End-stage Chronic Liver Disease Research Articles

Liver cirrhosis: molecular mechanisms and therapeutic interventions.

Liver cirrhosis is the end-stage of chronic liver disease, characterized by inflammation, necrosis, advanced fibrosis, and regenerative nodule formation. Long-term inflammation can cause continuous damage to liver tissues and hepatocytes, along with increased vascular tone and portal hypertension. Among them, fibrosis is the necessary stage and essential feature of liver cirrhosis, and effective antifibrosis strategies are commonly considered the key to treating liver cirrhosis. Although different therapeutic strategies aimed at reversing or preventing fibrosis have been developed, the effects have not be more satisfactory. In this review, we discussed abnormal changes in the liver microenvironment that contribute to the progression of liver cirrhosis and highlighted the importance of recent therapeutic strategies, including lifestyle improvement, small molecular agents, traditional Chinese medicine, stem cells, extracellular vesicles, and gut remediation, that regulate liver fibrosis and liver cirrhosis. Meanwhile, therapeutic strategies for nanoparticles are discussed, as are their possible underlying broad application and prospects for ameliorating liver cirrhosis. Finally, we also reviewed the major challenges and opportunities of nanomedicine‒biological environment interactions. We hope this review will provide insights into the pathogenesis and molecular mechanisms of liver cirrhosis, thus facilitating new methods, drug discovery, and better treatment of liver cirrhosis.

Waiting list mortality and 5-year transplant survival benefit of patients with MASLD: An Italian liver transplant registry study

BackgroundInternational consensus has recently introduced a new definition of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). We sought to analyse epidemiological trends, prognostic features, and transplant survival benefits of MASLD and non-MASLD patients waiting for liver transplantation (LT) in Italy. Materials and methodsUtilising the Italian Liver Transplant Registry database, we analysed data from adult patients listed for primary LT due to end-stage chronic liver disease between January 2012 and December 2022. Independent multivariable waiting lists and post-transplant survival models were developed for patients with and without hepatocellular carcinoma (HCC). A Monte Carlo simulation was employed to create 5-year transplant benefit distributions based on the presence of MASLD, HCC, and MELD-sodium values. ResultsA total sample of 1,941 MASLD and 11,201 non-MASLD was considered. A significant increase in the prevalence of MASLD as an indication for liver transplantation was observed from 2012 to 2022, both for HCC (from 17.7 to 30%) and non-HCC (from 9.5 to 11.8%) cohorts. Projections suggest that, as early as next year, MASLD will overcome HCV as the second most common indication for transplantation after alcoholic liver disease in Italy. According to univariate and multivariate analyses, MASLD was not an independent predictive factor for patient survival after transplantation. However, it increased the risk of death for patients on the waiting list without HCC (hazard ratio 1.62, p <0.001). At the same MELD-sodium, the 5-year transplant benefit was higher in patients with non-HCC MASLD, followed by patients with HCC, while it was lower in non-HCC patients without MASLD. ConclusionsNon-HCC MASLD patients had an increased waitlist mortality and 5-year transplant survival benefit compared to other candidates.

Preservation of fat mass at the expense of lean mass in children with end-stage chronic liver disease.

Sarcopenia predicts morbidity and mortality in end-stage chronic liver disease (ESCLD). Here, we describe changes in body composition in children with ESCLD before and after liver transplantation (LT). Retrospective analysis of whole body DXA scans performed before and after LT over 4 years. Appendicular and whole-body fat mass and lean mass were expressed as fat mass (FMI) and lean mass (LMI) index z-scores. Sarcopenia was defined as leg LMI z-score <-1.96. Eighty-three DXA scans of children before or after LT were studied. Sarcopenia had a positive correlation with weight (0.8, p < .01), height (0.48, p < .05), and BMI z-score (0.77, p < .01), as well as arm, trunk, and total mean mass indices. It correlated negatively with indices of hypersplenism: PLTs (-0.57, p < .01), Neu (-0.50, p < .05), WCC (-0.44, p < .05), and days to discharge (-0.46, p < .05). At baseline: 13/25 (52%) children were sarcopenic and stayed in the hospital after LT for longer. Eight were stunted with a higher WCC and Ne/Ly ratio. All had normal FM indices. One year after LT, 12/26 children remained sarcopenic. Seven were stunted. Two years after LT, 5/15 were sarcopenic, and 5 were stunted. Three years after LT, 1/10 was sarcopenic, and 2 were stunted. By 4 years after LT, 1/7 was sarcopenic, and the same one was stunted. FM indices remained normal. Sarcopenic patients stayed longer in the hospital after LT. Lean mass indices were mostly within the normal range by 4 years after LT. 32% of children were stunted, and markers of inflammation were correlated with stunting. Fat mass was preserved at the cost of lean mass.

