• Cardiogenic shock
• Hepatic dysfunction
• Secondary sclerosing cholangitis

• Humans
• Shock, Cardiogenic/complications
• Shock, Cardiogenic/epidemiology
• Shock, Cardiogenic/diagnosis
• Male
• Female
• Middle Aged
• Retrospective Studies
• Cholangitis, Sclerosing/epidemiology
• Cholangitis, Sclerosing/etiology
• Cholangitis, Sclerosing/diagnosis
• Germany/epidemiology
• Aged
• Cholangiopancreatography, Endoscopic Retrograde
• Hospital Mortality/trends
• Follow-Up Studies
• Incidence
• Critical Illness

• Checkpoint inhibitors
• Cholestasis
• DILI
• Hepatotoxicity
• Immunotherapy
• Secondary Sclerosing Cholangitis

• Humans
• Cholangitis, Sclerosing/chemically induced
• Cholangitis, Sclerosing/epidemiology
• Cholangitis, Sclerosing/diagnosis
• Immune Checkpoint Inhibitors/adverse effects
• Nivolumab/adverse effects
• Antibodies, Monoclonal, Humanized/adverse effects

• IgG4-related sclerosing cholangitis
• PSC
• cholangiopathy
• cholangitis

• Acute liver failure
• Acute-on-chronic liver failure
• Cholestasis
• Critically illness
• Sclerosing cholangitis

• Humans
• Intensive Care Units
• Liver Diseases/therapy
• Liver Diseases/diagnosis
• Liver Diseases/mortality
• Liver Cirrhosis/complications
• Liver Cirrhosis/therapy
• Liver Cirrhosis/diagnosis
• Cross-Sectional Studies
• Acute-On-Chronic Liver Failure/therapy
• Acute-On-Chronic Liver Failure/diagnosis
• Acute-On-Chronic Liver Failure/mortality
• Critical Care
• Liver Failure, Acute/therapy
• Liver Failure, Acute/diagnosis
• Liver Failure, Acute/mortality
• Prognosis
• Critical Illness

• Humans
• Liver Transplantation/standards
• Germany
• Gastroenterology/standards
• Practice Guidelines as Topic
• Societies, Medical

• COVID-19
• bile duct diseases
• cholangiopathy
• cholestasis
• pathology
• post-COVID-19 cholangiopathy
• sclerosing cholangitis
• secondary sclerosing cholangitis in critically ill patients

• COVID-19
• SARS-CoV-2
• SSC
• incidence
• long COVID syndrome
• retrospective observational study
• secondary sclerosing cholangitis

• COVID-19
• SARS-CoV-2
• coronavirus
• liver transplantation

• Humans
• COVID-19
• Liver Transplantation
• COVID-19 Testing
• Living Donors
• Retrospective Studies

• Autoimmune hepatitis
• Cholangiocarcinoma
• Gadolinium
• Primary sclerosing cholangitis
• Ursodeoxycholic acid

• Humans
• Cholangitis, Sclerosing/complications
• Cholangitis, Sclerosing/diagnosis
• Cholangitis, Sclerosing/therapy
• Gadolinium
• Liver Transplantation/adverse effects
• Liver Cirrhosis/complications

The biliary system consists of intrahepatic and extrahepatic bile ducts lined by biliary epithelial cells (cholangiocytes). Bile ducts and cholangiocytes are affected by a variety of disorders called cholangiopathies, which differ in aetiology, pathogenesis, and morphology. Classification of cholangiopathies is complex and reflects pathogenic mechanisms (immune-mediated, genetic, drug- and toxin-induced, ischaemic, infectious, neoplastic), predominant morphological patterns of biliary injury (suppurative and non-suppurative cholangitis, cholangiopathy), and specific segments of the biliary tree affected by the disease process. While the involvement of large extrahepatic and intrahepatic bile ducts is typically visualised using radiology imaging, histopathological examination of liver tissue obtained by percutaneous liver biopsy still plays an important role in the diagnosis of cholangiopathies affecting the small intrahepatic bile ducts. To increase the diagnostic yield of a liver biopsy and determine the optimal therapeutic approach, the referring clinician is tasked with interpreting the results of histopathological examination. This requires knowledge and understanding of basic morphological patterns of hepatobiliary injury and an ability to correlate microscopic findings with results obtained by imaging and laboratory methods. This minireview describes the morphological aspects of small-duct cholangiopathies pertaining to the diagnostic process.

