Impact of patatin-like phospholipase domain containing 3 rs738409 G/G genotype on hepatic decompensation and mortality in patients with portal hypertension.

BACKGROUND: The rs738409 C>G p.I148M variant in the patatin-like phospholipase domain containing 3 (PNPLA3)-gene promotes triglyceride accumulation in hepatocytes and hepatic stellate cell activation and has previously been linked to hepatic steatosis/liver fibrosis. AIM: To investigate its impact on hepatic decompensation and (liver-related) mortality in patients who had already developed portal hypertension. Moreover, we assessed its link with hepatic steatosis as evaluated by controlled attenuation parameter. METHODS: We performed a retrospective analysis in prospectively characterised patients with viral hepatitis/fatty liver disease-induced portal hypertension (hepatic venous pressure gradient [HVPG] ≥ 6 mm Hg) diagnosed at the Medical University of Vienna who underwent HVPG measurement (until 2013; n = 372; longitudinal study) or simultaneous HVPG and controlled attenuation parameter measurement (2014-2017; n = 153; cross-sectional study). RESULTS: While survival was similar between PNPLA3-C/C and -C/G patients, we observed substantially increased mortality in PNPLA3-G/G patients. PNPLA3-G/G had no impact on mortality in the subgroup of patients with viral hepatitis; however, we observed a strong independent association between PNPLA3-G/G and hepatic decompensation (adjusted subdistribution hazard ratio [aSHR]: 2.1, 95% confidence interval [95% CI]: 1.1-4; P = 0.024) as well as mortality (overall: aSHR: 2.2, 95% CI: 1.22-3.98; P = 0.009; liver-related: aSHR: 2.2, 95% CI: 1.08-4.46; P = 0.029) in patients with fatty liver disease. Interestingly, even in the subgroup of patients who had already progressed to clinically significant portal hypertension (HVPG ≥ 10 mm Hg), PNPLA3-G/G substantially increased mortality (aSHR: 2.33, 95% CI: 1.27-4.29; P = 0.006). PNPLA3-genotype had no influence on controlled attenuation parameter or the prevalence of values ≥248 dB/m. CONCLUSION: PNPLA3-G/G-genotype seems to double the risks of hepatic decompensation and (liver-related) mortality in patients with portal hypertension due to fatty liver disease. Further studies are warranted to investigate potential underlying pathophysiological mechanisms unrelated to hepatic steatosis.

A multicentre, open-label, phase-I/randomised phase-II study to evaluate safety, pharmacokinetics, and efficacy of nintedanib vs. sorafenib in European patients with advanced hepatocellular carcinoma.

BACKGROUND: This multicentre, open-label, phase-I/randomised phase-II trial evaluated safety, pharmacokinetics, maximum-tolerated-dose (MTD) per dose-limiting toxicities (DLTs), and efficacy of nintedanib vs. sorafenib in European patients with unresectable advanced hepatocellular carcinoma (aHCC). METHODS: Phase I: Patients were stratified into two groups per baseline aminotransferase/alanine aminotransferase and Child-Pugh score; MTD was determined. Phase II: Patients were randomised 2:1 to nintedanib (MTD) or sorafenib (400-mg bid) in 28-day cycles until intolerance or disease progression. Time-to-progression (TTP, primary endpoint), overall survival (OS) and progression-free survival (PFS) were determined. RESULTS: Phase-I: no DLTs observed; nintedanib MTD in both groups was 200 mg bid. Phase-II: patients (N = 93) were randomised to nintedanib (n = 62) or sorafenib (n = 31); TTP was 5.5 vs. 4.6 months (HR = 1.44 [95% CI, 0.81-2.57]), OS was 11.9 vs. 11.4 months (HR = 0.88 [95% CI, 0.52-1.47]), PFS was 5.3 vs. 3.9 months (HR = 1.35 [95% CI, 0.78-2.34]), respectively (all medians). Dose intensity and tolerability favoured nintedanib. Fewer patients on nintedanib (87.1%) vs. sorafenib (96.8%) had drug-related adverse events (AEs) or grade ≥ 3 AEs (67.7% vs. 90.3%), but more patients on nintedanib (28 [45.2%]) had AEs leading to drug discontinuation than did those on sorafenib (7 [22.6%]). CONCLUSIONS: Nintedanib may have similar efficacy to sorafenib in aHCC.