Two sides to every story: Reappraising the early history of liver transplantation at Addenbrooke's Hospital, Cambridge.

Over the course of the past six decades, liver transplantation has evolved to become the treatment of choice for chronic end-stage liver disease and some cases of acute hepatic failure. Currently, more than 34,000 liver transplants are conducted worldwide per annum, and overall one year survival rates exceed 90%. However, the early years of human liver transplantation were beset by failure. Eyewitness reports from this period make for tragic, yet compelling reading. Volume 12 of The History of Anaesthesia Society Proceedings contains one such account, written by Dr Elizabeth Gibbs. This outlined the experience of single-handedly anaesthetising the recipient of the first liver transplant to be undertaken at Addenbrooke's Hospital, Cambridge, UK, in June 1967. Despite the best efforts of the team, the patient died from uncontrollable haemorrhage 19 hours after the start of the procedure. While this tragic outcome might have been expected in the early days of liver transplantation, Gibbs included an unsettling postscript in her paper. This stated that all of the patient's records had apparently been 'lost', and the date of the first Cambridge liver transplant was publicly reported as 2 May 1968, some 11 months after the events described. This article outlines the results of research aimed at critically appraising this postscript. In doing so a number of unexpected discoveries were made. These highlight some important lessons for medical historians and demonstrate that if you look hard enough, there really are two sides to every story.

Palliative long-term abdominal drains vs large volume paracenteses for the management of refractory ascites in end-stage liver disease.

Long-term abdominal drains (LTAD) are a cost-effective palliative measure to manage malignant ascites in the community, but their use in patients with end-stage chronic liver disease and refractory ascites is not routine practice. The safety and cost-effectiveness of LTAD are currently being studied in this setting, with preliminary positive results. We hypothesised that palliative LTAD are as effective and safe as repeat palliative large volume paracentesis (LVP) in patients with cirrhosis and refractory ascites and may offer advantages in patients' quality of life. To compare the effectiveness and safety of palliative LTAD and LVP in refractory ascites secondary to end-stage chronic liver disease. A retrospective, observational cohort study comparing the effectiveness and safety outcomes of palliative LTAD and regular palliative LVP as a treatment for refractory ascites in consecutive patients with end-stage chronic liver disease followed-up at our United Kingdom tertiary centre between 2018 and 2022 was conducted. Fisher's exact tests and the Mann-Whitney U test were used to compare qualitative and quantitative variables, respectively. Kaplan-Meier survival estimates were generated to stratify time-related outcomes according to the type of drain. Thirty patients had a total of 35 indwelling abdominal drains and nineteen patients underwent regular LVP. The baseline characteristics were similar between the groups. Prophylactic antibiotics were more frequently prescribed in patients with LTAD (P = 0.012), while the incidence of peritonitis did not differ between the two groups (P = 0.46). The incidence of acute kidney injury (P = 0.014) and ascites/drain-related hospital admissions (P = 0.004) were significantly higher in the LVP group. The overall survival was similar in the two groups (log-rank P = 0.26), but the endpoint-free survival was significantly shorter in the LVP group (P = 0.003, P < 0.001, P = 0.018 for first ascites/drain-related admission, acute kidney injury and drain-related complications, respectively). The use of LTAD in the management of refractory ascites in palliated end-stage liver disease is effective, safe, and may reduce hospital admissions and utilisation of healthcare resources compared to LVP.

