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In the management of patients with decompensated liver cirrhosis, transjugular intrahepatic portosystemic shunt (TIPS) insertion is well-established but common recommendations in the follow up management are inconsistent. Doppler sonography is commonly used for detection for TIPS dysfunction whilst data on the impact of elective invasive examinations are scarce. The aim of this retrospective analysis is to evaluate potential benefits of elective invasive examinations in the follow up management of patients after TIPS insertion METHODS: Data of all patients receiving TIPS at the university hospitals of Muenster and Bonn between 2013 and 2018 (n = 534) were collected. The impact of performance of elective invasive examinations at 12 months after TIPS insertion on the occurrence of liver related events (LREs) and frequency of TIPS revisions within 24 months after TIPS insertion was analyzed. No significant differences were found concerning occurrence of liver related events after 24 months depending on whether an elective invasive examination was performed. Occurrence of hepatic encephalopathy, relapse of initial indication for TIPS, as well as death or liver transplantation all did not differ. These findings were verified by a subgroup analysis including only patients who did not experience a LRE or TIPS revision within the first 12 months after TIPS procedure. The analyzed data suggest no evidence for a beneficial impact due to implementation of an elective invasive examination program after TIPS insertion. Invasive examinations should remain reserved to patients with suspected TIPS dysfunction. Die Anlage eines transjugulären intrahepatischen portosystemischen Shunts ist ein etabliertes Verfahren in Patienten mit dekompensierter Leberzirrhose, es fehlen jedoch einheitlich Empfehlungen in der Patientennachsorge. Die Doppler-Sonografie wird regelhaft zur Kontrolle des Shunts genutzt. Aktuell gibt es keine Daten in Bezug auf elektive invasive Kontrollen. ZIEL: Ziel dieser retrospektiven Arbeit ist die Evaluation des Einflusses elektiver invasiver TIPS-Kontrollen in der Patientennachsorge. Es wurden Daten aller Patienten, die eine TIPS Implantation an den Universitätskliniken Münster und Bonn zwischen 2013 und 2018 erhalten haben, erhoben. Der Einfluss elektiver invasiver Kontrollen zwölf Monate nach TIPS Implantation bezüglich des Auftretens leber-assoziierter Ereignisse sowie der Häufigkeit von Shunt-Revisionen wurde analysiert. Es zeigten sich keine signifikanten Unterschiede bezüglich Leber-assoziierter Ereignisse nach 24 Monaten. Unterschiede bezüglich der Häufigkeit von Episoden hepatischer Enzephalopathien, einer Rekurrenz der initialen TIPS-Indikation, sowie Todesfällen oder Lebertransplantationen konnten nicht nachgewiesen werden. In einer Subgruppen-Analyse wurden nur Patienten, die innerhalb der ersten zwölf Monate kein leber-assoziiertes Ereignis oder eine TIPS-Revision hatten, analysiert: Auch hier wurden keine Unterschiede festgestellt. Unsere Daten zeigen keinen Vorteil für Patienten durch die Implementierung elektiver invasiver Kontrollen. Invasive Kontrollen sollten Patienten mit Hinweisen auf eine Shunt-Dysfunktion vorbehalten werden.