Carvedilol for reducing portal pressure in primary prophylaxis of variceal bleeding: a dose-response study.

BACKGROUND: Sequential measurements of hepatic venous pressure gradient (HVPG) are used to assess the haemodynamic response to nonselective betablockers (NSBBs) in patients with portal hypertension. AIMS: To assess the rates of HVPG response to different doses of carvedilol. METHODS: Consecutive patients with cirrhosis undergoing HVPG-guided carvedilol therapy for primary prophylaxis of variceal bleeding between 08/2010 and 05/2015 were retrospectively included. After baseline HVPG measurement, carvedilol 6.25 mg/d was administered and HVPG response (HVPG-decrease ≥20% or to ≤12 mm Hg) was assessed after 3-4 weeks. In case of nonresponse, carvedilol dose was increased to 12.5 mg/d and a third HVPG-measurement was performed after 3-4 weeks. We also assessed HVPG-response rates according to the Baveno VI consensus (HVPG decrease ≥10% or to ≤12 mm Hg) and changes in systolic arterial pressure (SAP). RESULTS: Seventy-two patients (Child A, 37%; B, 35%; C, 28%) were included. 28 (39%) patients achieved a HVPG-decrease ≥ 20% with carvedilol 6.25 mg/d and another 10 (14%) with carvedilol 12.5 mg/d. Forty (56%) patients had a HVPG decrease ≥10% with carvedilol 6.25 mg/d and 24 (33%) with carvedilol 12.5 mg/d. Thus, in total, a HVPG-response of ≥20% and ≥10% and was achieved in 38 (53%) and 55 (76%) and of patients respectively. Notably, 6 patients (n = 4 with ascites) did not tolerate an increase to 12.5 mg/d due to hypotension/bradycardia. However, none of the other patients had a SAP < 90 mm Hg at the final HVPG measurement. CONCLUSION: Carvedilol 12.5 mg/d was more effective than 6.25 mg/d in decreasing HVPG in primary prophylaxis. A total of 76% of patients achieved a HVPG-response of ≥ 10% to carvedilol 12.5 mg/d, however, arterial hypotension might occur, especially in patients with ascites.

Hepatitis C: The beginning of the end-key elements for successful European and national strategies to eliminate HCV in Europe.

Hepatitis C virus (HCV) infection is a major public health problem in the European Union (EU). An estimated 5.6 million Europeans are chronically infected with a wide range of variation in prevalence across European Union countries. Although HCV continues to spread as a largely "silent pandemic," its elimination is made possible through the availability of the new antiviral drugs and the implementation of prevention practices. On 17 February 2016, the Hepatitis B & C Public Policy Association held the first EU HCV Policy Summit in Brussels. This summit was an historic event as it was the first high-level conference focusing on the elimination of HCV at the European Union level. The meeting brought together the main stakeholders in the field of HCV: clinicians, patient advocacy groups, representatives of key institutions and regional bodies from across European Union; it served as a platform for one of the most significant disease elimination campaigns in Europe and culminated in the presentation of the HCV Elimination Manifesto, calling for the elimination of HCV in Europe by 2030. The launch of the Elimination Manifesto provides a starting point for action in order to make HCV and its elimination in Europe an explicit public health priority, to ensure that patients, civil society groups and other relevant stakeholders will be directly involved in developing and implementing HCV elimination strategies, to pay particular attention to the links between hepatitis C and social marginalization and to introduce a European Hepatitis Awareness Week.

Betablockers do not increase efficacy of band ligation in primary prophylaxis but they improve survival in secondary prophylaxis of variceal bleeding.

