Hepatitis and Vasodilatory Shock due to an Unsuspected Culprit: A Rare Presentation of Multisystem Langerhans Cell Histiocytosis.

Introduction: Langerhans cell histiocytosis (LCH) is a rare hematologic condition which can affect multiple organ systems and has variable presentation. LCH is more commonly seen as a malignancy of childhood. LCH in adulthood can have poor outcomes depending on the involvement of critical organs. Case Presentation: We report a case of a 71-year-old female who presented with progressive weakness, weight loss, diarrhea, and jaundice, and had been undergoing outpatient workup for elevated liver enzymes for the last 2 years. She required admission to the intensive care unit for vasodilatory shock, requiring vasopressor and chronotropic support. Imaging showed an underlying multiorgan process involving the gastrointestinal tract, liver, spleen, and central nervous system. A repeat liver biopsy after a prior inconclusive one revealed the diagnosis of multisystem LCH presenting as secondary sclerosing cholangitis. Conclusion: The uniqueness of this multisystem LCH case lies not only in its rarity but also in the diagnostic journey that necessitated a repeat biopsy for a conclusive diagnosis. Early identification and targeted intervention can help in ensuring better patient outcomes, especially when the presentation can overlap with various other possible conditions.

Biliary Cast Syndrome and Secondary Sclerosing Cholangitis in Critically Ill Patient after Long-Term Treatment in the Intensive Care Unit.

Introduction: Secondary sclerosing cholangitis in critically ill patients (SSC-CIP) is a rare but underdiagnosed entity that occurs after life-threatening events and treatment in the intensive care unit (ICU). The etiology of SSC-CIP is not fully understood but may be caused by ischemic bile duct injury. SSC-CIP is a cholestatic liver disease that rapidly progresses to liver cirrhosis, with a high mortality rate in the first year of 50%. Endoscopic retrograde cholangiopancreatography (ERCP), which is the gold standard for diagnosing SSC-CIP, shows primary SC-like changes, usually in the intrahepatic bile ducts. Biliary cast formation is pathognomonic for SSC-CIP. No proven effective conservative treatment is available for SSC-CIP, and liver transplantation is the only curative therapy when liver cirrhosis or recurrent cholangitis occurs. Case Presentation: We report the case of a 47-year-old male patient who developed cholestasis after a long treatment in the ICU for severe pneumonia. ERCP showed characteristic findings with rarefication and multiple segmental stenosis in the intrahepatic bile ducts. We removed multiple biliary casts from the bile ducts. Conclusion: SSC-CIP should be considered for ICU patients with unclear cholestasis, especially when the cholestasis persists after recovery from the underlying disease. Early diagnosis is important to achieve better outcomes; without liver transplantation, the prognosis is generally poor.

Incidence of Secondary Sclerosing Cholangitis in Hospitalized Long COVID-19 Patients: A Retrospective Single Center Study.

BACKGROUND: SARS-CoV-2 infection and associated COVID-19 disease can lead to critical illness with a risk of developing a multiple organ failure. Subsequently, this may lead to various pathological sequelae, such as secondary sclerosing cholangitis after surviving COVID-19 (SSC-COVID). OBJECTIVE: The aim is to retrospectively analyze a cohort of hospitalized patients with first-wave (February 2020-June 2020) SARS-CoV-2 infection and persisting unclear cholangiopathy to determine the incidence of SSC-COVID and its risk factors. RESULTS: A total of 249 patients were hospitalized at the university hospital in Tübingen, Germany, with SARS-CoV-2 infection during the first wave of the pandemic. Of these, 35.3% (88/249) required intensive care treatment; 16.5% (41/249) of them died due to the complications of COVID-19; 30.8% (64/208) of surviving patients could be followed up und were retrospectively analyzed at our center. The incidence of confirmed SSC-COVID was 7.8% (5/64). All SSC-COVID patients had an ICU stay >20 days, for invasive ventilation, positioning treatment, vasopressor treatment, but possible risk factors for SSC were not significant due to the small number of patients. CONCLUSIONS: SSC-COVID is an emerging disease in post-COVID patients with a high incidence in our single-center cohort. SSC-COVID should be considered as a differential diagnosis, if unclear cholangiopathy or cholestasis persists after SARS-CoV-2 infection.

COVID-19-associated secondary sclerosing cholangitis with liver transplantation.

