Bridging the critically ill patient with acute to chronic liver failure to liver transplantation.

Liver transplantation (LT) has emerged as an effective therapy for severe forms of acute-on-chronic liver failure (ACLF), an entity characterized by the development of multiorgan failure and high short-term mortality. The aim of critical care management of ACLF patients is to rapidly treat precipitating events and aggressively support failing organs to ensure that patients may successfully undergo LT or, less frequently, recover. Malnutrition and sarcopenia are frequently present, adversely impacting the prognosis of these patients. Management of critical care patients with ACLF is complex and requires the participation of different specialties. Once the patient is stabilized, a rapid evaluation for salvage LT should be performed because the time window for LT is often narrow. The development of sepsis and prolonged organ support may preclude LT or diminish its chances of success. The current review describes strategies to bridge severe ACLF patients to LT, highlights the minimal evaluation required for listing and the currently suggested contraindications to proceed with LT, and addresses different aspects of management during the perioperative and early posttransplant period.

PROGNOSTIC FACTORS OF LIVER TRANSPLANTATION FOR ACUTE-ON-CHRONIC LIVER FAILURE.

BACKGROUND: Liver transplantation (LT) is the only treatment that can provide long-term survival for patients with acute-on-chronic liver failure (ACLF). Although several studies identify prognostic factors for patients in ACLF who do not undergo LT, there is scarce literature about prognostic factors after LT in this population. AIM: Evaluate outcomes of ACLF patients undergoing LT, studying prognostic factors related to 1-year and 90 days post-LT. METHODS: Patients with ACLF undergoing LT between January 2005 and April 2021 were included. Variables such as chronic liver failure consortium (CLIF-C) ACLF values and ACLF grades were compared with the outcomes. RESULTS: The ACLF survival of patients (n=25) post-LT at 90 days, 1, 3, 5 and 7 years, was 80, 76, 59.5, 54.1 and 54.1% versus 86.3, 79.4, 72.6, 66.5 and 61.2% for patients undergoing LT for other indications (n=344), (p=0.525). There was no statistical difference for mortality at 01 year and 90 days among patients with the three ACLF grades (ACLF-1 vs. ACLF-2 vs. ACLF-3) undergoing LT, as well as when compared to non-ACLF patients. CLIF-C ACLF score was not related to death outcomes. None of the other studied variables proved to be independent predictors of mortality at 90 days, 1 year, or overall. CONCLUSIONS: LT conferred long-term survival to most transplant patients. None of the studied variables proved to be a prognostic factor associated with post-LT survival outcomes for patients with ACLF. Additional studies are recommended to clarify the prognostic factors of post-LT survival in patients with ACLF.

Dynamic evaluation based on acute-on-chronic liver failure predicts survival of patients after liver transplantation: a cohort study.