BACKGROUND: Endoscopic band ligation (EBL) is used for primary (PP) and secondary prophylaxis (SP) of variceal bleeding. Current guidelines recommend combined use of non-selective beta-blockers (NSBBs) and EBL for SP, while in PP either NSBB or EBL should be used. AIM: To assess (re-)bleeding rates and mortality in cirrhotic patients receiving EBL for PP or SP for variceal bleeding. METHODS: (Re-)bleeding rates and mortality were retrospectively assessed with and without concomitant NSBB therapy after first EBL in PP and SP. RESULTS: Seven hundred and sixty-six patients with oesophageal varices underwent EBL from 01/2005 to 06/2015. Among the 284 patients undergoing EBL for PP, n = 101 (35.6%) received EBL only, while n = 180 (63.4%) received EBL + NSBBs. In 482 patients on SP, n = 163 (33.8%) received EBL only, while n = 299 (62%) received EBL + NSBBs. In PP, concomitant NSBB therapy neither decreased bleeding rates (log-rank: P = 0.353) nor mortality (log-rank: P = 0.497) as compared to EBL alone. In SP, similar re-bleeding rates were documented in EBL + NSBB vs EBL alone (log-rank: P = 0.247). However, EBL + NSBB resulted in a significantly lower mortality rate (log-rank: P<0.001). A decreased risk of death with EBL + NSBB in SP (hazard ratio, HR: 0.50; P<0.001) but not of rebleeding, transplantation or further decompensation was confirmed by competing risk analysis. Overall NSBB intake reduced 6-months mortality (HR: 0.53, P = 0.008) in SP, which was most pronounced in patients without severe/refractory ascites (HR: 0.37; P = 0.001) but not observed in patients with severe/refractory ascites (HR: 0.80; P = 0.567). CONCLUSIONS: EBL alone seems sufficient for PP of variceal bleeding. In SP, the addition of NSBB to EBL was associated with an improved survival within the first 6 months after EBL.

Von Willebrand factor indicates bacterial translocation, inflammation, and procoagulant imbalance and predicts complications independently of portal hypertension severity.

BACKGROUND: Elevated plasma von Willebrand factor antigen (vWF) has been shown to indicate the presence of clinically significant portal hypertension, and thus, predicts the development of clinical events in patients with cirrhosis. AIM: To investigate the impact of bacterial translocation and inflammation on vWF, as well as the association between vWF and procoagulant imbalance. Moreover, we assessed whether vWF predicts complications of cirrhosis, independent of the severity of portal hypertension. METHODS: Our study population comprised 225 patients with hepatic venous pressure gradient (HVPG) ≥ 10 mm Hg without active bacterial infections or hepatocellular carcinoma. RESULTS: vWF correlated with markers of bacterial translocation (lipopolysaccharide-binding protein [LBP; ρ = 0.201; P = 0.021]), inflammation (interleukin 6 [IL-6; ρ = 0.426; P < 0.001] and C-reactive protein [CRP; ρ = 0.249; P < 0.001]), and procoagulant imbalance (factor VIII/protein C ratio; ρ = 0.507; P < 0.001). Importantly, the associations between vWF and these parameters were independent of HVPG. Moreover, vWF (per 10%) independently predicted variceal bleeding (hazard ratio [HR]: 1.08 [95% confidence interval (95% CI): 1.01-1.16]; P = 0.023), requirement of paracentesis (HR: 1.05 [95% CI: 1.01-1.1]; P = 0.023) and bacterial infections (HR: 1.04 [95% CI: 1-1.09]; P = 0.04) including spontaneous bacterial peritonitis (HR: 1.09 [95% CI: 0.999-1.18]; P = 0.053) on a trend-wise level. After backward elimination, vWF (HR: 1.05 [95% CI: 1.02-1.08]; P = 0.003) and CRP (per 10 mg/L; HR: 1.53 [95% CI: 1.14-2.05]; P = 0.005) remained in the final model for transplant-free mortality. Finally, the independent prognostic value of vWF/CRP groups for mortality was confirmed by competing risk analysis. CONCLUSION: Our results demonstrate that vWF is not only a marker of portal hypertension but also independently linked to bacterial translocation, inflammation and procoagulant imbalance, which might explain its HVPG-independent association with most clinical events. Prognostic groups based on vWF/CRP efficiently discriminate between patients with a poor 5-year survival and patients with a favourable prognosis.

Randomised clinical study: the effects of oral taurine 6g/day vs placebo on portal hypertension.

