Inhibition of the renal apical sodium dependent bile acid transporter prevents cholemic nephropathy in mice with obstructive cholestasis.

BACKGROUND & AIMS: Cholemic nephropathy (CN) is a severe complication of cholestatic liver diseases for which there is no specific treatment. We revisited its pathophysiology with the aim of identifying novel therapeutic strategies. METHODS: Cholestasis was induced by bile duct ligation (BDL) in mice. Bile flux in kidneys and livers was visualized by intravital imaging, supported by MALDI mass spectrometry imaging and liquid chromatography-tandem mass spectrometry. The effect of AS0369, a systemically bioavailable apical sodium-dependent bile acid transporter (ASBT) inhibitor, was evaluated by intravital imaging, RNA-sequencing, histological, blood, and urine analyses. Translational relevance was assessed in kidney biopsies from patients with CN, mice with a humanized bile acid (BA) spectrum, and via analysis of serum BAs and KIM-1 (kidney injury molecule 1) in patients with liver disease and hyperbilirubinemia. RESULTS: Proximal tubular epithelial cells (TECs) reabsorbed and enriched BAs, leading to oxidative stress and death of proximal TECs, casts in distal tubules and collecting ducts, peritubular capillary leakiness, and glomerular cysts. Renal ASBT inhibition by AS0369 blocked BA uptake into TECs and prevented kidney injury up to 6 weeks after BDL. Similar results were obtained in mice with humanized BA composition. In patients with advanced liver disease, serum BAs were the main determinant of KIM-1 levels. ASBT expression in TECs was preserved in biopsies from patients with CN, further highlighting the translational potential of targeting ASBT to treat CN. CONCLUSIONS: BA enrichment in proximal TECs followed by oxidative stress and cell death is a key early event in CN. Inhibiting renal ASBT and consequently BA enrichment in TECs prevents CN and systemically decreases BA concentrations. IMPACT AND IMPLICATIONS: Cholemic nephropathy (CN) is a severe complication of cholestasis and an unmet clinical need. We demonstrate that CN is triggered by the renal accumulation of bile acids (BAs) that are considerably increased in the systemic blood. Specifically, the proximal tubular epithelial cells of the kidney take up BAs via the apical sodium-dependent bile acid transporter (ASBT). We developed a therapeutic compound that blocks ASBT in the kidneys, prevents BA overload in tubular epithelial cells, and almost completely abolished all disease hallmarks in a CN mouse model. Renal ASBT inhibition represents a potential therapeutic strategy for patients with CN.

Efficacy and Safety of Rivaroxaban for Postoperative Thromboprophylaxis in Patients After Bariatric Surgery: A Randomized Clinical Trial.

Importance: Venous thromboembolism (VTE) is a leading cause of morbidity and mortality after bariatric surgery. Clinical end point studies on thromboprophylaxis with direct oral anticoagulants in patients undergoing bariatric surgery are lacking. Objective: To assess the efficacy and safety of a prophylactic dose of 10 mg/d of rivaroxaban for both 7 and 28 days after bariatric surgery. Design, Setting, and Participants: This assessor-blinded, phase 2, multicenter randomized clinical trial was conducted from July 1, 2018, through June 30, 2021, with participants from 3 academic and nonacademic hospitals in Switzerland. Intervention: Patients were randomized 1 day after bariatric surgery to 10 mg of oral rivaroxaban for either 7 days (short prophylaxis) or 28 days (long prophylaxis). Main Outcomes and Measures: The primary efficacy outcome was the composite of deep vein thrombosis (symptomatic or asymptomatic) and pulmonary embolism within 28 days after bariatric surgery. Main safety outcomes included major bleeding, clinically relevant nonmajor bleeding, and mortality. Results: Of 300 patients, 272 (mean [SD] age, 40.0 [12.1] years; 216 women [80.3%]; mean body mass index, 42.2) were randomized; 134 received a 7-day and 135 a 28-day VTE prophylaxis course with rivaroxaban. Only 1 thromboembolic event (0.4%) occurred (asymptomatic thrombosis in a patient undergoing sleeve gastrectomy with extended prophylaxis). Major or clinically relevant nonmajor bleeding events were observed in 5 patients (1.9%): 2 in the short prophylaxis group and 3 in the long prophylaxis group. Clinically nonsignificant bleeding events were observed in 10 patients (3.7%): 3 in the short prophylaxis arm and 7 in the long prophylaxis arm. Conclusions and Relevance: In this randomized clinical trial, once-daily VTE prophylaxis with 10 mg of rivaroxaban was effective and safe in the early postoperative phase after bariatric surgery in both the short and long prophylaxis groups. Trial Registration: ClinicalTrials.gov Identifier: NCT03522259.