To analyze safety and effectiveness of simultaneous portal and hepatic vein embolization (PHVE) or sequential hepatic vein embolization (HVE) compared to portal vein embolization (PVE) for future remnant liver (FRL) hypertrophy prior to major hepatic surgery. Patients undergoing PVE, PHVE or HVE at our tertiary care center between 2018 and 2020 were retrospectively included. FRLV, standardized FRLV (sFRLV) and sFRLV growth rate per day were assessed via volumetry, as well as laboratory parameters. 36 patients (f = 15, m = 21; median 64.5 y) were included, 16 patients received PHVE and 20 patients PVE, of which 4 received sequential HVE. Significant increase of FRLV was achieved with both PVE and PHVE compared to baseline (p 0.0001). sFRLV growth rate did not significantly differ following PHVE (2.2 ± 1.2 %/d) or PVE (2.2 ± 1.7 %/d, p = 0.94). Left portal vein thrombosis (LPVT) was observed after PHVE in 6 patients and in 1 patient after PVE. Sequential HVE showed a considerably high growth rate of 1.42 ± 0.45 %/d after PVE. PHVE effectively induces FRL hypertrophy but yields comparable sFRLV to PVE. Sequential HVE further induces hypertrophy after insufficient growth due to PVE. Considering a potentially higher rate of LPVT after PHVE, PVE might be preferred in patients with moderate baseline sFRLV, with optional sequential HVE in non-sufficient responders.ZIEL: Analyse von Sicherheit und Effektivität der future remnant liver (FRL) Hypertrophieinduktion vor Leberresektion durch eine simultane Pfortader- und Lebervenenembolisation (PHVE) oder sequentiellen Lebervenenembolisation (HVE) im Vergleich zur Pfortaderembolisation (PVE). Alle Patienten mit PVE, PHVE oder HVE zwischen 2018 und 2020 aus einem Universitätsklinikum wurden retrospektiv eingeschlossen. FRLV, standardisiertes FRLV (sFRLV) und sFRLV Wachstumsrate pro Tag sowie die Laborwerte wurden analysiert. 36 Patienten (f = 15, m = 21; Median: 64,5 Jahre) wurden eingeschlossen; 16 Patienten erhielten eine PHVE und 20 Patienten eine PVE (4 davon sequentielle HVE). Eine signifikante FRLV-Zunahme wurde mit der PVE und der PHVE erzielt (p 0,0001). Die sFRLV Wachstumsrate zeigte keinen signifikanten Unterschied zwischen PHVE (2,2 ± 1,2 %/d) und PVE (2,2 ± 1,7 %/d, p = 0,94). 6 bzw.1 Patient zeigten eine linksseitige Thrombose nach PHVE bzw. PVE. Die sequentielle HVE zeigte eine deutliche sFRLV Wachstumsrate von 1,42 ± 0,45 %/d. Die PHVE führt effektiv zu einer Hypertrophie, die Wachstumsrate ist jedoch vergleichbar zur PVE. Die sequentielle HVE induziert jedoch eine zusätzliche Hypertrophie nach insuffizienter PVE. Unter Berücksichtigung einer womöglich höheren Thromboserate nach PHVE, sollte die PVE bei moderatem FRL-Ausgangsvolumen bevorzugt werden, mit der Option zu einer sequentiellen HVE bei insuffizienter PVE.

Background: Transjugular intrahepatic portosystemic shunt (TIPS) implantation is an established procedure to treat portal hypertension with hepatic encephalopathy (HE) as a common complication. There is lack of evidence concerning HE prophylaxis after TIPS. Methods: N = 233 patients receiving TIPS between 2011 and 2018 at a German tertiary care center were included. Of them, 21% (n = 49) had a history of HE. The follow-up period was 12 months. The risk factors of post-TIPS HE were analyzed via multivariate analysis. The efficacy of prophylactic medication regimens was studied. The results show that 35.6% (n = 83) received no medication (NM), 36.5% (n = 85) received lactulose monoprophylaxis (LM), 2.6% (n = 6) rifaximin monoprophylaxis (RM) and 25.3% (n = 59) lactulose and rifaximin (LR) of which 64.4% received l-ornithin-l-aspartate (LOLA) additionally (LR + LOLA) and 36.6% did not (LRonly). Results: Multivariate analysis revealed higher age (p = 0.003) and HE episodes prior to TIPS (p = 0.004) as risk factors for HE after TIPS. LM has no prophylactic effect. LR prevents HE recurrence at 1, 3 and 12 months after TIPS (p = 0.003, p = 0.003, p = 0.006) but does not prevent HE in patients with no history of HE (p = 0.234, p = 0.483, p = 0.121). LR prevents HE recurrence compared with LM/NM (25.0% vs. 64.7%, p = 0.007) within 12 months after TIPS, whereas de novo occurrence is unaffected (p = 0.098). The additional administration of LOLA to LR has no benefit (LRonly: 25.0%, LR + LOLA: 29.7%, p = 0.780). Conclusions: Higher age and previous HE are risk factors post-TIPS HE. In patients with HE prior to TIPS, effective prophylaxis of HE is feasible via combination of lactulose and rifaximin with no additional benefit from LOLA.