BACKGROUND: The amino sulphonic acid taurine reduces oxidative endoplasmatic reticulum stress and inhibits hepatic stellate cell activation, which might lead to reduction of portal pressure in cirrhosis. AIM: To assess the haemodynamic effects of taurine supplementation in patients with cirrhosis and varices. METHODS: Patients with hepatic venous pressure gradient (HVPG) ≥12 mm Hg were included in this prospective proof of concept study. Concomitant nonselective beta-blockers therapy was not allowed. Patients received either 4 weeks of oral taurine (6 g/day), or placebo, prior to evaluation of HVPG response. RESULTS: Thirty patients were screened and 22 included in the efficacy analysis (12 taurine/10 placebo; 64% male, mean age: 52 ± 11 years, Child A: 9%, B:64%, C:27%, ascites:68%). In the taurine group, mean HVPG dropped from 20 mm Hg (±4) at baseline to 18 mm Hg (±4) on day 28 (mean relative change: -12%, P = .0093). In the placebo group, mean HVPG increased from 20 mm Hg (±5) at baseline to 21 mm Hg (±5) on day 28 (mean relative change:+2%, P = .4945). Taurine had no significant effects on systemic haemodynamics. Seven of 12 patients (58%) on taurine achieved a HVPG response >10%, compared to none in the placebo group (P = .0053). In a multivariate linear model, HVPG reduction was significantly larger in the taurine group compared to placebo group (P = .0091 and P = .0109 for absolute and relative change respectively). Treatment-related adverse events included gastrointestinal discomfort and fatigue, and were usually mild and comparable between treatment groups. CONCLUSION: Taurine is safe and may reduce portal pressure in cirrhotic patients. More studies on the underlying mechanisms of action and long-term effects of taurine supplementation are warranted.

Interferon-free regimens improve portal hypertension and histological necroinflammation in HIV/HCV patients with advanced liver disease.

BACKGROUND: HIV/HCV co-infected patients show accelerated fibrosis progression and higher risk for complications of portal hypertension (PHT). AIM: To assess the effects of interferon-free therapy on portal pressure, liver histology and plasma biomarkers in HIV/HCV-coinfected patients with PHT. METHODS: Twenty-two patients with paired hepatic venous pressure gradient (HVPG) measurements prior and after successful treatment (SVR) with interferon-free regimens were included. Liver stiffness was assessed by transient elastography and biopsies were scored according to METAVIR. Plasma biomarkers were determined by ELISA. RESULTS: Overall, HVPG decreased from 10.7 ± 4.1 mmHg at baseline to 7.4 ± 4.2 mmHg after HCV treatment (Δ:-3.3 ± 2.7 mmHg; p < 0.001). In patients with clinically significant PHT (HVPG≥10 mmHg, n = 11), HVPG decreased from 14.1 ± 2.9 to 10.4 ± 3.9 mmHg (Δ:-3.7 ± 3.3 mmHg; p = 0.004) and a haemodynamic response (HVPG decrease ≥10%) was observed in 73%. In 64% of patients with subclinical PHT (HVPG 6-9 mmHg, n = 11), portal pressure normalised at SVR. Mean liver stiffness decreased from 20.8 kPa to 11.5 kPa (Δ:-8.8 ± 7.4 kPa; p < 0.001). Fifty percent (7/14) of patients with cirrhosis were re-classified as METAVIR ≤F3 and all patients with decompensated cirrhosis improved their Child-Pugh stage. After successful HCV treatment, 39% still had persistent histological necroinflammatory activity (METAVIR A1), which correlated with less HVPG response and more steatosis. While most biomarkers improved with SVR, METAVIR A1 patients had significantly higher plasma levels of fibrogenic (PDGF, TGF-ß) and angiogenic (VEGF, Angiopoietin1) biomarkers. CONCLUSIONS: Interferon-free therapy reduces PHT and halts histological necroinflammatory activity in the majority of HIV/HCV-coinfected patients after SVR, which may lead to re-compensation of liver function in cirrhosis. Biomarkers could identify patients with persisting hepatic necroinflammation.

Sorafenib with or without everolimus in patients with advanced hepatocellular carcinoma (HCC): a randomized multicenter, multinational phase II trial (SAKK 77/08 and SASL 29).

