Surveillance of hepatocellular carcinoma - next level

Universitatea de Stat de Medicină şi Farmacie „Nicolae Testemiţanu”, Chişinău, Republica MoldovaIntroducere. Incidența la nivel mondial a CHC-carcinomului hepatocelular este intens eterogenă datorită prevalenței variabile a factorilor de risc implicați. Beneficiile potențiale ale programelor de supraveghere trebuie cântărite, ținând cont de consecințele severe ale diagnosticării tardive a CHC. Scopul studiului. Să analizeze datele bibliografice privind direcțiile viitoare și cele mai bune practici actuale în ceea ce privește supravegherea CHC. Metode și Material. S-a efectuat o căutare avansată în bazele de date PubMed ținând cont de articole relevante, publicate în ultimii 5 ani. Termenii de căutare în limba engleză utilizați au fost: „Surveillance for Hepatocellular Carcinom”, „Alpha-Fetoprotein (AFP)”, „biological markers”.Rezultate. Supravegherea CHC se referă la screening-ul pacienților cu risc crescut, la intervale regulate, cu scopul imediat de detecție într-un stadiu incipient. Supravegherea semestrială ecografică manifestă sensibilitate scăzută pentru detecția dimensiunilor mici. Se fac eforturi centrate substanțial pe biomarkerii serologici, AFP fiind cel mai utilizat, parțial secretat de celulele CHC, poate sugera oprirea maturării celulare într-o stare pseudoembrionară. Utilizarea este controversată cu sensibilitate și specificitate scăzută, prag optim diagnostic de 400 ng/mL. Limitarea utilizării indusă de CHC AFP-negativ < 20 ng/mL. În practică se utilizează scorul GALAD, combinând sex, vârstă, AFP, AFP-L3% și DCP pentru diagnostic și supraveghere, validat extern cu desemnare FDA. Adoptarea supravegherii CHC rămâne suboptimală, în ciuda asocierii cu o mortalitate mai scăzută legată de cancer la pacienții cu ciroză. Concluzie. Supravegherea CHC este subutilizată în practica clinică, ceea ce îi poate reduce eficacitatea – astfel, îmbunătățirea aplicării metodelor imagistice, biomarkerilor biologici, hepatologiei de tele-sănătate este o țintă pentru eforturile de intervenție.Background. The worldwide incidence of HCC-hepatocellular carcinoma is highly heterogeneous due to the variable prevalence of underlying risk factors. The potential benefits of surveillance programs must be weighed against the severe consequences of late diagnosis of HCC. Aim of the study. To analyze the bibliographic data regarding the future directions and best current practice regarding surveillance for HCC. Methods and materials. An advanced search was performed in PubMed database taking into account relevant articles published in the last 5 years. The search English terms used were: „Surveillance for Hepatocellular Carcinoma”, „Alpha-Fetoprotein (AFP)”, „biological markers”. Results. HCC surveillance refers to the screening of high-risk patients at regular intervals with the immediate aim of early detection. Semiannual ultrasound surveillance shows low sensitivity for detecting small HCC. Efforts are focused substantially on serological biomarkers, AFP being the most used, partially secreted by HCC cells, may suggest arrest of cellular maturation in a pseudoembryonic state. Its use is controversial with low sensitivity and specificity, optimal diagnostic threshold of 400 ng/mL. Limitation of use is induced by AFP-negative HCC < 20 ng/mL. In practice, the GALAD score combining sex, age, AFP, AFP-L3% and DCP is used for diagnosis and surveillance, externally validated with FDA designation. Uptake of HCC surveillance remains suboptimal despite its association with lower cancer-related mortality in cirrhotic patients. Conclusion. HCC surveillance is underutilized in clinical practice, which may reduce its effectiveness – thus, improving the application of imaging methods, biological biomarkers, and telehealth hepatology is a target for intervention efforts