Background and Aims The organ shortage especially in blood group 0 forces transplant professionals to discuss new approaches to expand the donor pool. Recently, the successful therapy of HCV with direct antiviral agents in kidney transplanted patients has made the transplantation of HCV-infected kidneys to uninfected patients possible. Furthermore, these organs promise an above-average organ function as HCV-infected donors are usually young and have fewer comorbidities. Since there is no standard procedure for the treatment of kidney recipients with HCV grafts, we compared a preemptive and a prophylactic approach using direct antiviral drugs after kidney transplantation of two patients. Method We report the transplantation of two HCV-positive kidneys. One recipient was a 49-year-old female patient, who suffered from ESRD caused by an atypical hemolytic uremic syndrome. The other recipient had autosomal dominant polycystic kidney disease. Since the genotype of the HCV donor was unknown at the time of transplantation, we decided to use the pangenotypic, fixed-dose combinations Glecaprevir/Pibrentasvir and Sofosbuvir/Velpatasvir. Results Both patients had blood group 0 and received an AB0-compatible kidney transplant. The initial immunosuppressive therapy consisted of prednisolone, mycophenolate sodium, and tacrolimus. Furthermore, an induction therapy with Basiliximab was given. The first patient received Glecaprevir/Pibrentasvir immediately post-surgery. Treatment was carried on for eight weeks as a prophylactic approach. Frequent HCV-PCRs showed negative results over six months. However, the patient developed anti-HCV antibodies within six days after transplantation. The graft started working on postoperative day four, and the serum creatinine decreased to 1.33 mg/dl on the discharge day and stabilized on this level during further follow-up. Following a preemptive approach, our second patient was treated with Sofosbuvir/Velpatasvir after detection of HCV RNA and rising levels of transaminases on post-transplant day 7. This patient also received Entecavir because of a previous HBV-infection of the donor (non-viremic on the day of transplantation). The graft started working on day two, and the serum creatinine decreased to 1.28 mg/dl on the discharge day and stabilized on this level. Further HCV-PCRs also showed negative results. Conclusion We conclude that kidneys from HCV-viremic donors can be transplanted with precaution. Both therapeutic strategies showed equally good results and can easily be implemented into kidney transplantation. Especially, the combination of Glecaprevir/Pibrentasvir offers a safe HCV prophylaxis without the need of adaptions to the renal function or HCV genotype. In case of a permanent absence of a HCV infection, the preemptive approach offers a chance to avoid the HCV-therapy. On the other hand, causing an iatrogenic infection of HCV in a patient with immunosuppression brings up ethical issues due to the risk of HCV-related liver diseases. Therefore, we favor the prophylactic approach. Further studies are needed to identify the optimal time frame for direct antiviral agents in HCV (D+/R-) transplantations.

Background With regard to quality of life and organ shortage, follow-up after liver transplantation (LT) should consider risk factors for allograft failure in order to avoid the need for re-LT and to improve the long-term outcome of recipients. Therefore, the aim of this study was to explore potential risk factors for allograft failure after LT. Material and methods A total of 489 consecutive LT recipients who received follow-up care at the University Hospital of Muenster were included in this study. Database research was performed, and patient data were retrospectively reviewed. Risk factors related to donor and recipient characteristics potentially leading to allograft failure were statistically investigated using binary logistic regression analysis. Graft failure was determined as graft cirrhosis, need for re-LT because of graft dysfunction, and/or allograft-associated death. Results The mean age of recipients at the time of LT was 50.3 ± 12.4 years, and 64.0 % were male. The mean age of donors was 48.7 ± 15.5 years. Multivariable statistical analysis revealed male recipient gender (p = 0.04), hepatitis C virus infection (HCV) (p = 0.014), hepatocellular carcinoma (HCC) (p = 0.03), biliary complications after LT (p Conclusion Male recipients, patients who received LT for HCV or HCC, those with pretransplant diabetes mellitus, and LT recipients with biliary complications are at high risk for allograft failure and thus should be monitored closely.

