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Copyright of Der Gastroenterologe is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: In recent years substantial progress has been made in the treatment, surveillance and understanding of the pathogenesis of primary sclerosing cholangitis (PSC); however, in most cases liver transplantation (LTX) is still the only curative option for cancer or end-stage liver disease (ELD). In rare cases a partial liver resection is a possible curative treatment of a PSC-associated cholangiocellular carcinoma (CCC). These operations represent a significant additional burden for PSC patients., Objective: Due to the rarity of PSC detailed studies regarding hepato-pancreato-biliary (HPB) surgery are lacking. The aim of this study was to analyze the surgical indications and prognosis of PSC patients., Patients and Methods: A single center retrospective cohort study from 1990 to 2020 was carried out. In this study patients with PSC were included and investigated with respect to factors associated with surgery and the prognosis., Results: As a consequence of PSC-associated conditions, in 62 patients (36%) a major HPB operation or explorative laparotomy was necessary. The prevalence of chronic inflammatory bowel disease was significantly higher in these patients (P < 0.019). An LTX was carried out in 46 patients (73%) because of ELD. A liver resection (LR) was performed in 8 patients (11%) and 9 patients only underwent an explorative laparotomy. The overall survival in the LTX subgroup was significantly longer than patients who underwent LR and explorative laparotomy (258 months; 95% confidence interval, CI 210-306 months vs. 88 months; 95% CI 16-161 months vs. 13 months; 95% CI 3-23 months; p < 0.05, respectively)., Conclusion: The majority of patients with PSC have to be operated on because of the disease with substantial risks for morbidity and mortality. Curative treatment options are lacking, thus underlining the need for effective early detection and treatment strategies for PSC-CCC.

Background: The indications, implementation and reporting of liver biopsies for deceased organ donation are not mandatory or regulated. Reliable data on outcome quality and prognostic relevance are therefore not available. Defined standards are thus required to enable meaningful studies and to ensure high data quality of a national transplantation registry., Objective: Presentation of a synopsis of available studies and literature-based recommendations., Results and Conclusion: Against the background of an organ shortage and a growing number of older donors, pretransplantation liver histology is of significant relevance to guide clinical decision making. With the joint recommendations of the German Transplantation Society (DTG), the German Society of Pathology (DGP) and the German Organ Transplantation Foundation (DSO) standardized procedures are defined for the first time.

For nearly 30 years ursodeoxycholic acid (UDCA) represented the only pharmacological treatment option available for primary biliary cholangitis (PBC). This changed at the end of 2016 when obeticholic acid was licensed in Europe for PBC patients not responding to UDCA. Novel treatment concepts involving the modulation of nuclear receptor signaling in cholestatic and other liver diseases have led to a host of new potential options, studies and drug candidates for the treatment of PBC. The analysis of large multinational cohorts has additionally confirmed the effectiveness of UDCA in slowing PBC progression, and has led to the development of new definitions for the risk assessment of PBC patients under therapy, which will be an asset for clinical decision making. One issue that remains unresolved is the therapeutic management of extrahepatic symptoms associated with PBC, namely fatigue and pruritus, which are the main factors influencing the quality of life of affected individuals. Their pathophysiological basis is poorly understood and treatment remains unsatisfactory.

A 59-year-old woman suffered from fever and upper abdominal pain. The computed tomography (CT) scan revealed a liver lesion. Conventional imaging techniques (CT, magnetic resonance imaging, contrast-enhanced ultrasonography) did not allow for a consistent diagnosis. Fine needle biopsy of the liver lesion was performed. Histologically, fibrotic inflammation was found and an inflammatory pseudotumor (IPT) diagnosed. Despite treatment with steroids and antibiotics, the size of the IPT increased; thus, surgical resection was necessary. In case of fever of unknown origin, IPT should be considered as a potential diagnosis.

