Evaluation of the "Burgenland PREvention trial of colorectal cancer Disease with ImmunologiCal Testing" (B-PREDICT)-a population-based colorectal cancer screening program.

BACKGROUND: The colorectal cancer (CRC) screening program B-PREDICT is a population based invited two stage screening project using a faecal immunochemical test (FIT) for initial screening followed by a colonoscopy for those with a positive FIT. B-PREDICT was compared with the opportunistic screening colonoscopy (OPP-COL), performed in course of the nationwide screening program. METHODS: Within B-PREDICT all residents of the Austrian federal state Burgenland, aged between 40 and 80 are annually invited to FIT testing. All individuals who underwent initial colonoscopy in Burgenland between 01/2003 and 12/2014, were included in this study. Individuals from the FIT-triggered invited screening program B-PREDICT were compared with those from the non-FIT triggered OPP-COL. RESULTS: 15 133 individuals from B-PREDICT were compared to 10 045 individuals with OPP-COL. CRC detection rates were 1.34% (CI-95%, [1.15; 1.52]) in B-PREDICT compared to 0.54% in OPP-COL (95%-CI, [0.39; 0.68] p < 0.001). The decrease in the age standardized incidence rates of CRC was more pronounced in the population screened with FIT than in the general population screened with colonoscopy. Changes in incidence rates per year were -4.4% (95%-CI, [-5.1; -3.7]) vs. -1.8% (95%-CI, [-1.9; -1.6] p < 0.001). CONCLUSIONS: B-PREDICT shows a two-fold higher detection rate of CRC as well as HRA compared to OPP-COL.

Predicting survival in patients with 'non-high-risk' acute variceal bleeding receiving ß-blockers+ligation to prevent re-bleeding.

BACKGROUND & AIMS: Pre-emptive transjugular intrahepatic portosystemic shunt (TIPS) is the treatment of choice for high-risk acute variceal bleeding (AVB; i.e., Child-Turcotte-Pugh [CTP] B8-9+active bleeding/C10-13). Nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation for secondary prophylaxis. We investigated prognostic factors for re-bleeding and mortality in 'non-high-risk' AVB to identify subgroups who may benefit from more potent treatments (i.e., TIPS) to prevent further decompensation and mortality. METHODS: A total of 2,225 adults with cirrhosis and variceal bleeding were prospectively recruited at 34 centres between 2011-2015; for the purpose of this study, case definitions and information on prognostic indicators at index AVB and on day 5 were further refined in low-risk patients, of whom 581 (without failure to control bleeding or contraindications to TIPS) who were managed by non-selective beta-blockers/endoscopic variceal ligation, were finally included. Patients were followed for 1 year. RESULTS: Overall, 90 patients (15%) re-bled and 70 (12%) patients died during follow-up. Using clinical routine data, no meaningful predictors of re-bleeding were identified. However, re-bleeding (included as a time-dependent co-variable) increased mortality, even after accounting for differences in patient characteristics (adjusted cause-specific hazard ratio: 2.57; 95% CI 1.43-4.62; p = 0.002). A nomogram including CTP, creatinine, and sodium measured at baseline accurately (concordance: 0.752) stratified the risk of death. CONCLUSION: The majority of 'non-high-risk' patients with AVB have an excellent prognosis, if treated according to current recommendations. However, about one-fifth of patients, i.e. those with CTP ≥8 and/or high creatinine levels or hyponatremia, have a considerable risk of death within 1 year of the index bleed. Future clinical trials should investigate whether elective TIPS placement reduces mortality in these patients. IMPACT AND IMPLICATIONS: Pre-emptive transjugular intrahepatic portosystemic shunt placement improves outcomes in high-risk acute variceal bleeding; nevertheless, some 'non-high-risk' patients have poor outcomes despite the combination of non-selective beta-blockers and endoscopic variceal ligation. This is the first large-scale study investigating prognostic factors for re-bleeding and mortality in 'non-high-risk' acute variceal bleeding. While no clinically meaningful predictors were identified for re-bleeding, we developed a nomogram integrating baseline Child-Turcotte-Pugh score, creatinine, and sodium to stratify mortality risk. Our study paves the way for future clinical trials evaluating whether elective transjugular intrahepatic portosystemic shunt placement improves outcomes in presumably 'non-high-risk' patients who are identified as being at increased risk of death.