• Bile duct
• Cholangiocytes
• Cholangiopathy
• Cholangitis
• Liver biopsy
• Histopathology

• COVID-19
• Critical care
• Liver diseases
• SARS-CoV-2
• Sclerosing cholangitis

• acquired coagulation disorders
• extracorporal circulation
• von Willebrand disease

In recent years, humanity has been confronted with a global pandemic due to coronavirus disease 2019 (COVID-19), which has caused an unprecedented health and economic crisis worldwide. Apart from the respiratory symptoms, which are considered the principal manifestations of COVID-19, it has been recognized that COVID-19 constitutes a systemic inflammatory process affecting multiple organ systems. Across the spectrum of organ involvement in COVID-19, acute liver injury (ALI) has been gradually gaining increasing attention by the international scientific community. COVID-19 associated liver impairment can affect a considerable proportion of COVID-19 patients and seems to correlate with the severity of the disease course. Indeed, COVID-19 patients hospitalized in the intensive care unit (ICU) run a greater risk of developing ALI due to the severity of their clinical condition and in the context of multi-organ failure. The putative pathophysiological mechanisms of COVID-19 induced ALI in ICU patients remain poorly understood and appear to be multifactorial in nature. Several theories have been proposed to explain the occurrence of ALI in the ICU setting, such as hypoperfusion and ischemia due to hemodynamic instability, passive liver congestion as a result of congestive heart failure, ischemia-reperfusion injury, hypoxia due to respiratory failure, mechanical ventilation itself, sepsis and septic shock, cytokine storm, endotheliitis with concomitant coagulopathy, drug-induced liver injury, parenteral nutrition and direct cytopathic viral effect. It should be noted that no specific therapy for COVID-19 induced ALI exists. Therefore, the therapeutic approach lies in preventive measures and is exclusively supportive once ALI ensues. The aim of the current review is to scrutinize the existing evidence on COVID-19 associated ALI in ICU patients, explore its clinical implications, shed light on the underlying pathophysiological mechanisms and propose potential therapeutic approaches. Ongoing research on the particular scientific field will further elucidate the pathophysiology behind ALI and address unresolved issues, in the hope of mitigating the tremendous health consequences imposed by COVID-19 on ICU patients.

• Liver injury
• COVID-19
• Intensive care
• Pathophysiological mechanisms
• Cytokine storm
• Multi-organ failure

• Humans
• COVID-19/complications
• SARS-CoV-2
• Intensive Care Units
• Shock, Septic
• Liver

The 2019 coronavirus disease (COVID-19), resulting from the severe acute respiratory syndrome 2 virus, has transformed our globe and provided a new perspective on respiratory tract infections. However, COVID-19 would not be recognized as a condition restricted to only pneumonia. This narrative review was conducted by searching manuscripts in several databases, including PubMed/ MEDLINE, Web of Science, and Reference Citation Analysis, from December 2019 to July 2022. Many studies have revealed a broad spectrum of potential systemic symptoms, including biliary complications. Although biliary injury has been observed in a very low proportion of COVID-19 patients, it is associated with increased mortalities and long-term morbidities. We identify a cholangiopathy condition in individuals during infection and after recovering from severe COVID-19, defined by a significant increase in serum alkaline phosphatase and signs of bile duct injury. Understanding the pathogeneses behind this condition would help us develop new techniques to prevent these complications. This review thoroughly discusses and summarizes the current information regarding COVID-19-associated cholangiopathy. In addition, the possible explanations for COVID-19-associated cholangiopathy are presented. Since the exact pathogenesis may not be concluded, this review could provide relevant information to encourage additional investigations shortly.