BACKGROUND: Sorafenib (S), a multitargeted tyrosine kinase inhibitor, is the standard of care for first-line systemic treatment of advanced hepatocellular carcinoma (HCC). Everolimus (E) is a potent inhibitor of mTOR, a pathway frequently activated in HCC. Preclinical data suggest that the combination S + E has additive effects compared with single-agent S. PATIENTS AND METHODS: Patients with unresectable or metastatic HCC and Child-Pugh ≤7 liver dysfunction were randomized to receive daily S 800 mg alone or with E 5 mg until progression or unacceptable toxicity. The primary end point was progression-free survival at 12 weeks (PFS12). The secondary end points included response rate, PFS, time to progression (TTP), overall survival (OS), duration of disease stabilization (DDS), safety, and quality-of-life (QoL) assessments. RESULTS: A total of 106 patients were randomized: 46 patients received S and 60 patients received S + E. Ninety-three patients were assessable for the primary end point and 105 patients for the safety analysis. The PFS12 rate was 70% [95% confidence interval (CI) 54-83] and 68% (95% CI 53-81) in patients randomized to S and S + E, respectively. The RECIST (mRECIST) response rate was 0% (23%) in the S arm and 10% (35%) in the S + E arm. Median PFS (6.6 versus 5.7 months), TTP (7.6 versus 6.3 months), DDS (6.7 versus 6.7 months), and OS (10 versus 12 months) were similar in the S and S + E arms, respectively. Grade 3/4 adverse events occurred in 72% and 86% of patients in arm S and arm S + E, respectively. Patients had similar QoL scores over time, except for a greater worsening in physical well-being and mood in the arm S + E. CONCLUSIONS: No evidence was found that S + E improves the efficacy compared with S alone. Combining 5 mg E with full-dose S is feasible, but more toxic than S alone. Further testing of this drug combination in molecularly unselected HCCs appears unwarranted. CLINICALTRIALSGOV: NCT01005199.

Polymorphisms in EGFR and IL28B are associated with spontaneous clearance in an HCV-infected Iranian population.

Although most hepatitis C virus (HCV)-infected individuals develop chronic infection, about 25% of them are able to clear the virus spontaneously without any therapeutic intervention. The aim of the present study was to identify genes associated with spontaneous HCV clearance in a population of Iranian patients. We genotyped 110 single-nucleotide polymorphisms (SNPs) in 59 selected--candidate--genes in a cohort of 107 HCV-infected participants who spontaneously cleared the infection and 176 participants whose infection persisted. Three out of the 110 SNPs were found to be associated with HCV outcome (P-values<0.03). rs11506105 in EGFR (epidermal growth factor receptor gene), and rs11881222 and rs12979860 in IL28B (interferon-λ3 gene). Multivariate logistic regression of the three markers showed that the A/A genotypes in both rs11506105 (EFGR) and rs11881222 (IL28B), and the C/C genotype in rs12979860 (IL28B) are associated with HCV clearance (recessive model: odds ratio (OR)=2.06, 95% confidence interval (95% CI)=1.09-3.88, P=0.025; OR=2.09, 95% CI=1.23-3.60, P=0.007; and OR=1.95, 95% CI=1.15-3.35, P=0.014 for rs11506105, rs12979860 and rs11881222, respectively). In conclusion, EGFR and IL28B SNPs are strong independent predictive markers of spontaneous viral clearance.

Interferon-free regimens for chronic hepatitis C overcome the effects of portal hypertension on virological responses.

BACKGROUND: Portal hypertension is the strongest predictor of virological response to pegylated interferon (IFN)/ribavirin in patients with chronic hepatitis C (CHC)-related cirrhosis. AIM: To investigate the effects of portal pressure assessed by hepatic venous pressure gradient (HVPG) measurement on virological responses in patients treated with IFN-free regimens outside of clinical trials. METHODS: Fifty-six patients with CHC and cirrhosis who underwent HVPG measurement before starting an IFN-free therapy were retrospectively studied. Patients were treated with sofosbuvir in combination with daclatasvir (n = 32), ribavirin (n = 12) or simeprevir (n = 11), or the combination of simeprevir/daclatasvir (n = 1), for 12-24 weeks. RESULTS: Hepatic venous pressure gradient values ≥10 mmHg and ≥16 mmHg were observed in 41 (73%) and 31 (55%) patients respectively. The distributions of treatment regimens and durations were comparable between patients with or without portal hypertension. Patients with portal hypertension had lower platelet counts and albumin levels, while bilirubin levels, INR, MELD and Child-Pugh scores were higher than in patients without portal hypertension. Importantly, rates of on-treatment virological response and viral kinetics, as well as the rates of sustained virological response 12 weeks after the end of therapy [96% (54/56)] were not affected by portal hypertension. Anti-viral therapy improved liver stiffness, platelet count, serum albumin and bilirubin levels, as well as prothrombin time. CONCLUSIONS: This is the first study to demonstrate that IFN-free regimens overcome the negative effect of portal hypertension on virological responses and viral kinetics. Improvements in liver stiffness and platelet count might reflect an anti-portal hypertensive effect of IFN-free treatments.