Портальный тромбоз при прогрессирующем заболевании печени: обзор литературы

Rezumat. Scopul lucrării prezente constă în studierea mecanismelor de dezvoltare ale trombozei de sistem venos port la pacienții cu boală hepatică avansată, impactul asupra evoluției bolii, perspective fiziopatologice. A fost efectuată o căutare în baza de date electronice PubMed, fiind luate în considerare articolele relevante, publicate în ultimii 10 ani. Termenii de căutare utilizați (în limba engleză) au fost: “Portal vein thrombosis”, “Liver cirrhosis”, “Hypercoagulability”, “Anticoagulation”,” Direct oral anticoagulants”, “Portal hypertension”,” protrombotic state”. Tromboza de venă portă reprezintă o complicație binecunoscută în cursul natural al bolii hepatice avansate , variind de la cazuri asimptomatice până la afecțiuni care pun viața în pericol, legate de hipertensiunea portală și decompensarea hepatică. Staza fluxului portal, tulburările complexe de hipercoagulare dobândite și factorii exogeni care conduc la disfuncția endotelială se prezintă ca factori cheie pentru dezvoltarea TVP. Cu toate acestea, apariția TVP rămâne imprevizibilă și multe aspecte legate de istoria sa naturală, semnificația prognostică și tratamentul sunt încă evazive. Deși rezoluția spontană sau stabilitatea bolii apar în majoritatea cazurilor de TVP , factorii care predispun la progresia sau recidiva bolii după recanalizarea spontană nu sunt încă clarificați. În plus, impactul TVP asupra progresiei cirozei hepatice este încă dezbătut, deoarece TVP poate reprezenta în sine o consecință a progresiei fibrozei hepatice și a disfuncției hepatice. Boala hepatică avansată nu mai este considerată o afecțiune asociată cu un risc scăzut de apariție a evenimentelor trombotice. Tromboza de venă portă reprezintă o complicație comună și potențială a cirozei hepatice. În ciuda cunoștințelor avansate în patogeneza și diagnosticul TVP , multe aspecte privind istoria sa naturală și rezultatul prognostic rămân evazive.Summary. Portal vein thrombosis is a well-known complication in the natural course of advanced liver disease, ranging from asymptomatic cases to life-threatening conditions related to portal hypertension and hepatic decompensation. Portal flow stasis, complex acquired hypercoagulation disorders and exogenous factors leading to endothelial dysfunction appear as key factors for the development of PVT. However, the occurrence of PVT remains unpredictable and many aspects of its natural history, prognostic significance and treatment are still elusive. Although spontaneous resolution or disease stability occurs in most cases of PVT, the factors that predispose to disease progression or recurrence after spontaneous recanalization are still unclear. Furthermore, the impact of PVT on the progression of liver cirrhosis is still debated, as PVT itself may represent a consequence of the progression of liver fibrosis and liver dysfunction. Advanced liver disease is no longer considered a condition associated with a low risk of thrombotic events. Portal vein thrombosis is a common and potentially life-threatening complication of liver cirrhosis. Despite advanced knowledge in the pathogenesis and diagnosis of PVT, many aspects regarding its natural history and prognostic outcome remain elusive.Резюме. Тромбоз воротной вены является хорошо известным осложнением естественного течения прогрессирующего заболевания печени, начиная от бессимптомных случаев до угрожающих жизни состояний, связанных с портальной гипертензией и печеночной декомпенсацией. Ключевыми факторами развития ТВB являются стаз портального кровотока, комплекс приобретенных нарушений гиперкоагуляции и экзогенные факторы, приводящие к эндотелиальной дисфункции. Однако возникновение ТВB остается непредсказуемым, и многие аспекты его естественного течения, прогностического значения и лечения до сих пор неясны. Хотя в большинстве случаев ТВB происходит спонтанное разрешение или стабилизация заболевания, факторы, предрасполагающие к прогрессированию или рецидиву заболевания после спонтанной реканализации, до сих пор неясны. Кроме того, влияние ТВB на прогрессирование цирроза печени все еще обсуждается, поскольку сам ТBВ может быть следствием прогрессирования фиброза печени и дисфункции печени. Прогрессирующее заболевание печени больше не считается состоянием, связанным с низким риском тромботических событий. Тромбоз воротной вены является распространенным и потенциально опасным для жизни осложнением цирроза печени. Несмотря на передовые знания в области патогенеза и диагностики ТВ, многие аспекты естественного течения и прогностического исхода остаются неясными