We report on two cases of orthotopic liver transplantation (OLTX) due to SARS-Cov2-associated secondary sclerosing cholangitis (SSC) following long-term artificial respiration and extra-corporal membrane oxygenation in intensive care. Under these conditions, SSC is a rapidly progredient biliary disease featuring degenerative cholangiopathy, loss of bile ducts, ductular and parenchymal cholestasis, biliary fibrosis, and finally cirrhosis. Reduced perfusion and oxygenation of the peribiliary plexus, severe concurrent infections, and secondary medico-toxic effects appear to play a crucial role in the pathogenesis of the disease. A direct cytopathic effect of SARS-Cov2 on endothelial cells followed by thrombosis and fibrosing obliteration in all parts of the vascular bed of the liver may enhance the virus-associated liver disease and particularly SSC.

BISCIT: Biliary interventions in critically ill patients with secondary sclerosing cholangitis-a study protocol for a multicenter, randomized, controlled parallel group trial.

BACKGROUND: Progress of cholangitis to cholangiosepsis is a frequent observation in patients with secondary sclerosing cholangitis in critically ill patients (SSC-CIP). Adequate biliary drainage may reduce episodes of cholangiosepsis and therefore stabilize liver function and improve survival. The primary objective of the BISCIT study is to demonstrate that scheduled biliary interventions will reduce incidence of cholangiosepsis, liver transplantation, or death in patients with SSC-CIP. METHODS: A total of 104 patients will be randomized at ten study sites. Patients with SSC-CIP, confirmed by endoscopic retrograde cholangiography (ERC), will be randomized 1:1 either in the intervention group which will be treated with scheduled biliary interventions (i.e., therapeutic ERC) every 8 weeks for 6 months or in the control group which will receive standard of care. The randomization will be stratified by center. The composite primary efficacy endpoint is defined as (1) occurrence of death, (2) necessity of liver transplantation, or (3) occurrence of cholangiosepsis within 6 months following randomization. DISCUSSION: Prospective evaluation of endoscopic treatment procedures is urgently needed to establish an evidence-based therapeutic treatment algorithm in SSC-CIP. A positive trial result could change the current standard of care for patients with SSC-CIP. The results of this study will be disseminated through presentations at international congresses, workshops, and peer-reviewed publications. TRIAL REGISTRATION: The trial was registered at ClinicalTrials.gov (NCT05396755, date of registration: May 31, 2022, last update: May 31, 2022).

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.

Implications of anaemia and response to anaemia treatment on outcomes in patients with cirrhosis.

Background & Aims: Anaemia is frequently observed in patients with cirrhosis and was identified as a predictor of adverse outcomes, such as increased mortality and occurrence of acute-on-chronic liver failure. To date, the possible effects of iron supplementation on these adverse outcomes are not well described. We therefore aimed to assess the role of iron supplementation in patients with cirrhosis and its capability to improve prognosis. Methods: Laboratory diagnostics were performed in consecutive outpatients with cirrhosis admitted between July 2018 and December 2019 to the University Hospital Essen. Associations with transplant-free survival were assessed in regression models. Results: A total of 317 outpatients with cirrhosis were included, of whom 61 received a liver transplant (n = 19) or died (n = 42). In multivariate Cox regression analysis, male sex (hazard ratio [HR] = 3.33, 95% CI [1.59, 6.99], p = 0.001), model for end-stage liver disease score (HR = 1.19, 95% CI [1.11, 1.27], p <0.001) and the increase of haemoglobin levels within 6 months (ΔHb6) (HR = 0.72, 95% CI [0.63, 0.83], p <0.001) were associated with transplant-free survival. Regarding the prediction of haemoglobin increase, intake of rifaximin (beta = 0.50, SD beta = 0.19, p = 0.007) and iron supplementation (beta = 0.79, SD beta = 0.26, p = 0.003) were significant predictors in multivariate analysis. Conclusions: An increase of haemoglobin levels is associated with improvement of transplant-free survival in patients with cirrhosis. Because the prediction of haemoglobin increase significantly depends on rifaximin and iron supplementation, application of these two medications can have an important impact on the outcome of these patients. Impact and implications: Anaemia is very common in patients with cirrhosis and is known to be a predictor of negative outcomes, but little is known about the effect of iron substitution in these individuals. In our cohort, increase of haemoglobin levels improved transplant-free survival of patients with cirrhosis. The increase of haemoglobin levels was mainly induced by iron supplementation and was even stronger in the case of concomitant use of iron and rifaximin. Clinical trial registration: UME-ID-10042.

Secondary Sclerosing Cholangitis After Emphysematous Cholecystitis.

A 64-year-old woman was diagnosed with emphysematous cholecystitis. An open cholecystectomy was performed immediately. After the cholecystectomy, jaundice and multiple bile duct strictures that were not present preoperatively appeared. The patient was diagnosed with sclerosing cholangitis secondary to emphysematous cholecystitis. Endoscopic biliary stenting and endoscopic biliary balloon dilatation were performed. However, jaundice did not improve. She developed candidemia 75 days after cholecystectomy. The patient died of multiple organ failures 92 days after cholecystectomy. Although rare, secondary sclerosing cholangitis occurred after emphysematous cholecystitis, and endoscopic treatment was ineffective in this case.

