Primary antiphospholipid syndrome as a cause of impaired left ventricular diastolic function: experience from a Serbian cohort.

OBJECTIVES: Cardiovascular manifestations, encountered in antiphospholipid syndrome, may develop as a consequence of acquired thrombophilia mediated by antiphospholipid antibodies and accelerated atherosclerosis as well. Our study aims to assess the impairment of the left ventricular diastolic performance, as early evidence of myocardial involvement in primary antiphospholipid syndrome (PAPS). METHODS: We analysed 101 PAPS patients, with the average age of 47.70±13.14y. Anticardiolipin antibodies (aCL IgG/IgM), anti-ß2 glycoprotein-I (anti-ß2GPI IgG/IgM), and lupus anticoagulant (LAC) were determined. Abnormal cut-off values used for left ventricular diastolic dysfunction (LVDD) were septal E ́<7 cm/sec, lateral E ́ <10 cm/sec, average E/E ́ ratio >14, LA volume index (LAVI) >34 mL/m2, and peak tricuspid regurgitation velocity >2.8 m/sec. LVDD was present if more than half parameters were with abnormal values. The results were compared to 90 healthy, age and sex-matched controls. RESULTS: LVDD was significantly more prevalent in PAPS patients compared to healthy controls (24.8% vs. 2.2%, p=0.001). In PAPS patients, it was signi cantly related to age, body mass index, hyperlipidaemia, thromboses and LAC positivity (p=0.0001, p=0.008, p=0.039, p=0.001, p=0.047 respectively). Patients with PAPS had higher LAVI (29.76±6.40 ml/m2 vs. 26.62±7.8 ml/m2, p=0.012), higher isovolumic relaxation time, lower lateral É velocity and lower E/É ratio compared to controls (p=0.0001, p=0.020, p=0.038, respectively). In multivariate analysis, thromboses in PAPS were significant, and independent predictors of LVDD. CONCLUSIONS: Thrombotic PAPS patients are at higher risk of LVDD development. Strong action against standard atherosclerotic risk factors and adequate therapy regimes seems to be crucial to preserve good diastolic performance of the left ventricle in PAPS.

Dimerisation of the Yeast K+ Translocation Protein Trk1 Depends on the K+ Concentration.

In baker's yeast (Saccharomyces cerevisiae), Trk1, a member of the superfamily of K-transporters (SKT), is the main K+ uptake system under conditions when its concentration in the environment is low. Structurally, Trk1 is made up of four domains, each similar and homologous to a K-channel α subunit. Because most K-channels are proteins containing four channel-building α subunits, Trk1 could be functional as a monomer. However, related SKT proteins TrkH and KtrB were crystallised as dimers, and for Trk1, a tetrameric arrangement has been proposed based on molecular modelling. Here, based on Bimolecular Fluorescence Complementation experiments and single-molecule fluorescence microscopy combined with molecular modelling; we provide evidence that Trk1 can exist in the yeast plasma membrane as a monomer as well as a dimer. The association of monomers to dimers is regulated by the K+ concentration.

The Accuracy of Serum Biomarkers in the Diagnosis of Steatosis, Fibrosis, and Inflammation in Patients with Nonalcoholic Fatty Liver Disease in Comparison to a Liver Biopsy.

Background and Objective: This study was conducted to evaluate the diagnostic performance of various biomarkers for steatosis, fibrosis, and inflammation in comparison to a liver biopsy (LB) in patients with nonalcoholic fatty liver disease (NAFLD). Materials and Methods: This was a cross-sectional study that included 135 patients with biopsy-proven NAFLD. Fatty liver index (FLI), hepatic steatosis index (HSI), cell death markers (CK-18 M30 and CK-18 M65), FIB-4 index, NAFLD fibrosis score (NFS), BARD, and AST to platelet ratio index (APRI) were calculated and analysed. Results: FLI, HSI scores, and the cell death biomarkers showed poor diagnostic accuracy for steatosis detection and quantification, with an area under the curve (AUC) of <0.70. The cell death biomarkers likewise did not perform well for the detection of nonalcoholic steatohepatitis (NASH) (AUC < 0.7). As for the fibrosis staging, only APRI and the cell death biomarkers had moderate accuracy (AUC > 0.7) for advanced fibrosis, whereas FIB-4, BARD, and NFS scores demonstrated poor performance (AUC < 0.70). However, a combination of FIB-4 and NFS with the cell death biomarkers had moderate accuracy for advanced (≥F3) fibrosis detection, with an AUC of >0.70. Conclusions: In this first study on Croatian patients with NAFLD, serum biomarkers demonstrated poor diagnostic performance for the noninvasive diagnosis of liver steatosis and NASH. APRI and the cell death biomarkers had only moderate accuracy for diagnosing advanced fibrosis, as did the combination of FIB-4 and NFS with the cell death biomarkers. Further studies regarding serum biomarkers for all NAFLD stages are needed.

