Комплексное лечение больных с циррозом печени, осложненным кровотечением

This article deals with analysis of own experience of treatment of portal hypertension patients complicated with variceal bleeding. There were 390 patients with cirrhosis complicated with variceal bleeding under our supervision from 2006 to 2012. Endoscopic hemostasis was carried out in 296 patients, 158 patients of them were conducted endoscopic sclerotherapy, 98 — endoscopic clipping and ligation and 40 patients — endoscopic sealing. After a stop of bleeding and stabilization of patient condition in 82 cases for prevention of recurrence of bleedings we carried out endovascular embolization of a splenic artery by the technique which we elaborated ourselves. In 52 cases for the purpose of bleedings recurrence prevention we performed laparoscopic operations which consisted in coagulation and ligation of short veins and stomach arteries on big curvature. The remote results after only an endoscopic hemostasis, and an endoscopic hemostasis with the subsequent performance of laparoscopic and endovascular operations have been observed in 190 patients during 3 years. The most effective method of a local hemostasis is the endoscopic ligation and clipping of varices. Endovascular embolization of the splenic artery and also a laparoscopic devascularization of cardiac part of the stomach and abdominal part of the esophagus allows to reduce considerably frequency of bleedings recurrence and lethality in the remote period.В этой статье мы проанализировали наш опыт лечения пациентов с портальной гипертензией, осложненной кровотечениями из варикозно расширенных вен. С 2006 по 2012 гг. под нашим наблюдением было 390 пациентов с циррозом, осложненным кровотечением из варикозно расширенных вен. Из 296 пациентов, которым мы выполняли эндоскопический гемостаз, 158 больным выполняли эндоскопическую склеротерапию, 98 — эндоскопическое лигирование и 40 — прошивание через стенку желудка. После остановки кровотечения и стабилизации состояния пациентов в 82 случаях для профилактики рецидивов кровотечений мы выполняли эндоваскулярную эмболизацию селезеночной артерии по методике, модифицированной нами. В 52 случаях для профилактики рецидивов кровотечений мы выполняли лапароскопические операции портоазигального разобщения с коагуляцией и клипированием сосудов желудка. Эндоваскулярная эмболизация и лапароскопическая деваскуляризация сосудов желудка и нижней трети пищевода позволили значительно сократить частоту рецидивов кровотечений и летальность у этой тяжелой категории больных в ближайшем и отдаленном периодах

Атезолизумаб и бевацизумаб у пациентов с гепатоцеллюлярной карциномой в реальной клинической практике

   Randomized clinical trials and actual clinical practice differsignificantly. Evidence-based medicine develops new agents referring to, primarily, pharmaceutical findings, preclinical studies and, most importantly, randomized clinical trials. Hepatocellular carcinoma is the most common primary malignancy of the liver, and one of the main causes of fatal outcomes among cancer patients worldwide, including in the Asia-Pacific region, with an estimated 800,000 deaths annually. For more than 10 years, sorafenib, a tyrosine kinase inhibitor, was the only authorized treatment for advanced hepatocellular carcinoma. The next stage in the development of drug therapy for hepatocellular carcinoma involved immune checkpoint inhibitors. The combination of atezolizumab with bevacizumab in the phase III trial (IMbrave150) improved outcomes of advanced hepatocellular carcinoma, such as overall survival and progression-free survival (6.8 versus 4.3). The paper presents the trials of atezolizumab and bevacizumab combination, demonstrates comparable data on the treatment of patients with HCC in real clinical practice and data on the phase III IMbrave150. To further analyze the efficacy of the combination of atezolizumab and bevacizumab, prospective clinical trials should include heterogeneous patient groups.   Рандомизированные клинические исследования и реальная клиническая практика имеют много различий. Создание новых лекарственных средств во время доказательной медицины основано прежде всего на фармацевтических разработках, проведении доклинических исследований и, самое основное, рандомизированных клинических исследованиях. Гепатоцеллюлярная карцинома является наиболее распространенной первичной злокачественной опухолью печени и одной из ведущих причин смертности среди онкологических пациентов во всем мире с примерным количеством 800 000 смертей ежегодно. Более 10 лет тирозинкиназный ингибитор сорафениб был единственным зарегистрированным средством лечения распространенной гепатоцеллюлярной карциномы. Следующим этапом развития лекарственной терапии гепатоцеллюлярной карциномы явилась терапия ингибиторами контрольных точек иммунитета. Комбинация атезолизумаба с бевацизумабом в исследовании III фазы (IMbrave150) улучшила результаты лечения распространенной гепатоцеллюлярной карциномы, такие как общая выживаемость и выживаемость без прогрессирования (6,8 против 4,3). Приведенные в статье исследования комбинации атезолизумаба и бевацизумаба демонстрируют сопоставимые данные при лечении пациентов с ГЦК в реальной клинической практике и в исследовании III фазы IMbrave150. Проспективные клинические испытания, которые включают разнородные группы пациентов, необходимы для дальнейшего анализа эффективности комбинации атезолизумаба и бевацизумаба

