BACKGROUND: Surgical factors and direct cytotoxicity of bile salts on cholangiocytes may play a role in the development of ischemic cholangiopathy (IC) after liver transplantation (LTx). There is no validated consensus on how to protect the bile ducts during procurement, static preservation, and LTx. Meanwhile, IC remains the most troublesome complication after LTx. AIM: To characterize bile duct management techniques during the LTx process among European transplant centers in cases of donation after brain death (DBD) and circulatory death (DCD). METHOD: An European Liver and Intestine Transplant Association-European Liver Transplant Registry web survey designed to conceal respondents' personal information was sent to surgeons procuring and/or transplanting livers in Europe. RESULTS: Sixty-five percent of responses came from large transplant centers (>50 procurements/y). In 8% of DBDs and 14% of DCDs the bile duct is not rinsed. In 46% of DBDs and 52% of DCDs surgeons prefer to remove the gallbladder after graft reperfusion. Protocols concerning preservation solutions (nature, pressure, volume) are extremely heterogeneous. In 54% of DBDs and 61% of DCDs an arterial back table pressure perfusion is performed. Steroids (20%-10%), heparin (72%-60%), prostacyclin (3%-7%), and fibrinolytics (4%-11%) are used as donor-protective interventions in DBD and DCD cases, respectively. In 2% of DBD and 6% of DCD cases a hepatic artery reperfusion is performed first. In 4% of DBD and 6% of DCD cases, fibrinolytics are administered through the hepatic artery during the bench and/or implantation. CONCLUSION: This European web survey shows for the first time the heterogeneity in the management of bile ducts during procurement, preservation, and transplantation in Europe. In the context of sharing more marginal liver grafts, an expert meeting must be organized to formulate guidelines to be applied to protect liver grafts against IC.

• MeSH
• Cholangitis etiology   MeSH
• Ischemia etiology   MeSH
• Humans MeSH
• Tissue and Organ Harvesting adverse effects   methods   MeSH
• Perfusion adverse effects   methods   MeSH
• Postoperative Complications etiology   MeSH
• Graft Survival MeSH
• Surveys and Questionnaires MeSH
• Reperfusion adverse effects   methods   MeSH
• Liver Transplantation adverse effects   MeSH
• Organ Preservation adverse effects   methods   MeSH
• Bile Ducts blood supply   transplantation   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Europe MeSH

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.

• Publication type
• Journal Article MeSH
• Review MeSH

ATP-binding cassette (ABC) subfamily B member 4 (ABCB4), also known as multidrug resistance protein 3 (MDR3), encoded by ABCB4, is involved in biliary phospholipid secretion, protecting hepatobiliary system from deleterious detergent and lithogenic properties of the bile. ABCB4 mutations altering canalicular ABCB4 protein function and expression may have variable clinical presentation and predispose to several human liver diseases. Well-established phenotypes of ABCB4 deficit are: progressive familial intrahepatic cholestasis type 3, gallbladder disease 1 (syn. low phospholipid associated cholelithiasis syndrome), high ɣ-glutamyl transferase intrahepatic cholestasis of pregnancy, chronic cholangiopathy, and adult biliary fibrosis/cirrhosis. Moreover, ABCB4 aberrations may be involved in some cases of drug induced cholestasis, transient neonatal cholestasis, and parenteral nutrition-associated liver disease. Recently, genome-wide association studies have documented occurrence of malignant tumours, predominantly hepatobiliary malignancies, in patients with ABCB4/MDR3 deficit. The patient's age at the time of the first presentation of cholestatic disease, as well as the severity of liver disorder and response to treatment are related to the ABCB4 allelic status. Mutational analysis of ABCB4 in patients and their families should be considered in all individuals with cholestasis of unknown aetiology, regardless of age and/or time of onset of the first symptoms.

• MeSH
• Alleles MeSH
• Liver Cirrhosis, Biliary genetics   MeSH
• Cholagogues and Choleretics therapeutic use   MeSH
• Cholelithiasis genetics   MeSH
• Cholestasis genetics   MeSH
• Cholestasis, Intrahepatic genetics   MeSH
• Pregnancy Complications genetics   MeSH
• Ursodeoxycholic Acid therapeutic use   MeSH
• Chemical and Drug Induced Liver Injury genetics   MeSH
• Humans MeSH
• Liver Diseases etiology   genetics   MeSH
• Gallbladder Diseases genetics   MeSH
• Bile Duct Diseases genetics   MeSH
• ATP Binding Cassette Transporter, Subfamily B deficiency   genetics   metabolism   MeSH
• Parenteral Nutrition adverse effects   MeSH
• Age of Onset MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Review MeSH