Secondary sclerosing cholangitis and IgG4-sclerosing cholangitis - A review of cholangiographic and ultrasound imaging.

Sclerosing cholangitis (SC) represents a spectrum of chronic progressive cholestatic diseases of the intrahepatic and/or extrahepatic biliary system characterized by patchy inflammation, fibrosis, and stricturing. Primary and secondary SC must be distinguished given the different treatment modalities, risks of malignancy, and progression to portal hypertension, cirrhosis, and hepatic failure. This review focuses on secondary SC and the pathogenic mechanisms, risk factors, clinical presentation, and novel imaging modalities that help to distinguish between these conditions. We explore the detailed use of cholangiography and ultrasound imaging techniques.

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.

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.

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.

Meta-analysis and systematic review of liver transplantation as an ultimate treatment option for secondary sclerosing cholangitis.

Introduction: Secondary sclerosing cholangitis (SSC) is a chronic cholestatic biliary disease, characterized by inflammation, obliterative fibrosis of the bile ducts, stricture formation, and progressive destruction of the biliary tree, which leads to biliary cirrhosis. In recent years, the development of secondary sclerosing cholangitis in critically ill patients (SSC-CIP) has increasingly been perceived as a separate disease entity. Aim: To perform a systematic review and meta-analysis of secondary sclerosing cholangitis and ischaemic cholangiopathy in post organ transplant patients and intensive care unit (ICU). Material and methods: A comprehensive search strategy using the PubMed, Biosis, and EMBASE databases was designed to retrieve relevant clinical data from the published literature up to 2020. Demographic characteristics, laboratory, transplantation, mortality rate, and follow-up data undergoing liver transplantation were extracted from the inclusion studies. We used DerSimonian-Laird random-effects meta-analysis. Analysis was carried out using R statistical software version 4.02. Results: A total of 862 patients with SSC-CIP were extracted from 16 studies. Eighteen studies were searched for the meta-analysis, out of which 16 studies were eligible for the meta-analysis and 2 were excluded. A proportion meta-analysis was performed on liver transplant patients with SSC-CIP and on mortality rate. Significant results were found (Prop = 0.30, 95% CI: 0.12-0.49, p < 0.01), with high heterogeneity among the studies (I 2 = 98%, p < 0.01) and (Prop = 0.45; 95% CI: 0.35-0.56 with I 2 = 80, p < 0.01), respectively. No indication of publication bias, as confirmed by the funnel plot and the risk of bias in the included studies, shows that the study reporting is adequate to judge that no major or minor sources of bias are likely to influence results. Conclusions: The systematic review and meta-analysis show that liver transplantation is a valid option for patients with SSC-CIP, with excellent long-term outcome and improvement of quality of life.

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.

Long-term sequelae of drug-induced liver injury.

Drug-induced liver injury (DILI) has a very variable clinical and biochemical phenotype and differs widely in severity, from mild injury to life-threatening liver failure. Chronic injury has also been reported to occur at a variable frequency, ranging from 3.4% to 39%, 6-12 months after discontinuing the implicated agent. This wide range is probably related to various definitions of chronic liver injury and variable selection of patients. The long-term sequalae of this chronic injury in terms of morbidity and mortality are unclear, although rare vanishing bile duct syndrome is associated with an unfavourable prognosis, with increased risk of chronic liver failure and need for liver transplantation. Other forms of long-term sequalae associated with DILI are progressive fibrosis, autoimmune-like hepatitis, secondary sclerosing cholangitis, sinusoidal obstruction syndrome and, as a common final stage, the development of cirrhosis, portal hypertension and its complications. Immune checkpoint inhibitors, which can cause an autoimmune-like phenotype have also recently been shown to cause sclerosing cholangitis with cytotoxic T CD8+ cell infiltration in biliary tracts. DILI has been shown to have a significant impact on health-related quality of life but very little is known about its psychological consequences in the long-term. Further investigations with structured long-term follow-up and periodic quality of life surveys are needed to assess the impact of DILI on psychological outcomes, particularly in those with chronic sequelae.

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.

Diagnosis of Secondary Sclerosing Cholangitis by Port Site Metastasis.

Port site metastasis is an uncommon but challenging pathological entity whereby metastatic cancer is discovered at the operative port site after surgery. Secondary sclerosing cholangitis is a multifocal stricture disease of the biliary system as the result of extra-biliary pathology; rarely, it is due to an infiltrative disorder such as neoplasia. This is the first reported case of secondary sclerosing cholangitis that was diagnosed with metastatic cancer following the discovery of port site metastasis after laparoscopic cholecystectomy.