Indications and results in cholestatic liver disease - PSC, SSC, PBC.

Primary sclerosing cholangitis (PSC), secondary sclerosing cholangitis (SSC), and primary biliary cholangitis (PBC) are impor-tant indications for liver transplantation. An emerging indication for liver transplantation in selected cases is SSC after severe COVID-19 infection. The clinical presenta-tion of these cholestatic diseases is highly heterogeneous - from asymptomatic and mild elevations of liver enzymes to severe disease-specific complications like recurrent cholangitis or severe bone disorder to de-compensated liver cirrhosis. Such disease-specific clinical complications, disease-spe-cific scores, as well as the MELD score, need to be considered when selecting patients for liver transplantation.Copyright © 2023 Dustri-Verlag Dr. K. Feistle.

Hepatobiliary long-term consequences of COVID-19: dramatically increased rate of secondary sclerosing cholangitis in critically ill COVID-19 patients.

BACKGROUND: Increasing evidence suggests that secondary sclerosing cholangitis (SSC), which can lead to cirrhosis or liver failure, may be a hepatobiliary long-term complication of COVID-19. The aim of this study was to estimate the frequency and outcome of this COVID-19 sequela and to identify possible risk factors. METHODS: This observational study, conducted at University Hospital Charité Berlin and Unfallkrankenhaus Berlin, Germany, involved hospitalized patients with COVID-19 pneumonia, including 1082 ventilated COVID-19 patients. We compared COVID-19 patients who developed SSC with a COVID-19 control group by univariate and multivariate analyses. RESULTS: SSC occurrence after COVID-19 was observed exclusively in critically ill patients with invasive ventilation, albeit with extreme clustering among them. One in every 43 invasively ventilated COVID-19 patients developed this complication. Risk factors preceding the development of secondary sclerosing cholangitis in critically ill COVID-19 patients (SSC-CIP) were signs of systemic reduced blood oxygen supply (e.g., low PaO2/FiO2, ischemic organ infarctions), multi-organ failure (high SOFA score) at admission, high fibrinogen levels and intravenous ketamine use. Multivariate analysis confirmed fibrinogen and increased plasma lactate dehydrogenase as independent risk factors associated with cholangiopathy onset. The 1-year transplant-free survival rate of COVID-19-associated SSC-CIP was 40%. CONCLUSIONS: COVID-19 causes SSC-CIP in a substantial proportion of critically ill patients. SSC-CIP most likely develops due to severe tissue hypoxia and fibrinogen-associated circulatory disturbances. A significant increase of patients with SSC-CIP is to be expected in the post-COVID era.

COVID-19 and liver diseases.

In patients with coronavirus disease 2019 (COVID-19), hepatic involvement occurs in up to 53% of all cases. Via the primary target for severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), the angiotensin-converting enzyme 2 (ACE2) receptor, expressed on cholangiocytes, sinusoidal endothelial cells, and hepatocytes, direct damage to the liver may occur. Furthermore, indirect (= not receptor-mediated) damage to the liver plays a crucial role in the context of COVID-19 due to severe systemic inflammation with cytokine storm, hepatic thrombosis, and systemic hypoxia. In COVID-19, liver enzymes are considered significant predictors of outcome. Thus, it is essential to rule out other causes of liver enzyme elevation, such as other viral infections, drug-induced liver injury, and metabolic, autoimmune and other liver diseases. Secondary sclerosing cholangitis in critically ill patients (SSC-CIP) is highly relevant in treating critically ill patients in the intensive care unit (ICU). Risk factors for SSC-CIP include high doses of catecholamines, high positive end-expiratory pressure (PEEP), and extracorporeal membrane oxygenation (ECMO) therapy. Early recognition of this disease and treatment by endoscopic retrograde cholangiography (ERC) is crucial. Furthermore, liver transplantation should be evaluated. Some patients with COVID-19 are diagnosed with SSC, which is termed COVID-19-associated SSC. COVID-19-associated SSC and SSC-CIP are comparable with regard to clinical phenotype, risk factors, prognosis, and graft-free survival. Patients with pre-existing liver disease are not at increased risk for infection with SARS-CoV-2 but show more severe clinical courses of COVID-19 than patients without pre-existing liver disease. Patients with pre-existing liver cirrhosis may develop acute-on-chronic liver failure (ACLF) upon infection with SARS-CoV-2. ACLF has a high mortality rate, which must be treated in the ICU.Copyright © 2023, The Author(s).