Multidisciplinary recommendations for essential baseline functional and laboratory tests to facilitate early diagnosis and management of immune-related adverse events among cancer patients.

Immune checkpoint inhibitors (ICIs) have fundamentally changed the treatment landscape of various cancers. While ICI treatments result in improved survival, quality of life and are cost-effective, the majority of patients experience at least one immune-related adverse event (irAE). Many of these side effects cause little discomfort or are asymptomatic; however, irAEs can affect any organ and are potentially life-threatening. Consequently, early diagnosis and appropriate treatment of irAEs are critical for optimizing long-term outcomes and quality of life in affected patients. Some irAEs are diagnosed according to typical symptoms, others by abnormal findings from diagnostic tests. While there are various guidelines addressing the management of irAEs, recommendations for the early recognition of irAEs as well as the optimal extent and frequency of laboratory tests are mostly lacking. In clinical practice, blood sampling is usually performed before each ICI administration (i.e., every 2-3 weeks), often for several months, representing a burden for patients as well as health care systems. In this report, we propose essential laboratory and functional tests to improve the early detection and management of irAEs and in cancer patients treated with ICIs. These multidisciplinary expert recommendations regarding essential laboratory and functional tests can be used to identify possible irAEs at an early time point, initiate appropriate interventions to improve patient outcomes, and reduce the burden of blood sampling during ICI treatment.

Gastroesophageal Junction and Pylorus Distensibility Before and After Sleeve Gastrectomy-pilot Study with EndoFlipTM.

Sleeve gastrectomy (SG) is the most frequently performed bariatric surgical intervention worldwide. Gastroesophageal reflux disease (GERD) is frequently observed after SG and is a relevant clinical problem. This prospective study investigated the gastroesophageal junction (GEJ) and pyloric sphincter by impedance planimetry (EndoFlipTM) and their association with GERD at a tertiary university hospital center. Between January and December 2018, patients undergoing routine laparoscopic SG had pre-, intra-, and postoperative assessments of the GEJ and pyloric sphincter by EndoFlipTM. The distensibility index (DI) was measured at different volumes and correlated with GERD (in accordance with the Lyon consensus guidelines). Nine patients were included (median age 48 years, preoperative BMI 45.1 kg/m2, 55.6% female). GERD (de novo or stable) was observed in 44.4% of patients one year postoperatively. At a 40-ml filling volume, DI increased significantly pre- vs. post-SG of the GEJ (1.4 mm2/mmHg [IQR 1.1-2.6] vs. 2.9 mm2/mmHg [2.6-5.3], p VALUE=0.046) and of the pylorus (6.0 mm2/mmHg [4.1-10.7] vs. 13.1 mm2/mmHg [7.6-19.2], p VALUE=0.046). Patients with postoperative de novo or stable GERD had a significantly increased preoperative DI at 40 ml of the GEJ (2.6 mm2/mmHg [1.9-3.5] vs. 0.5 mm2/mmHg [0.5-1.1], p VALUE=0.031). There was no significant difference in DI at 40 mL filling in the preoperative pylorus and postoperative GEJ or pylorus. In this prospective study, the DI of the GEJ and the pylorus significantly increased after SG. Postoperative GERD was associated with a significantly higher preoperative DI of the GEJ but not of the pylorus.

A new framework for advancing in drug-induced liver injury research. The Prospective European DILI Registry.