Hepatic encephalopathy is not a contraindication to pre-emptive TIPS in high-risk patients with cirrhosis with variceal bleeding.

BACKGROUND: A pre-emptive transjugular intrahepatic portosystemic shunt (pTIPS) reduces mortality in high-risk patients with cirrhosis (Child-Pugh C/B+active bleeding) with acute variceal bleeding (AVB). Real-life studies point out that <15% of patients eligible for pTIPS ultimately undergo transjugular intrahepatic portosystemic shunt (TIPS) due to concerns about hepatic encephalopathy (HE). The outcome of patients undergoing pTIPS with HE is unknown. We aimed to (1) assess the prevalence of HE in patients with AVB; (2) evaluate the outcome of patients presenting HE at admission after pTIPS; and (3) determine if HE at admission is a risk factor for death and post-TIPS HE. PATIENTS AND METHODS: This is an observational study including 2138 patients from 34 centres between October 2011 and May 2015. Placement of pTIPS was based on individual centre policy. Patients were followed up to 1 year, death or liver transplantation. RESULTS: 671 of 2138 patients were considered at high risk, 66 received pTIPS and 605 endoscopic+drug treatment. At admission, HE was significantly more frequent in high-risk than in low-risk patients (39.2% vs 10.6%, p<0.001). In high-risk patients with HE at admission, pTIPS was associated with a lower 1-year mortality than endoscopic+drug (HR 0.374, 95% CI 0.166 to 0.845, p=0.0181). The incidence of HE was not different between patients treated with pTIPS and endoscopic+drug (38.2% vs 38.7%, p=0.9721), even in patients with HE at admission (56.4% vs 58.7%, p=0.4594). Age >56, shock, Model for End-Stage Liver Disease score >15, endoscopic+drug treatment and HE at admission were independent factors of death in high-risk patients. CONCLUSION: pTIPS is associated with better survival than endoscopic treatment in high-risk patients with cirrhosis with variceal bleeding displaying HE at admission.

Bacterial infections in patients with acute variceal bleeding in the era of antibiotic prophylaxis.

BACKGROUND & AIMS: Antibiotic prophylaxis reduces the risk of infection and mortality in patients with cirrhosis and acute variceal bleeding (AVB). This study examines the incidence of, and risk factors for, bacterial infections during hospitalization in patients with AVB on antibiotic prophylaxis. METHODS: A post hoc analysis was performed using the database of an international, multicenter, observational study designed to examine the role of pre-emptive transjugular intrahepatic portosystemic shunts in patients with cirrhosis and AVB. Data were collected on patients with cirrhosis hospitalized for AVB (n = 2,138) from a prospective cohort (October 2013-May 2015) at 34 referral centers, and a retrospective cohort (October 2011-September 2013) at 19 of these centers. The primary outcome was incidence of bacterial infection during hospitalization. RESULTS: A total of 1,656 patients out of 1,770 (93.6%) received antibiotic prophylaxis; third-generation cephalosporins (76.2%) and quinolones (19.0%) were used most frequently. Of the patients on antibiotic prophylaxis, 320 patients developed bacterial infection during hospitalization. Respiratory infection accounted for 43.6% of infections and for 49.7% of infected patients, and occurred early after admission (median 3 days, IQR 1-6). On multivariate analysis, respiratory infection was independently associated with Child-Pugh C (odds ratio [OR] 3.1; 95% CI 1.4-6.7), grade III-IV encephalopathy (OR 2.8; 95% CI 1.8-4.4), orotracheal intubation for endoscopy (OR 2.6; 95% CI 1.8-3.8), nasogastric tube placement (OR 1.7; 95% CI 1.2-2.4) or esophageal balloon tamponade (OR 2.4; 95% CI 1.2-4.9). CONCLUSION: Bacterial infections develop in almost one-fifth of patients with AVB despite antibiotic prophylaxis. Respiratory infection is the most frequent, is an early event after admission, and is associated with advanced liver failure, severe hepatic encephalopathy and use of nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade. LAY SUMMARY: Bacterial infections develop during hospitalization in close to 20% of patients with acute variceal bleeding despite antibiotic prophylaxis. Respiratory bacterial infections are the most frequent and occur early after admission. Respiratory infection is associated with advanced liver disease, severe hepatic encephalopathy and a need for a nasogastric tube, orotracheal intubation for endoscopy or esophageal balloon tamponade.