Modification of Cardiovascular Risk Factors and the Evolution of The Cardiovascular Phenotype of Liver Transplant Recipients in the Long -Term Postoperative Period.

To evaluate the contribution of traditional and additional cardiovascular risk factors (CVRFs) to the development of chronic ischemic heart disease (CIHD) in liver transplant recipients during the long-term postoperative period. A single-center prospective cohort study was conducted. The study included 740 patients with chronic end-stage liver disease (CESLD) and cirrhotic cardiomyopathy (CCMP). During the observation period (5.4±2.29 years), patients were divided into two groups: liver transplant recipients (n=420) and patients with CESLD on the waiting list who did not receive a donor organ (n=320). In patients enrolled to the study upon inclusion in the waiting list, CVRFs, history, clinical and laboratory and instrumental data were studied at all stages of the hepato-cardiac continuum. During the long-term postoperative period, liver transplant recipients belonged to the group of high cardiovascular risk: over a 5-year observation period, 35.7% (n=150) of them developed metabolic syndrome (MS), 9.8% developed verified CIHD associated with MS. The incidence of traditional CVRFs was high (arterial hypertension, 88.6%; obesity, 36.6%; hypercholesterolemia, 77.8%; hypertriglyceridemia, 43.6%; reduced concentration of high-density lipoprotein cholesterol, 35.4%; increased concentrations of low-density lipoprotein cholesterol, 66.8% and very low-density lipoprotein cholesterol, 51.2%; increased atherogenic index, 61.5%). During the long-term postoperative period as compared to the period when patients were on the waiting list, additional CVRFs appeared: increases in body mass index, calcium index, nitric oxide metabolites, endothelin-1, homocysteine, intercellular adhesion molecules VCAM-1 and ICAM-1, and decreases in endothelium-dependent vasodilation and glomerular filtration rate to less than 60 ml/min/1.73 m2. A model for the development of CIHD was created. The model uses a complex of independent risk factors and demonstrates a predictive accuracy of 84.6%. The study results indicate a modification of CVRFs and a dynamic change in the cardiovascular phenotype of liver transplant recipients: progression of CCMP during their stay on the waiting list, regression of CCMP manifestations during the first 12 months after orthotopic liver transplantation, and increases in the total cardiovascular risk and likelihood of CIHD in the long-term postoperative period.

Evaluating clinical outcomes and prognosis in patients with cirrhosis and portal hypertension: a retrospective observational cohort study

ObjectiveCirrhosis describes the end-stage of chronic liver disease. Irreversible changes in the liver cause portal hypertension, which can progress to serious complications and death. Only a few studies with small...

#3739 SHUNT PORTOSYSTEMIC COMPLICATED BY HYPERAMMONEMIA AND HEPATIC ENCEPHALOPATHY SUPPORTED BY DAILY DIALYSIS IN A CHRONIC HEMODIALYSIS PATIENT