• MeSH
• Liver Diseases MeSH
• Gallbladder Diseases MeSH
• Biliary Tract Diseases MeSH
• Bile Duct Diseases MeSH
• Publication type
• Congress MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• gastroenterologie

Úvod: Transplantace jater je etablovanou život zachraňující metodou pro pacienty s akutním nebo chronickým jaterním selháním, některými vybranými malignitami jater. Vzhledem k nedostatku orgánů k transplantaci a současně narůstajícímu počtu pacientů na čekací listině, se dárci se smrtí oběhu (DCD) stávají stále důležitější možným zdrojem jaterních štěpů, s potenciálem částečně vyplnit mezeru mezi počtem dárců a příjemců.Metody: Retrospektivní analýza DCD dárců a transplantací jater. Výsledky: V období květen 2016 až září 2019 jsme provedli v naší instituci celkem 9 transplantací jater od DCD dárců. Všechny výkony vyjma jednoho byly primotransplantace. Příjemci byli muži v 5 případech (56 %), ženy byly 4 (44 %). Průměrný věk DCD dárce byl 41±12 (22–57) let, doba strávená na umělé plicní ventilaci 7±1, teplá ischémie 19±3 minut. Průměrný věk příjemce byl 51±22 (4–73) let, doba studené ischémie 3h:59m±27m, manipulační čas 23±5 minut. Časně po transplantaci zemřel 1 pacient (11 %). V jednom případě jsme zaznamenali rekurenci hepatitidy C (11 %). Průběrná doba sledování je 19±13 (7–37) měsíců. Dosud jsme nezaznamenali ani jediný případ ischemické cholangiopatie. Závěr: Transplantace jater od DCD dárců umožňuje navýšit počet jater k transplantaci od zemřelých dárců, současně tak pro pacienty snižuje dobu na čekací listině. Prezentovaný soubor dokumentuje první zkušenosti s touto metodou v České Republice.

Introduction: Liver transplantation is established as a lifesaving procedure for patients with acute and chronic liver failure, as well as certain selected malignancies. Due to a continuing organ shortage and ever-growing patient waiting lists, donation after cardiac death (DCD) is becoming more frequently utilized in order to close the gap between “supply and demand”. Methods: A retrospective analysis of DCD and subsequent liver transplantations was performed. Results: From May 2016 to September 2019, a total of 9 DCD liver transplantations were performed in our institution. All cases except one were primary liver transplantations. The recipients comprised 5 (56%) males and 4 (44%) females. The mean DCD donor age was 41±12 (22–57) years, with ventilation duration of 7±1 days and warm ischemia time 19±3 minutes. The average recipient age was 51±22 (4–73) years, with an average cold ischemia 3h:59m±27m and manipulation time of 23±5 minutes. Periprocedural mortality was 1 (11%). Hepatitis C recurrence was documented in 1 (11%) patient. The mean follow-up time was 19±13 (7–37) months. Until now, we have not observed any signs of ischemic cholangiopathy. Conclusion: DCD liver transplantation allows us to enlarge the pool of potential liver grafts, thus decreasing the time spent on the liver recipient waiting list. This paper documents the first series of DCD liver transplantations in the Czech Republic.

• Keywords
• dárci po nevratné zástavě oběhu,
• MeSH
• Tissue Donors MeSH
• Humans MeSH
• Retrospective Studies MeSH
• Liver Transplantation * methods   MeSH
• Check Tag
• Humans MeSH