Non-Alcoholic Fatty Liver Disease and COVID-19-Two Pandemics Hitting at the Same Time.

The COVID-19 pandemic was and still is a global burden with more than 178,000,000 cases reported so far. Although it mainly affects respiratory organs, COVID-19 has many extrapulmonary manifestations, including, among other things, liver injury. Many hypotheses have been proposed to explain direct and indirect impacts of the SARS-CoV-2 virus on the liver. Studies have shown that around 15-30% of patients with COVID-19 have underlying liver disease, and 20-35% of patients with COVID-19 had altered liver enzymes at admission. One of the hypotheses is reactivation of an underlying liver disease, such as non-alcoholic fatty liver disease (NAFLD). Some studies have shown that NAFLD is associated with severe COVID-19 and poor outcome; nevertheless, other studies showed no significant difference between groups in comparing complications and clinical outcomes. Patients with NAFLD may suffer severe COVID-19 due to other comorbidities, especially cardiovascular diseases. The link between NAFLD and COVID-19 is not clear yet, and further studies and research are needed.

CROATIAN GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF NONALCOHOLIC FATTY LIVER DISEASE.

Nonalcoholic fatty liver disease (NAFLD) is a term describing excessive accumulation of fat in hepatocytes, and is associated with metabolic syndrome and insulin resistance. NAFLD prevalence is on increase and goes in parallel with the increasing prevalence of metabolic syndrome and its components. That is why Croatian guidelines have been developed, which cover the screening protocol for patients with NAFLD risk factors, and the recommended diagnostic work-up and treatment of NAFLD patients. NAFLD screening should be done in patients with type 2 diabetes mellitus, or persons with two or more risk factors as part of metabolic screening, and is carried out by noninvasive laboratory and imaging methods used to detect fibrosis. Patient work-up should exclude the existence of other causes of liver injury and determine the stage of fibrosis as the most important factor in disease prognosis. Patients with initial stages of fibrosis continue to be monitored at the primary healthcare level with the management of metabolic risk factors, dietary measures, and increased physical activity. Patients with advanced fibrosis should be referred to a gastroenterologist/hepatologist for further treatment, monitoring, and detection and management of complications.

Epidemiological and clinical features of primary biliary cholangitis in two Croatian regions: a retrospective study.

AIM: To assess the measures of disease frequency and determine the clinical features of primary biliary cholangitis (PBC) in two Croatian regions. METHODS: Databases of two tertiary hospitals, one located in the continental and one in the coastal region of Croatia, were retrospectively searched for PBC patients diagnosed from 2007 to 2018. Epidemiologic data analysis was restricted to patients from each hospital's catchment area. We analyzed factors related to response to therapy and event-free survival (EFS), defined as absence of ascites, variceal bleeding, encephalopathy, hepatocellular carcinoma, liver transplantation (LT), or death. In addition, we determined clinical and demographic data of transplanted PBC patients. RESULTS: Out of 83 PBC patients, 86.7% were female, with a median age at diagnosis of 55 years. Average PBC incidence for the 11-year period was 0.79 and 0.89 per 100000 population, whereas the point prevalence on December 31, 2017 was 11.5 and 12.5 in the continental and coastal region, respectively. Of 76 patients with complete medical records, 21% had an advanced disease stage, 31.6% had an associated autoimmune condition, and all received ursodeoxycholic acid. EFS rate at 5 years was 95.8%. In an age and sex-adjusted multivariate Cox regression model, the only factor significantly associated with inferior EFS was no response to therapy (HR=18.4; P=0.018). Of all Croatian patients who underwent LT, 3.8% had PBC, with the survival rate at 5 years after LT of 93.4%. CONCLUSION: This study gives pioneer insights into the epidemiological and clinical data on PBC in Croatia, thus complementing the PBC map of Southeast Europe.

