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Platelets participate in the development of liver fibrosis in animal models, but little is known about the benefit of antiplatelet agents in preventing liver fibrosis in humans. We therefore explored the relationship between the use of antiplatelet agents and liver fibrosis in a prospective cohort study of patients at high risk of liver fibrosis and cardiovascular events. Consecutive patients undergoing elective coronary angiography at the University Hospital Frankfurt were prospectively included in the present study. Associations between use of antiplatelet agents (acetyl salicylic acid, P2Y12 receptor antagonists) and liver fibrosis were assessed in regression models, and the relationship between platelet‐derived growth factor beta (PDGF‐β) serum concentration, platelets, liver fibrosis, and use of antiplatelet agents was characterized. Out of 505 included patients, 337 (67%) received antiplatelet agents and 134 (27%) had liver fibrosis defined as a FibroScan transient elastography (TE) value ≥7.9 kPa. Use of antiplatelet agents was inversely associated with the presence of liver fibrosis in univariate and multivariate analyses (multivariate odds ratio [OR], 0.67; 95% confidence interval [CI], 0.51‐0.89; P = 0.006). Use of antiplatelet agents was also inversely associated with FibroTest values (beta, –0.38; SD beta, 0.15; P = 0.02). Furthermore, there was a significant correlation between platelet counts and PDGF‐β serum concentration (rho, 0.33; P < 0.0001), but PDGF‐β serum levels were not affected by antiplatelet agents. Conclusion: There is a protective association between the use of antiplatelet agents and occurrence of liver fibrosis. A randomized controlled trial is needed to explore causality and the potential of antiplatelet agents as antifibrotic therapy in patients at risk for liver fibrosis progression.
Objective: Liver stiffness measurement (LSM) is a tool used to screen for significant fibrosis and portal hypertension. The aim of this retrospective multicentre study was to develop an easy tool using LSM for clinical outcomes in advanced chronic liver disease (ACLD) patients.
Design: This international multicentre cohort study included a derivation ACLD patient cohort with valid two-dimensional shear wave elastography (2D-SWE) results. Clinical and laboratory parameters at baseline and during follow-up were recorded. LSM by transient elastography (TE) was also recorded if available. The primary outcome was overall mortality. The secondary outcome was the development of first/further decompensation.
Results: After screening 2148 patients (16 centres), 1827 patients (55 years, 62.4% men) were included in the 2D-SWE cohort, with median liver SWE (L-SWE) 11.8 kPa and a model for end stage liver disease (MELD) score of 8. Combination of MELD score and L-SWE predict independently of mortality (AUC 0.8). L-SWE cut-off at ≥20 kPa combined with MELD ≥10 could stratify the risk of mortality and first/further decompensation in ACLD patients. The 2-year mortality and decompensation rates were 36.9% and 61.8%, respectively, in the 305 (18.3%) high-risk patients (with L-SWE ≥20 kPa and MELD ≥10), while in the 944 (56.6%) low-risk patients, these were 1.1% and 3.5%, respectively. Importantly, this M10LS20 algorithm was validated by TE-based LSM and in an additional cohort of 119 patients with valid point shear SWE-LSM.
Conclusion: The M10LS20 algorithm allows risk stratification of patients with ACLD. Patients with L-SWE ≥20 kPa and MELD ≥10 should be followed closely and receive intensified care, while patients with low risk may be managed at longer intervals.
Background and aims: Liver steatosis has shown to be associated with coronary artery disease (CAD). The aim of our study was to evaluate the association between the presence and severity of CAD and Non-alcoholic fatty liver disease (NAFLD) assessed by transient elastography (TE) and controlled attenuation parameter (CAP).
Methods: 576 Patients undergoing coronary angiography were enrolled in this prospective study, receiving at least 10 TE and CAP measurements using the FibroScan® M-probe. Clinically relevant CAD (CAD 3) was defined as stenosis with ≥75% reduction of the luminal diameter. NAFLD was determined by CAP ≥234 dB/m. NAFLD with advanced fibrosiswas determined by TE-values ≥7.9kPa in the presence of NAFLD and absence of congestive or right-sided heart failure. Rates and 95% confidence intervals are shown.