BACKGROUND AND AIMS: Dynamic evaluation of critically ill patients is the key to predicting their outcomes. Most scores based on the Model for End-stage Liver Disease (MELD) and acute-on-chronic liver failure (ACLF) utilize point-in-time assessment. This study mainly aimed to investigate the impact of dynamic clinical course change on post-liver transplantation (LT) survival. METHODS: This study included 637 adults (overall cohort) with benign end-stage liver diseases. The authors compared the MELD scores and our ACLF-based dynamic evaluation scores. Patients enrolled or transplanted with ACLF-3 were defined as the ACLF-3 cohort ( n =158). The primary outcome was 1-year mortality. ΔMELD and ΔCLIF-OF (Chronic Liver Failure-Organ Failure) represented the respective dynamic changes in liver transplant function. Discrimination was assessed using the area under the curve. A Cox regression analysis identified independent risk factors for specific organ failure and 1-year mortality. RESULTS: Patients were grouped into three groups: the deterioration group (D), the stable group (S), and the improvement group (I). The deterioration group (ΔCLIF-OF ≥2) was more likely to receive national liver allocation ( P =0.012) but experienced longer cold ischemia time ( P =0.006) than other groups. The area under the curves for ΔCLIF-OF were 0.752 for the entire cohort and 0.767 for ACLF-3 cohorts, both superior to ΔMELD ( P <0.001 for both). Compared to the improvement group, the 1-year mortality hazard ratios (HR) of the deterioration group were 12.57 (6.72-23.48) for the overall cohort and 7.00 (3.73-13.09) for the ACLF-3 cohort. Extrahepatic organs subscore change (HR=1.783 (1.266-2.512) for neurologic; 1.653 (1.205-2.269) for circulation; 1.906 (1.324-2.743) for respiration; 1.473 (1.097-1.976) for renal) were key to transplantation outcomes in the ACLF-3 cohort. CLIF-OF at LT (HR=1.193), ΔCLIF-OF (HR=1.354), and cold ischemia time (HR=1.077) were independent risk factors of mortality for the overall cohort, while ΔCLIF-OF (HR=1.384) was the only independent risk factor for the ACLF-3 cohort. Non-ACLF-3 patients showed a higher survival rate than patients with ACLF-3 in all groups ( P =0.002 for I, P =0.005 for S, and P =0.001 for D). CONCLUSION: This was the first ACLF-based dynamic evaluation study. ΔCLIF-OF was a more powerful predictor of post-LT mortality than ΔMELD. Extrahepatic organ failures were core risk factors for ACLF-3 patients. CLIF-OF at LT, ΔCLIF-OF, and cold ischemia time were independent risk factors for post-LT mortality. Patients with a worse baseline condition and a deteriorating clinical course had the worst prognosis. Dynamic evaluation was important in risk stratification and recipient selection.

Liver Transplantation Within 7-Days of Listing Improves Survival in ACLF-3.

BACKGROUND AND AIMS: Patients with acute on chronic liver failure (ACLF-3) have a very high short-term mortality without liver transplantation (LT). Our objective was to determine whether early LT (ELT; ≤ 7 days from listing) had an impact on 1 year patient (PS) in patients with ACLF-3 compared to late LT (LLT; days 8-28 from listing). METHODS: All adults with ACLF-3 listed for LT with the United Network for Organ Sharing (UNOS) between 2005 and 2021 were included. We excluded status one patients and those with liver cancer or listed for multi-organ or living donor transplants. ACLF patients were identified using the European Association for the Study of the Liver-Chronic Liver Failure criteria. Patients were categorized as ACLF-3a and ACLF-3b. RESULTS: During the study period, 7607 patients were listed with ACLF-3 (3a-4520, 3b-3087); 3498 patients with ACLF-3 underwent ELT and 1308 had LLT. The overall 1 year PS after listing was 64.4% in ACLF-3a and 50% in ACLF-3b. In 4806 ACLF-3 patients who underwent LT, 1 year PS was 86.2%, but those who had ELT had higher survival (87.1 vs. 83.6%, P = 0.001) than the LLT group. These survival benefits were seen in both ACLF-3a and ACLF-3b. On multivariable analysis, age (HR 1.02, CI 1.01-1.03), diabetes (HR 1.40, CI 1.16-1.68), respiratory failure (HR 1.76, CI 1.50-2.08), donor risk index > 1.7 (HR 1.24, CI 1.06-1.45), and LLT (HR 1.20, CI 1.02-1.43) were independent predictors of higher 1 year mortality while higher albumin (HR 0.89, CI 0.80-0.98) was associated with reduced mortality. CONCLUSION: Early LT (≤ 7 days from listing) in ACLF-3 is associated with better 1 year survival compared to late LT (days 8-28 from listing).

Status 1B designation does not adequately prioritize children with acute-on-chronic liver failure for liver transplantation.