Abstract Background and Aims Hepatic encephalopathy is a neuropsychiatric syndrome that may develop as a consequence of liver insufficiency. In acute liver failure, hepatic encephalopathy suggests the severity of the disease. In end-stage chronic liver diseases, episodes of hepatic encephalopathy are frequently fully and spontaneously reversible. Clinical manifestations vary from mild neuropsychiatric disorders to coma. The pathogenesis of hepatic encephalopathy is complex and not clearly understood. Ammonia plays a key role. In the healthy individual, ammonia is, during its first hepatic passage, directly degraded into urea, itself excreted by the kidney and the stools, and to a lesser degree in glutamine. Ammonia is also metabolized by the muscle striped. In case of liver failure and/or shunts portosystemic, there is a defect in hepatic clearance ammonia which is then found in excess in systemic circulation. Decreased muscle mass, linked to malnutrition, frequent in the patient cirrhotic and chronic hemodialysis, also helps to decrease metabolism ammonia. Due to the increase in permeability of the blood-brain barrier, the brain is exposed to excessive concentrations ammonia causing functional brain abnormalities and structural, which can partly explain the signs neurology of hepatic encephalopathy. In end stage chronic renal failure, clearance of ammonia via extracorporeal treatment has not been systematically evaluated. Several studies with small samples have demonstrated the effectiveness of hemodialysis, compared to peritoneal dialysis, in terms of ammonium purification in chronic renal failure, on dialysis or not on dialysis. The aim of this study was to evaluate the effectiveness of daily dialysis for the purification of ammoniumin a chronic hemodialysis patient with hepatic encephalopathy. Case Report A 40-year-old man undergoing chronic hemodialysis was referred to gastroenterology department of Mohammed VI University center of Marrakesh for inoperable shunt portosystemic complicated by hyperammonemia causing hepatic encephalopathy consisting of headaches and seizures. His medical history was significant for liver cirrhosis caused by infection with hepatitis B, end stage kidney disease due to membranoproliferative glomerulonephritis, for which the patient is on hemodialysis at the rate of 3 sessions per week. The patient went on to develop portal hypertension and ascites requiring frequent hospital admissions and treatment with diuretics. He was on a low-protein and low-sodium diet. While on oral furosemide 250 mg daily and spironolactone 100 mg daily, his diuresis was adequate. Before referral, this patient had already suffered 4 episodes of tonic clonic seizures. His 1st hemodialysis session in our training was on January 10, 2023, he was given daily hemodialysis sessions with daily blood tests, including immediate pre and post dialysis ammonia. Pre-dialytic ammonia levels varied between 103 and 161 µmol/l, as well as post-dialytic ammonia levels varied between 24 and 37 µmol/l, knowing that the normal value of laboratory ammonia varied between 10 and 51 µmol/l. The evolution was marked by a clear clinical improvement, with a disappearance of the seizures without a significant drop in ammonia after 14 daily hemodialysis sessions. Serum creatinine and urea declined, and sodium increased. Accumulation of ascites slowed and the patient could eat and sleep normally and was again independent with self care. The patient returned home on January 24. Conclusion This study shows the interest of daily hemodialysis sessions as a potential treatment for hyperammonemia in a patient on chronic intermittent hemodialysis, with a portosystemic shunt. The interest lies in the fact that the improvement is mainly clinical than biological (persistent hyperammonemia).

Radiological assessment of skeletal muscle index and myosteatosis and their impact postoperative outcomes after liver transplantation

Abstract Background Liver transplantation offers curative treatment to patients with acute and chronic end-stage liver disease. The impact of nutritional status on postoperative outcomes after liver transplantation remains poorly understood. The present study investigated the predictive value of radiologically assessed skeletal muscle index (SMI) and myosteatosis (MI) on postoperative outcomes. Patients and methods Data of 138 adult patients who underwent their first orthotopic liver transplantation were retrospectively analysed. SMI and MI in computer tomography (CT) scan at the third lumbar vertebra level were calculated. Results were analyzed for the length of hospitalisation and postoperative outcomes. Results In 63% of male and 28.9% of female recipients, low SMI was found. High MI was found in 45(32.6%) patients. Male patients with high SMI had longer intensive care unit (ICU) stay (P &lt; 0.025). Low SMI had no influence on ICU stay in female patients (P = 0.544), length of hospitalisation (male, P &gt; 0.05; female, P = 0.843), postoperative complication rates (males, P = 0.883; females, P = 0.113), infection rate (males, P = 0.293, females, P = 0.285) and graft rejection (males, P = 0.875; females, P = 0.135). The presence of MI did not influence ICU stay (P = 0.161), hospitalization (P = 0.771), postoperative complication rates (P = 0.467), infection rate (P = 0.173) or graft rejection rate (P = 0.173). Conclusions In our study, changes in body composition of liver transplant recipients observed with SMI and MI had no impact on postoperative course after liver transplantation. CT body composition analysis of recipients and uniformly accepted cut-off points are crucial to producing reliable data in the future.

The shaping of gut immunity in cirrhosis.