Vitamin D Deficiency: Consequence or Cause of Obesity?

Obesity is defined as an excess amount of body fat and represents a significant health problem worldwide. High prevalence of vitamin D (VD) deficiency in obese subjects is a well-documented finding, most probably due to volumetric dilution into the greater volumes of fat, serum, liver, and muscle, even though other mechanisms could not completely be excluded, as they may contribute concurrently. Low VD could not yet be excluded as a cause of obesity, due to its still incompletely explored effects through VD receptors found in adipose tissue (AT). VD deficiency in obese people does not seem to have consequences for bone tissue, but may affect other organs, even though studies have shown inconsistent results and VD supplementation has not yet been clearly shown to benefit the dysmetabolic state. Hence, more studies are needed to determine the actual role of VD deficiency in development of those disorders. Thus, targeting lifestyle through healthy diet and exercise should be the first treatment option that will affect both obesity-related dysmetabolic state and vitamin D deficiency, killing two birds with one stone. However, VD supplementation remains a treatment option in individuals with residual VD deficiency after weight loss.

Liver Disease During Pregnancy: A Challenging Clinical Issue.

One of the least studied topics in the field of obstetrics is liver disease during pregnancy, which creates a challenge for both gynecologists and hepatologists. Approximately 3% of pregnant women are affected by some form of liver disease during pregnancy. Some of these conditions can be fatal for both the mother and child. In addition, 3 types of liver disease need to be differentiated during pregnancy. One type is liver disease directly related to pregnancy, which can occur at a specific time during pregnancy. Another type is liver disease not related to pregnancy, which can occur at any time, such as viral- or drug-induced hepatitis. Furthermore, pregnancy can occur in women with pre-existing liver disease. It is essential that the clinicians are familiar with this disorder so they can respond promptly and appropriately in all of these situations, especially when emergency delivery is needed and must not be postponed.

Metabolic syndrome and non-alcoholic fatty liver disease after liver or kidney transplantation.

Transplantation is a definitive treatment option for patients with end-stage liver disease, and for some patients with acute liver failure, hepatocellular carcinoma or end-stage renal disease. Long-term post-transplantation complications have become an important medical issue, and cardiovascular diseases (CVD) are now the leading cause of mortality in liver or kidney transplant recipients. The increased prevalence of metabolic syndrome (MS) likely plays a role in the high incidence of post-transplantation CVD. MS and its hepatic manifestation, non-alcoholic fatty liver disease (NAFLD), are prevalent among the general population and in pre- and post-transplantation settings. MS components are associated with recurrent or de novo NAFLD in transplant recipients, potentially influencing post-transplantation survival. Moreover, recent data reveal an important association between NAFLD and risk of incident of chronic kidney disease (CKD). Therefore, NAFLD identification could represent an additional clinical feature for improving the stratification of liver and kidney transplant recipients with regards to risks of CVD, CKD and renal allograft dysfunction. All MS components are potentially modifiable; therefore, it is crucial that hepatologists, nephrologists and primary care physicians become more engaged in managing post-transplantation metabolic complications. The present review discusses the recent clinical evidence regarding the importance of MS and its components after liver and kidney transplantation, as well as the link between MS and NAFLD after liver and kidney transplantation.

The Role of Iron and Iron Overload in Chronic Liver Disease.

The liver plays a major role in iron homeostasis; thus, in patients with chronic liver disease, iron regulation may be disturbed. Higher iron levels are present not only in patients with hereditary hemochromatosis, but also in those with alcoholic liver disease, nonalcoholic fatty liver disease, and hepatitis C viral infection. Chronic liver disease decreases the synthetic functions of the liver, including the production of hepcidin, a key protein in iron metabolism. Lower levels of hepcidin result in iron overload, which leads to iron deposits in the liver and higher levels of non-transferrin-bound iron in the bloodstream. Iron combined with reactive oxygen species leads to an increase in hydroxyl radicals, which are responsible for phospholipid peroxidation, oxidation of amino acid side chains, DNA strain breaks, and protein fragmentation. Iron-induced cellular damage may be prevented by regulating the production of hepcidin or by administering hepcidin agonists. Both of these methods have yielded successful results in mouse models.

Cardiac manifestations in alcoholic liver disease.