Acute-on-chronic liver failure (ACLF) is an acute decompensation of chronic liver disease leading to multiorgan failure and mortality. The objective of this study was to evaluate characteristics and outcomes of children with ACLF who are at the highest priority for liver transplantation (LT) on the United Network for Organ Sharing (UNOS) database-listed as status 1B. The characteristics and outcomes of 478 children with ACLF listed as status 1B on the UNOS LT waiting list from 2007-2019 were compared with children with similar or higher priority listing for transplant: 929 with acute liver failure (ALF) listed as status 1A and 808 with metabolic diseases and malignancies listed as status 1B (termed "non-ACLF"). Children with ACLF had comparable rates of cumulative organ failures compared with ALF (45% vs. 44%; p > 0.99) listings, but higher than non-ACLF (45% vs. 1%; p < 0.001). ACLF had the lowest LT rate (79%, 84%, 95%; p < 0.001), highest pre-LT mortality (20%, 11%, 1%; p < 0.001), and longest waitlist time (57, 3, 56 days; p < 0.001), and none recovered without LT (0%, 4%, 1%; p < 0.001). In survival analyses, ACLF was associated with an increased adjusted hazard ratio (HR) for post-LT mortality (HR, 1.50 vs. ALF [95% confidence interval, CI, 1.02-2.19; p = 0.04] and HR, 1.64 vs. non-ACLF [95% CI, 1.15-2.34; p = 0.01]). ACLF has the least favorable waitlist and post-LT outcomes of all patients who are status 1A/1B. Increased prioritization on the LT waiting list may offer children with ACLF an opportunity for enhanced outcomes.

[Current status of liver transplantation for adult patients with acute-on-chronic liver failure].

Acute-on-chronic liver failure(ACLF) is the most severe form of acute decompensation that develops in patients with chronic liver disease or liver cirrhosis,and is always accompanied by one or more extrahepatic organ failure, and has an extremely poor short-term prognosis. The causes triggering ACLF are complex and diverse,and the clinical stage and the type and the definition of organ failure differ greatly from one another. Therefore, a universally accepted diagnostic criteria for ACLF is not to be defined, and the epidemiological data and patient outcomes on ACLF are not easy to predict and compare among different regions. Accumulating evidence has shown that liver transplantation(LT) plays a significant role in the surgical treatment of patients with ACLF,but its clinical value is still controversial. The specific management and treatment strategy after the admission of patients with ACLF has not yet formed a unified and standardized process or opinions, which includes the monitoring in the ICU,the support and maintenance of organ functions, the selection of the surgical indication and the timing for LT and so on. Moreover, there still exists many controversies concerning, for example, whether patients with ACLF should receive greater priority for organ allocation compared to other potential candidates on the waiting list. Besides, more prospective controlled studies are urgently needed to investigate the role of the artificial liver support system in the bridging therapy to LT. The aim of this article is to review the indication selection of patients with ACLF suitable for LT,the survival outcomes and prognostic factors after LT, the selection of timing, the organ allocation policy and the bridging therapy to LT, which intends to provide new direction for designing the future clinical studies on LT in patients with ACLF.

Liver Transplantation for Acute-on-Chronic Liver Failure Associated With Acute Necrotizing Pancreatitis: A Case Report.

Liver transplantation (LT) for acute-on-chronic liver failure (ACLF) accompanied by acute necrotizing pancreatitis is still unclear. We have a reported case of LT for ACLF associated with acute necrotizing pancreatitis. The postoperative multiorgan dysfunction and secondary infection were successfully managed under close supervision. The patient was a 47-year-old man with chronic hepatitis B virus infection presented with ACLF and acute necrotizing pancreatitis. After receiving LT from a deceased donor, the patient's liver functioning rapidly reverted to a normal level, and the acute pancreatitis was simultaneously stabilized. However, the patient later developed multiorgan dysfunction secondary to multidrug resistant bacteria infection, which was treated successfully with repeated percutaneous drainage, sensitive antibiotics, continuous renal replacement therapy, microbial balance, and best supportive care. LT can be considered for ACLF associated with acute necrotic pancreatitis without absolute contraindication. Moreover, we recommend a close observation of possible postoperative severe infection, and cautious multidisciplinary management was needed for the prevention of organ dysfunction.