BACKGROUND & AIMS: No multi-national prospective study of drug-induced liver injury (DILI) has originated in Europe. The design of a prospective European DILI registry, clinical features and short-term outcomes of the cases and controls is reported. METHODS: Patients with suspected DILI were prospectively enrolled in the United Kingdom, Spain, Germany, Switzerland, Portugal and Iceland, 2016-2021. DILI cases or non-DILI acute liver injury controls following causality assessment were enrolled. RESULTS: Of 446 adjudicated patients, 246 DILI patients and 100 had acute liver injury due to other aetiologies, mostly autoimmune hepatitis (n = 42) and viral hepatitis (n = 34). DILI patients (mean age 56 years), 57% women, 60% with jaundice and 3.6% had pre-existing liver disease. DILI cases and non-DILI acute liver injury controls had similar demographics, clinical features and outcomes. A single agent was implicated in 199 (81%) DILI cases. Amoxicillin-clavulanate, flucloxacillin, atorvastatin, nivolumab/ipilimumab, infliximab and nitrofurantoin were the most commonly implicated drugs. Multiple conventional medications were implicated in 37 (15%) and 18 cases were caused by herbal and dietary supplements. The most common single causative drug classes were antibacterials (40%) and antineoplastic/immunomodulating agents (27%). Overall, 13 (5.3%) had drug-induced autoimmune-like hepatitis due to nitrofurantoin, methyldopa, infliximab, methylprednisolone and minocycline. Only six (2.4%) DILI patients died (50% had liver-related death), and another six received liver transplantation. CONCLUSIONS: In this first multi-national European prospective DILI Registry study, antibacterials were the most commonly implicated medications, whereas antineoplastic and immunomodulating agents accounted for higher proportion of DILI than previously described. This European initiative provides an important opportunity to advance the study on DILI.

Mycophenolate mofetil as second line treatment in autoimmune hepatitis - A retrospective single center analysis.

Background: Most patients with autoimmune hepatitis respond to standard treatment with steroids and azathioprine. While the disease is usually fatal if untreated, patients who respond well to therapy have an excellent prognosis. Nevertheless, second-line treatment is necessary in approximately 20% of patients, due to either intolerance or insufficient response to first line treatment.While data for mycophenolate mofetil (MMF) in patients intolerant to azathioprine is encouraging, MMF seems of less benefit in patients with insufficient response to first line treatment, but analyzed data on this issue is limited. Aim: To evaluate the efficacy and safety of MMF as a second-line therapy in patients with AIH. Methods: Retrospective analysis of a monocentric database of AIH patients who received medical care from 2000 to 2022. Clinical, immunological and biochemical parameters were assessed at different time points including last follow-up. Results: Overall, 144 patients with AIH were identified. Fifty out of 144 (35%) AIH patients received MMF. Forty (80%) received MMF due to first line treatment intolerance, while ten (20%) due to insufficient response to first line treatment.Remission with MMF monotherapy was 81.5% in the intolerance group versus 30% in the insufficient response group. Patients switched to MMF because of an insufficient response, more often needed additional prednisolone doses higher than 5 mg/day, a switch to third-line treatment or combination regiments, to achieve disease control. Conclusions: Patients treated with MMF because of intolerance to first line treatment show a good disease control under MMF in the majority of cases. Efficacy is considerably lower in the patients switched to MMF because of an insufficient response to first line treatment.

Management of transthyretin amyloidosis.

Transthyretin amyloidosis (ATTR amyloidosis) is a disease caused by deposition of transthyretin fibrils in organs and tissues, which causes their dysfunction. The clinical heterogeneity of ATTR amyloidosis and the variable presentation of symptoms at early disease stages, historically meant treatment delays. Diagnostic tools and therapy options of ATTR amyloidosis have markedly improved in recent years. The first Swiss Amyloidosis Network (SAN) meeting (Zurich, Switzerland, January 2020) aimed to define a consensus statement regarding the diagnostic work-up and treatment for systemic amyloidosis, tailored to the Swiss healthcare system. A consortium of 45 clinicians and researchers from all Swiss regions and universities was selected by the SAN committee to represent all sub-specialty groups involved in care of patients with amyloidosis. A steering committee conducted the literature search and analysis, wrote the critical synthesis and elaborated a list of statements that were evaluated by all the participants. These recommendations will improve outcomes and quality of life for patients with ATTR amyloidosis. A global review of these guidelines is planned every 3 years with a formal meeting of all the involved experts.