Increased IGF-1: IGFBP-3 ratio in patients with hepatocellular carcinoma

BACKGROUND: The development of hepatocellular carcinoma in liver cirrhosis is associated with altered synthesis and secretion of several growth factors. AIM: The aim of this prospective study was to investigate the potential implication of IGF-I and its major binding protein (IGFBP-3) in the development of hepatocellular carcinoma. PATIENTS AND METHODS: IGF-I and IGFBP-3 were measured in 150 healthy subjects, 40 patients with liver cirrhosis and 63 with liver cirrhosis and untreated hepatocellular carcinoma. The ratio between IGF-I and IGFBP-3 was also calculated. RESULTS: Serum IGF-I (70 ± 10 and 65 ± 7 vs. 185 ± 6.4 μg/l, P < 0.001) and IGFBP-3 levels (1225 ± 113 and 984 ± 67 vs. 3017 ± 80 μg/l, P < 0.001) were lower in patients with liver cirrhosis, without or with hepatocellular carcinoma, than in controls. Age was negatively correlated with IGF-I levels In patients with liver cirrhosis (r = -0.6; P = 0.0002) as well as in controls (r = -0.8, P < 0.0001), but not in patients with hepatocellular carcinoma (r = -0.2; P = 0.2). Additionally, in patients with liver cirrhosis (r = -0.54; P = 0.0003) and more weakly in those with hepatocellular carcinoma (r = -0.24; P = 0.04) IGF-I levels were negatively correlated with liver failure measured according with Child class. Despite patients with class C hepatocellular carcinoma being older than those in the same functional class with cirrhosis (64 ± 2 vs. 57 ± 2 years, P < 0.01), they had a significantly increased IGF-I : IGFBP-3 ratio (0.18 ± 0.05 vs. 0.41 ± 0.09, P = 0.04), due mostly to increased IGF-I levels (27.1 ± 5.6 vs. 42 ± 6.2 μg/l) as IGFBP-3 levels were similar to patients with cirrhosis (734 ± 81 vs. 679 ± 83 μg/l). CONCLUSIONS: Hepatocellular carcinoma is associated with a higher IGF-I : IGFBP-3 ratio than that found in patients with liver cirrhosis and a similar degree of liver failure

Targeted therapy of hepatocellular carcinoma with sorafenib. Finally a breakthrough or maybe just the beginning of a long way?