Alcoholic liver disease is the most prevalent cause of progressive liver disease in Europe. Alcoholic cirrhosis occurs in 8%-20% of cases of alcoholic liver disease. It has significant influence on cardiovascular system and haemodynamics through increased heart rate, cardiac output, decreased systemic vascular resistance, arterial pressure and plasma volume expansion. Cirrhotic cardiomyopathy is characterised by systolic and diastolic dysfunction and electrophysiological abnormalities, if no other underlying cardiac disease is present. It is often unmasked only during pharmacological or physiological stress, when compensatory mechanisms of the heart become insufficient to maintain adequate cardiac output. Low-to-moderate intake of alcohol can be cardioprotective. However, heavy drinking is associated with an increased risk of cardiovascular diseases, such as alcoholic cardiomyopathy, arterial hypertension, atrial arrhythmias as well as haemorrhagic and ischaemic stroke. Alcoholic cardiomyopathy is characterised by dilated left ventricle (LV), increased LV mass, normal or reduced LV wall thickness and systolic dysfunction.

APPROACH TO THE PATIENT WITH NONALCOHOLIC FATTY LIVER DISEASE.

XNonalcoholic fatty liver disease (NAFLD) has become a common cause of elevated liver tests. The association between fatty liver and metabolic syndrome (MS) is well documented and widely accepted. Cirrhosis due to nonalcoholic steatohepatitis (NASH) is currently the second most common indication for liver transplant with increasing incidence. Gastroenterologists/hepathologists and primary care physicians have more questions than answers regarding the NAFLD. The most common questions are which NAFLD patients have a risk of progression to NASH, fibrosis, cirrhosis and hepa- tocellular carcinoma, and which patients with NAFLD have a need for liver biopsy. In addition, a number of non-invasive diagnostic methods in the approach to the patient with NAFLD are investigated. How to approach these patients in routine clinical practice, is more of an art than a science at this time. In this article we will try to provide more recent recommenda- tions of how to approach the patients with NAFLD.

[NONALCOHOLIC FATTY LIVER DISEASE ­ A MULTISYSTEM DISEASE?].

With the increasing incidence of obesity and metabolic syndrome the incidence of nonalcoholic fatty liver ­disease (NAFLD) is increasing as well. These patients have a significant risk of progression to the end-stage liver disease, but also these patients are at increased risk of developing hepatocellular carcinoma. In recent years there is a growing ­number of publications that support the idea that NAFLD is not just a disease that is limited to the liver, but is associated with a number of extrahepatic manifestations. For example, NAFLD increases the risk of type 2 diabetes mellitus, cardiovascular diseases and chronic kidney disease. Consequently NAFLD has become a growing public health problem. A number of sub-specialists as well as primary care physicians should be aware of these potential extrahepatic associations, given the availability of numerous methods for screening in clinical practice. The above approach is important in order to recognize potentially modifiable events in the early stages, and thus manage them and at least prevent the progression of certain diseases.

Non-alcoholic fatty liver disease proven by transient elastography in hemodialysis patients: is it a new risk factor for adverse cardiovascular events?

BACKGROUND/AIMS: Cardiovascular diseases (CVD) are the leading cause of mortality in hemodialysis (HD) patients. Recently, non-alcoholic fatty liver disease (NAFLD) has been recognized as a new risk factor for adverse CVD events in the general population. Our aim was to analyze the incidence of NAFLD in HD patients by using transient elastography and to analyze whether the presence of NAFLD is associated with a higher CVD risk in HD patients. METHODS: The subjects were 72 HD patients and 50 sex- and age-matched controls. RESULTS: NAFLD was found in 52.8% of HD patients. HD patients with NAFLD showed more carotid atherosclerosis and more adverse CVD events than HD patients without NAFLD and control subjects. CONCLUSION: We showed for the first time that HD patients have a high prevalence of NAFLD. HD patients with NAFLD show an advanced carotid atherosclerosis. Detection of NAFLD by transient elastography should alert to the existence of an increased cardiovascular risk in HD patients.

[Evaluation of viral hepatitis in solid organ transplantation]. / Evaluacija virusnih hepatitisa u transplantaciji solidnih organa.