Ramucirumab in patients with previously treated advanced hepatocellular carcinoma: Impact of liver disease aetiology.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) is a common complication of chronic liver disease with diverse underlying aetiologies. REACH/REACH-2 were global phase III studies investigating ramucirumab in advanced HCC (aHCC) following sorafenib treatment. We performed an exploratory analysis of outcomes by liver disease aetiology and baseline serum viral load. METHODS: Meta-analysis was conducted in patients with aHCC and alpha-fetoprotein (AFP) ≥400 ng/mL (N = 542) from REACH/REACH-2 trials. Individual patient-level data were pooled with results reported by aetiology subgroup (hepatitis B [HBV] or C [HCV] and Other). Pre-treatment serum HBV DNA and HCV RNA were quantified using Roche COBAS AmpliPrep/COBAS TaqMan. Overall survival (OS) and progression-free survival (PFS) were evaluated using the Kaplan-Meier method and Cox proportional hazard model (stratified by study). RESULTS: Baseline characteristics were generally balanced between arms in each subgroup (HBV: N = 225, HCV: N = 127, Other: N = 190). No significant difference in treatment effect by aetiology subgroup was detected (OS interaction P-value = .23). Median OS (ramucirumab vs placebo) in months was 7.7 versus 4.5 (HR 0.74, 95% CI 0.55-0.99) for HBV, 8.2 versus 5.5 (HR 0.82, 95% CI 0.55-1.23) for HCV and 8.5 versus 5.4 (HR 0.56, 95% CI 0.40-0.79) for Other. Ramucirumab showed similar overall safety profiles across subgroups. Worst outcomes were noted in patients with a detectable HBV load. Use of HBV antiviral therapy, irrespective of viral load, was beneficial for survival, liver function and liver-specific adverse events. CONCLUSIONS: Ramucirumab improved survival across aetiology subgroups with a tolerable safety profile, supporting its use in patients with aHCC and elevated AFP.

Primary biliary cholangitis with normal alkaline phosphatase: A neglected clinical entity challenging current guidelines.

BACKGROUND & AIM: The diagnosis of primary biliary cholangitis (PBC), an uncommon immune-mediated cholestatic liver disease, is based on positive circulating anti-mitochondrial (AMA) and/or PBC-specific anti-nuclear autoantibodies (ANA), coupled with elevated serum alkaline phopsphatase (ALP) levels. Timely initiation of treatment with ursodeoxycholic acid prevents progression to cirrhosis and liver failure. We aimed at investigating liver histology in patients with normal ALP level and positive AMA and/or PBC-specific ANA. METHODS: We searched the Swiss PBC Cohort Study database, which includes subjects with positive PBC autoimmune serology and normal ALP levels, for patients who underwent a liver biopsy. Histological slides were centrally reviewed by an expert liver pathologist, and sera were centrally re-tested for AMA and ANA. RESULTS: 30 patients were included; 90% females, median age 53 (range 27-72) years. Twenty-four (80%) had liver histology typical for (n = 2), consistent with (n = 16) or suggestive of (n = 6) PBC, including three of four AMA-negative ANA-positive patients. Among 22 ursodeoxycholic acid treated patients, 14 had elevated GGT levels before treatment; a significant decrease of the median GGT level between pre- (1.46 x ULN) and post- (0.43 x ULN) treatment (p = 0.0018) was observed. CONCLUSIONS: In our series, a high proportion of AMA positive patients with normal ALP levels have PBC. For the first time we show histological diagnosis of PBC in AMA-negative/PBC-specific ANA-positive subjects and the potential role of GGT as a biomarker in PBC patients with normal baseline ALP levels. Current guidelines for the diagnosis of PBC do not cover the whole extent of PBC presentation, with important clinical implications in terms of timely treatment initiation.