BACKGROUND & AIMS: Despite strong evidence for improved preservation of donor livers by machine perfusion, longer post-transplant follow-up data are urgently needed in an unselected patient population. We aimed to assess long-term outcomes after transplantation of hypothermic oxygenated machine perfusion (HOPE)-treated donor livers based on real-world data (i.e., IDEAL-D stage 4). METHODS: In this international, multicentre, observational cohort study, we collected data from adult recipients of HOPE-treated livers transplanted between January 2012 and December 2021. Analyses were stratified by donation after brain death (DBD) and donation after circulatory death (DCD), sub-divided by their respective risk categories. The primary outcome was death-censored graft survival. Secondary outcomes included the incidence of primary non-function (PNF) and ischaemic cholangiopathy (IC). RESULTS: We report on 1,202 liver transplantations (64% DBD) performed at 22 European centres. For DBD, a total number of 99 benchmark (8%), 176 standard (15%), and 493 extended-criteria (41%) cases were included. For DCD, 117 transplants were classified as low risk (10%), 186 as high risk (16%), and 131 as futile (11%), with significant risk profile variations among centres. Actuarial 1-, 3-, and 5-year death-censored graft survival rates for DBD and DCD livers were 95%, 92%, and 91%, vs. 92%, 87%, and 81%, respectively (log-rank p = 0.003). Within DBD and DCD strata, death-censored graft survival was similar among risk groups (log-rank p = 0.26, p = 0.99). Graft loss due to PNF or IC was 2.3% and 0.4% (DBD), and 5% and 4.1% (DCD). CONCLUSIONS: This study shows excellent 5-year survival after transplantation of HOPE-treated DBD and DCD livers with low rates of graft loss due to PNF or IC, irrespective of their individual risk profile. HOPE treatment has now reached IDEAL-D stage 4, which further supports its implementation in routine clinical practice. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05520320. IMPACT AND IMPLICATIONS: This study demonstrates the excellent long-term performance of hypothermic oxygenated machine perfusion (HOPE) treatment of donation after circulatory and donation after brain death liver grafts irrespective of their individual risk profile in a real-world setting, outside the evaluation of randomised-controlled trials. While previous studies have established safety, feasibility, and efficacy against the current standard, according to the IDEAL-D evaluation framework, HOPE treatment has now reached the final IDEAL-D stage 4, which further supports its implementation in routine clinical practice.

• MeSH
• Tissue Donors statistics & numerical data   MeSH
• Adult MeSH
• Cohort Studies MeSH
• Middle Aged MeSH
• Humans MeSH
• Perfusion * methods   instrumentation   MeSH
• Graft Survival * MeSH
• Aged MeSH
• Hypothermia, Induced methods   MeSH
• Liver Transplantation * methods   adverse effects   MeSH
• Organ Preservation * methods   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH

Po dobu 12 měsíců byla sledována medikace pacientů léčených statiny, u kterých bylo současně přítomno alespoň jedno předem definované onemocnění potenciálně léčitelné farmaky, která mohou se statiny vyvolávat středně závažné nebo závažné lékové interakce. Celkem bylo sledováno 1969 pacientů, 1042 mužů a 927 žen. Jejich průměrný věk byl 62,96 ± 9,97 roku, jejich průměrná tělesná hmotnost dosahovala 84,89 ± 15,37 kg, jejich obvod pasu činil 97,39 ± 13,34 cm a jejich průměrný BMI představoval 29,47 ± 4,53 kg/m2. Nejčastějším současným onemocněním byla hypertenze (n = 1790), ICHS (n = 839) a zánětlivé onemocnění pohybového aparátu (n = 394). Pacienti byli průměrně léčeni 4,29 druhu léčiva, nejvíce v případě simvastatinu (4,48) a nejméně v případě fluvastatinu (3,93). U 9 pacientů byly podávány 2 různé statiny současně, u 28 pacientů byly podávány 2 různé léčivé přípravky obsahující inhibitory ACE, u 34 pacientů byly podávány 2 různé přípravky ze skupiny nesteroidních protizánětlivých léčiv (NSAID); 4 pacienti byli dokonce současně léčeni 3 NSAID současně. Vyskytlo se jedno současné podávání dvou různých ß-blokátorů. Pacienti léčení statiny (simvastatin, fluvastatin, atorvastatin) byli shodně exponováni tzv. kritickým léčivům (tj. léčivům potenciálně schopným vyvolat při současném podávání se statiny lékovou interakci). Míra expozice tzv. kritickým léčivům činila 13,71 na 100 pacientoroků v případě fluvastatinu, 14,74 na 100 pacientoroků v případě simvastatinu a 14,96 na 100 pacientoroků v případě atorvastatinu, tyto rozdíly nebyly statisticky významné. Riziko vzniku potenciální lékové interakce (klinicky středně závažné až závažné) činilo 4,39 na 100 pacientoroků v případě fluvastatinu, 14,74 na 100 pacientoroků v případě simvastatinu a 14,96 na 100 pacientoroků v případě atorvastatinu. Celkově bylo pozorováno 124 nežádoucích účinků u 73 pacientů. Pozorovány byly dva případy rhabdomyolýzy (simvastatin) a 11 dalších závažných nežádoucích účinků (z toho 2krát křeče a parestezie ve svalech, 3krát myalgie, 1krát zvýšení hodnot ALT a 1krát cholangiopatie). Relativní výskyt pozorovaných nežádoucích účinků činil 6,12 % u pacientů léčených simvastatinem, 3,34 % u pacientů léčených atorvastatinem a 1,05 % u pacientů léčených fluvastatinem.