Results: 505 patients were available for analysis of NAFLD. However, only 392 patients were available for analysis of NAFLD with advanced fibrosis, since 24 patients had to be excluded due to non valid TE-measurements and 89 patients due to congestive or right-sided heart failure or suspected concomitant liver disease, respectively. 70.5% (66.3%-74.4%) of patients had CAD 3, 71.5% (67.3%-75.4%) were diagnosed with NAFLD, and 11.2% (8.3%-14.8%) with NAFLD with advanced fibrosis. Patients with CAD 3 had higher median CAP-values (273±61 vs. 260±66 dB/m; p = 0.038) and higher degrees of steatosis as compared to patients without CAD 3. While NAFLD was significantly more often diagnosed in patients with CAD 3 (75.0% vs. 63.1%, p = 0.0068), no significant difference was found for NAFLD with advanced fibrosis (10.7% vs. 12.5%, p = 0.60).
Conclusions: Clinically relevant CAD is frequently associated with the presence of NAFLD, but not NAFLD with advanced fibrosis.
Background: MicroRNA-21 (miR-21) is up-regulated in tumor tissue of patients with malignant diseases, including hepatocellular carcinoma (HCC). Elevated concentrations of miR-21 have also been found in sera or plasma from patients with malignancies, rendering it an interesting candidate as serum/plasma marker for malignancies. Here we correlated serum miR-21 levels with clinical parameters in patients with different stages of chronic hepatitis C virus infection (CHC) and CHC-associated HCC.
Methodology/Principal Findings: 62 CHC patients, 29 patients with CHC and HCC and 19 healthy controls were prospectively enrolled. RNA was extracted from the sera and miR-21 as well as miR-16 levels were analyzed by quantitative real-time PCR; miR-21 levels (normalized by miR-16) were correlated with standard liver parameters, histological grading and staging of CHC. The data show that serum levels of miR-21 were elevated in patients with CHC compared to healthy controls (P<0.001); there was no difference between serum miR-21 in patients with CHC and CHC-associated HCC. Serum miR-21 levels correlated with histological activity index (HAI) in the liver (r = −0.494, P = 0.00002), alanine aminotransferase (ALT) (r = −0.309, P = 0.007), aspartate aminotransferase (r = −0.495, P = 0.000007), bilirubin (r = −0.362, P = 0.002), international normalized ratio (r = −0.338, P = 0.034) and γ-glutamyltransferase (r = −0.244, P = 0.034). Multivariate analysis revealed that ALT and miR-21 serum levels were independently associated with HAI. At a cut-off dCT of 1.96, miR-21 discriminated between minimal and mild-severe necroinflammation (AUC = 0.758) with a sensitivity of 53.3% and a specificity of 95.2%.
Conclusions/Significance: The serum miR-21 level is a marker for necroinflammatory activity, but does not differ between patients with HCV and HCV-induced HCC.
Aim: To compare clinical success and complications of uncovered self-expanding metal stents (SEMS) vs covered SEMS (cSEMS) in obstruction of the small bowel.
Methods: Technical success, complications and outcome of endoscopic SEMS or cSEMS placement in tumor related obstruction of the duodenum or jejunum were retrospectively assessed. The primary end points were rates of stent migration and overgrowth. Secondary end points were the effect of concomitant biliary drainage on migration rate and overall survival. The data was analyzed according to the Strengthening the Reporting of Observational Studies in Epidemiology guidelines.
Results: Thirty-two SEMS were implanted in 20 patients. In all patients, endoscopic stent implantation was successful. Stent migration was observed in 9 of 16 cSEMS (56%) in comparison to 0/16 SEMS (0%) implantations (P = 0.002). Stent overgrowth did not significantly differ between the two stent types (SEMS: 3/16, 19%; cSEMS: 2/16, 13%). One cSEMS dislodged and had to be recovered from the jejunum by way of laparotomy. Time until migration between SEMS and cSEMS in patients with and without concomitant biliary stents did not significantly differ (HR = 1.530, 95%CI 0.731-6.306; P = 0.556). The mean follow-up was 57 ± 71 d (range: 1-275 d).