Background Portal hypertension is a major complication of liver cirrhosis. Transjugular intrahepatic portosystemic shunt is effective in treatment of portal hypertension. However, decreased parenchymal portal venous flow after transjugular intrahepatic portosystemic shunt insertion favours ischaemic liver injury which has been discussed to induce hepatocarcinogenesis causing hepatocellular cancer. Aim This study aimed to explore the association between transjugular intrahepatic portosystemic shunt placement and the development of hepatocellular cancer. Methods A total of 1338 consecutive liver cirrhosis patients were included in this retrospective study between January 2004–December 2015. Data were analysed with regard to development of hepatocellular cancer during follow-up. Binary logistic regression and Kaplan-Meier analyses were conducted for the assessment of risk factors for hepatocellular cancer development. In a second step, to rule out confounders of group heterogeneity, case-control matching was performed based on gender, age, model of end-stage liver disease score and underlying cause of cirrhosis (non-alcoholic steatohepatitis, alcoholic liver disease and viral hepatitis). Results Besides established risk factors such as older age, male gender and underlying viral hepatitis, statistical analysis revealed the absence of transjugular intrahepatic portosystemic shunt insertion as a risk factor for hepatocellular cancer development. Furthermore, matched-pair analysis of 432 patients showed a significant difference ( p = 0.003) in the emergence of hepatocellular cancer regarding transjugular intrahepatic portosystemic shunt placement versus the non-transjugular intrahepatic portosystemic shunt cohort. Conclusion In patients with end-stage liver disease, transjugular intrahepatic portosystemic shunt insertion is significantly associated with reduced rates of hepatocellular cancer development.

Objective To evaluate the effectiveness of interventional therapy in acute, non-malignant, non-cirrhotic portal vein thrombosis. Methods We present a retrospective study of eight consecutive patients who presented with an acute non-malignant, non-cirrhotic portal vein thrombosis and were treated by mechanical recanalization using an escalating scheme including local aspiration, thrombolysis, rheolysis and the implantation of transjugular intrahepatic portosystemic shunt or other visceral stents. Results Recanalization rates applying the escalating scheme were good, with a success rate of 75%. However, major complications occurred in 50% of patients, mostly due to bleeding at the percutaneous access site, and minor complications in 12.5% of patients. Conclusion Interventional therapy is effective in acute portal vein thrombosis, but should only be performed at specialized centers and based on an individual treatment decision.

Background Liver transplantation (LTx) is a potentially curative treatment option for hepatocellular carcinoma (HCC) in cirrhosis. However, patients, where HCC is already a systemic disease, LTx may be individually harmful and has a negative impact on donor organ usage. Thus, there is a need for improved selection criteria beyond nodule morphology to select patients with a favorable outcome for LTx in multifocal HCC. Evolutionary distance measured from genome-wide single-nucleotide polymorphism data between tumor nodules and the cirrhotic liver may be a prognostic marker of survival after LTx for multifocal HCC. Methods In a retrospective multicenter study, clinical data and formalin-fixed paraffin-embedded specimens of the liver and 2 tumor nodules were obtained from explants of 30 patients in the discovery and 180 patients in the replication cohort. DNA was extracted from formalin-fixed paraffin-embedded specimens followed by genome wide single-nucleotide polymorphism genotyping. Results Genotype quality criteria allowed for analysis of 8 patients in the discovery and 17 patients in the replication set. DNA concentrations of a total of 25 patients fulfilled the quality criteria and were included in the analysis. Both, in the discovery (P = 0.04) and in the replication data sets (P = 0.01), evolutionary distance was associated with the risk of recurrence of HCC after transplantation (combined P = 0.0002). In a univariate analysis, evolutionary distance (P = 7.4 × 10−6) and microvascular invasion (P = 1.31 × 10−5) were significantly associated with survival in a Cox regression analysis. Conclusions Evolutionary distance allows for the determination of a high-risk group of recurrence if preoperative liver biopsy is considered., The authors of this multicenter retrospective study assess whether the evolutionary distance measured from genome-wide single nucleotide polymorphism (SNP) data between tumor nodules and the cirrhotic liver may be a prognostic marker of survival after liver transplantation for multifocal hepatocellular carcinoma. Supplemental digital content is available in the text.

Perihilar cholangiocarcinomas are often considered incurable. Late diagnosis is common. Advanced disease therefore frequently causes questioning of curative surgical outcome.This study aimed to develop a prediction model of curative surgery in patients suffering from perihilar cholangiocarcinomas based on preoperative endosonography and computer tomography.A cohort of 81 patients (median age 67 (54-75) years, 62% male) with perihilar cholangiocarcinoma was retrospectively analyzed. Multivariate logistic regression analysis of staging variables taken from the European Staging System was performed and applied to ROC analysis.The correlation of predicted rates of eligibility for surgery with actual rates reached AUC values between 0.652 and 0.758 for endosonography and computer tomography (Our predictive web-based model pSurg with inclusion of T, N, M, B, PV, HA and V stage of the recently published European Staging System for perihilar cholangiocarcinoma results in highly significant predictability for curative surgery when combining preoperative endosonography and computer tomography, thus allowing for better patient selection in terms of possibility of curative surgery.