Recent non-cirrhotic and non-malignant splanchnic vein thrombosis is now defined as extrahepatic portal vein thrombosis with or without involvement of the mesenteric vein according to the Baveno VI consensus from 2015. An early diagnosis is often challenging due to unspecific symptoms with abdominal pain or diarrhea but extremely important because of the potential acute and chronic complications, such as mesenteric ischemia and portal hypertension; therefore, rapid treatment is crucial. We present two cases of severe splanchnic vein thrombosis, which were treated with catheter-directed local thrombolysis and thrombus aspiration. These minimally invasive catheter-directed techniques have recently been successfully used in selected patients. A review of the literature is provided in this article. In summary, the management of splanchnic vein thrombosis must be individually planned for each patient and should be performed at experienced centers, which can provide all therapeutic options. In selected cases with the correct indications transjugular transhepatic catheter-directed local thrombolysis is a safe option with a good outcome.

With the approval of new direct acting antiviral agents (DAA), therapeutic options for patients with chronic hepatitis C virus (HCV) infection are now generally available before and after liver transplantation (LT). Interferon-free DAA regimens are highly effective therapies and provide a good safety profile. However, the body of clinical evidence in this patient population is limited and the best treatment strategies for patients on the waiting list with (de)compensated cirrhosis and after LT are not well defined. The following recommendations for antiviral therapy in the context of LT are based on the currently available literature and clinical experience of experts in the field, and have been discussed in an expert meeting. The aim of this article is to guide clinicians in the decision making when treating patients before and after LT with DAAs., (© Georg Thieme Verlag KG Stuttgart · New York.)

Donor organs for transplantations are a scarce commodity; therefore, allocation systems are needed that guarantee an ethically acceptable distribution to patients on the waiting list (equal treatment and fairness) but also take the probability of survival of the transplant in each recipient into consideration. In this article the allocation systems for lung, liver, kidney and pancreas transplants are presented.For lung transplantations an allocation system based on the lung allocation score (LAS) is currently used. The LAS predicts the probability of survival on the waiting list and the survival rate following transplantation. Organs with a limited range of utilization are distributed in a so-called mini-match procedure.For post-mortem kidney and pancreas transplantations a relatively complex but transparent allocation system has been created in which patients are subdivided into groups, each of which has its own allocation rules. The allocation is principally carried out according to criteria of fairness of distribution and according to the prospects of success. The probability of a mismatch also plays a role. The urgency is important for children and for patients who do not have the possibility of dialysis. Combined pancreas and kidney transplantations have priority over kidney transplantations alone.The criterion for the urgency of liver transplantation in Germany is currently the model for end-stage liver disease (MELD), which aims to reduce the waiting list mortality and to prioritize transplantations for those most in need. Because the system insufficiently describes the priority of transplantation for patients with tumors or genetic liver diseases, there is an additional set of rules for so-called standard exceptions.

The interdisciplinary guidelines at the S3 level on the diagnosis of and therapy for hepatocellular carcinoma (HCC) constitute an evidence- and consensus-based instrument that is aimed at improving the diagnosis of and therapy for HCC since these are very challenging tasks. The purpose of the guidelines is to offer the patient (with suspected or confirmed HCC) adequate, scientifically based and up-to-date procedures in diagnosis, therapy and rehabilitation. This holds not only for locally limited or focally advanced disease but also for the existence of recurrences or distant metastases. Besides making a contribution to an appropriate health-care service, the guidelines should also provide the foundation for an individually adapted, high-quality therapy. The explanatory background texts should also enable non-specialist but responsible colleagues to give sound advice to their patients concerning specialist procedures, side effects and results. In the medium and long-term this should reduce the morbidity and mortality of patients with HCC and improve their quality of life., (© Georg Thieme Verlag KG Stuttgart · New York.)