Cirrhosis is the common end-stage of chronic liver diseases of different etiology. The altered bile acids metabolism in the cirrhotic liver and the increase in the blood-brain barrier permeability, along with the progressive dysbiosis of intestinal microbiota, contribute to gut immunity changes, from compromised antimicrobial host defense to pro-inflammatory adaptive responses. In turn, these changes elicit a disruption in the epithelial and gut vascular barriers, promoting the increased access of potential pathogenic microbial antigens to portal circulation, further aggravating liver disease. After summarizing the key aspects of gut immunity during homeostasis, this review is intended to update the contribution of liver and brain metabolites in shaping the intestinal immune status and, in turn, to understand how the loss of homeostasis in the gut-associated lymphoid tissue, as present in cirrhosis, cooperates in the advanced chronic liver disease progression. Finally, several therapeutic approaches targeting the intestinal homeostasis in cirrhosis are discussed.

Long-term outcomes of pediatric liver transplantation in acute liver failure vs end-stage chronic liver disease: A retrospective observational study.

Children with acute liver failure (ALF) who meet the criteria are eligible for super-urgent transplantation, whereas children with end-stage chronic liver disease (ESCLD) are usually transplanted electively. Pediatric liver trans plantation (PLT) in ALF and ESCLD settings has been well described in the literature, but there are no studies comparing the outcomes in these two groups. To determine if there is a difference in post-operative complications and survival outcomes between ALF and ESCLD in PLT. This was a retrospective observational study of all primary PLTs performed at a single center between 2000 and 2019. ALF and ESCLD groups were compared for pretransplant recipient, donor and operative parameters, and post-operative outcomes including graft and patient survival. Over a 20-year study period, 232 primary PLTs were performed at our center; 195 were transplanted for ESCLD and 37 were transplanted for ALF. The ALF recipients were significantly older (median 8 years vs 5.4 years; P = 0.031) and heavier (31 kg vs 21 kg; P = 0.011). Living donor grafts were used more in the ESCLD group (34 vs 0; P = 0.006). There was no difference between the two groups concerning vascular complications and rejection, but there were more bile leaks in the ESCLD group. Post-transplant patient survival was significantly higher in the ESCLD group: 1-, 5-, and 10-year survival rates were 97.9%, 93.9%, and 89.4%, respectively, compared to 78.3%, 78.3%, and 78.3% in the ALF group (P = 0.007). However, there was no difference in 1-, 5-, and 10-year graft survival between the ESCLD and ALF groups (90.7%, 82.9%, 77.3% vs 75.6%, 72.4%, and 66.9%; P = 0.119). Patient survival is inferior in ALF compared to ESCLD recipients; the main reason is death in the 1st year post-PLT in ALF group. Once the ALF children overcome the 1st year after transplant, their survival stabilizes, and they have good long-term outcomes.

Satellite liver transplant centres significantly improve transplant assessment outcomes for patients with chronic liver disease but not hepatocellular carcinoma: a retrospective cohort study

IntroductionLiver transplantation (LT) remains integral to the management of end-stage chronic liver disease (CLD). However, referral thresholds and assessment pathways remain poorly defined. Distance from LT centre has been demonstrated...

Gut microbiota might influence the risk of rejection after liver transplantation

IntroductionLiver transplantation is the only radical treatment option available for patients with end-stage chronic liver disease. However, severe post-transplant complications remain relevant, including acute graft rejection and infection. Thus, the impact of gut microbiota on the frequency of these complications is highly promising. Materials and methodsThis prospective, cohort, closed-label study included 24 adults who underwent liver transplantation. The mean age was 49.2 ± 13.4 years; Child-Turcotte-Pugh A, B, and C classes were distributed as follows: A: 8 (33.3%); B: 11 (45.8%); C: 5 (20.8%). Gut microbiota was evaluated using 16S RNA new-generation sequencing. Study registrationNCT04281797. ResultsAccording to etiological distribution, significant differences were observed in the number of Firmicutes (p = 0.03) and Chlorobi (p = 0.009) harbored by the patients of alcoholic liver disease. Similarly, the severity of hepatic decompensation varied significantly for patients harboring Chlorobi (p = 0.01) and coprothermobacterota (p = 0.03). The association between sarcopenia and the microbiota was not significant among all taxa (p>0.1). Acute graft rejection differences between groups were found: Protobacteria (p = 0.001); Chlamydiae (p = 0.02); Gammaproteobacteria (p = 0.01); Chloroflexia (p = 0.004); Chlamydiia (p = 0.01); Enterobacteriaceae (p = 0.001); and Candidatus Saccharibacteria (p = 0.04), the median of which was found to be lower in patients with an acute graft rejection episode. ConclusionsObtained results prove a reliable interaction between gut microbiota and the incidence of acute liver graft rejection in dominant taxa and Candidatus Saccharibacteria that had not yet been observed in patients with rejection episodes.