Хронические диффузные заболевания печени – внепеченочные проявления на уровне аденогипофиза, фоликулостимулирующего и лютеинизирующего гормонов

Laboratorul Gastroenterologie, USMF N. Testemiţanu, Disciplina Gastroenterologie, Depart. Medicină Internă 4, USMF N. Testemiţanu, Al IV-lea Congres Naţional de Gastroenterologie şi Hepatologie cu participare internaţională 25 - 26 iunie 2015 Chişinău, Republica MoldovaHypogonadism and feminization are well recognized complications of cirrhosis of alcoholic origin. At the same time, recent studies have confirmed that hypogonadism may be, however, extrahepatic manifestations of non-alcoholic chronic liver diseases both in men and women. Studies have shown that one mechanism provoke amenorrhea in young women with nonalcoholic chronic liver disease, probably been one mechanism of development hypothalamic-pituitary dysfunction. There is a relationship between serum luteinizing hormone (LH) and skin thickness in patients with chronic liver disease, which in general stresses the importance of malnutrition as a cause of hypothalamic amenorrhea occurrence. Polycystic ovary syndrome (PCOS) is the most common endocrine abnormality in premenopausal women. There is convincing evidence that shows that the prevalence of insulin-resistance / hyperinsulinemia increases significantly in patients with PCOS. LH values are lower in patients with chronic hepatitis compared with patients affected with liver cirrhosis of the same HBV etiology. Hormonal disorders have no correlations with viremia levels and liver process activity (according cytolytic syndrome). Gonadotropic insufficiency is common in patients with chronic HCV infection, and can be diminished by antiviral treatment. Гипогонадизм и феминизация являются хорошо известными осложнениями цирроза алкогольного генеза. Тем не менее, недавние исследования подтвердили, что гипогонадизм может быть, однако, внепеченочным проявлением хронического безалкогольного заболевания печени, как у мужчин, так и у женщин. Исследования показали, что один механизм возникновения аменореи встречается у молодых женщин с хроническими безалкогольными заболеваниями печени, являясь вероятным механизмом развития гипоталамо-гипофизарной дисфункции. Существует взамосвязь между концентрацией лютеинизирующего гормона (ЛГ) сыворотки крови и толщиной кожи у пациентов с хроническим заболеванием печени, которая в целом подчеркивает важность недоедания в качестве причины гипоталамической аменореи. Синдром поликистозных яичников (СПКЯ) является наиболее распространенной эндокринной аномалией у женщин в пременопаузе. Существует убедительное доказательство, которое показывает, что частота инсулинорезистентности / гиперинсулинемии значительно увеличиватся у пациентов с синдромом поликистозных яичников. У больных с хроническим гепатитом значения ЛГ ниже по сравнению с пациентами, страдающими от цирроза печени той же HBV этиологии. Гормональные нарушения не имеют корреляции с уровнем виремии и активностью процесса в печени (согласно синдрому цитолиза). Гонадотропная недостаточность встречается у пациентов с хронической инфекцией гепатита С и может быть компенсирована при помощи противовирусного лечени