COVID-19-associated secondary sclerosing cholangitis - A case series of 4 patients.

We report a case series of four patients diagnosed with COVID-19-associated secondary sclerosing cholangitis (SSC), a recently described rare late complication of severe COVID-19. Following prolonged stays in the intensive care unit, these patients developed marked sustained cholestasis and jaundice despite clinical improvement. Cholangiography showed beaded appearance of intra-hepatic bile ducts and bile casts were removed in one patient. None of the patients reached normalization of liver enzymes and at least one progressed to liver cirrhosis (follow-up time of 11 to 16 months). COVID-19-associated SSC has a dismal prognosis with rapid progression to advanced chronic liver disease.

Secondary sclerosing cholangitis: mimics of primary sclerosing cholangitis.

Sclerosing cholangitis is a chronic cholestatic disease characterized by stricturing, beading, and obliterative fibrosis of the bile ducts. Sclerosing cholangitis is considered primary (PSC) if no underlying etiology is identified or secondary (SSC) if related to another identifiable cause. In this article, we will review the clinical features, pathogenesis, diagnosis, and imaging findings of PSC and SSC, with an emphasis on features that may aid in the distinction of these entities. We will also discuss various etiologies of SSC including recurrent pyogenic cholangitis, other infectious etiologies, ischemic damage, toxic insults, and immunologic, congenital, and miscellaneous causes, highlighting the unique imaging findings and clinical context of each diagnosis.

Secondary sclerosing cholangitis in a young COVID-19 patient resulting in death: A case report.

BACKGROUND: With the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019 in Wuhan, China, liver injury in patients with coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection has been regularly reported in the literature. There are a growing number of publications describing the occurrence of secondary sclerosing cholangitis (SSC) after SARS-CoV-2 infection in various cases. We present a case of sudden onset SSC in a critically ill patient (SSC-CIP) following COVID-19 infection who was previously healthy. CASE SUMMARY: A 33-year old female patient was admitted to our University Hospital due to increasing shortness of breath. A prior rapid antigen test showed a positive result for SARS-CoV-2. The patient had no known preexisting conditions. With rapidly increasing severe hypoxemia she required endotracheal intubation and developed the need for veno-venous extracorporeal membrane oxygenation in a setting of acute respiratory distress syndrome. During the patient´s 154-d stay in the intensive care unit and other hospital wards she underwent hemodialysis and extended polypharmaceutical treatment. With increasing liver enzymes and the development of signs of cholangiopathy on magnetic resonance cholangiopancreatography (MRCP) as well as endoscopic retrograde cholangiopancreatography (ERCP), the clinical setting was suggestive of SSC. At an interdisciplinary meeting, the possibility of orthotopic liver transplantation and additional kidney transplantation was discussed due to the constant need for hemodialysis. Following a deterioration in her general health and impaired respiratory function with a reduced chance of successful surgery and rehabilitation, the plan for transplantation was discarded. The patient passed away due to multiorgan failure. CONCLUSION: SSC-CIP seems to be a rare but serious complication in patients with SARS-CoV-2 infection, of which treating physicians should be aware. Imaging with MRCP and/or ERCP seems to be indicated and a valid method for early diagnosis. Further studies on the effects of early and late SSC in (post-) COVID-19 patients needs to be performed.

Early detection of COVID-19 cholangiopathy using cholangioscopy-a case report of two critically ill patients.