Nuclear Factor Erythroid 2-Related Factor 2 Versus Reactive Oxygen Species: Potential Therapeutic Approach on Fighting Liver Fibrosis

Chronic liver disease (CLD) is a progressive deterioration of the liver due to exposure to viruses, drugs, fat accumulation, and toxicity which lead to an imbalance between extracellular matrix accumulation and degradation. Accumulation of the extracellular matrix is a normal liver response at the beginning of the injury. However, increasing extracellular matrix accumulation leads to fibrosis, cirrhosis, and organ failure. Until today, liver transplant is the gold standard therapy for end-stage CLD. Unfortunately, the liver transplant itself faces difficulties such as finding a compatible donor and dealing with complications after treatment. This review provides further information about nuclear factor erythroid 2-related factor 2 (Nrf2) as an alternative approach to fight liver fibrosis. Transformation of hepatic stellate cell (HSC) to myofibroblast has been known as the main mechanism that occurs in fibrosis while epithelial-mesenchymal transition (EMT) and mitochondrial dysfunction become the mechanism followed. In these conditions, oxidative stress is the great promoter which builds a vicious cycle leading to CLD progressivity. Hence, Nrf2 as antioxidant regulator becomes the potential target to break the cycle. While reactive oxygen species (ROS) in oxidative stress induce HSC activation, EMT, and mitochondrial dysfunction through activation of many signaling pathways, Nrf2 acts to diminish ROS directly by regulating secreted antioxidants and its scavenging action. Nrf2 also inactivates fibrosis signaling pathways and plays a role in maintaining mitochondrial health. Therefore, Nrf2 can be a potential target for liver fibrosis therapy.

Mesenchymal Stromal Cell on Liver Decellularised Extracellular Matrix for Tissue Engineering

In end-stage chronic liver disease, transplantation represents the only curative option. However, the shortage of donors results in the death of many patients. To overcome this gap, it is mandatory to develop new therapeutic options. In the present study, we decellularised pig livers and reseeded them with allogeneic porcine mesenchymal stromal cells (pMSCs) to understand whether extracellular matrix (ECM) can influence and/or promote differentiation into hepatocyte-like cells (HLCs). After decellularisation with SDS, the integrity of ECM-scaffolds was examined by histological staining, immunofluorescence and scanning electron microscope. DNA quantification was used to assess decellularisation. pMSCs were plated on scaffolds by static seeding and maintained in in vitro culture for 21 days. At 3, 7, 14 and 21 days, seeded ECM scaffolds were evaluated for cellular adhesion and growth. Moreover, the expression of specific hepatic genes was performed by RT-PCR. The applied decellularisation/recellularisation protocol was effective. The number of seeded pMSCs increased over the culture time points. Gene expression analysis of seeded pMSCs displayed a weak induction due to ECM towards HLCs. These results suggest that ECM may address pMSCs to differentiate in hepatocyte-like cells. However, only contact with liver-ECM is not enough to induce complete differentiation.

Immunology of simultaneous liver and kidney transplants with identification and prevention of rejection.