Longterm Outcomes of Patients Undergoing Liver Transplantation for Acute-on-Chronic Liver Failure.

Recent data have demonstrated >80% 1-year survival probability after liver transplantation (LT) for patients with severe acute-on-chronic liver failure (ACLF). However, longterm outcomes and complications are still unknown for this population. Our aim was to compare longterm patient and graft survival among patients transplanted across all grades of ACLF. We analyzed the United Network for Organ Sharing database for the years 2004-2017. Patients with ACLF were identified using the European Association for the Study of the Liver-Chronic Liver Failure criteria. Kaplan-Meier and Cox regression methods were used to determine patient and graft survival and associated predictors of mortality in adjusted models. A total of 56,801 patients underwent transplantation of which 31,024 (54.6%) had no ACLF, 8757 (15.4%) had ACLF grade 1, 9039 (15.9%) had ACLF grade 2, and 7891 (14.1%) had ACLF grade 3. The 5-year patient survival after LT was lower in the ACLF grade 3 patients compared with the other groups (67.7%; P < 0.001), although after year 1, the percentage decrease in survival was similar among all groups. Infection was the primary cause of death among all patient groups in the first year. Infection was the primary cause of death among all patient groups in the first year. After the first year, infection was the main cause of death in patients transplanted with ACLF grade 1 (32.1%), ACLF grade 2 (33.9%), and ACLF grade 3 (37.6%), whereas malignancy was the predominant cause of death in those transplanted with no ACLF (28.5%). In conclusion, patients transplanted with ACLF grade 3 had lower 5-year survival as compared with patients with ACLF grades 0-2, but mortality rates were not significantly different after the first year following LT. Graft survival was excellent across all ACLF groups.

Liver transplantation for acute-on-chronic liver failure.

Acute-on-chronic liver failure (AoCLF) represents a newly defined entity in patients with liver disease leading to multiple organ failures and increased mortality. To date, no universally accepted definition exists, and different academic societies developed guidelines on the early diagnosis and classification of AoCLF. Recently published trials focused on factors associated with a poor outcome and on the development of severity scores aimed to identify patients who may benefit for advanced monitoring and treatment. No specific therapies are demonstrated to improve survival, and liver transplantation (LT) remains the only treatment associated with improved outcome. Our review focuses on current evidence for early diagnosis and prognostication of disease in patients with AoCLF, as well of criteria for intensive care unit admission, indication, and futility markers of LT, as well as bridging therapy and optimal timing of surgery.

The Development and Outcome of Acute-on-Chronic Liver Failure After Surgical Interventions.

Acute-on-chronic liver failure (ACLF) is a syndrome with high short-term mortality. Precipitating events, including hemorrhage and infections, contribute to ACLF development, but the role of surgery remains unknown. We investigated the development of ACLF in patients with cirrhosis undergoing surgery. In total, 369 patients with cirrhosis were included in the study. The clinical and laboratory data were collected prior to and on days 1-2, 3-8, and 9-28, and at 3 and 12 months after surgery. Surgery type was classified as limited or extensive, as well as liver and nonliver surgery. A total of 39 patients had baseline ACLF. Surgery was performed during acute decompensation in 35% of the rest of the 330 patients, and 81 (24.5%) developed ACLF within 28 days after surgery. Surrogate markers of systemic inflammation were similar in patients who developed ACLF or not. Age, sex, serum sodium, baseline bacterial infection, and abdominal nonliver surgery were independent predictors for the development of ACLF after surgery. Patients who developed ACLF within 28 days after surgery had a higher mortality at 3, 6, and 12 months. Survival did not differ between patients with ACLF at surgery and those developing ACLF after surgery. Development of ACLF within 28 days after surgery and elevated alkaline phosphatase and international normalized ratio were independent predictors of 90-day mortality. Independent predictors of 1-year all-cause mortality were alkaline phosphatase, Model for End-Stage Liver Disease score, and preoperative hepatic encephalopathy, whereas nonliver surgery was associated with improved survival. ACLF frequently develops in patients with cirrhosis undergoing surgery, especially in those with active bacterial infection, lower serum sodium, and kidney or coagulation dysfunction. Prognoses of ACLF both at and after surgery are similarly poor. Patients with cirrhosis should be carefully managed perioperatively.