Background: The coronavirus disease 2019 (COVID-19) crisis caused by the severe respiratory distress syndrome coronavirus 2 (SARS-CoV-2) rapidly led to a pandemic. While the majority of SARS-CoV-2-infected patients present with fever and respiratory symptoms, gastrointestinal symptoms may also occur. In addition, serious hepatic manifestations like cholangiopathy and liver failure have been described. Patients and methods: We identified two critically ill patients suffering from SARS-CoV­2 infection in our intensive care unit (ICU). In both patients, laboratory testing revealed elevated liver chemistries weeks after initial diagnosis with COVID-19. Results: During repeated endoscopic retrograde cholangiopancreatography (ERCP) with cholangioscopy, a severely destructed biliary mucosa with ischemia and epithelial roughness was seen in both patients. Due to the prolonged course of COVID-19 and chronic liver damage with ongoing sepsis, both patients succumbed to the disease. Conclusion: In our opinion, a COVID-19 infection can lead to development of cholangiopathy in critically ill patients. Cholangioscopy performed early can confirm the diagnosis of COVID-19-associated cholangioscopy.

Gamma-glutamyltransferase is a strong predictor of secondary sclerosing cholangitis after lung transplantation for COVID-19 ARDS.

BACKGROUND: Lung transplantation (LTx) can be considered for selected patients suffering from COVID-19 acute respiratory distress syndrome (ARDS). Secondary sclerosing cholangitis in critically ill (SSC-CIP) patients has been described as a late complication in COVID-19 ARDS survivors, however, rates of SSC-CIP after LTx and factors predicting this detrimental sequela are unknown. METHODS: This retrospective analysis included all LTx performed for post-COVID ARDS at 8 European LTx centers between May 2020 and January 2022. Clinical risk factors for SSC-CIP were analyzed over time. Prediction of SSC-CIP was assessed by ROC-analysis. RESULTS: A total of 40 patients were included in the analysis. Fifteen patients (37.5%) developed SSC-CIP. GGT at the time of listing was significantly higher in patients who developed SSC-CIP (median 661 (IQR 324-871) vs 186 (109-346); p = 0.001). Moreover, higher peak values for GGT (585 vs 128.4; p < 0.001) and ALP (325 vs 160.2; p = 0.015) were found in the 'SSC' group during the waiting period. Both, GGT at the time of listing and peak GGT during the waiting time, could predict SSC-CIP with an AUC of 0.797 (95% CI: 0.647-0.947) and 0.851 (95% CI: 0.707-0.995). Survival of 'SSC' patients was severely impaired compared to 'no SSC' patients (1-year: 46.7% vs 90.2%, log-rank p = 0.004). CONCLUSIONS: SSC-CIP is a severe late complication after LTx for COVID-19 ARDS leading to significant morbidity and mortality. GGT appears to be a sensitive parameter able to predict SSC-CIP even at the time of listing.

Secondary Sclerosing Cholangitis in a Critically Ill Patient with Severe SARS-CoV-2 Infection: A Possibly Emergent Entity during the Current Global Pandemic.

A 46-year-old woman without previous history of hepatobiliary disease was admitted to the intensive care unit due to SARS-CoV-2 infection. Admission blood tests revealed impending hyperinflammation in the context of systemic inflammatory response syndrome. She required 12 days of mechanical ventilation and vasopressor support. After admission, liver function tests became deranged in a cholestatic pattern and continued to worsen despite overall clinical improvement. Magnetic resonance cholangiopancreatography revealed liver abscesses, intrahepatic bile duct dilation with multiple strictures and some linear repletion defects at the bifurcation of the common hepatic duct. During endoscopic retrograde cholangiopancreatography, biliary casts were retrieved confirming the diagnosis of secondary sclerosing cholangitis in the critically ill patient triggered by a severe SARS-CoV-2 infection. Other causes of cholestasis and secondary sclerosing cholangitis were properly excluded. We present an illustrative case and discuss the current literature, focusing on SARS-CoV-2 infection contribution to the development of this potentially underdiagnosed and severe condition.