• COVID-19
• Cholestatic injury
• Cholangiopathy
• Alkaline phosphatase

• biliary tract
• cholestatic liver disease
• cirrhosis
• endoscopy
• liver

• Covid-19
• critically ill patients
• liver
• lung transplantation
• secondary sclerosing cholangitis

• Adult
• Child
• Cholangitis, Sclerosing/complications
• Cholangitis, Sclerosing/diagnosis
• Cholangitis, Sclerosing/therapy
• Humans
• Prognosis

• SARS-CoV-2
• cholangiopathy
• cirrhosis
• intensive care unit
• multidrug resistance

• ARDS
• acidic pathway
• adaptive response
• bile acid pattern
• bile acids

Hyperbilirubinaemia has been shown to compromise wound healing in severely burned patients. The therapy options for patients with impairment of wound healing and subsequent severe liver dysfunction are limited. A novel extracorporeal treatment, CytoSorb^® (CytoSorbents Corp, USA), is a whole blood adsorber composed of highly biocompatible and porous polystyrene divinylbenzene copolymer beads covered in a polyvinylpyrrolidone coating. It is capable of extracting mainly hydrophobic middle-sized (up to 55 kDa) molecules from blood via size exclusion, including cytokines and bilirubin. We performed therapy with CytoSorb^® on a severely burned (48% Total Body Surface Area-TBSA) patient with secondary sclerosing cholangitis (SCC) to promote the wound healing process by reducing bilirubin concentrations and to bridge the time to spontaneous liver regeneration or eventually to liver transplantation after two skin transplantations had failed to provide wound closure. In the first 6 days the cartridge was changed on a daily basis and later after every 2–4 days. The therapy with six adsorbers decreased a total bilirubin concentration from 14.02 to 4.29 mg/dl. By maintaining a stable bilirubin concentration under 5 mg/dl, debridement of abdomen and upper extremities with autologous skin grafting and, 4 weeks later, autologous skin grafting of the back from scrotum and lower extremities were performed successfully. After wound healing had been achieved, the CytoSorb therapy was discontinued after 57 days and 27 adsorber changes. CytoSorb therapy can be a promising support of wound and skin graft healing in patients with severe burns and liver dysfunction due to a significant reduction of total bilirubin concentration.

• CytoSorb
• burn trauma
• hemoadsorption
• liver failure
• secondary sclerosing cholangitis

• Liver
• burns
• dysfunction
• liver function
• meta-analysis
• transaminases

• COVID‐19
• SARS‐CoV‐2
• biliary epithelium
• cholangiopathy
• liver injury
• secondary sclerosing cholangitis

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.

• SC-CIP
• cholestatic liver disease
• critically ill
• gastrointestinal bleeding
• secondary sclerosing cholangitis in critically ill patients

The gut-liver axis describes the physiological interplay between the gut and the liver and has important implications for the maintenance of health. Disruptions of this equilibrium are an important factor in the evolution and progression of many liver diseases. The composition of the gut microbiome, the gut barrier, bacterial translocation, and bile acid metabolism are the key features of this cycle. Chronic cholestatic liver diseases include primary sclerosing cholangitis, the generic term secondary sclerosing cholangitis implying the disease secondary sclerosing cholangitis in critically ill patients and primary biliary cirrhosis. Pathophysiology of these diseases is not fully understood but seems to be multifactorial. Knowledge about the alterations of the gut-liver axis influencing the pathogenesis and the outcome of these diseases has considerably increased. Therefore, this review aims to describe the function of the healthy gut-liver axis and to sum up the pathological changes in these cholestatic liver diseases. The review compromises the actual level of knowledge about the gut microbiome (including the mycobiome and the virome), the gut barrier and the consequences of increased gut permeability, the effects of bacterial translocation, and the influence of bile acid composition and pool size in chronic cholestatic liver diseases. Furthermore, therapeutic implications and future scientific objectives are outlined.

• SC-CIP
• gut-liver axis
• microbiome
• primary biliary cholangitis
• primary sclerosing cholangitis

• Animals
• Bacterial Translocation
• Bile Acids and Salts
• Cholangitis, Sclerosing/drug therapy
• Cholangitis, Sclerosing/microbiology
• Cholestasis/microbiology
• Cholestasis/pathology
• Dysbiosis
• Gastrointestinal Microbiome/physiology
• Gastrointestinal Tract/metabolism
• Humans
• Inflammation
• Liver/metabolism
• Liver Cirrhosis, Biliary/microbiology
• Liver Diseases
• Oxidative Stress