Liver transplantation represents an established component of the therapeutic repertoire for irreversible chronic liver diseases. Liver transplantation is confronted by a shortage of donor allografts as well as by an increasing overall number of potentially useful indications, which leads to a rationing of this therapeutic option. Since December 2006 the priority for liver transplantation is determined by the model for end-stage liver disease (MELD) and not by the length of waiting time. The evaluation of indications which are prioritized according to laboratory values (serum creatine, serum bilirubin and coagulation) and the so-called standard exception categories which have to fulfil specific criteria place increased demands on the interdisciplinary transplantation team, on the evaluation for liver transplantation and the prediction of the success of transplantation required by the Transplantation Act. The establishment and implementation of robust, objective and transparent systems to assess not only preoperative priorities but also postoperative benefits represents a major challenge for transplantation medicine.

We report on a 25-year-old female patient who presented with recurrent cholestasis following liver transplantation due to primary sclerosing cholangitis. Abdominal ultrasound and computed tomography showed intrahepatic bile duct dilatation and stenosis of the common hepatic artery with flow acceleration and decreased resistance index. The patient developed a severe secondary sclerosing cholangitis (SSC) with biliary casts - despite interventional stent placement of the common hepatic artery - thus requiring retransplantation. After prolonged intensive care unit treatment the patient was discharged in a good general condition. This case report describes SSC as a rare cause for graft failure. In unclear cholestasis after liver transplantation SSC has to be considered as the underlying cause., (© Georg Thieme Verlag KG Stuttgart · New York.)

Since the 1950s, autoimmune hepatitis has been recognized as a chronic liver disease that responds to treatment with steroids. Nevertheless, even today 25% of all diagnosed patients still present with liver cirrhosis, which emphasizes the importance of a timely and efficient diagnosis. Steroid-containing immunosuppression is characterized by a high rate of unwanted side effects. For non-cirrhotic patients, the synthetic steroid budesonide, which is characterized by high first-pass metabolism, represents a study-evaluated alternative. In the new guidelines for the management of primary sclerosing cholangitis, the therapeutic role of ursodeoxycholic acid has been modified, with no other effective alternative drugs being available. Management of sclerosing cholangitis is also made more difficult by the high risk of cholangiocarcinoma and colon carcinoma in addition to new differential diagnoses such as secondary sclerosing cholangitis and IgG4-associated cholangitis. IgG4-associated cholangitis can mimic primary sclerosing cholangitis but--in contrast-- can respond to the administration of steroid-containing immunosuppression.

Liver transplantation represents a successful and well-established therapeutic concept for patients with advanced liver diseases. Organ donor shortage continues to pose a significant problem. To ensure fair and transparent allocation of too few post-mortem grafts, the model of end-stage liver disease (MELD)-based allocation was implemented in December 2006. This has decreased waiting list mortality from 20 to 10 % but at the same time has reduced post OLT survival (1-year survival from almost 90% to below 80%), which is largely due to patients with a labMELD score > 30. Following MELD introduction the regular allocation threshold has increased from a matchMELD of initially 25 to meanwhile 34. At the same time the quality of donor organs has seen a continuous deterioration over the last 10 - 15 years: 63% of organs are "suboptimal" with a donor risk index of > 1.5. Moreover, the numbers of living-related liver transplantations have decreased. In Germany incentives for transplant centres are inappropriate: patients with decompensated cirrhosis, high MELD scores and high post-transplant mortality as well as marginal liver grafts are accepted for transplantation without the necessary consideration of outcomes, and against a background of the still absent publication and transparency of outcome results. The outlined development calls for measures for improvement: (i) the increase of donor grafts (e. g., living donation, opt-out solutions, non-heart beating donors), (ii) the elimination of inappropriate incentives for transplant centres, (iii) changes of allocation guidelines, that take the current situation and suboptimal donor grafts into account, and (iv) the systematic and complete collection of transplant-related data in order to allow for the development of improved prognostic scores., (© Georg Thieme Verlag KG Stuttgart · New York.)