Conclusion: SEMS and cSEMS placement is safe in small bowel tumor obstruction. However, cSEMS is accompanied with a high rate of migration in comparison to uncovered SEMS.
Background: Patients with head and neck cancer (HNC) are at high risk for malnutrition because of tumour localisation and therapy. Prophylactic percutaneous endoscopic gastrostomy (PEG) tube placement is common practice to prevent malnutrition.
Objective: To investigate the benefits of prophylactic PEG tube placement for HNC patients in terms of the influence on patients’ nutritional status, utilisation rate, complications and to identify the predictors of PEG tube utilisation.
Methods: All consecutive HNC patients who underwent prophylactic PEG tube insertion between 1 January 2011 and 31 December 2012 prior to therapy were enrolled. The PEG tube utilisation rate, complications, the patients’ nutritional status and tumour therapy were evaluated with the help of electronic patient charts and telephone interviews.
Results: A total of 181 patients (48 female, median 67.5 years) were included. The PEG utilisation rate in the entire cohort was 91.7%. One hundred and forty‐nine patients (82.3%) used the PEG tube for total enteral nutrition, 17 patients (9.4%) for supplemental nutrition and 15 patients (8.3%) made no use of the PEG tube. Peristomal wound infections were the most common complications (40.3%) in this study. A high Nutritional Risk Screening (NRS) score prior to tube insertion was found to be independently associated with PEG utilisation. No significant weight changes were observed across the three patient subgroups.
Conclusions: The overall PEG tube utilisation rate was high in this study. However, given the high rate of infections, diligent patient selection is crucial in order to determine which patients benefit most from prophylactic PEG tube insertion.
Chronic viral hepatitis is associated with substantial morbidity and mortality worldwide. The aim of our study was to assess the ability of point shear‐wave elastography (pSWE) using acoustic radiation force impulse imaging for the prediction of the following liver‐related events (LREs): new diagnosis of HCC, liver transplantation, or liver‐related death (hepatic decompensation was not included as an LRE). pSWE was performed at study inclusion and compared with liver histology, transient elastography (TE), and serologic biomarkers (aspartate aminotransferase to platelet ratio index, Fibrosis‐4, FibroTest). The performance of pSWE and TE to predict LREs was assessed by calculating the area under the receiver operating characteristic curve and a Cox proportional‐hazards regression model. A total of 254 patients with a median follow‐up of 78 months were included in the study. LRE occurred in 28 patients (11%) during follow‐up. In both patients with hepatitis B virus and hepatitis C virus (HCV), pSWE showed significant correlations with noninvasive tests and TE, and median pSWE and TE values were significantly different between patients with LREs and patients without LREs (both P < 0.0001). In patients with HCV, the area under the receiver operating characteristic curve for pSWE and TE to predict LREs were comparable: 0.859 (95% confidence interval [CI], 0.747‐0.969) and 0.852 (95% CI, 0.737‐0.967) (P = 0.93). In Cox regression analysis, pSWE independently predicted LREs in all patients with HCV (hazard ratio, 17.9; 95% CI, 5.21‐61‐17; P < 0.0001) and those who later received direct‐acting antiviral therapy (hazard ratio, 17.11; 95% CI, 3.88‐75.55; P = 0.0002). Conclusion: Our study shows good comparability between pSWE and TE. pSWE is a promising tool for the prediction of LREs in patients with viral hepatitis, particularly those with chronic HCV. Further studies are needed to confirm our data and assess their prognostic value in other liver diseases.