Background The primary therapeutic goals in the treatment of liver injury are to support liver regeneration or bridge the gap to liver transplantation (LT). Molecular adsorbent recirculating system (MARS) therapy has shown beneficial effects for specific symptoms of liver failure; however, general survival advantages have not yet been demonstrated. Aim We studied the effects of MARS therapy compared to standard medical treatment (SMT) in two patient cohorts: in patients with an acute liver injury and in those with graft dysfunction (GD). Methods We report on our experience over a 6.5-year period with 73 patients treated with SMT or with SMT and MARS (MARS group). In total, 53 patients suffered from acute liver injury in their native liver without a preexisting liver disease (SMT: n = 31, MARS: n = 22), and 20 patients showed a severe GD after LT (SMT: n = 10, MARS: n = 10). Results The entire cohort was predominantly characterized by hemodynamically and respiratorily stable patients with a low hepatic encephalopathy (HE) grade and a model of end-stage liver disease (MELD) score of 20.57 (MARS) or 22.51 (SMT, p = 0.555). Within the MARS group, the median number of extracorporeal therapy sessions was four (range = 3–5 sessions). Independent of the underlying etiology, MARS improved the patients’ bilirubin values in the short term compared to SMT alone. In patients with acute liver injury, this response was sustained even after the end of MARS therapy. By contrast, the majority of patients with GD and an initial response to MARS therapy experienced worsened hyperbilirubinemia. No differences in 28-day mortality were observed with respect to acute liver injury (MARS 5.3% (95% CI: 0–15.3); SMT 3.3% (95% CI: 0–9.8), p = 0.754) or GD (MARS 20.0% (95% CI: 0–44.7), SMT 11.1% (95% CI: 0–31.7), p = 0.478). Conclusions Although it did not improve 28-day mortality, MARS therapy improved the short-term response in patients with acute liver injury as well as in those with GD. In cases of acute hepatic injury, the use of MARS therapy resulted in the sustained stabilization of liver function and improved liver regeneration. A short-term response to MARS may predict the future course of the disease.

AIM To evaluate cholangioscopy in addition to endoscopic retrograde cholangiopancreatography (ERCP) for management of biliary complications after liver transplantation (LT). METHODS Twenty-six LT recipients with duct-to-duct biliary reconstruction who underwent ERCP for suspected biliary complications between April and December 2016 at the university hospital of Muenster were consecutively enrolled in this observational study. After evaluating bile ducts using fluoroscopy, cholangioscopy using a modern digital single-operator cholangioscopy system (SpyGlass DS™) was performed during the same procedure with patients under conscious sedation. All patients received peri-interventional antibiotic prophylaxis and bile was collected during the intervention for microbial analysis and for antibiotic susceptibility testing. RESULTS Thirty-three biliary complications were found in a total of 22 patients, whereas four patients showed normal bile ducts. Anastomotic strictures were evident in 14 (53.8%) patients, non-anastomotic strictures in seven (26.9%), biliary cast in three (11.5%), and stones in six (23.1%). A benefit of cholangioscopy was seen in 12 (46.2%) patients. In four of them, cholangioscopy was crucial for selective guidewire placement prior to planned intervention. In six patients, biliary cast and/or stones failed to be diagnosed by ERCP and were only detectable through cholangioscopy. In one case, a bile duct ulcer due to fungal infection was diagnosed by cholangioscopy. In another case, signs of bile duct inflammation caused by acute cholangitis were evident. One patient developed post-interventional cholangitis. No further procedure-related complications occurred. Thirty-seven isolates were found in bile. Sixteen of these were gram-positive (43.2%), 12 (32.4%) were gram-negative bacteria, and Candida species accounted for 24.3% of all isolated microorganisms. Interestingly, only 48.6% of specimens were sensitive to prophylactic antibiotics. CONCLUSION Single-operator cholangioscopy can provide important diagnostic information, helping endoscopists to plan and perform interventional procedures in LT-related biliary complications.