Метаболический синдром и стеатоз печени

USMF N. Testemițanu, Laboratorul Gastroenterologie, USMF N. Testemiţanu, Departamentul Medicină Internă, Conferința naţională de gastroenterologie şi hepatologie cu participare internaţională ”Actualităţi în gastroenterologie şi hepatologie” 16 iunie 2016 Chișinău, Republica MoldovaMetabolic syndrome (MS) is a complex of risk factors that occur as a result of the combination of insulin resistance, depositing excess of body fat (visceral abdominal, blood vessels, internal organs including liver and pancreas), with a major impact on cardio-vascular system, frequently accompanied by liver involvement. The aim of this study was to detect the frequency of liver alteration associated with MS, in patients that addressed the consultation of a gastroenterologist. Of 263 patients who were seen by a gastroenterologist, in 85 (32,7%) were diagnosed MS. The average age was 50,95 years, the ratio males: females – 1: 1.02. In 80 (94,12%) patients of the studied group with MS was established hepatic involvement: non-alcoholic fatty liver disease, (NAFLD) – 27 (33,75%) cases, chronic viral infection (B, C, D) in 10 (12,5%) cases, the association of chronic viral infection and liver steatosis – 43 (53,75%) cases. In 5 (5,88%) cases were diagnosed other pathologies of gastrointestinal tract: chronic pancreatitis, chronic cholecystitis, gastroesophageal reflux disease. MS is meeting frequently in patients with hepatic pathology of different etiology. Non-alcoholic liver steatosis is a risk factor commonly associated with MS, therefore the clinician has to be ready in diagnosing this pathology on outpatients level in order to stop the chronic hepatic disease unfavorable evolution and progression.Метаболический синдром (МС) представляет собой комплекс факторов риска, которые возникают как результат резистентности тканей к инсулину, избыточного жироотложения (увеличение массы висцерального жира, отложения на передней брюшной стенке, в сосудах, во внутренних органах, включая печень и поджелудочную железу), с негативным воздействием на сердечно-сосудистую систему, что зачастую сопровождается вовлечением печени в патологический процесс. Целью данного исследования было выявление частоты ассоциированного с МС поражения печени среди пациентов, обратившихся за консультацией к врачу-гастроэнтерологу. Среди 263 пациентов, осмотренных гастроэнтерологом, у 85 (32,7%) был констатирован диагноз МС. Средний возраст составил 50,95 лет. Соотношение по полам мужчин и женщин составило 1:1,02. У 80 (94,12%) пациентов в исследуемой группе с МС было выявлено поражение печени: неалкогольная жировая болезнь печени – 27 (33,75%) случаев, хронические вирусные инфекции (B, C, D) – в 10 (12,5%) случаях, комбинация хронической вирусной инфекции и стеатоза печени – в 43 (53,75%) случаях. В 5 (5,88%) случаях были диагностированы другие патологии желудочнокишечного тракта: хронический панкреатит, хронический холецистит, гастроэзофагеальный рефлюкс. МС встречается часто среди пациентов с печеночной патологией различной этиологии. Неалкогольная жировая болезнь печени это фактор риска, достаточно часто встречающийся совместно с МС. Таким образом, клиницисты должны быть готовы диагностировать данную патологию при амбулаторном обследовании, чтобы своевременно предотвратить возможную неблагоприятную эволюцию

Scientists support Medical University "Nicolae Testemițanu" in the development of the Department of Gastroenterology and Hepatology in Republic of Moldova

Laboratorul de Gastroenterologie, USMF "Nicolae Testemițanu", Chișinău, Republica Moldova, Departamentul Medicină Internă, Disciplina de Gastroenterologie, USMF "Nicolae Testemițanu", Chișinău, Republica, Conferința Națională de Gastroenterologie și Hepatologie cu participare internațională „Actualități în gastroenterologie și hepatologie” MoldovaAfter the end of the Second World War, for the homeland defense, the entire staff of the Leningrad Institute of Medicine was transferred to Chișinău together with students and the entire teaching staff and was named the State Institute of Medicine from Chișinău. The Institute began his work on 20 October 1945 with a single faculty – that of General Medicine. The first rector was appointed Sorocean Evpatii Christoforovici. Teachers within the USSR (Russia) had a great influence on the evolution of Moldova's medicine, including in the area of gastroenterology and hepatology. The modern development of Gastroenterology and hepatology in our country had a permanent success because of the support of university rectors. A big contribution had and still have health care ministers from Moldova. The gastroenterology work progress in clinical and scientific field is determined by a permanent contact with chiefs of the university clinical bases and with colleagues from other specialties. The progress of medical science, both of gastroenterology and hepatology is due to a correct and proper management. The enormouswork, both in the past as well as currently, of the entire team of scientists and illustrious physicians contributed and still contributes to the development of national medicine, including gastroenterology and hepatology.После окончания Второй Мировой Войны, весь коллектив Ленинградского Медицинского Института был переведен в Кишинев вместе с студентами и всеми проффесорами под названием Медицинский Государственный Институт Кишинева. Институт начал свою деятельность 20 октября 1945 года, имея всего один факультет – Общая Медицина. Первым ректором был назван Сорочан Евпатий Кристофорович. Профессоры СССР (Россия) имели особенное влияние на развитие медицины в Молдове, включая гастроэнтерологию и гепатологию. Развитие современной гастроэнтерологии и гепатологии в нашей стране имеет успех благодаря постоянной поддержки ректоров университета. Большой вклад внесли и вносят по сей день министры Здрaвоохранения Молдовы. Процветание клинической и научной деятельности осуществляется при постоянном сотрудничестве с глав-врачами клинической базы университета и при помощи коллег других специальностей. Прогресс медицинских наук, гастроэгтерологии, а также гапатологии, обусловлен правильным и подходящим менеджментом. Огромную работу, как в прошлом, так и в настоящим проделал весь коллектив прославленных ученных и врачей, которые способствовали и способствуют в дальнейшем развитию медицины, включая национальную гастроэнтерологию и гепатологию