Acute kidney injury in cirrhosis: implications for liver transplantation.

PURPOSE OF REVIEW: Acute kidney injury (AKI) in cirrhosis consists of varying phenotypes, with hepatorenal syndrome (HRS) representing a single entity. Prompt recognition and diagnosis of AKI cause identifies appropriate therapeutic measures. This review provides an overview of AKI definitions, highlights challenges in quantifying renal impairment in cirrhosis, lists novel diagnostic AKI biomarkers, and summarizes transplantation implications. RECENT FINDINGS: Biomarkers (neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, interleukin-18, and liver-type fatty acid-binding protein) may assist in the identification of underlying acute tubular necrosis. Of these, neutrophil gelatinase-associated lipocalin is the most promising; however, significant overlap occurs among AKI phenotypes, with diagnostic values yet to be defined. Mainstay treatment of HRS consists of albumin and vasopressors. Acute-on-chronic liver failure grade independently predicts response to terlipressin treatment. Many end-stage liver disease patients with AKI have underlying chronic kidney disease with important implications on pre and postliver transplantation mortality. Simultaneous liver-kidney transplant candidacy is based on low likelihood of renal recovery. SUMMARY: Novel biomarkers may assist in identification of acute tubular necrosis and persistent/severe AKI. Norepinephrine has been suggested to be inferior to terlipressin, with additional research required. Increasing acute-on-chronic liver failure grade correlates with lower likelihood of vasopressor response in HRS. Severe preliver transplantation AKI confers significantly worse postliver transplantation renal outcomes.

Challenges and future developments in liver transplantation.

Liver transplantation (LT) has become the treatment of choice for a wide range of liver diseases in both adult and pediatric patients. Until recently, the largest proportion of LT in adults, were performed in patients with hepatitis C (HCV) related cirrhosis. The recent availability of safe and effective direct antiviral agents to cure HCV infection in almost all patients whatever the HCV genotype and severity of liver disease, will reduce the need for LT in this category of recipients. Thus, it is presumed that in the next 1 to 2 decades HCV related liver disease will diminish substantially, whereas non-alcoholic steato-hepatitis (NASH) will correspondingly escalate as an indication for LT. The greatest challenges facing LT remain the limited supply of donor organs, and the need for chronic immunosuppression, which represent the true obstacles to the greater application and durable success of the LT procedure. This review aimed to highlight, in different sections, the main open issues and future developments in LT. These will be focused to explore current and future strategies to maximize the use of limited organs, to offer an update on potential new approaches to immunosuppression and to imagine new indications for LT when the number of patients awaiting transplants for HCV related liver disease is reduced.

The assessment of multipotent cell transplantation in acute-on-chronic liver failure: a systematic review and meta-analysis.

Acute-on-chronic liver failure (ACLF) is a serious life-threatening disease with high prevalence. Liver transplantation is the only efficient clinical treatment for ACLF. Because of the rapid progression and lack of liver donors, it is urgent to find an effective and safe therapeutic approach to ACLF. Recent studies showed that multipotent cell transplantation could improve the patients' liver function and enhance their preoperative condition. Cells such as mesenchymal stem cells, bone marrow mononuclear cells and autologous peripheral blood stem cells, which addressed in this study have all been used in multipotent cell transplantation for liver diseases. However, its clinical efficiency is still debatable. This systematic review and meta-analysis explored the clinical efficiency of multipotent cell transplantation as a therapeutic approach for patients with ACLF. A detailed search of the Cochrane Library, MEDLINE, and Embase databases was conducted from inception to November 2017. The outcome measures were serum albumin, prothrombin time, alanine aminotransferase, total bilirubin, platelets, hemoglobin, white blood cells, and survival time. The quality of evidence was assessed using GRADEpro and Jaded scores. A literature search resulted in 537 citations. Of these, 9 articles met the inclusion criteria. It was found that multipotent cell transplantation was able to alleviate liver damage and improve liver function. Multipotent cell transplantation can also enhance the short-term and medium-term survival rates of ACLF. All 9 research articles included in this analysis reported no statistically significant adverse events, side effects, or complications. In conclusions, this study suggested that multipotent cell transplantation could be recommended as a potential therapeutic supplementary tool in clinical practice. However, clinical trials in large-volume centers still needed.