Expert recommendation from the Swiss Amyloidosis Network (SAN) for systemic AL-amyloidosis.

Systemic amyloidosis is a heterogeneous group of diseases associated with protein misfolding into insoluble beta-sheet rich structures that deposit extracellularly in different organs, eventually compromising their function. There are more than 30 different proteins, known to be amyloidogenic with “light chain” (AL)-amyloidosis being the most common type, followed by transthyretin (ATTR)-, and amyloid protein A (AA)-amyloidosis. Systemic amyloidosis is a rare disease with an incidence of around 10 patients in 1 million inhabitants. Recently several new therapeutic options have been developed for subgroups of amyloidosis patients, and the introduction of novel therapies for plasma cell myeloma has led to an increase in the therapeutic armamentarium for plasma cell disorders, including AL amyloidosis. Among them, proteasome inhibitors, immunomodulatory agents (-imids), and monoclonal antibodies have been successfully introduced into clinical practice. Still, high-quality data from randomised controlled trials regarding the benefit of these cost-intensive drugs in AL amyloidosis are widely lacking, and due to the rarity of the disease many physicians will not gain routine experience in the management of these frail patients. The diagnosis of AL amyloidosis relies on a close collaboration between clinicians, pathologists, imaging experts, and sometimes geneticists. Diagnosis and treatment options in this complex disorder should be discussed in dedicated multidisciplinary boards. In January 2020, the first meeting of the Swiss Amyloidosis Network took place in Zurich, Switzerland. One aim of this meeting was to establish a consensus guideline regarding the diagnostic work-up and the treatment recommendations for systemic amyloidosis tailored to the Swiss health care system. Forty-five participants from different fields in medicine discussed many aspects of amyloidosis. These are the Swiss Amyloidosis Network recommendations which focus on diagnostic work-up and treatment of AL-amyloidosis.

Transjugular intrahepatic portosystemic shunt and alfapump® system for refractory ascites in liver cirrhosis: Outcomes and complications.

BACKGROUND: Treatment of refractory ascites in liver cirrhosis is challenging. Transjugular intrahepatic portosystemic shunt and alfapump® have been proposed for the management, but few data comparing both exist. AIMS: The aim of this study was to evaluate the characteristics and outcomes of patients treated with transjugular intrahepatic portosystemic shunt and alfapump® for refractory ascites at our centre. METHODS: All consecutive patients were retrospectively reviewed for baseline characteristics, efficacy of treatment, complications and survival. RESULTS: In total, 19 patients with transjugular intrahepatic portosystemic shunt and 40 patients with alfapump® were included. Patients with transjugular intrahepatic portosystemic shunt had better liver function and less hepatic encephalopathy at baseline. Fifty-eight per cent of patients developed hepatic encephalopathy in the first six months after transjugular intrahepatic portosystemic shunt. In patients with alfapump®, renal function decreased and 58% developed prerenal impairment and 43% hepatorenal syndrome in the first six months. Alfapump® patients with new catheters required less reinterventions (26% versus 57% with old catheters, p = 0.049). Transplant-free survival at 1 year was 25% in alfapump® and 65% in transjugular intrahepatic portosystemic shunt. Hepatic encephalopathy predicted transplant-free survival in patients with alfapump® (hazard ratio 2.00, 95% confidence interval 0.99-4.02, p = 0.05). In a sensitivity analysis comparing patients with similar liver function, the rate of hepatorenal syndrome and prerenal impairment was higher in patients with alfapump® and these patients were hospitalised more frequently, whereas the rate of hepatic encephalopathy was similar in both treatment groups. CONCLUSIONS: Both transjugular intrahepatic portosystemic shunt and alfapump® were effective treatments for refractory ascites in cirrhosis. Patients treated with transjugular intrahepatic portosystemic shunt had a better one-year transplant-free survival but had less negative prognostic factors at baseline. Selecting patients without hepatic encephalopathy prior to implantation of an alfapump® might improve transplant-free survival.