Uma mulher de 46 anos sem antecedentes de patologia hepatobiliar foi admitida na unidade de cuidados intensivos no contexto de infeção por SARS-CoV-2. Apresentava alterações analíticas interpretadas no contexto de síndrome de resposta inflamatória sistémica. Houve necessidade de suporte vasopressor e ventilação mecânica invasiva durante 12 dias. Após a admissão, verificou-se uma alteração das provas hepáticas com padrão colestático, com agravamento contínuo apesar da melhoria do quadro infecioso. A colangiografia por ressonância magnética revelou a presença de abcessos hepáticos, dilatação das vias biliares intrahepáticas com múltiplas estenoses e com alguns defeitos de repleção lineares na bifurcação do ducto hepático comum. Na colangiopancreatografia endoscópica retrógrada foram removidos cilindros bilares da via biliar, confirmando o diagnóstico de colangite esclerosante secundária associada aos cuidados intensivos, no contexto de uma infeção grave por SARS-CoV-2. Foram excluídas outras causas de colestase e colangite esclerosante secundária de forma exaustiva. Apresentamos um caso clínico ilustrativo com respetiva iconografia e revisão da literatura, com especial enfoque na contribuição da infeção por SARS-CoV-2 no desenvolvimento desta entidade clínica, potencialmente grave e subdiagnosticada.

Kinetics of Bilirubin and Ammonia Elimination during Hemadsorption Therapy in Secondary Sclerosing Cholangitis Following ECMO Therapy and Severe COVID-19.

In critically ill patients, liver dysfunction often results in coagulopathy and encephalopathy and is associated with high mortality. Extracorporeal clearance of hepatotoxic metabolites, including bilirubin and ammonia, aims to attenuate further hepatocyte damage and liver injury, resulting in decreased mortality. The efficacy of hemadsorption combined with conventional hemodialysis to eliminate bilirubin and ammonia to support the liver's excretory function in acute liver injury has been described previously. However, the optimal use of liver support systems in chronic liver dysfunction due to secondary sclerosing cholangitis in critically ill patients (SSC-CIP) has not been defined yet. We herein describe the kinetics of successful bilirubin and ammonia elimination by hemadsorption in a patient with SSC-CIP after extracorporeal membrane oxygenation (ECMO) therapy for severe acute respiratory distress syndrome (ARDS) in a patient with coronavirus disease 2019 (COVID-19). During the course of the disease, the patient developed laboratory signs of liver injury during ECMO therapy before clinically detectable jaundice or elevated bilirubin levels. A diagnosis of SSC-CIP was confirmed by endoscopic retrograde cholangiopancreatography (ERCP) based on intraductal filling defects in the intrahepatic bile ducts due to biliary casts. The patient showed stable elevations of bilirubin and ammonia levels thereafter, but presented with progressive nausea, vomiting, weakness, and exhaustion. Based on these laboratory findings, hemadsorption was combined with hemodialysis treatment and successfully eliminated bilirubin and ammonia. Moreover, direct comparison revealed that ammonia is more efficiently eliminated by hemadsorption than bilirubin levels. Clinical symptoms of nausea, vomiting, weakness, and exhaustion improved. In summary, bilirubin and ammonia were successfully eliminated by hemadsorption combined with hemodialysis treatment in SSC-CIP following ECMO therapy and severe COVID-19. This observation is particularly relevant since it has been reported that a considerable subset of critically ill patients with COVID-19 suffer from liver dysfunction associated with high mortality.

A case of secondary sclerosing cholangitis due to COVID-19.