Perceptions on the management of varices and on the use of albumin in patients with cirrhosis among GI specialists in Austria.

BACKGROUND: Portal hypertension (PH) causes severe complications in patients with liver cirrhosis, such as variceal bleeding and ascites; however, data on the knowledge and perceptions on guideline recommendations for the management of varices and the use of albumin is scarce. METHODS: We designed two structured surveys on (i) the management of varices and (ii) the use of albumin for Austrian physicians of specialized Gastro-Intestinal (GI) centers. The interviewed physicians were confronted spontaneously and provided ad hoc responses to the questionnaire. RESULTS: In total, 158 surveys were completed. Interestingly, many specialists (30%) would recommend a follow-up gastroscopy after 1 year in patients with compensated cirrhosis without varices (i.e., overtreatment). For small varices, 81.5% would use non-selective beta blockers (NSBB) for primary prophylaxis (PP). For PP in patients with large varices, endoscopic band ligation (EBL) plus NSBB was preferred by 51.4% (i.e., overtreatment). Knowledge on the indication criteria for early TIPS (transjugular intrahepatic portosystemic shunt) was reported by 54.3%, but only 20% could report these criteria correctly. The majority (87.1%) correctly indicated a preference to use NSBB and EBL for secondary prophylaxis (SP). The majority of participating gastroenterologists reported no restrictions on the use of albumin (89.8%) in their hospitals. Of the interviewed specialists, 63.6% would use albumin in patients with SBP; however, only 11.4% would use the doses recommended by guidelines. The majority of specialists indicated using albumin at the recommended doses for hepatorenal syndrome (HRS-AKI, 86.4%) and for large volume paracentesis (LVP, 73.3%). The individual responses regarding albumin use for infections/sepsis, hyponatremia, renal impairment, and encephalopathy were heterogeneous. CONCLUSION: The reported management of PH and varices is mostly adherent to guidelines, but endoscopic surveillance in patients without varices is too intense and EBL is overused in the setting of PP. Knowledge on the correct use of early TIPS must be improved among Austrian specialists. Albumin use is widely unrestricted in Austria; however, albumin is often underdosed in established indications.

Anemia and iron deficiency in compensated and decompensated cirrhosis: Prevalence and impact on clinical outcomes.

BACKGROUND AND AIM: Iron deficiency anemia (IDA)is the leading cause of anemia worldwide. Data on prevalence and clinical impact of anemia in cirrhosis are scarce. Aim was to report on the following:(i) prevalence of anemia and IDA in cirrhosis and (ii) its possible impact on clinical outcomes. METHODS: Consecutive cirrhotic patients from a prospective registry study were included. Anemia was defined as hemoglobin concentration ≤ 12 g/dL. IDA was defined as Hb ≤ 12 g/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 1244 patients was used to validate our findings. RESULTS: Two hundred forty-two 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 Child-Pugh Score (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. Model for End-Stage Liver Disease (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-IDA vs 12 [7-23] IDA; P < 0.001) and within anemic patients IDA was more common in patients with MELD <15 (58%) versus >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 in the 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.

The von Willebrand Factor antigen to platelet ratio (VITRO) score predicts hepatic decompensation and mortality in cirrhosis.

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.

The value of different CT-based methods for diagnosing low muscle mass and predicting mortality in patients with cirrhosis.

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.

Transjugular aspiration liver biopsy performed by hepatologists trained in HVPG measurements is safe and provides important diagnostic information.

BACKGROUND: Transjugular liver biopsy (TJLB) represents an alternative to percutaneous liver biopsy especially in patients with impaired coagulation and ascites. AIMS: To describe safety and diagnostic yield of aspiration TJLB performed by hepatologists experienced in hepatic venous pressure gradient (HVPG) measurements. METHODS: 445 TJLB of 399 patients between 01/2007-12/2016 were retrospectively assessed. RESULTS: Histological diagnosis was obtained in 423 (95.1%) biopsies - including 11 (100%) patients with acute liver failure and 34 (97.1%) patients after liver transplantation. A median number of 5 portal tracts (interquartile range:2-9) was obtained. HVPG negatively correlated with sample length (Spearman ρ = -0.310; p < 0.001) and number of portal tracts (ρ = -0.212; p < 0.001). Among n = 151 patients with unknown etiology of liver disease, etiology was successfully identified on liver histology in 126 patients (83.4%). Complications occurred in 28 biopsies (6.3%) including 25 (5.6%) minor and 3 (0.7%) major complications. No deaths due to TJLB were observed. Neither the presence of ascites (6.6% complications) nor of coagulopathy (platelets<50G/L and/or prothrombin time<50%; 4.8% complications) increased the risk for complications. CONCLUSIONS: TJLB performed by hepatologists experienced in HVPG measurements is safe - even in patients with ascites or coagulopathy. TJLB has good diagnostic value for histological evaluation of liver disease and acute liver failure.