Hyper-coagulability in obese patients accurately identified by combinations of global coagulation assay parameters.

BACKGROUND: Routine laboratory methods are insensitive to hyper-coagulation, which may be detected by global hemostasis tests. Calibrated Automated Thrombogram (CAT) is a gold standard method to measure thrombin generation and coagulation potential. Thrombodynamics (TD) is a new global assay that monitors the spatio-temporal propagation of blood coagulation, separating initiation from amplification/propagation phases of coagulation and visualizing fibrin clot formation. AIM: We investigated whether CAT and/or TD can identify hyper- and hypo-coagulable states in patients with well-characterized phenotypes and which parameters could be used as potential predictors of thrombotic risk. METHODS: Blood was collected from: (1) forty healthy volunteers; (2) twelve obese patients scheduled for bariatric surgery (BMI ≥ 35 kg/m2); (3) nine patients under therapy with vitamin K-antagonists (median INR 2.7); (4) eight patients treated with low molecular weight heparins (anti-Xa activity between 0.5 and 0.7 U anti-Xa/ml); (5) ten patients with hemophilia A or B. Tissue factor induced thrombin generation was measured with CAT. Propagation of thrombin generation and clot growth from a tissue factor coated surface were monitored with TD. RESULTS: Thrombin generation and fibrin clot formation parameters were significantly higher in obese patients compared to healthy volunteers and anticoagulated or hemophilic patients. ROC analysis of combined CAT or CAT/TD parameters (integrating thrombin generation and fibrin clot formation) demonstrated an excellent accuracy in detecting hyper-coagulability. CONCLUSION: Combinations of CAT assay parameters and of parameters of thrombin generation burst with final fibrin clot properties allow recognizing accurately hyper-coagulable plasma and may represent predictive markers for thrombotic events.

Tailored access to the hepatobiliary system in post-bariatric patients: a tertiary care bariatric center experience.

BACKGROUND: In bariatric surgery patients, pancreaticobiliary access via endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging and the optimal approach for the evaluation and treatment of biliary tree-related pathologies has been debated. Besides laparoscopy-assisted ERCP (LA-ERCP) as standard of care, EUS-directed transgastric ERCP (EDGE) and hepaticogastrostomy (HGS) with placement of a fully covered metal stent have emerged as novel techniques. The objective of this study was to evaluate safety and efficacy of three different endoscopic approaches (LA-ERCP, EDGE, and HGS) in bariatric patients. METHODS: In this retrospective review, consecutive patients with Roux-en-Y gastric bypass (RYGB) and Sleeve Gastrectomy (SG) who underwent from 2013 to 2019 a LA-ERCP, an EDGE, or a HGS at a tertiary care reference center for bariatric surgery were analyzed. Patient demographics, type of procedure and indication, data regarding cannulation and therapeutic intervention of the common bile duct (procedure success), and clinical outcomes were analyzed. RESULTS: A total of 19 patients were included. Indications for LA-ERCP, EDGE, or HGS were mostly choledocholithiasis (78.9%) and in a few cases papillitis stenosans. Eight patients (57.1%) with LA-ERCP underwent concomitant cholecystectomy. Procedure success was achieved in 100%. Adverse events (AEs) were identified in 15.7% of patients (all ERCP related). All AEs were rated as moderate and there were no serious AEs. CONCLUSION: This case series indicates that ERCP via a transgastric approach (LA-ERCP, EDGE, or HGS) is a minimally invasive, effective, and feasible method to access the biliary tree in bariatric patients. These techniques offer an appealing alternative treatment option compared to percutaneous transhepatic cholangiography and drainage- or deep enteroscopy-assisted ERCP. In bariatric patients who earlier had a cholecystectomy, EUS-guided techniques were the preferred treatment options for biliary pathologies.

Controlled attenuation parameter reflects steatosis in compensated advanced chronic liver disease.