Chronic Mesobuthus gibbosus scorpionism related to the sting in vein.

BACKGROUND: A small amount of data is already presented in the relevant literature related to the medical facts of scorpionism caused by Yellow scorpion (Mesobuthus gibbosus: M. gibbosus). Undoubtedly, it is considered as dangerous to human health. This paper presents an unusual case of scorpionism after the sting in vein. CASE REPORT: A 25 year old male was bitten by M. gibbosus. He experienced extremely severe intermittent pain in the right feet, followed by pulsating and glowing sensations, cold sweat and paleness. 15 minutes after the sting, the pain started to spread through the medial side of the leg, up to the inguinal region. Patient became excited, and experienced occasional spasms of leg muscles. A month after, the bitten vein of dorsal arch of the foot and v. sephena magna became non-uniformly tortuously spread through the entire length. On physical examination four years after the sting, the enlargement of the veins still exists, periodical tingling, and occasional muscle twitches during the night. CONCLUSIONS: M. gibbosus is endemic in Mediterranean area and represents a real hazard for local inhabitants and tourists. The medical treatment of this type of scorpionism is exclusively symptomatic.

Evaluation of portal hypertension and varices by acoustic radiation force impulse imaging of the liver compared to transient elastography and AST to platelet ratio index.

BACKGROUND: Acoustic radiation force impulse imaging (ARFI) is a new method of liver stiffness measurement (LSM). The aim was to compare ARFI, transient elastography (TE) and AST to platelet ratio index (APRI) for the noninvasive diagnosis of clinically significant portal hypertension (CSPH, hepatic venous pressure gradient; HVPG ≥ 10 mmHg) and esophageal varices (EV). MATERIALS AND METHODS: LSM via ARFI and TE was performed in 88 consecutive patients with cirrhosis prior to HVPG measurement. The mean liver stiffness for ARFI was calculated out of 5 measurements for each lobe. RESULTS: LSM by TE and ARFI was not successful in 22 (25%) patients and 1 (1 %) patient, respectively, due to ascites or obesity. Both TE (r = 0.765; p < 0.001) and ARFI (r = 0.646; p < 0.001) correlated significantly with HVPG. At the optimal cut-off (16.8 kPa), TE (area under the curve, AUC 0.870) yielded a sensitivity and specificity of 89.7% and 75%, respectively, for predicting CSPH. At the optimal cut-off (2.58 m/s), the sensitivity and specificity for ARFI (AUC 0.855) were 71.4% and 87.5%, respectively. Using an APRI (AUC 0.838), the sensitivity and specificity were 69% and 87.5%, respectively. The AUC for the diagnosis of EV was 0.802 for TE (cut-off: 27.9 kPa), 0.743 for ARFI (cut-off: 2.74 m/s), and 0.805 for APRI (cut-off: 1.90). CONCLUSION: ARFI shows a higher applicability particularly in obese and ascitic patients. All three investigated methods show a high diagnostic accuracy for CSPH. Notably, APRI performed not significantly different compared to ARFI for the diagnosis of CSPH.

Non-invasive evaluation of patients with viral hepatitis.

Liver fibrosis evaluation is essential in patients with chronic viral liver disease with major impact on treatment decisions. Liver biopsy is still considered the "gold-standard", but it is an invasive method, non-totally risk free, not very well accepted by patients, and unsuitable for regular follow-up examinations. In the last 10-15 years, several non-invasive methods for liver fibrosis assessment were developed: serological tests (simple or complex), ultrasound based elastographic methods (which can be classified in shear wave elastography methods and strain elastography methods) and magnetic resonance elastography. Today in clinical practice, ultrasound based elastographic methods are mostly used. From this category of methods, the oldest and more used is transient elastography, which was included also in several guidelines for assessing liver fibrosis in chronic hepatitis B and C patients. Each method has his advantages and weakness and today there is no consensus regarding which method should be considered the best "surrogate" for liver biopsy. Here we will try to give a comprehensive overview about the different techniques and depict the advantages and disadvantages of each of these methods.