Dysbalanced sex hormone status is an independent predictor of decompensation and mortality in patients with liver cirrhosis.

AIMS: Endocrinological abnormalities, including low testosterone levels, are prevalent in cirrhosis. We assessed sexual hormone status in regard to hemodynamic abnormalities and its impact on hepatic decompensation and survival. METHODS: Males with cirrhosis were prospectively included in this study since 2010. Sexual hormones including bioavailable testosterone, total testosterone, luteinizing hormone, follicle-stimulating hormone, prolactin, and sex hormone-binding globulin as well as Child-Pugh score, Model for End-stage Liver Disease (MELD) score, and hepatic venous pressure gradient were recorded. Sarcopenia was also assessed in patients with available computed tomography scans. Clinical follow-up for hepatic decompensation, liver transplantation, and death was recorded until May 2017. RESULTS: One hundred fourteen male cirrhotic patients were included: age 55 ± 9.4 years, MELD 13.5 (range, 7-20.7). Etiologies were alcoholic liver disease in 61(53.5%) patients, viral in 30 (26.3%) patients, and other in 23 (20.2%). Child-Pugh scores were A in 32 (28.1%) patients, B in 48 (42.1%), and C in 34 (29.8%). Levels of bioavailable testosterone and total testosterone decreased with advanced Child-Pugh score (P < 0.001 and P < 0.001) whereas prolactin increased (P = 0.002). Median bioavailable testosterone (0.8 ng/mL [0.1-2] vs. 1.68 ng/mL [0.07-2.65]; P = 0.004) and total testosterone (2.7 ng/mL [0.23-12.34] vs. 7 ng/mL [0.25-10]; P = 0.041) levels were lower in patients with severe portal hypertension (hepatic venous pressure gradient >12 mmHg). Median bioavailable testosterone (0.25 ng/mL [0.07-1.7] vs. 0.97 ng/mL [0.15-2.74)]; P = 0.017) and total testosterone levels (1.28 ng/mL [0.25-7.32] vs. 4.32 ng/mL [0.43-13.47]; P = 0.031) were significantly lower in sarcopenic patients. Median follow-up was 13 months (0.2-75 months) and liver-related events were recorded in 46 patients (40.4%; death, 31 [27.2%]). Low total testosterone was associated with an increased risk for hepatic decompensation and/or death, even after adjusting for Child-Pugh score, MELD, and other relevant factors (Child-Pugh score model: hazard ratio 2.503, 95% confidence interval, 1.214-5.157, P = 0.013; MELD model: hazard ratio 3.065, 95% confidence interval, 1.523-6.169, P = 0.002). CONCLUSION: In parallel to increasing severity of cirrhosis, levels of testosterone decline whereas prolactin levels increase. However, low testosterone levels are independently associated with a higher risk for hepatic decompensation and mortality.

Erectile dysfunction in cirrhosis is impacted by liver dysfunction, portal hypertension, diabetes and arterial hypertension.