COVID-19 was first recognized by the World Health Organization (WHO) in December 2019 and declared a global pandemic in March 2020. Although COVID-19 primarily results in pulmonary symptoms, it is becoming apparent that it can lead to multisystemic manifestations. Liver damage with elevated AST and ALT is seen in patients with COVID-19. Although the etiology of liver damage is still debated, biliary damage is rarely seen. This case demonstrates a potential complication of COVID-19 in a previously healthy patient. The patient contracted COVID-19 in March 2020 and endured a complicated course including intubation, multiple readmissions, and chronic abdominal pain. He is now awaiting a liver transplant. Our case portrays biliary damage as an additional possible complication of COVID-19 and the importance of imaging in its diagnosis.

Secondary sclerosing cholangitis as a complication of severe COVID-19: A case report and review of the literature.

This case of secondary sclerosing cholangitis (SSC-CIP) emphasizes the need to provide follow-up care for patients that have recovered from COVID-19 in order to understand the complexity of SARS-CoV-2 associated sequela.

High Rate of Gastrointestinal Bleeding in Patients with Secondary Sclerosing Cholangitis in Critically Ill Patients (SC-CIP).

Secondary sclerosing cholangitis in critically ill patients (SC-CIP) is a rare cholestatic liver disease triggered by long-term intensive care treatment. The aim of this study was to evaluate the frequency and characteristics of gastrointestinal bleeding in SC-CIP. Patients with diagnosed SC-CIP were retrospectively identified and compared to a control group of patients with cardiac surgery and intensive care treatment but without the development of SC-CIP. Fifty-three patients with SC-CIP and 19 controls were included in the study. The frequency of gastrointestinal bleeding was 30% in SC-CIP (16 patients) and 5% in the control group (1 patient) (p = 0.03). Bleeding occured in the mean 13 months after admission to an intensive care unit in SC-CIP, three patients (19%) suffered bleeding during intensive care treatment. Three SC-CIP patients (19%) had cirrhosis at the time of bleeding, five (31%) had splenomegaly, and four (25%) received oral anticoagulation. In SC-CIP, 13 bleedings were identified in the upper gastrointestinal tract, two in the lower, and one remained unknown. The most common reasons for bleeding were gastroduodenal ulcers. In total, 80% of patients needed blood units, and one death due to bleeding occurred in SC-CIP. In conclusion, gastrointestinal bleeding is a frequent complication in patients with SC-CIP. Whether the liver disease itself or cofactors cause the susceptibility for bleeding remains unclear.

Secondary sclerosing cholangitis as cause of persistent jaundice in patients with severe COVID-19.

BACKGROUND & AIMS: Little is known about cholestasis, including its most severe variant secondary sclerosing cholangitis (SSC), in critically ill patients with coronavirus disease 19 (COVID-19). In this study, we analysed the occurrence of cholestatic liver injury and SSC, including clinical, serological, radiological and histopathological findings. METHODS: We conducted a retrospective single-centre analysis of all consecutive patients admitted to the intensive care unit (ICU) as a result of severe COVID-19 at the University Hospital Zurich to describe cholestatic injury in these patients. The findings were compared to a retrospective cohort of patients with severe influenza A. RESULTS: A total of 34 patients with severe COVID-19 admitted to the ICU were included. Of these, 14 patients (41%) had no cholestasis (group 0), 11 patients (32%, group 1) developed mild and 9 patients (27%, group 2) severe cholestasis. Patients in group 2 had a more complicated disease course indicated by significantly longer ICU stay (median 51 days, IQR 25-86.5) than the other groups (group 0: median 9.5 days, IQR 3.8-18.3, P = .001; and group 1: median 16 days, IQR 8-30, P < .05 respectively). Four patients in group 2 developed SSC compared to none in the influenza A cohort. The available histopathological findings suggest an ischaemic damage to the perihilar bile ducts. CONCLUSIONS: The development of SSC represents an important complication of critically ill COVID-19 patients and needs to be considered in the diagnostic work up in prolonged cholestasis. The occurrence of SSC is of interest in the ongoing pandemic since it is associated with considerable morbidity and mortality.