The clinical course of cirrhosis

Introduction. Cirrhosis represents the culmination of decades of liver injury and is thought to represent an irreversible disease. The clinical course of cirrhosis includes several disease states which require multistate models and competing risks analysis for proper assessment. Clinical states are defined according to the type of decompensation and increasing mortality. The traditional multistate models of cirrhosis have been validated in several studies and are currently widely used in clinical practice but mainly focus on the natural history of patients that are relatively stable. Aim of study. Liver cirrhosis is characterized by a silent phase until decompensation, which is defined by ascites, bleeding from esophageal varices or hepatic encephalopathy. Herein, we aimed to analyze and characterize the clinical course and survival in cirrhosis. Methods and materials. An advanced search was performed in the PubMed, Medline, and ScienceDirect databases, taking into account relevant articles, published in the last 10 years. The search English terms used were: ”Cirrhosis”,”Portal hypertension”,”Clinical states”,” Multistate model”,”Prognosis” Results. Cirrhosis is classified as compensated or decompensated, based on the absence or presence of complication such as variceal bleeding, ascites, jaundice or encephalopathy. More recently, it has been recognized that increasing portal hypertension and several major clinical events are followed by a marked worsening in prognosis, and disease states have been proposed accordingly in a multistate model. The clinical course of cirrhosis may not be considered as unidirectional anymore . Aetiological treatment of cirrhosis may halt or even reverse the clinical course of the disease, particularly when it is still in a compensated state. Therefore, watchful follow-up of patients in whom the cause of cirrhosis has been successfully treated is recommended. Several clinical conditions associated with significantly different outcomes have been proposed as relevant clinical states during the course of the disease. Clinical states of cirrhosis are based on distinct outcome patterns and have a prognostic classification value. The progression of cirrhosis across clinical states is not predictable, although it parallels the progression of liver damage with its haemodynamic, inflammatory and functional consequences. However, it is notable that there is no predictable sequence of such clinical states and that they may not be considered as progressive disease stages. However, clinical states enable the classification of patients according to increasing mortality risk. Moreover, assessing transitions across states may facilitate the description of the clinical course of the disease in a multistate model. Compensated cirrhosis without varices (state 1). This is the earliest clinical state with a low incidence rate of decompensation and very low mortality. Compensated cirrhosis with varices (state 2). These patients are at risk of variceal bleeding and decompensation. Thus, they require a different monitoring schedule and specific treatment according to the severity of risk. Variceal bleeding (state 3). Patients with bleeding alone have better outcomes than patients with ascites without bleeding, and much better outcomes than patients with bleeding and ascites. First non-bleeding decompensation (state 4). Ascites is the most frequent first non-bleeding decompensating event and is in fact considered the hallmark of decompensation. Further decompensation (state 5). Following any first decompensating event, most patients develop further decompensation before dying. The most frequent combination is bleeding and ascites, although jaundice and encephalopathy are also frequent. Late advanced decompensation (state 6). The progressive increase in splanchnic vasodilatation, hyperdynamic circulation, bacterial translocation and systemic inflammation result in a more advanced, late decompensation state where multi-organ dysfunction becomes clinically evident. Conclusion. The development of multistate models implies the assessment of the probabilities of more than one possible outcome from each disease state. Recognising different clinical states of cirrhosis may have important implications on the most likely clinical outcomes. Hence, clinical states may be used to inform treatment interventions to prevent disease progression