Patients on statins suffering from at least one predefined concomitant disease whose treatment may cause moderate to serious drugdrug interactions with statins were followed up for 12 months. The study set included 1969 patients, 1042 males and 927 females, mean age 62.96 ± 9.97 years, mean body weight 84.89 ± 15.37 kg, mean waist circumference 97.39 ± 13.34 cm and mean BMI 29.47 ± 4.53 kg/m2. The most common comorbidities were hypertension (n = 1790), CAD (n = 839) and inflammatory locomotor disease (n = 394). The patients received 4.29 types of drugs on average, ranging from 4.48 types in the patients on simvastatin to 3.93 types in those on fluvastatin. Nine patients were cotreated with two different statins, 28 patients were given two different agents containing ACE inhibitors, 34 received two types of nonsteroidal anti-inflammatory drugs (NSAIDs) and 4 patients were even cotreated with 3 NSAIDs. One patient was coprescribed two different ß-blockers. The patients on statins (simvastatin, fluvastatin, atorvastatin) were exposed to so-called critical drugs (with a potential to cause drug interactions when given in addition to statins). The levels of exposure to such critical drugs were 13.71 per 100 patient-years for fluvastatin therapy, 14.74 per 100 patient-years for simvastatin therapy and 14.96 per 100 patient-years for atorvastatin therapy; the differences were not statistically significant. The drug-drug interaction (intermediate to serious) risk rates were 4.39 per 100 patient-years for fluvastatin, 14.74 per 100 patient-years for simvastatin and 14.96 per 100 patient- years for atorvastatin. A total of 124 adverse events were observed in 73 patients. Two cases of rhabdomyolysis (simvastatin) and 11 other serious adverse effects (including 2 cases of muscle cramps and paresthesia, 3 cases of myalgia, 1 case of elevated ALT and 1 case of cholangiopathy) were reported. The relative incidence rates of adverse effects were 6.12 % for simvastatin therapy, 3.34 % for atorvastatin therapy and 1.05 % for fluvastatin therapy.

• MeSH
• Dyslipidemias drug therapy   MeSH
• Financing, Organized MeSH
• Comorbidity MeSH
• Drug Interactions MeSH
• Humans MeSH
• Polypharmacy MeSH
• Retrospective Studies MeSH
• Aged MeSH
• Hydroxymethylglutaryl-CoA Reductase Inhibitors administration & dosage   pharmacology   adverse effects   MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Clinical Trial MeSH

IgG4-related sclerosing cholangitis, a biliary manifestation of an IgG4-related disease, belongs to the spectrum of sclerosing cholangiopathies which result in biliary stenosis. It presents with signs of cholestasis and during differential diagnosis it should be distinguished from cholangiocarcinoma or from other forms of sclerosing cholangitis (primary and secondary sclerosing cholangitis). Despite increasing information and recently established diagnostic criteria, IgG4-related sclerosing cholangitis remains underdiagnosed in routine clinical practice. The diagnosis is based on a combination of the clinical picture, laboratory parameters, histological findings, and a cholangiogram. Increased serum IgG4 levels are nonspecific but are indeed a part of the diagnostic criteria proposed by the Japan Biliary Association and the HISORt criteria for IgG4-SC. High serum IgG4 retains clinical utility depending on the magnitude of elevation. Approximately 90% of patients have concomitant autoimmune pancreatitis, while 10% present with isolated biliary involvement only. About 26% of patients have other organ involvement, such as IgG4-related dacryoadenitis/sialadenitis, IgG4-related retroperitoneal fibrosis, or IgG4-related renal lesions. A full-blown histological finding characterized by IgG4-enriched lymphoplasmacytic infiltrates, obliterative phlebitis, and storiform fibrosis is difficult to capture in practice because of its subepithelial localization. However, the histological yield is increased by immunohistochemistry, with evidence of IgG4-positive plasma cells. Based on a cholangiogram, IgG-4 related sclerosing cholangitis is classified into four subtypes according to the localization of stenoses. The first-line treatment is corticosteroids. The aim of the initial treatment is to induce clinical and laboratory remission and cholangiogram normalization. Even though 30% of patients have a recurrent course, in the literature data, there is no consensus on chronic immunosuppressive maintenance therapy. The disease has a good prognosis when diagnosed early.