Renal transplantation has significantly improved survival of patients with end-stage renal disease (ESRD). Transplantation is the best treatment in this population of patients. Despite the introduction of various preventive measures, viral hepatitis, i.e. hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, are still a major problem because they are common in patients on renal replacement therapy as well as in allograft recipients. They are a significant cause of morbidity and mortality in this patient population. In recent years, hepatitis E virus (HEV) infection has been added as an emergent cause of chronic hepatitis in solid organ transplantation, mainly in renal and liver allograft recipients. Most studies show higher mortality in renal transplant recipients (RTRs) infected with HBV, compared with RTRs without HBV infection, although this topic is still under debate. Furthermore, HCV infection in RTRs is associated with a significant reduction in patient and graft survival due to liver disease and septic complications related to cirrhosis and immunosuppressive therapy. The immunosuppressive therapy prescribed after transplantation modifies the natural history of chronic HCV infection. Given the high prevalence of HCV and HBV infections in RTRs, a growing incidence of hepatocellular carcinoma and the possible contribution of immunosuppression might be expected in these patients. Therefore, after renal transplantation, early screening with abdominal ultrasound (every 3 months in cirrhotic patients and every 6-12 months in non-cirrhotic RTRs) is necessary when the risk factors such as HBV and HCV are present. The European Association for the Study of the Liver (EASL) recommends that all HbsAg-positive patients who are candidates for solid organ transplantation should be treated with nucleoside analogs. The KDIGO guidelines recommend that all HbsAg-positive RTRs receive prophylaxis with tenofovir, entecavir or lamivudine; however, tenofovir and entecavir are preferable to lamivudin. Viral suppression by inhibiting necro-inflammation may result in reduced fibrosis, thereby improving transplant survival. Active HCV infection in a dialysis patient requires evaluation of liver fibrosis. Antiviral therapy should be given to all HCV-infected dialysis patients in order to achieve a sustained virologic response (SVR) not only to avoid subsequent hepatic deterioration but also to limit the risks of HCV-related posttransplant de novo glomerulonephritis. Systematic vaccination of all HbsAg-negative patients is the best preventive treatment of HBV infection. HbsAg positive donors are only used occasionally, whereas the use of hepatitis B core antibody (HbcAb)+, HbsAg negative donors is more common but remains somewhat controversial. The presence of antibody to HCV is indicative of HCV infection because antibody to HCV appears in peripheral blood within two months of HCV exposure. However, it is important to emphasize that detection of antibody to HCV by serologic screening of the donor is not predictive of HCV transmission. Approximately 50% of patients positive for antibody to HCV have detectable hepatitis C viremia by PCR analysis of peripheral blood. Therefore, all organ donors with PCR analysis positive for HCV will transmit HCV to RTRs. On the other hand, the risk of transmission from an organ donor with negative PCR analysis is unclear. Another problem in the evaluation of the potential donors of solid organs is the fact that antibody testing by enzyme-linked immunosorbent assays (ELISAs) will not detect recent infections. The use of nucleid acid testing (NAT) could be useful because it involves amplification of viral gene products and thus is not dependent on antibody formation. Therefore, by using this method the period between the infection and detectability, which is known as the window period, could be reduced. However, this method is expensive and time consuming.

Correlation of the severity of the clinical presentation of SARS-CoV-2 pneumonia with respiratory function parameters in the post-COVID period.

INTRODUCTION: Since COVID-19 first surfaced in 2019, it has seriously threatened public health. The most prevalent symptoms are respiratory ones. This study aimed to present the correlation between the severity of the clinical presentation of the disease and the results of respiratory function tests conducted within 6 months after hospital discharge. METHODOLOGY: This retrospective study included 99 patients with confirmed SARS-CoV-2 virus infection. Of all patients 24.2% had accentuated bronchovascular pattern, 9.1% had unilateral, and 29.3% had bilateral pneumonia. In comparison, 35.4% patients had diffuse changes, which were described as acute respiratory distress syndrome (ARDS) on computed tomography (CT). RESULTS: Patients with unilateral, bilateral pneumonia or diffuse lung damage had significantly lower forced vital capacity (FVC) values. They were treated with non-invasive mechanical ventilation (NIV) or invasive mechanical ventilation (MV) and had lower FVC values (0.039). A negative, weak correlation existed between CT findings during the infection and Diffusing capacity for carbon monoxide (DLCO) measured after the infection (0.003). A negative, weak correlation was found between oxygen therapy, the use of NIV, and MV findings during the infection with DLCO. A negative correlation was noted between leukocyte values during the infection and forced expiratory volume in the first second (FEV1) and FVC after the infection. CONCLUSIONS: Patients with COVID-19 infection who need oxygen support and MV continue to suffer from loss of respiratory function after the resolution of COVID-19 infection. These findings highlight the negative predictive value of pulmonary tests in the long-term follow-up for the development of PC-ILD as well as decreased pulmonary capacity.