Intestinal intussusception in the adult is often idiopathic but also known to be associated with chronic inflammatory bowel disease, coeliac disease, tumours or previous abdominal operations. A 22-year-old women after liver transplantation due to Crigler Najar Syndrome suffered from repeated episodes of abdominal pain. The diagnosis of repeated self-limited intestinal intussusceptions was made by computed tomography and ultrasonography. A laparoscopy revealed no cause for the intussusceptions. During a new episode of abdominal pain caused again by an intussusception a colonoscopy was performed that showed aspects of a discreet colitis. In the biopsies CMV was detected by qualitative PCR, while blood tests for CMV pp65 antigen were negative. A therapy with gancyclovir was initiated which lead to remission of the patient's symptoms. A colonoscopy six weeks later showed a completely normal colon, while in the biopsies CMV was not detectable. After a follow-up of one year the patient has not suffered from any further episodes. This case demonstrates the role of chronic intestinal CMV infection as a possible causative factor for repeated intussusceptions in immunosuppressed patients. Whenever possible a PCR for CMV in colon biopsies should be carried out to detect an intestinal CMV infection because as shown in our case results for immunohistopathology and CMV pp65 can be negative despite a chronic infection., (Georg Thieme Verlag KG Stuttgart. New York.)

Hepatopulmonary syndrome, portopulmonary hypertension and hepatic hydrothorax are typical pulmonary complications in patients with liver cirrhosis. Whereas hepatopulmonary syndrome and portopulmonary hypertension represent pulmonary vascular diseases, the development of hepatic hydrothorax is associated with the presence of ascites and phrenic lesions. For severe hepatopulmonary syndrome and refractory hepatic hydrothorax, liver transplantation is the treatment of choice. In severe portopulmonary hypertension specific medical treatment is indicated. In selected patients, beside intravenous prostanoids, oral endothelin receptor antagonists and phosphodiesterase type-5 inhibitors are possible treatment options.

In Germany, around 800.000 to 1 million individuals are chronically infected with either the hepatitis B or the hepatitis C virus. Viral hepatitis is therefore highly relevant for the everyday management in clinical practice. For the treatment of hepatitis B, potent antiviral drugs have become available that, in the majority of patients, induce viral suppression. This requires a strategic therapeutic planning in view of a likelihood of long term administration and the prevention of viral resistance. Recent advances in the treatment of hepatitis C are based on a therapeutic individualization based upon viral kinetics and genotypes that also requires strategic planning. In contrast to hepatitis B, viral elimination can be reached in 50-90% of hepatitis C patients. Hepatitis D is associated with a migration background, is most likely under diagnosed and does not yet have a satisfactory curative treatment option. An effective vaccine exists for hepatitis A that offers protection lasting decades. Hepatitis A does not lead to chronic infection. This was also assumed for hepatitis E. However, reports indicate chronic courses in selected patient groups. A vaccine for hepatitis E is currently not yet available.

After around 64,000 transplantations in Europe since 1988 liver transplantation has emerged as a standard treatment option for otherwise incurable chronic liver diseases. Cirrhosis of different etiologies represents the most frequent transplant indication. Overall survival in this group amounts to 72% after 5 years, and 62% after 10 years. In Germany, the main indications include alcoholic liver cirrhosis, tumors with increasing numbers in recent years, as well as viral diseases leading to cirrhosis. Since December 2006 the priority for liver transplantation is determined by the model for end stage liver disease (MELD) and not by the length of waiting time. MELD is a statistical model based on serum creatinine, serum bilirubin and coagulation, which describes the probability of 3-month mortality of a potential transplant candidate. Not all liver diseases are adequately represented by MELD necessitating the additional use of a defined number of standard exceptions that have been last updated in 2008. As a consequence of these developments indications, selection of recipients and the management of the waiting list have seen profound change.