Subcentimetric Incidental Intrahepatic Cholangiocarcinoma in an Explant Liver: Diagnostic Difficulty of a Rare Entity.

Incidental intrahepatic cholangiocarcinoma (iCCA) is a rare neoplastic lesion in the explant liver specimens with an approximate incidence of 0.7%. The detection of iCCA is associated with poor prognosis in the posttransplant setting. The occurrence of a subcentimetric iCCA is very rare and poses a major diagnostic challenge to the pathologist. This article presents a rare case of subcentimetric iCCA in a young male in the background of advanced stage chronic liver disease resulting from autoimmune hepatitis possibly with chronic cholangiopathy along with the histomorphological differentials.

Fibrosis in small syngeneic rat liver grafts because of damaged bone marrow stem cells from chronic alcohol consumption.

A patient with liver failure due to chronic and acute alcohol abuse under consideration for an urgent liver transplant shortly after stopping alcohol may have residual abnormalities that threaten transplant success, particularly for a small graft. To address this, we studied a model in which reduced-size (50%) Lewis rat livers are transplanted into green fluorescence protein transgenic Lewis recipients after they are fed alcohol or a control diet for 5 weeks. Here we show that normal small Lewis grafts transplanted to alcohol-fed Lewis hosts developed fibrosis, whereas no fibrosis was observed in control-fed recipients. Host-derived CD133 + 8-hydroxy-2'-deoxyguanosine (8-OHdG) cells were significantly increased in livers recovered from both alcohol-fed and control recipients, but only alcohol-fed recipients demonstrated co-staining (a marker of oxidative DNA damage). α smooth muscle actin (α-SMA) staining, a marker for myofibroblasts, also co-localized with CD133 + cells only in the livers of alcohol-fed recipients. Immunostaining and polymerase chain reaction analysis confirmed that chronic alcohol consumption decreased the proportion of bone marrow stem cells (BMSCs) expressing CD133, c-Kit, and chemokine (C-X-C motif) receptor 4 markers and caused oxidative mitochondria DNA (mtDNA) damage. Culture of CD133 + cells from normal rats with medium containing 3% ethanol for 48 hours resulted in elevated mitochondrial 8-OHdG and mtDNA deletion, and ethanol exposure diminished CD133 expression but dramatically increased α-SMA expression. In conclusion, oxidative mtDNA damage and deletions occur in BMSCs of chronic alcohol-fed recipients, and these damaged cells mobilize to the small liver grafts and become myofibroblasts where they play a key role in the subsequent development of fibrosis. Liver Transplantation 23 1564-1576 2017 AASLD.

Impact of preoperative infection on outcome after liver transplantation.

BACKGROUND: Bacterial infection in patients with liver failure can lead to a dramatic clinical deterioration. The indications for liver transplantation and outcome in these patients is still controversial. METHODS: All adult patients who underwent liver transplantation between 1 January 2010 and 31 December 2015 were selected from an institutional database. Characteristics of the donors and recipients, and clinical, biochemical and surgical parameters were retrieved from the database. Post-transplant survival rates and complications, including grade III-IV complications according to the Dindo-Clavien classification, were compared between patients with an infection 1 month before transplantation and patients without an infection. RESULTS: Eighty-four patients with an infection had statistically significant higher Model for End-stage Liver Disease (MELD), D-MELD and Balance of Risk (BAR) scores and a higher rate of acute-on-chronic liver failure compared with findings in 343 patients with no infection. The rate of infection after liver transplantation was higher in patients who had an infection before the operation: 48 per cent versus 30·6 per cent in those with no infection before transplantation (P = 0·003). The percentage of patients with a postoperative complication (42 versus 40·5 per cent respectively; P = 0·849) and the 90-day mortality rate (8 versus 6·4 per cent; P = 0·531) was no different between the groups. Multivariable analysis showed that a BAR score greater than 18 and acute-on-chronic liver failure were independent predictors of 90-day mortality. CONCLUSION: Bacterial infection 1 month before liver transplantation is related to a higher rate of infection after transplantation, but does not lead to a worse outcome.