BACKGROUND & AIMS: Controlled attenuation parameter (CAP) for steatosis assessment has not been validated in compensated advanced chronic liver disease compensated advanced chronic liver disease (cACLD). We primarily aimed at assessing the accuracy of CAP for the diagnosis and quantification of steatosis in cACLD. Secondary aim: to assess the validity of non-invasive criteria for cACLD according to liver stiffness measurement (LSM). METHODS: This is a single-centre retrospective study including patients with cACLD defined as LSM ≥10 kPa, CAP measurement and liver biopsy (reference standard for steatosis and fibrosis) observed in 06/2015-06/2017. Steatosis was graded as S0 (<5%), S1 (5%-32%), S2 (33%-66%) and S3 (>66%). The diagnostic performance of CAP for any grade of steatosis and for high-grade steatosis (≥S2) was studied. RESULTS: Among 461 consecutive patients, 111 with LSM-based diagnosis of cACLD were included (63% male, median age 55 years, median body mass index 28.1 Kg/m2 , aetiology: 32% non-alcoholic fatty liver disease/non-alcoholic steatohepatitis, 32% alcohol or viral + metabolic syndrome, 15% viral, 6% autoimmune, 4% alcohol, 11% others). Median LSM and CAP were 16.1 kPa and 277 dB/m respectively. On liver biopsy, steatosis was found in 88/111 patients (79%); 44 patients (43 with metabolic syndrome) had high-grade steatosis. CAP was accurate in identifying any grade of steatosis (area under the receiving operating characteristic curves 0.847; 95% CI 0.767-0.926, P < .0001), and ≥S2 steatosis (0.860; 95% CI 0.788-0.932, P < .0001). CAP performed similarly in patients with CAP- interquartile range (IQR) ≥ or <40 dB/m. CONCLUSIONS: Steatosis is frequent in patients with cACLD and metabolic syndrome. CAP diagnostic accuracy for any steatosis and high-grade steatosis is good in this population. A CAP-IQR ≥40 dB/m does not impair CAP diagnostic accuracy in cACLD.

Continuous low flow ascites drainage through the urinary bladder via the Alfapump system in palliative patients with malignant ascites.

BACKGROUND: Malignant Ascites (MA) is a therapeutic dilemma significantly impairing patients' quality of life (QoL). The Sequana Medical alfapump System (AP), a subcutaneous, externally rechargeable, implantable device, continually draining ascites via the urinary bladder, has been well established in liver cirrhosis, but not yet in MA. The AP-system was evaluated in cancer patients in reducing the need for large volume paracentesis (LVP). METHODS: A retrospective multicentre evaluation of all eligible patients who received an AP for MA-palliation was performed. AP was evaluated for its ability to reduce LVP and cross-correlated with adverse events (AE), survival and retrospective physician-reported QoL. RESULTS: Seventeen patients with median age of 63 years (range: 18-81), 70.6% female, across 7 primary tumour types were analysed. Median duration of AP-implantation was 60 min (range: 30-270) and median post-implantation hospital stay: 4 days (range: 2-24). Twelve protocol-defined AE occurred in 5 patients (29.4%): 4 kidney failures, 4 pump/catheter-related blockages, 3 infections/peritonitis and 1 wound dehiscence. Median ascitic volume (AV) pumped daily was 303.6 ml/day (range:5.6-989.3) and median total AV drained was 28 L (range: 1-638.6). Median patient post-AP-survival was 111 days (range:10-715) and median pump survival was 89 days (range: 0-715). Median number of paracenteses was 4 (range: 1-15) per patient pre-implant versus 1 (range: 0-1) post-implant (p = 0.005). 71% of patients were reported to have an improvement of at least one physician reported QoL-parameters. CONCLUSIONS: AP appears to be effective in palliating patients with MA by an acceptable morbidity profile. Its broader implementation in oncology services should be further explored. TRIAL REGISTRATION: NCT03200106; June 27, 2017.

Nutritional Challenges in Patients with Advanced Liver Cirrhosis.