BACKGROUND: Although several risk factors for erectile dysfunction may be present in patients with cirrhosis, data on the actual prevalence and cause of erectile dysfunction is limited. The International Index of Erectile Function-5 (IIEF-5) is a well-validated survey to determine the presence and severity of erectile dysfunction in men. We assessed (i) the prevalence and severity of erectile dysfunction, and (ii) risk factors for erectile dysfunction in patients with cirrhosis. METHODS: In this prospective study, erectile dysfunction was defined as: absent (>21 IIEF-5-points), mild (12-21) and severe (5-11). Patients with overt hepatic encephalopathy, active alcohol abuse, extrahepatic malignancy, previous urologic surgery, previous liver transplantation and severe cardiac conditions were excluded. RESULTS: Among n = 151 screened patients, n = 41 met exclusion criteria and n = 30 were sexually inactive. Thus, a final number of n = 80 male patients with cirrhosis were included. Patient characteristics: age: 53 ± 9 years; model for end-stage liver disease score (MELD): 12.7 ± 3.9; Child-Pugh score (CPS) A: 30 (37.5%), B: 35 (43.8%), C: 15 (18.7%); alcohol: 38 (47.5%), viral: 25 (31.3%), alcohol/viral: 7 (8.8%) and others: 10 (12.5%). The presence of erectile dysfunction was found in 51 (63.8%) patients with 44 (55%) and 7 (8.8%) suffering from mild-to-moderate and moderate-to-severe erectile dysfunction. Mean MELD and hepatic venous pressure gradient (HVPG) were significantly higher in patients with erectile dysfunction (P = .021; P = .028). Child-Pugh score C, MELD, creatinine, age, arterial hypertension, diabetes, low libido, low testosterone and high HVPG were associated with the presence of erectile dysfunction. Interestingly, beta-blocker therapy was not associated with an increased risk. In multivariate models, arterial hypertension (OR: 6.36 [1.16-34.85]; P = .033), diabetes (OR: 7.40 [1.31-41.75]; P = .023), MELD (OR: 1.19 [1.03-1.36]; P = .015) and increasing HVPG (n = 48; OR: 1.11 [1.002-1.23]; P = .045) were independent risk factors for the presence of erectile dysfunction. CONCLUSION: About two-thirds of male patients with cirrhosis show erectile dysfunction. Severity of liver dysfunction, portal hypertension, arterial hypertension and diabetes were identified as risk factors for erectile dysfunction.

Follow-up of sustained virological responders with hepatitis C and advanced liver disease after interferon/ribavirin-free treatment.

BACKGROUND: The introduction of direct-acting antivirals (DAA) has increased sustained virological response (SVR) rates in patients with advanced liver disease and chronic hepatitis C(CHC)infection. At present, data on clinical outcome and long-term durability of viral eradication after successful DAA therapy are scarce. AIM: To evaluate the long-term success of viral eradication in patients with advanced fibrosis or cirrhosis treated with DAAs. METHODS: Five hundred and fifty-one patients with advanced fibrosis (n = 158) or cirrhosis (CPS-A:317,CPS-B/C:76) and SVR after interferon and ribavirin-free DAA therapy treated between October 2013 and April 2016 were studied with a median follow-up of 65.6 (13.0-155.3) weeks. Only patients without hepatocellular carcinoma (HCC) at baseline and without liver transplantation were included. RESULTS: Twelve patients (2.2%) died during follow-up: the mortality rate was 0.6% in F3, 2.2% in CPS-A and 5.3% in CPS-B/C patients (P = .08). During follow-up 36 patients with cirrhosis (9.1%) developed a liver related event, including 16 with de-novo HCC (4.1%). Seven patients were transplanted at a median of 9.7 (range 3.8-21.7) months after EOT. History of decompensation was significantly associated with liver related events during follow-up (HR 7.9; 95% CI 2.7-22.6; P < .001), and with mortality (HR 5.5; 95% CI 1.5-20.2, P = .01). CONCLUSIONS: Eradication of HCV by DAA therapy was durable irrespective of the DAA combination used. Most of the cured patients had an excellent long-term clinical prognosis. Nevertheless, the risk of new occurrence of HCC remains worrisome and thus regular surveillance is obligatory even after clinical stabilization and improvement of the patient.

Plasma renin concentration represents an independent risk factor for mortality and is associated with liver dysfunction in patients with cirrhosis.