Simultaneous liver and kidney (SLK) transplantation is considered the best treatment modality among selected patients with both chronic kidney disease (CKD) and end-stage liver disease (ESLD). Since the first SLK transplant in 1983, the number of SLK transplants has increased worldwide, and particularly in the United States since the implementation of the MELD system in 2002. SLK transplants are considered a relatively low immunological risk procedure evidenced by multiple studies displaying the immunomodulatory properties of the liver on the immune system of SLK recipients. SLK recipients demonstrate lower rates of both cellular and antibody-mediated rejection on the kidney allograft when compared to kidney transplant-alone recipients. Therefore, SLK transplants in the setting of preformed donor-specific HLA antibodies (DSA) are a common practice, at many centers. Acceptance and transplantation of SLKs are based solely on ABO compatibility without much consideration of crossmatch results or DSA levels. However, some studies suggest an increased risk for rejection for SLK recipients transplanted across high levels of pre-formed HLA DSA. Despite this, there is no consensus regarding acceptable levels of pre-formed DSA, the role of pre-transplant desensitization, splenectomy, or immunosuppressive management in this unique population. Also, the impact of post-transplant DSA monitoring on long-term outcomes is not well-studied in SLK recipients. In this article, we review recent and relevant past articles in this field with a focus on the immunological risk factors among SLK recipients, and strategies to mitigate the negative outcomes among them.

S1319 Etiologies for In-Hospital Mortality in Patients With Compensated and Decompensated Hepatic Cirrhosis

Introduction: Cirrhosis is the end-stage of chronic liver disease and is generally associated with poor outcome, increased hospitalizations, and mortality. The occurrence of decompensated cirrhosis further markedly increases mortality. Knowledge regarding the causes of mortality and hospitalization can help risk stratify hospitalized patients with cirrhosis. Methods: Using the US Nationwide readmissions database 2014, we identified hospitalized patients who had cirrhosis and died during their hospitalization. In this cohort, we identified rates of cirrhotic and non-cirrhotic complications and etiologies for hospitalization. Causes of death were identified by the primary discharge diagnosis. Decompensated cirrhosis was defined as the presence of hepatic encephalopathy (HE), ascites, jaundice, variceal bleeding (VB), spontaneous bacterial peritonitis (SBP), hepatorenal syndrome (HRS), or hepatocellular carcinoma (HCC). Appropriate ICD-9 codes were used to identify all diagnoses and procedures. Results: We studied 291,368 patients with cirrhosis of whom 38,394 patients (13.2%) died in-hospital. Around 19% of patients who had decompensation (53% of all patients) and 6.7% of patients who had compensated cirrhosis (47%) died during a hospitalization. Decompensated cirrhosis was present in 76.1% (N=29,212) of patients with mortality. Ascites was present in 50.3%, HE in 32.1%, VB in 23.2%, HRS in 19.4%, SBP in 9.1%, jaundice in 5.6% and HCC in 8.7%. In the overall cohort, the most common causes of death were sepsis (31.2%) followed by decompensated cirrhosis (13.6%), viral hepatitis (3.9%), respiratory failure (3.8%), and gastrointestinal bleeding (non-variceal) (3.8%). In patients with compensated cirrhosis, major causes of death were sepsis (33.8%), respiratory failure (6.3%), stroke (5.1%), congestive heart failure (3.4%), and traumatic intracranial injury (3.3%). When decompensation was present, major causes of death were sepsis (30.4%), decompensated cirrhosis (17.9%), gastrointestinal bleeding (4.6%), viral hepatitis (4.5%), and respiratory failure (3.1%). Conclusion: In the US, 1 in 7 hospitalized patients with cirrhosis, 1 in 5 with decompensated cirrhosis, and 1 in 14 with compensated cirrhosis had in-hospital mortality. Sepsis is the most common cause of death (1/3rd) in cirrhotic patients, in both compensated and decompensated cirrhosis. These data can help risk stratify and improve management strategies of hospitalized patients with cirrhosis.