Liver transplantation has been reported to reach excellent results for selected indications. We analysed the results of liver transplantation in our centre over a period of 23 years, with a total of 2,114 consecutive liver transplants in 1,773 patients (eras I-III 5.5 years each, era IV 6.5 years). Overall 20-year survival after liver transplantation was 29.8%. The most frequent leading causes of death were infections of various origins (30%), tumour recurrence (14.2%), and pneumonia (8.4%). The most frequent leading causes for graft loss were infection of various origins (19.6%), initial nonfunction of the graft (14.6%), and tumour recurrence (9.6%). Both long-term patient and graft survival were significantly better after primary liver transplantation than after first retransplantation (P<0.001). Patient and graft long-term survival improved significantly across all four consecutive eras (P<0.001). In era IV, the most recent, 5-year patient survival reached 96% for PBC, 89.4% for PSC, 78.5% for biliary atresia, 70% for acute liver failure, 69.1% for HBV-related cirrhosis, 61.3% for hepatocellular carcinoma, and 56% for HCV-related cirrhosis.

The success of transplantation with good long-term outcome is closely related to the possibilities of iatrogenic immunosuppression. Progress in immunosuppression combines basic scientific research of alloimmunity with practical clinical management of transplanted patients, their underlying diseases, and management of immunosuppressant side effects. Calcineurin inhibitors and steroids form the basis of immunosuppression in liver transplantation. To prevent steroid side effects and most importantly nephrotoxicity, the roles of antimetabolites such as mycophenolate and calcineurin inhibitor reduction have become more important. Developments in the 1990s provided specific antibodies and induction protocols renabling the delayed application of calcineurin inhibitors and a reduction in side effects. Against the background of a range of indications reaching from chronic viral infection to tumors, the progress of immunosuppression is characterized by the calculated combination of synergistic individual immunosuppressants. Novel drugs and strategies for the induction of tolerance are under development.

Autoimmune diseases of the liver are chronic inflammatory diseases leading to an etiologically undefined immune-mediated attack aimed at the hepatocyte, small microscopic bile ducts, and the entire biliary system detectable by cholangiography, respectively. From the standpoint of clinical disease three entities can be distinguished: autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC), and primary sclerosing cholangitis (PSC). These are not only different regarding their clinical profile but also differ in diagnostic strategy, therapeutic regimen and probability of remission, as well as their association with other immune-mediated diseases and cancer. PBC and PSC are cholestatic diseases. PBC is most often diagnosed in women. The diagnosis is readily reached by the detection of specific antimitochondrial autoantibodies directed against pyruvate dehydrogenase (PDH-E2), is associated with an array of rheumatological extrahepatic syndromes and responds unsatisfactorily to immunosuppressive drugs. Ursodeoxycholic acid leads to biochemical and possibly histological benefits. In contrast, PSC affects younger men who suffer from inflammatory bowel disease in 75% of cases. PSC is not characterized by specific serum autoantibodies. The diagnosis is reached by histology and typical findings upon cholangiography. In 10-20% PSC is associated with cholangiocarcinoma and also with colon cancer. PSC also does not respond well to immunosuppression. Therapeutic interventions include mechanical endoscopic manipulation of the bile ducts, treatment of cholangitis and ursodeoxycholic acid. AIH is a classical autoimmune disease with a female predisposition, circulating autoantibodies, elevated immunoglobulins, the association of other extrahepatic autoimmune diseases, and a dramatic response to immunosuppression with normalization of the patient's prognosis upon remission and prevention of cirrhosis. However, the diagnosis is only reached by the exclusion of other liver diseases also characterized by biochemical, histological and clinical features of chronic hepatitis. In this light, the precise diagnosis is essential. In spite of the clear distinctions of the three diseases overlapping syndromes do exist. These can be characterized as the coexistence of serological parameters of PBC and AIH, of cholestasis and hepatitis, of autoantibodies and viral markers, or the consecutive manifestation of PBC and AIH, or AIH and PSC. However, the overlap of genuine autoimmune diseases is rare. This is relevant regarding therapy and must lead to the precise clinical and diagnostic discrimination of serological autoimmunity (autoantibodies) and genuine autoimmune disease (i.e. AIH) for the initiation of efficatious therapeutic measures. AIH, PBC and PSC are well established indications for liver transplantation with good results. Transplantation is required when cirrhosis is progressive despite therapy and is likely to lead to liver failure.