• MeSH
• Diagnosis, Differential MeSH
• Immunoglobulin G MeSH
• Humans MeSH
• Neoplasm Recurrence, Local MeSH
• Bile Duct Neoplasms * diagnosis   MeSH
• Cholangitis, Sclerosing * diagnosis   MeSH
• Rare Diseases MeSH
• Bile Ducts, Intrahepatic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Východisko. Magneticko-rezonanční cholangiopankreatikografie (MRCP) je založena na využití těžce vážených ETSE (echo-train spin echo) T2 sekvencí s potlačením tuku, které poskytují vizualizaci pomalu proudící či stagnující tekutiny. Jde o krátké sekvence v koronární rovině se šíří vrstvy 8 cm nebo 4 mm. V práci jsou předloženy vlastní zkušenosti s MRCP vyšetřeními za posledních 12 měsíců. Metody a výsledky. Celkově autoři provedli 88 vyšetření, z toho do souboru zařadili 67 vyšetření, která byla jednoznačně klinicky indikovaná a technicky zdařilá. Z 67 pacientů bylo 20 mužů ve věku 25–83le t a 47 žen ve věku 19–82 let. Pacienti byli rozděleni do 4 základních indikačních skupin (I. – přechodná cholestáza, normální ultrazvukové vyšetření, II. – jednoznačná cholestáza, III. – patologie pankreatu, IV. – nezařazení). Nejpočetnější skupinou se stala skupina I. (35 pacientů). U 7 (20 %) z nich byla nalezena patologická odchylka převážně charakteru choledocholithiázy a stenóz včetně mnohočetných stenóz při později ověřené primární sklerotizující cholangoitidě. MRCP bylo jednoznačně diagnosticky přínosné u pacientů s cholestázou (16 pacientů ve skupině II.), u nichž MRCP jednoznačně odpovědělo na otázku žádanou klinikem. Ujednoho pacienta (z celkových čtyř) s primární sklerotizující cholangoitidou nebyly však na MRCP zachyceny všechny intrahepatální stenózy, které byly zobrazeny na ERCP. MRCP přesvědčivě zobrazila u tohoto pacienta pouze extrahepatální stenózy. Závěry. MRCP by měla zaujmout pevné místo ve vyšetřovacím algoritmu pacientů s patologií žlučových cest. Má význam nejen u pacientů, u kterých je endoskopická cholangiopankreatikografie (ERCP) kontraindikována či se nezdaří, ale přínosné je i u pacientů s přechodnou cholestázou s negativním ultrazvukovým nálezem.

Background. Magnetic resonance cholangiopancreaticography (MRCP) is based on heavily weighted T2 sequences (ETSE – echo-train spin echo) with suppression of fat, giving visualisation of slowly flowing or stagnating fluid. MRCP are short sequences in coronary plane with thickness of 8 cm or 4 mm. Retrospective analysis of all MRCP examinations performed during last 12 months is presented. Methods and Results. Eighty-eight examinations were done, of which 67 ones with both adequate technical quality and clinical indication were included into the study (20 males aged 25–83ye ars, 47 women aged 19–82 years). Patients were divided into 4 groups regarding to the indications (group I. – temporary cholestasis, normal abdominal ultrasound, II. – definite cholestasis, III. – pathologic findings on pancreas, IV. – other). Vast majority of patients were included into group I (35 subjects). In 7 (20 %) of them choledocholithiasis and/or stenoses (including multiple stenoses in primary sclerotizing cholangoitis) were found. MRCP brought diagnostic information in subjects with cholestasis (group II.) and answered questions given by clinicians. However, in 1 of 4 subjects with primary sclerotizing cholangoitis,MRCP did not reveal intra-hepatic stenoses, which were later visualised by classical ERCP. Only the extrahepatic stenoses were diagnosed by MRCP in the latter subject. Conclusions. MRCP should become a standard examination in the diagnostic algorithm in patients with cholangiopathies. MRCP has its value not only in subjects with unsuccessful or contraindicated ERCP, but also in subjects with temporary cholestasis with negative ultrasound finding.

• MeSH
• Cholangiopancreatography, Endoscopic Retrograde contraindications   methods   adverse effects   MeSH
• Cholestasis diagnosis   ultrasonography   MeSH
• Adult MeSH
• Klatskin Tumor diagnosis   ultrasonography   MeSH
• Middle Aged MeSH
• Humans MeSH
• Magnetic Resonance Imaging contraindications   methods   MeSH
• Aged MeSH
• Sensitivity and Specificity MeSH
• Gallstones diagnosis   ultrasonography   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Review MeSH
• Comparative Study MeSH

• MeSH
• Diagnostic Techniques, Digestive System MeSH
• Gastrointestinal Diseases * radiography   MeSH
• Radiography, Abdominal methods   MeSH
• Publication type
• Handbook MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• gastroenterologie
• radiologie, nukleární medicína a zobrazovací metody