Patients with advanced liver cirrhosis are at risk of malnutrition and nutrition-associated complications. Significant ascites, a frequent finding in these patients, has an especially negative impact on oral nutrition. A negative caloric and protein balance can further deteriorate the already impaired synthetic function of the cirrhotic liver. An important factor in this situation is the diminished capacity of glycogen production and storage in the cirrhotic liver and, consequently, a reduced tolerability for fasting episodes. These episodes are frequently observed in hospitalized patients, e.g., while waiting for investigations, interventions or surgery. A comprehensive work-up of patients with advanced liver cirrhosis should include not only a thorough assessment regarding nutritional deficits, but also a muscularity analysis to identify patients with sarcopenia. The overall nutritional treatment goal is to cover caloric deficits and assure a sufficiently high protein intake. Furthermore, vitamin and micronutrient deficiencies should be identified and corrective measures implemented where required. Ideally, optimal nutrition management can not only prevent the progression of malnutrition and sarcopenia in patients with advanced liver cirrhosis, but positively influence the evolution of the liver disease.

Mental Illness Has a Negative Impact on Weight Loss in Bariatric Patients: a 4-Year Follow-up.

BACKGROUND: Mental health disorders are highly prevalent among bariatric surgery patients. Bariatric surgery induces weight loss with continuous health improvements. However, long-term follow-up data on weight loss and quality of life data of patients who have a mental illness after bariatric surgery are scarce, and it is not clear whether mental illness is associated with more pronounced weight regain. The aim was to investigate the impact of preoperative mental illness on the course of long-term weight changes after bariatric surgery. METHODS: Patients with sleeve gastrectomy (SG) or Roux-en-Y gastric bypass surgery (RYGB) between 2005 and 2013 with a follow-up of at least 3 years were included. The study population was divided into two groups: patients with mental illness (MI) and patients without (No-MI). Weight loss outcomes over time were compared using mixed models up to 4 years after surgery. RESULTS: In total, 254 patients (RYGB 61.0%, SG 39%) were included. The distribution of baseline characteristics was similar between the MI (n = 108) and No-MI groups (n = 146). The most prevalent mental illness was depressive disorder (63.9%). In the MI group, the percent of total weight loss (%TWL) was significantly smaller over the study period. After 36 months, the predicted mean group-difference of %TWL was 4.6% (95% CI 1.9, 7.2; p = 0.001), and the predicted odds ratio for weight regain was 4.9 (95% CI 1.6, 15.1) for patients in the MI group. CONCLUSION: Preoperative mental illness leads to lower long-term weight loss and an increased risk of weight regain after bariatric surgery.

Recurrent and De Novo Autoimmune Hepatitis.

Clinical indications for liver transplantation (LT) in patients with autoimmune hepatitis (AIH) are identical to those of patients with other chronic liver diseases that end in acute or semiacute liver failure, decompensated cirrhosis, or hepatocellular carcinoma. Recurrent disease after LT has been reported in 10%-50% of patients with AIH, and the frequency of detection is influenced in part by the use of protocol or clinically indicated liver biopsy. De novo AIH connotes the development of AIH in patients transplanted for liver diseases other than AIH, and it has been reported in 5%-10% of pediatric and 1%-2% of adult recipients. Recurrent disease can negatively impact on graft and patient survival, and retransplantation has been required in 8%-23%. De novo AIH is within the spectrum of graft dysfunction that includes plasma cell-rich rejection, and it can also progress to cirrhosis and graft failure. Treatment for recurrent or de novo disease is based on the conventional regimens for AIH, and corticosteroid therapy alone or combined with azathioprine is standard. Better control of disease activity prior to LT has been associated with less recurrence, and maintenance corticosteroid treatment after LT can reduce its frequency. In conclusion, recurrent AIH is far more frequent than de novo AIH. Both may have negative impacts on graft and patient survival, and early detection and treatment are key objectives. Future investigations must codify the diagnostic criteria for each graft dysfunction, seek diagnostic biomarkers, and evaluate treatments that improve outcomes without increasing the risk of pre- and post-LT infections.