Is hepatitis-B immunization effective during chronic liver fibrosis? Investigation of secretory and cellular immune responses on an experimental model

Objective Adults with end-stage of chronic liver diseases have lower antibody titers after hepatitis-B vaccination. We have less amount of knowledge about the effect of non-viral cause chronic liver fibrosis on vaccination. In this study, we investigated the effect of non-viral chronic liver fibrosis on hepatitis B vaccine and the effect of tetanous toxoid co-administration at the level of humoral and cellular immune responses in an experimental model. Methods Hepatitis B vaccine was administered either alone or in combination with tetanus toxoid in thioacetamide-induced fibrotic BALB/c mice. Fibrosis level was determined by Knodell scoring. Anti-HBsAg, biochemical parameters, inflammatory (IL-1β, TNF-α), and anti-inflammatory (IL-10) cytokine levels were investigated in serum samples by automated systems and ELISA; respectively. Frequencies of activated lymphocytes were determined in flow cytometer. Results Antibody titers significantly decreased after immunization of fibrotic mice. However, co-administration of toxoid significantly elevated antibody titer. The percentage of CD19+CD69+ B lymphocytes was found to be lower in vaccinated fibrotic group compared to vaccinated naive group. Simultaneous administration of toxoid significantly increased the frequencies of CD4+ and CD8+ T cells expressing CD69 and CD127. Interestingly, CD19+CD5+CD1high Breg cells were significantly reduced in the group vaccinated with hepatitis B vaccine and toxoid, simultaneously. The reduction in Breg percentage did not expose a significant decrease in the level of IL-10. Conclusion Non-viral chronic liver fibrosis causes a reduction on specific antibody level after vaccination. Reduction on Breg cell frequency may have an effect on elevation of antibody level after co-administration of tetanus toxoid.

Platelet-Lymphocyte Ratio and Neutrophil-Lymphocyte Ratio as Early Mortality Predictors for Patients with End-Stage Chronic Liver Disease

Background: Chronic liver disease (CLD) often results in fatal complications. Child-Turcotte-Pugh (CTP) score is the earliest predictor of mortality but the Model for End-Stage Liver Disease (MELD) score is more objective. Studies showed platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) could become mortality predictors for chronic liver disease. We aimed to investigate NLR and PLR as early mortality predictors for CLD, in comparison with CTP and MELD scores. Method: This was a retrospective observational cohort study. We recruited patients with CLD (liver cirrhosis and hepatocellular carcinoma), from Saiful Anwar Hospital, Indonesia. Data regarding PLR, NLR, CTP, and MELD scores were obtained from the medical records. Participants were followed for 30 days to determine survival. Results: Ninety patients were recruited in the study. There were 31 deaths (34.4%) in 30 days. Mortality was higher in HCC patients than liver cirrhosis. Although NLR had similar sensitivity with CTP (51.6%), neither PLR (p 0.956) nor NLR (p 0.087) could significantly better predict mortality than CTP (p 0.001) or MELD scores (p 0.002). In opposite to PLR, NLR had a positive correlation with MELD and CTP scores. Conclusion: On the contrary to the PLR, the NLR positively correlated with the severity of the disease, NLR had the potential as a predictor of early mortality for patients with chronic liver disease as compared to CTP and MELD scores. But PLR could not substitute both CTP and MELD scores.

Diagnostic Accuracy of Splenic Index Measued on Ultrasound for Noninvasive Diagnosis of Esophageal Varices Keeping Endoscopy as Gold Standard

Background: End stage chronic liver disease results in the growth of fibrous tissue, the disruption of hepatic architecture, and the formation of nodules, which interfere with liver function and contribute to portal hypertension. Esophageal varices might arise when blood flow through liver is impeded, most typically by scar tissue in the liver caused by liver disease. For high-risk EV diagnosis, endoscopy is the gold standard, but is not available at most health centres in our nation. In individuals at high risk of esophageal varices, performing endoscopies on a yearly or biannual basis can be difficult. We wish to conduct a noninvasive investigation to gather local evidence and to confirm the accuracy of splenic index determined by ultrasonography in detection of EVs. Objective: To find out diagnostic accuracy of splenic index measured by Ultrasound for noninvasive diagnosis of esophageal varices keeping endoscopy as gold standard.