Diagnostic workup of primary sclerosing cholangitis: the benefit of adding gadoxetic acid-enhanced T1-weighted magnetic resonance cholangiography to conventional T2-weighted magnetic resonance cholangiography.

AIM: To evaluate the value of gadoxetic acid-enhanced T1-weighted (T1W) magnetic resonance cholangiography (MRC) versus conventional T2-weighted (T2W) MRC compared to endoscopic retrograde cholangiopancreatography (ERCP) in patients with primary sclerosing cholangitis (PSC). MATERIALS AND METHODS: Based on T1W MRC, PSC patients were classified into a regular (RG) and a delayed (DG) excreting group, with an absence of gadoxetic acid in the common bile duct at 20 min. Beading, pruning, and gradation of central bile duct stenosis, evaluated by T1W and T2W MRC, were compared to ERCP. Liver parenchymal enhancement was measured in both study groups and compared to a reference group (n = 20) without a history of liver disease. Two readers performed all measurements. RESULTS: Based on beading and pruning of the peripheral bile ducts, sensitivities, specificities, and accuracies for reader 1 were 0.17/0.43, 0/0.17, and 0.15/0.31 for T1W MRC, and 0.83/0.86, 1/0.83, and 0.85/0.85 for T2W MRC (p = 0.004). For reader 2 sensitivities, specificities, and accuracies were 0.25/0.57, 0/0.33, and 0.23/0.46 for T1W MRC, and 0.92/1, 1/0.83, and 0.92/0.92 for T2W MRC (p = 0.012). Compared to ERCP, central bile duct stenoses were significantly overestimated (p < 0.001) by T2W MRC. A significantly lower parenchymal enhancement was found in the DG (n = 7) compared to the RG (n = 13), and compared to the reference group (p < 0.001). CONCLUSION: The combined performance of T2W and T1W MRC may provide a comprehensive imaging workup of PSC, including morphological and functional information resulting in optimal management.

Von Willebrand Factor as a new marker for non-invasive assessment of liver fibrosis and cirrhosis in patients with chronic hepatitis C.

BACKGROUND: Staging of liver fibrosis in patients with chronic hepatitis C (CHC) is recommended prior to anti-viral therapy. As vWF-Ag was shown as a predictor of portal hypertension, decompensation and mortality in patients with liver cirrhosis, we performed this study to investigate if vWF-Ag is able to predict different fibrosis stages and if it is comparable to other fibrosis scores. AIM: To investigate if vWF-Ag is able to predict different fibrosis stages and if it is comparable to other fibrosis scores. METHODS: We analysed 294 patients with chronic hepatitis C who underwent biopsy. We assessed stage of liver fibrosis according to Metavir, measured vWF-Ag and calculated different fibrosis scores (APRI, FCI, FORNS, FI, Fib-4) and compared them by AUCs. We also calculated a new score: vWF-Ag/thrombocytes (VITRO score) for prediction of fibrosis. RESULTS: vWF-Ag levels were increasing with stage of fibrosis: F0: vWF-Ag was median 136.5%, FI 140.6%, FII 157.5%, FIII 171.0%, FIV 252.0%; P < 0.001. vWF-Ag and VITRO score produced AUCs of 0.7 and 0.72 for ≥F2, comparable to the AUCs of APRI, Fib-4, FORNS with 0.75, 0.65 and 0.64 (P > 0.05). For ≥F3 AUCs were 0.79 and 0.86 for vWF-Ag and VITRO score, comparable with AUCs of 0.79, 0.86 and 0.87 for APRI, Fib-4 and FORNS. Cirrhosis shows AUCs of 0.84 and 0.89 for vWF-Ag and VITRO score, APRI, Fib-4 and FORNS showed similar results with AUCs of 0.82, 0.88 and 0.87. CONCLUSIONS: vWF-Ag and VITRO score offer an easy possibility to evaluate the stage of fibrosis to diagnose subclinical cirrhosis in patients with chronic hepatitis C. Both vWF-Ag and VITRO score show equal performance in comparison to other fibrosis scores assessed in our study.