Transplant medicine has significantly changed the prognosis of diseases leading to terminal organ failure. It has evolved from an experimental procedure to standard therapy for liver, kidney and cardio-vascular diseases. Transplant medicine combines operative organ replacement with the management of severely ill patients before transplantation, as well as life-long follow-up of organ graft recipients. Ten year survival rates of 65% to over 90% have led to a steady increase of transplanted patients seen by general medical care providers which represents a challenge for practicing internists. Apart from organ-specific conditions, infectious, immunosuppressant-associated and metabolic consequences determine long-term survival. These include virus reactivation, graft rejection, anastomotic problems but more importantly general mortality determining factors such as diabetes, renal insufficiency and hypertension, which are often a consequence of immunosuppressant administration. They directly impact long-term survival. The awareness and treatment of these secondary conditions of organ transplantation in routine medical practice contributes significantly to secure the long term success of transplant medicine.

A 40-year-old female patient was admitted for work-up of multiple abdominal masses. The lymphoma-mimicking tumors were detected accidentally during an ultrasound course. The past medical history was unremarkable besides a status post-traumatic splenic rupture and splenectomy. The patient was asymptomatic, especially there were no complaints of fever, night sweats or weight loss. Laboratory tests did not show pathological results. Ultrasound of the abdomen revealed multiple hypoechoic mesenterial and peritoneal enlarged tumors as well as a subhepatic mass (30 x 20 mm). Transmission computed tomography (CT) showed a normal chest, excluded abnormal thoracal masses and confirmed the multiple abdominal nodules. Microparticles were trapped only by tissue with phagocytosis function as cells of the reticulohistiocytary system in liver and spleen. Uptake of (99 m)Tc-labeled microparticles is specific for splenic tissue. All abdominal masses were detectable by single photon emission computed tomography (SPECT) after intravenous administration of this radiotracer. Ultrasound-guided biopsy proved the presence of spleen tissue with follicular hyperplasia. In conclusion, we report a case of post-traumatic splenosis. In 16 - 67 % of patients who experienced traumatic splenic rupture autotransplanted spleen tissue can be detected. Splenosis therefore is an important differential diagnosis of abdominal masses in splenectomized patients.

Sirolimus is an m-TOR inhibitor without renal side effects and potentially protects against the development of malignancy. Due to a higher incidence of complications in two trials and an official warning in the drug information, the use of Sirolimus in liver transplantation is limited. The participants of this consensus meeting had to analyse and evaluate the literature with respect to the potential role of Sirolimus in liver transplantation. This consensus statement follows the scheme normally employed for the presentation of guidelines including the grading of evidence (1a-5) and the extent of recommendation (A-C). Moreover, the consensus included the experience of the authors with respect to the handling of Sirolimus after liver transplantation.

Hereditary hemorrhagic teleangiectasia (HHT) (Osler-Weber-Rendu-disease) is characterized by a combination of muccocutaneous vascular malformations with recurrent spontaneous bleeding and a familiar predisposition. Among visceral manifestations of this disease are only a few descriptions of hepatic involvement. We describe a 53-year-old woman with HHT whose first symptoms of hypercirculatory heart failure developed 1.5 years before the final diagnosis of HHT. We measured a heart-time-volume of 14-151/min. by echocardiography and a flow-volume of 5-9 l/min. in the proper hepatic artery by dopplersonography on admission. We were able to demonstrate multiple intra- and extra-hepatic and gastric arteriovenous malformations by arteriography. Branches of the proper hepatic artery and the left gastric artery were embolized in three serial sessions. By this procedure we were able to reduce the flow-volume in the proper hepatic artery from 5-9l/min. to 1.5l/min. and the heart-time-volume to a minimum of 9.8l/min. and thus stop progression of the hyperdynamic heart failure.