• critical illness
• hemodialysis
• illness trajectory
• infectious diseases
• quality improvement

• SC-CIP
• bile acids
• critical illness
• gut permeability
• microbiome
• secondary sclerosing cholangitis

• Acute-Phase Proteins
• Adult
• Aged
• Bacteria/classification
• Bile Acids and Salts
• Carrier Proteins
• Case-Control Studies
• Cholangitis, Sclerosing/complications
• Cholangitis, Sclerosing/microbiology
• Critical Care
• Critical Illness
• Female
• Gastrointestinal Microbiome/physiology
• Gastrointestinal Tract/microbiology
• Gastrointestinal Tract/physiology
• Haptoglobins
• Humans
• Leukocyte L1 Antigen Complex
• Liver/physiology
• Liver Cirrhosis/complications
• Male
• Membrane Glycoproteins
• Middle Aged
• Protein Precursors

• not applicable ÖGIAIN

• Hepatic artery thrombosis
• Intensive care
• Ischemic cholangiopathy
• Liver transplantation

• Bile Duct Diseases/diagnosis
• Bile Duct Diseases/therapy
• Bile Ducts/blood supply
• Humans
• Ischemia/diagnosis
• Ischemia/therapy
• Practice Guidelines as Topic

• CA19-9
• CEA
• ERCP
• biliary obstruction
• biliary stenosis
• cholangiocarcinoma
• cholangiopathy
• cholangitis
• cholestasis
• pancreatic cancer
• pancreatitis

• Critically ill patients
• Intensive care unit
• Secondary sclerosing cholangitis

• biomarkers
• chronic DILI
• diagnostic tools
• drug-induced liver injury
• phenotype
• prognostic models

• Adult
• Aged
• Chemical and Drug Induced Liver Injury/diagnosis
• Chemical and Drug Induced Liver Injury/epidemiology
• Chemical and Drug Induced Liver Injury/etiology
• Chemical and Drug Induced Liver Injury/therapy
• Fatty Liver/chemically induced
• Female
• Histocompatibility Testing
• Humans
• Liver Neoplasms/chemically induced
• Male
• Middle Aged
• Mitochondria/drug effects
• Practice Guidelines as Topic
• Risk Factors

Hepatic artery avulsion following politrauma is an extremely rare condition with a very high mortality rate. Management is based on damage control surgery given the precarious situation of these patients. Ligating the artery is one option under such circumstances, despite potential consequences including ischemic cholangiopathy (IC). Ischemic cholangiopathy, which can be caused by an insufficient blood supply to the bile duct, generally results in stricture and recurrent cholangitis, and the need for a liver transplant in extreme cases.

We present the case of a 37-year-old male with multiple traumas after falling from the third floor of a building. He was hemodynamically unstable upon arrival at the emergencies department, with no improvement on administration of aggressive fluid therapy. A Echo-FAST exam evidenced fluid in all quadrants, so the patient was transferred to the operating room where a 4-litre hemoperitoneum secondary to total avulsion of the proper hepatic artery was observed. The patient required massive transfusion and vasoactive drugs, with instability throughout the intervention; therefore, we decided to ligate the proper hepatic artery. Hepatic dysfunction and diffuse IC with multiple episodes of recurrent cholangitis were observed during the postoperative period. Given the irreversible clinical picture, we opted for a liver transplant 70 days after the patient’s initial admission. The patient died on Day 34 post-transplant due to irreversible ischemic brain damage and a right occipital hemorrhage.

Hepatic artery avulsion due to trauma is very rare and its management very complex, and in certain situations the artery must be ligated. The main consequence of ligating the hepatic artery is IC, which is more frequently observed secondary to iatrogenic lesions or systemic diseases, while very few cases have been published in which IC is secondary to hepatic artery avulsion caused by hepatic trauma. Treatment depends on the extent of ischemia, and when the damage is diffuse, as in our case, it may involve a liver transplant.

• eculizumab, secondary sclerosing cholangitis
• hemolytic uremic syndrome
• therapeutic plasma exchange

• Causal link
• Intensive care
• Liver failure
• Non-natural death
• Secondary sclerosing cholangitis in the critically ill patient (SSC-CIP)
• Traffic accident