Rak wątrobowokomórkowy (HCC) stanowi na świecie ponad 5% nowotworów złośliwych i jest trzecią pod względem częstości przyczyną zgonów z powodu nowotworów złośliwych. Najważniejsze czynniki ryzyka zachorowania na HCC to marskość wątroby wywołana wirusem zapalenia wątroby B lub C, nadużywaniem alkoholu oraz narażenie na aflatoksyny. Rokowanie jest złe - w Europie odsetek przeżyć 5-letnich wynosi 9%. Nie udowodniono, aby systemowa chemioterapia miała wpływ na czas przeżycia chorych na nieoperacyjnego HCC. W ostatnich latach w wyniku postępów osiągniętych w poznawaniu biologii HCC wprowadzono leczenie ukierunkowane molekularnie sorafenibem. Sorafenib jest inhibtorem multikinazowym, który hamuje aktywność receptorów błonowych (VEGFR 1-3, PDGFR-&#946;) oraz kinaz wewnątrzkomórkowych Raf. W dwóch badaniach III fazy - SHARP i badaniu azjatyckim - jednogłośnie wykazano, że czas przeżycia u chorych leczonych sorafenibem jest dłuższy niż u osób otrzymujących placebo. Jednak w żadnym z tych badań nie potwierdzono jakiegokolwiek wpływu takiego leczenia na czas wolny od progresji objawowej definiowanej jako istotne pogorszenie jakości życia, pogorszenie stanu sprawności według skali ECOG do stopnia 4 lub zgonu. Nie zidentyfikowano także pewnych klinicznych czynników predykcyjnych, jakkolwiek wydaje się, że u chorych z rozsiewem nowotworu poza wątrobą korzyść z zastosowania sorafenibu jest znacznie mniejsza niż u chorych z nowotworem ograniczonym wyłącznie do tego narządu. Lekarz powinien przed podjęciem leczenia sorafenibem wyczerpująco omówić z chorym te zagadnienia. Leczenie sorafenibem powinno się rozważać wyłącznie u pacjentów, u których czynność wątroby według skali Child-Pugh oceniono w kategorii A oraz których stan sprawności według klasyfikacji ECOG wynosi 0 lub 1. Niezwykle istotne jest jak najszybsze znalezienie molekularnych czynników predykcyjnych tej terapii.Hepatocellular carcinoma (HCC) accounts for more than 5% of all cancers and it is the third cause of cancerrelated deaths worldwide. The main risk factors of HCC include: cirrhosis related to infections caused by hepatitis B or C virus and to alcohol abuse, and exposure to aflatoxins. Prognosis is poor and a 5-year survival rate in Europe is 9%. Systemic chemotherapy in inoperable HCC has no proven impact on patient survival. In recent years due to advances in knowledge of the molecular biology of HCC a targeted therapy with sorafenib has been introduced. Sorafenib is a multikinase inhibitor that inhibits surface receptors (VEGFR 1-3, PDGFR-&#946;) and intracellular Raf kinases. Two randomized phase III trials, SHARP and the Asia-Pacific region trial consistently showed that patients treated with first-line sorafenib have longer survival in comparison with placebo. However, both failed to show any improvement in the time to symptomatic progression which was defined as a significant deterioration in quality of life, or a decrease in ECOG performance status to 4, or death. Moreover, no clear clinical predictive factors were identified. However, patients with extrahepatic spread seemed to benefit from sorafenib to far less extent in comparison with patients with disease confined to liver. A doctor should discuss with her/his patient these issues thoroughly prior to start of sorafenib therapy. Only patients with Child-Pugh class A liver function and ECOG 0&#8211;1 performance status should be considered for such treatment. The discovery of molecular predictive factors is eagerly awaited

Branched Chain Amino Acids Are Associated with Physical Performance in Patients with End-Stage Liver Disease