Single nucleotide polymorphism (SNP) rs738409 C>G in the patatin‐like phospholipase domain containing 3 (PNPLA3) gene results in an amino acid exchange from isoleucin to methionine at position I148M of PNPLA3. The expression of this loss‐of‐function mutation leads to impaired hepatocellular triglyceride hydrolysis and is associated with the development of liver steatosis, fibrosis, and hepatocellular carcinoma. In contrast to these well‐established associations, the relationship of the PNPLA3 rs738409 variant with other metabolic traits is incompletely understood. We therefore assessed the association of the PNPLA3 rs738409 genotype with relevant metabolic traits in a prospective study of patients at high risk for cardiovascular events, i.e., patients undergoing coronary angiography. In a total of 270 patients, known associations of the PNPLA3 rs738409 GG genotype with nonalcoholic steatohepatitis and liver fibrosis were confirmed. In addition, we found an association of the PNPLA3 rs738409 G allele with the presence of diabetes (22% versus 28% versus 58% for CC versus CG versus GG genotype, respectively; P = 0.02). In contrast to its association with nonalcoholic fatty liver disease, liver fibrosis, and diabetes, the minor G allele of PNPLA3 rs738409 was inversely associated with total serum cholesterol and low‐density lipoprotein serum levels (P = 0.003 and P = 0.02, respectively). Finally, there was a trend toward an inverse association between the presence of the PNPLA3 rs738409 G allele and significant coronary heart disease. Comparable trends were observed for the transmembrane 6 superfamily member 2 (TM6SF2) 167 K variant, but the sample size was too small to evaluate this rarer variant. Conclusion: The PNPLA3 rs738409 G allele is associated with liver disease but also with a relatively benign cardiovascular risk profile.
Stent insertion is an established technique of endoscopic retrograde cholangiopancreatography (ERCP) to treat symptomatic malignant or benign biliary strictures, and stent placement is accomplished by using the over-the-wire (OTW) method. In some cases, however, it might be challenging and sometimes time consuming to pass a complex biliary stricture with the guidewire. Stent-exchange technique with a guidewire left in place during stent removal might therefore be helpful to guarantee successful and time-sparing interventions.
A simple method is presented to remove the stent with the guidewire left in place, using the OTW stent-exchange method in ERCP. This technique simplifies stent OTW exchange by using a simple endoscopy snare. This article is part of an expert video encyclopedia.
Long-term effects on cirrhosis and portal hypertension of direct antiviral agent (DAA)-based eradication of hepatitis C virus (HCV) are still under debate. We analysed dynamics of liver and spleen elastography to assess potential regression of cirrhosis and portal hypertension 3 years post-treatment. Fifty-four patients with HCV-associated cirrhosis and DAA-induced SVR were included. Liver and spleen stiffness were measured at baseline (BL), end of treatment (EOT), 24 weeks after EOT (FU24) and 1, 2 and 3 (FU144) years post-treatment by transient liver elastography (L-TE) and point shear wave elastography (pSWE) using acoustic radiation force impulse (ARFI) of the liver (L-ARFI) and spleen (S-ARFI). Biochemical, virological and clinical data were also obtained. Liver stiffness assessed by L-TE decreased between BL [median (range), 32.5(9.1–75) kPa] and EOT [21.3(6.7–73.5) kPa; p < .0001] and EOT and FU144 [16(4.1–75) kPa; p = .006]. L-ARFI values improved between EOT [2.5(1.2–4.1) m/s] and FU144 [1.7(0.9–4.1) m/s; p = .001], while spleen stiffness remained unchanged. Overall, L-TE improved in 38 of 54 (70.4%) patients at EOT and 29 of 38 (76.3%) declined further until FU144, whereas L-ARFI values decreased in 30/54 (55.6%) patients at EOT and continued to decrease in 28/30 (93.3%) patients at FU144. Low bilirubin and high albumin levels at BL were associated with improved L-ARFI values (p = .048) at EOT or regression of cirrhosis (<12.5 kPa) by L-TE at FU144 (p = .005), respectively. Liver stiffness, but not spleen stiffness, continued to decline in a considerable proportion of patients with advanced liver disease after HCV eradication.