BACKGROUND AND AIM: Plasma renin concentration (PRC) is increased in patients with cirrhosis. The aims of this study were to evaluate the relation of PRC to (i) portal hypertension, (ii) degree of liver dysfunction, and (iii) survival. METHODS: Plasma renin concentration (range 2.8-39.9 µU/mL) was measured after 30 min in supine position. Also, hepatic venous pressure gradient (HVPG), Child-Pugh (CPS), model for end-stage liver disease scores and transient elastography values (TE, Fibroscan) were evaluated at this time. Mortality was recorded during follow-up. RESULTS: One hundred fifty cirrhotic patients (age 55 ± 11 years; 73% male; CPS A 41.3%/B 41.3%/C 17.3%) were included. Mean HVPG was 16.6 ± 6.5 mmHg. Median PRC according to CPS was A 15.45 µU/mL (95%CI 1.56-261.5), B 37.3 µU/mL (95%CI 4.29-1317.65), and C 175.3 µU/mL (95%CI 5.3-5684; P < 0.001). In patients with clinical significant portal hypertension (HVPG ≥ 10 mmHg, n = 123) median PRC was 31.2 µU/mL (95%CI 2.76-1345.4), in those without was 13.7 µU/mL (95%CI 2.7-428.2; P = 0.009). Significantly higher TE values (33.2 [13-75] vs 59.65 kPa [14.5-75]; P = 0.014) were found in patients with elevated PRC. Median follow up was 711 days (95%CI 24-1152). Twenty-two (36.1%) of the 61 patients with elevated PRC and 11 of the 89 (12.4%) with normal PRC died (P = 0.001). Median PRC was significantly higher in patients that died (83.6 µU/mL [3.39-4451.9] vs 21.5 µU/mL [2.6-1197.9]; P = 0.001). Elevated PRC (P = 0.005; HR 3.36; 95%CI 1.46-7.85), hepatocellular carcinoma (P < 0.001; HR 10.68; 95%CI 3.64-31.3), CPS B (P = 0.013; HR 3.69; 95%CI 1.31-10.4) and CPS C (P = 0.008; HR 5.36; 95%CI 1.54-18.62) emerged as independent risk factors for mortality. CONCLUSIONS: In cirrhotic patients PRC correlates with the severity of portal hypertension and liver dysfunction. Moreover, elevated PRC represents an independent risk factor for mortality.

Low 25-OH-vitamin D levels reflect hepatic dysfunction and are associated with mortality in patients with liver cirrhosis.

BACKGROUND AND AIMS: Vitamin D deficiency is frequent in patients with cirrhosis. The aims of this study were to evaluate the relation of vitamin D status to portal hypertension, degree of liver dysfunction and survival. METHODS: Patients with cirrhosis who have been tested for 25-OH-vitamin D levels were retrospectively included. Vitamin D deficiency was defined as 25-OH-vitamin D levels <10 ng/ml. Child-Pugh score, model for end-stage liver disease (MELD) and available hepatic venous pressure gradient (HVPG) were recorded. Mortality was documented during follow-up. RESULTS: A total of 199 patients were included. Prevalence of vitamin D deficiency (<10 ng/ml) was 40% (79/199), with 14% in Child-Pugh stage A, 39% in Child-Pugh stage B and 47% in Child-Pugh stage C (p = 0.001). Vitamin D deficiency was more common in patients with clinically significant portal hypertension (CSPH, HVPG ≥ 10 mm Hg) than in patients without (43.5% vs. 24.4%, p = 0.025). Significantly more deaths were observed in patients with vitamin D deficiency (32.9%, 26/79 vs. 13.3%, 16/120; p = 0.001). COX regression found presence of hepatocellular carcinoma (p < 0.001; HR: 5.763 95%CI:2.183-15.213), presence of CSPH (p = 0.026; HR: 5.487 95%CI: 1.226-24.55) and Child-Pugh stage C (p = 0.003; HR:5.429 95%CI: 1.771-16.638) as independent risk factors for mortality. Furthermore we could show a tendency towards group vitamin D deficiency being an independent risk factor (p = 0.060; HR: 1.86 95%CI:0.974-3.552). CONCLUSIONS: Vitamin D levels progressively decrease in more advanced Child stages and in patients with increasing HVPG. Vitamin D deficiency might be a valuable predictor of mortality in cirrhosis.

Endoscopic versus surgical management of biliary complications - Outcome analysis after 1188 orthotopic liver transplantations.

