE in combination with bevacizumab or placebo. Methods: Hepatic venous pressure gradient (HVPG) was measured at baseline (prior to first TACE), within nine days ("acute effects"), two months ("intermediate effects") and six months ("long-term effects") after the first TACE. Results: Of 28 patients with early-intermediate stage HCC, n = 20 (71%) had clinically significant portal hypertension (CSPH, HVPG ≥ 10 mmHg) at baseline (median, 12 (interquartile range (IQR): 9-19) mmHg). TACE had neither "acute effects" nor "intermediate effects" on HVPG. However, in 13 patients with available HVPG measurement at month 6, there was a significant increase in HVPG (median, 16 (IQR: 11-19) mmHg) compared with baseline (median, 10 (IQR: 5-12) mmHg; p = 0.007). Portal hypertension-related complications occurred exclusively in patients with CSPH (8 (40%) vs 0). Conclusions: Repeated TACE was associated with a significant long-term increase in HVPG. This should be considered when deciding whether to continue with TACE or switch to systemic treatment, since CSPH drives the development of complications.

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