Newly synthesized palladium(II) complexes with dialkyl esters of (S,S)-propylenediamine-N,N'-di-(2,2'-di-(4-hydroxy-benzil))acetic acid: in vitro investigation of biological activities and HSA/DNA binding.

The four new ligands, dialkyl esters of (S,S)-propylenediamine-N,N'-di-(2,2'-di-(4-hydroxy-benzil))acetic acid (R2-S,S-pddtyr·2HCl) (R = ethyl (L1), propyl (L2), butyl (L3), and pentyl (L4)) and corresponding palladium(II) complexes have been synthesized and characterized by microanalysis, infrared, 1H NMR and 13C NMR spectroscopy. In vitro cytotoxicity was evaluated using the MTT assay on four tumor cell lines, including mouse mammary (4T1) and colon (CT26), and human mammary (MDA-MD-468) and colon (HCT116), as well as non-tumor mouse mesenchymal stem cells. Using fluorescence spectroscopy were investigated the interactions of new palladium(II) complexes [PdCl2(R2-S,S-pddtyr)]; (R = ethyl (C1), propyl (C2), butyl (C3), and pentyl (C4)) with calf thymus human serum albumin (HSA) and DNA (CT-DNA). The high values of the binding constants, Kb, and the Stern-Volmer quenching constant, KSV, show the good binding of all complexes for HSA and CT-DNA. The mentioned ligands and complexes were also tested on in vitro antimicrobial activity against 11 microorganisms. Testing was performed by the microdilution method, where the minimum inhibitory concentration (MMC) and the minimum microbicidal concentration (MMC) were determined.

[Hepatitis C: who should be treated?]. / Hepatitis C: koga lijeciti?

Therapy is strongly recommended in patients with acute infection, patients with elevated ALT levels, patients with normal ALT level and F > or = 2 METAVIR score, in genotype 1 nonresponders and relapsers to antiviral therapy with triple therapy (pegylated interferon, ribavirin, bocaprevir or telaprevir), in patients with compensated cirrhosis and patients on hemodialysis. It is possible to treat patients with HBV and HIV co-infection, patients with severe HCV extrahepatic manifestations and patients with transplanted liver. Drug users and alcoholics can be treated after 6-month abstinence, but also with supportive therapy. This therapy is not recommended in patients with fulminant hepatitis, patients with persistent normal ALT levels and without fibrosis, in kidney transplant recipients and in pregnant women.

[Viralhepatitis. Croatian Consensus Statement 2013]. / Virusni hepatitis. Hrvatska konsenzus konferencija 2013.

Croatian Consensus Conferences on Viral Hepatitis took place in 2005 and 2009. Considering the numerous novel concepts on the epidemiology, diagnosis and management of viral hepatitis (chronic hepatitis C genotype 1 in particular) that have emerged in the past four years, a new Croatian Consensus Conference on Viral Hepatitis was held in Zagreb on February 28, 2013. The abridged text of the Croatian Consensus Conference on Viral Hepatitis 2013 presents the new concepts on the epidemiology of viral hepatitis, serologic and molecular diagnosis of viral hepatitis, determination of the IL-28 gene promoter polymorphism, fibrosis grading, algorithm for patient diagnostic follow up, treatment of chronic hepatitis C (genotypes 1-6) and hepatitis B, treatment of special populations (children, dialysis patients, transplanted patients, individuals with HIV/HCV co-infection), and therapy side effects.

[Acute-on-chronic liver failure (ACLF)--a new entity in hepatology?]. / Acute-on-chronic liver failure (ACLF)--novi entitet u hepatologiji?

Recently, acute-on-chronic liver failure has been recognized as a specific and unique clinical form of liver failure (usually related to acute insult) in patients with previously known or unknown compensated chronic liver disease. Its main feature is the reversibility, and high short-mortality due to multiorgan failure (MOF) in the absence of liver support system devices and/or liver transplantation. This article aims to introduce the definition and better understanding of this newly developed and unique profile of liver failure.