BACKGROUND AND AIM: After liver transplantation, the endoscopic approach has become the standard treatment modality for biliary complications. Aim of this study was to compare primary endoscopic with primary surgical management. PATIENTS AND METHODS: A retrospective review on 1188 consecutive liver transplant patients between 1989 and 2009 was performed. Management strategies (endoscopic, surgical or combined approach) were evaluated for treatment success as well as patient survival. RESULTS: Biliary complications after liver transplantation were diagnosed in 211 (18%) patients. Initial endoscopic approach (N=162, 77%) was successful in 97 of 162 (60%) patients. In 80% of patients, success was achieved within a median of four ERCPs. Sixty-one patients (38%) were referred to surgery after non-successful ERCP. Initial surgical approach was performed in 49/211 patients (23%) with successful management in 38/49 (78%) of patients. Patients presenting with intraluminal objects needed a significantly higher number of ERCPs to reach treatment success (median 3 versus 2 interventions, p=0.001) but had an equal endoscopic success rate (p=0.427). Patients with successful endoscopic treatment showed lower mortality compared to patients with primary surgical treatment (p=0.029). CONCLUSIONS: Endoscopic management should be considered as the primary approach for biliary complications after liver transplantation.

Sustained virologic response to interferon-free therapies ameliorates HCV-induced portal hypertension.

BACKGROUND & AIMS: We aimed to investigate the impact of sustained virologic response (SVR) to interferon (IFN)-free therapies on portal hypertension in patients with paired hepatic venous pressure gradient (HVPG) measurements. METHODS: One hundred and four patients with portal hypertension (HVPG ⩾6mmHg) who underwent HVPG and liver stiffness measurement before IFN-free therapy (baseline [BL]) were retrospectively studied. Among 100 patients who achieved SVR, 60 patients underwent HVPG and transient elastography (TE) after antiviral therapy (follow-up [FU]). RESULTS: SVR to IFN-free therapies significantly decreased HVPG across all BL HVPG strata: 6-9mmHg (BL: 7.37±0.28 vs. FU: 5.11±0.38mmHg; -2.26±0.42mmHg; p<0.001), 10-15mmHg (BL: 12.2±0.4 vs. FU: 8.91±0.62mmHg; -3.29±0.59mmHg; p<0.001) and ⩾16mmHg (BL: 19.4±0.73 vs. FU: 17.1±1.21mmHg; -2.3±0.89mmHg; p=0.018). In the subgroup of patients with BL HVPG of 6-9mmHg, HVPG normalized (<6mmHg) in 63% (12/19) of patients, while no patient progressed to ⩾10mmHg. Among patients with BL HVPG ⩾10mmHg, a clinically relevant HVPG decrease ⩾10% was observed in 63% (26/41); 24% (10/41) had a FU HVPG <10mmHg. Patients with Child-Pugh stage B were less likely to have a HVPG decrease (hazard ratio [HR]: 0.103; 95% confidence interval [CI]: 0.02-0.514; p=0.006), when compared to Child-Pugh A patients. In the subgroup of patients with BL CSPH, the relative change in liver stiffness (per %; HR: 0.972; 95% CI: 0.945-0.999; p=0.044) was a predictor of a HVPG decrease ⩾10%. The area under the receiver operating characteristic curve for the diagnosis of FU CSPH by FU liver stiffness was 0.931 (95% CI: 0.865-0.997). CONCLUSIONS: SVR to IFN-free therapies might ameliorate portal hypertension across all BL HVPG strata. However, changes in HVPG seemed to be more heterogeneous among patients with BL HVPG of ⩾16mmHg and a HVPG decrease was less likely in patients with more advanced liver dysfunction. TE might be useful for the non-invasive evaluation of portal hypertension after SVR. LAY SUMMARY: We investigated the impact of curing hepatitis C using novel interferon-free treatments on portal hypertension, which drives the development of liver-related complications and mortality. Cure of hepatitis C decreased portal pressure, but a decrease was less likely among patients with more pronounced hepatic dysfunction. Transient elastography, which is commonly used for the non-invasive staging of liver disease, might identify patients without clinically significant portal hypertension after successful treatment.

Liver transplantation reverses hypergammaglobulinemia in patients with chronic hepatic failure.