Liver transplantation in the context of organ shortage: toward extension and restriction of indications considering recent clinical data and ethical framework.

PURPOSE OF REVIEW: The scarcity of liver grafts requires to optimize the results of transplantation. Extensions and alternatives of liver transplantation have to be regularly evaluated. RECENT FINDINGS: Acute-on-chronic liver failure and severe alcoholic hepatitis may represent potential extensions of transplant indications. In these diseases, selected patients could obtain a significant benefit from liver transplantation, whereas long-term outcomes and global impact on waiting lists remain to be evaluated prospectively. Alternatives to transplantation may be represented by recent progress in the management of hepatitis C and the treatment of hepatocellular carcinoma. In hepatitis C, new drug combinations may improve the disease control, reducing the progression to cirrhosis and also the risk of post-transplant reinfection allowing to anticipate a future decrease in the indications for transplantation and retransplantation in these patients. In hepatocellular carcinoma, thanks to improvements in operative techniques and better identification of prognostic factors of cancer recurrency, surgical resection or radiofrequency destruction could appear now as true alternatives to transplant in highly selected patients. SUMMARY: Before implementation of these potential changes into decisional algorithms for listing and organ allocation, their consequences, either for patient's individual benefit or for global transplant outcomes, should be closely evaluated using objective long-term end points and taking into account the ethical recommendations for organ transplantation.

The liver protective effect of methylprednisolone on a new experimental acute-on-chronic liver failure model in rats.

BACKGROUND: Acute-on-chronic liver failure is a severe, life-threatening entity and the comprehension of this disease is incomplete. Currently, a reasonable surgical model of acute-on-chronic liver failure is still lacking. The aim of this study was to establish a new model of acute-on-chronic liver failure in rats and to investigate the protective effects of methylprednisolone on this model. METHODS: An obstructive jaundice model in rats was established. Two weeks later, the animals were subjected to a choledochoduodenostomy and a reduced-size hepatic ischaemia/reperfusion injury. Animals were randomly divided into a control group, a methylprednisolone injected via the tail vein group and a methylprednisolone injected via the portal vein group. The survival rates and serum levels of alanine transaminase, aspartate aminotransferase, total bilirubin, tumour necrosis factor alpha, and interferon gamma of the rats were measured and the pathological changes in liver tissues were observed. RESULTS: The survival rate was significantly improved in the methylprednisolone treatment groups. Serum levels of the biochemical indexes were the lowest in the portal vein injection group. Liver tissues under microscopy presented severe pathological injury in the control group. CONCLUSION: This model could be useful for further research into acute-on-chronic liver failure and methylprednisolone may be a potential therapeutic agent for this disease.

Comprehensive treatment of acute-on-chronic liver failure in a patient with hepatitis B: a case report.

The clinical data of a patient with acute-on-chronic liver failure were analyzed retrospectively. The patient has suffered from hepatitis B for 30 years. His liver function deteriorated, yielding Child-Pugh grade C and reaching a model for end-stage liver disease score of 33 points within a short period; this condition was complicated with highly active variceal bleeding and coagulation system failure (PT > 100 s). The patient also presented hepatocellular carcinoma. Comprehensive treatments included effective inhibition of hepatitis B virus replication and intensive care support. Piggyback orthotopic liver transplantation was performed as the final treatment. The patient recovered uneventfully and was discharged after surgery.