Decreased circulating branched chain amino acids (BCAA) represent a prominent change in amino acid profiles in patients with end-stage liver disease (ESLD). These alterations are considered to contribute to sarcopenia and hepatic encephalopathy and may relate to poor prognosis. Here, we cross-sectionally analyzed the association between plasma BCAA levels and the severity of ESLD and muscle function in participants of the liver transplant subgroup of TransplantLines, enrolled between January 2017 and January 2020. Plasma BCAA levels were measured by nuclear magnetic resonance spectroscopy. Physical performance was analyzed with a hand grip strength test, 4 m walking test, sit-to-stand test, timed up and go test, standing balance test and clinical frailty scale. We included 92 patients (65% men). The Child Pugh Turcotte classification was significantly higher in the lowest sex-stratified BCAA tertile compared to the highest tertile (p = 0.015). The times for the sit-to-stand (r = −0.352, p &lt; 0.05) and timed up and go tests (r = −0.472, p &lt; 0.01) were inversely correlated with total BCAA levels. In conclusion, lower circulating BCAA are associated with the severity of liver disease and impaired muscle function. This suggests that BCAA may represent a useful prognostic marker in the staging of liver disease severity.</p

Profoundly Disturbed Lipoproteins in Cirrhotic Patients:Role of Lipoprotein-Z, a Hepatotoxic LDL-like Lipoprotein

Detailed information regarding lipoprotein concentrations and subfractions in cirrhotic patients before and after orthotopic liver transplantation (OLT) is lacking. Lipoprotein-Z (LP-Z) is a recently characterised abnormal, hepatotoxic free cholesterol-rich low-density lipoprotein (LDL)-like lipoprotein. We determined the lipoprotein profiles, including LP-Z, in cirrhotic patients and OLT recipients and assessed the prognostic significance of LP-Z on the OLT waiting list. We performed analyses in cirrhotic transplant candidates and non-cirrhotic OLT recipients. A population-based cohort was used as reference. The setting was a University hospital. Lipoprotein particle concentrations and subfractions were measured by nuclear magnetic resonance spectroscopy. In the cirrhotic patients (N = 130), most measures of triglyceride-rich lipoproteins (TRL), LDL, and high-density lipoproteins (HDL) were much lower compared to the OLT recipients (N = 372) and controls (N = 6027) (p &amp;lt; 0.01). In the OLT recipients, many lipoprotein variables were modestly lower, but HDL-cholesterol, triglycerides, and TRL and HDL size were greater vs. the control population. LP-Z was measurable in 40 cirrhotic patients and 3 OLT recipients (30.8% vs. 0.8%, p &amp;lt; 0.001). The cirrhotic patients with measurable LP-Z levels had profoundly lower HDL-cholesterol and particle concentrations (p &amp;lt; 0.001), and worse Child Pugh Turcotte classifications and MELD scores. The presence of LP-Z (adjusted for age, sex, and MELD score) predicted worse survival in cirrhotic patients (HR per 1 LnSD increment: 1.11, 95%CI 1.03-1.19, p = 0.003). In conclusion, cirrhotic patients have considerably lower plasma concentrations of all major lipoprotein classes with changes in lipoprotein subfraction distribution. After OLT, these lipoprotein abnormalities are in part reversed. LP-Z is associated with cirrhosis. Its presence may translate in disturbed HDL metabolism and worse survival.</p

The impact of liver disease on cognitive functioning and mood.

The following review discusses some of the cognitive and functional problems in liver disease. Some medical literature is included which is consistent with difficulties reported by patients. Prevalence, possible causes, and types of liver disease are reviewed, including an outline of various complications associated with the disease. Hepatic encephalopathy (HE) is one such complication and a general background to this is given. It has been suggested that subgroups of patients with liver disease have mild cognitive deficits and demonstrate poorer performances on neuropsychological tests compared with matched controls. This has been termed minimal hepatic encephalopathy (MHE), a syndrome that occurs in patients with liver disease without overt symptoms of hepatic encephalopathy. The full spectrum of cognitive impairment in MHE is unknown (Collie, 2005). Research has attempted to understand the profile of cognitive deficits in patients with liver disease. Studies have investigated various areas of functioning (e.g. psychomotor skills, attention and memory) by neuropsychological testing. The main studies are presented in the review. Some of the limitations of the minimal hepatic encephalopathy hypothesis are discussed. There is some debate about possible causes of observed cognitive deficits and various psychological models including health (coping and quality of life) and clinical (mood issues) are proposed. Further research and clinical implications are also discussed