INTRODUCTION: Sparse data are available about the effect of therapy methods on antibody levels in patients with liver failure. The aim of this study was to determine serum immunoglobulin concentrations in patients with chronic hepatic failure (CHF), acute- (ALF), or acute-on-chronic liver failure (ACLF) and to evaluate the impact of MARS treatment or liver transplantation (LT) on antibody levels. MATERIALS AND METHODS: We followed ten patients with ALF, twelve with ACLF and 18 with CHF. Eight patients with ALF and seven with ACLF underwent MARS therapy, whereas the rest received LT. 13 healthy volunteers served as controls. Serum antibody concentrations were measured using ELISA-technique. RESULTS: Median serum levels of IgA, IgG and IgM were significantly increased in patients with CHF compared to ALF or controls (P<0.02, P<0.01, and P<0.01). IgM and IgG concentrations were also significantly elevated in patients with CHF compared to ACLF (IgM, 3.7 vs. 1 g/L, P<0.001; IgG, 8.7 vs. 3.1 g/L, P=0.004). Immediately after LT a significant decrease of IgA (6.9 vs. 3.1 g/L, P=0.004), IgG (8.7 vs. 5.1 g/L, P=0.02) and IgM (3.7 vs. 1.8 g/L, P=0.001) was detected in patients with CHF and antibody levels further decreased the days after LT reaching levels comparable to healthy individuals. MARS treatment had no apparent effect on the immunoglobulin profile in patients with ALF or ACLF. CONCLUSION: We provide evidence that LT reverses hypergammaglobulinemia in patients suffering from CHF within one day, which could be explained to a reconstituted hepatic antibody clearance, whereas MARS treatment has no immediate effect on immunoglobulin levels.

Performance of 2-D shear wave elastography in liver fibrosis assessment compared with serologic tests and transient elastography in clinical routine.

Liver stiffness values assessed with 2-D shear wave elastography (SWE), transient elastography (TE) and simple serologic tests were compared with respect to non-invasive assessment in a cohort of 127 consecutive patients with chronic liver diseases. The rate of reliable liver stiffness measurements was significantly higher with 2-D SWE than with TE: 99.2% versus 74.8%, p < 0.0001 (different reliability criteria used, according to current recommendations). In univariate analysis, liver stiffness measured with 2-D SWE correlated best with fibrosis stage estimated with TE (r = 0.699, p < 0.0001), followed by Forns score (r = 0.534, p < 0.0001) and King's score (r = 0.512, p < 0.0001). However, in multivariate analysis, only 2-D SWE-measured values remained correlated with fibrosis stage (p < 0.0001). The optimal 2-D SWE cutoff values for predicting significant fibrosis were 8.03 kPa for fibrosis stage ≥2 (area under the receiver operating characteristic curve = 0.832) and 13.1 kPa for fibrosis stage 4 (area under the receiver operating characteristic curve = 0.915), respectively. In conclusion, 2-D SWE can be used to obtain reliable liver stiffness measurements in almost all patients and performs very well in predicting the presence of liver cirrhosis.

Evaluation of a new balloon occlusion catheter specifically designed for measurement of hepatic venous pressure gradient.

BACKGROUND & AIMS: Despite the important clinical value of hepatic venous pressure gradient (HVPG) and its increasing use, no specific balloon occlusion catheters have been designed to cannulate liver veins. The aim of the study was to evaluate the clinical applicability of a novel balloon (NC) occlusion catheter specifically designed for HVPG measurement. METHODS: Comparison of a new CE-certified 7 French balloon occlusion catheter with a 150° angled tip and radiopaque markers (NC, Pejcl Medizintechnik, Austria), to a commonly used straight balloon catheter (SC; Boston Scientific, USA). Successful liver vein cannulation rate, need for extra equipment and total fluoroscopy time were recorded. Experts (>200) and novices (<20) in HVPG measurements were evaluated separately. RESULTS: 566 HVPG measurements taken by 11 investigators (five experts and six novices) were analysed. Overall, HVPG could be successfully measured in 98.7% of cases. The rate of successful liver vein cannulation at first attempt was significantly higher among experts when compared to novices (87.3% vs 67.3%, P < 0.001). Moreover, the rate of successful liver vein cannulation without need for any additional equipment was higher when using the NC, both among experts (NC:91.9% vs SC:80.6%, P = 0.03) and novices (NC:73.3% vs SC:50.7%, P = 0.001). The mean fluoroscopy time needed to cannulate the hepatic vein was significantly shorter in experts as compared to novices [2.37(0.10-26) vs 5.2(0.6-30.2] min, P < 0.0001), but not significantly different between catheters. CONCLUSIONS: Both novices and experts achieve higher liver vein cannulation rates using the new specifically designed catheter. The use of the novel catheter might increase rates of successful liver vein cannulation and reduce the need for additional equipment, especially in novices.