The impact of post-hepatectomy liver failure on long-term survival after liver resection for perihilar cholangiocarcinoma.

BACKGROUND: Although post-hepatectomy liver failure (PHLF) can accurately predict short-term mortality of liver resection for perihilar cholangiocarcinoma (pCCA), its significance in predicting long-term overall survival (OS) is still uncertain. METHODS: Retrospective analysis was performed on patients with pCCA who underwent liver resection between October 2013 and December 2018. The patients were divided into 3 groups; No PHF, PHLF (all grade) and grade B/C PHLF according to The International Study Group of Liver Surgery (ISGLS) criteria. RESULTS: A total of 177 patients were enrolled, 65 (36.7%) had PHLF; 25 (14.1%) had grade A, and 40 (22.6%) had grade B/C. Prior to surgery, patients with PHLF showed significantly greater bilirubin levels and CA 19-9 level than those without (11.5 vs 6.7 mg/dL, p = 0.002 and 232.4 vs 85.9 U/mL, p = 0.005, respectively). Additionally, pre-operative future liver remnant volume in PHLF group was lower than no PHLF group significantly (39.6% vs 43.5%, p = 0.006). Major complication and 90-day mortality were higher in PHLF group than no PHLF group (69.2% vs 20.5%, p < 0.001 and 29.2% vs 3.6%, p < 0.001, respectively). The OS in both grade A PHLF and grade B/C PHLF was significantly worse compared to no PHLF, with median survival times of 8.4, 3.3, and 19.2 months, respectively (p < 0.001 and p < 0.001, respectively). Multivariable analysis revealed that PHLF was independently prognostic factor for long-term survival. CONCLUSION: To achieve negative resection margin, the surgical resection in pCCA was aggressive, however this increased the risk of PHLF, which also affects the OS. Consequently, it is necessary for establishing a balance between aggressive surgery and PHLF.

Impact of Alcohol Use Disorder Treatment on Clinical Outcomes Among Patients With Cirrhosis.

BACKGROUND AND AIMS: Despite the significant medical and economic consequences of coexisting alcohol use disorder (AUD) in patients with cirrhosis, little is known about AUD treatment patterns and their impact on clinical outcomes in this population. We aimed to characterize the use of and outcomes associated with AUD treatment in patients with cirrhosis. APPROACH AND RESULTS: This retrospective cohort study included Veterans with cirrhosis who received Veterans Health Administration care and had an index diagnosis of AUD between 2011 and 2015. We assessed the baseline factors associated with AUD treatment (pharmacotherapy or behavioral therapy) and clinical outcomes for 180 days following the first AUD diagnosis code within the study time frame. Among 93,612 Veterans with cirrhosis, we identified 35,682 with AUD, after excluding 2,671 who had prior diagnoses of AUD and recent treatment. Over 180 days following the index diagnosis of AUD, 5,088 (14%) received AUD treatment, including 4,461 (12%) who received behavioral therapy alone, 159 (0.4%) who received pharmacotherapy alone, and 468 (1%) who received both behavioral therapy and pharmacotherapy. In adjusted analyses, behavioral and/or pharmacotherapy-based AUD treatment was associated with a significant reduction in incident hepatic decompensation (6.5% vs. 11.6%, adjusted odds ratio [AOR], 0.63; 95% confidence interval [CI], 0.52, 0.76), a nonsignificant decrease in short-term all-cause mortality (2.6% vs. 3.9%, AOR, 0.79; 95% CI, 0.57, 1.08), and a significant decrease in long-term all-cause mortality (51% vs. 58%, AOR, 0.87; 95% CI, 0.80, 0.96). CONCLUSIONS: Most Veterans with cirrhosis and coexisting AUD did not receive behavioral therapy or pharmacotherapy treatment for AUD over a 6-month follow-up. The reductions in hepatic decompensation and mortality suggest that future studies should focus on delivering evidence-based AUD treatments to patients with coexisting AUD and cirrhosis.

New prognostic factor for hepatitis B virus-related decompensated cirrhosis: Ratio of monocytes to HDL-cholesterol.

AIM: Hepatitis B virus-related decompensated cirrhosis (HBV-DeCi) has a high mortality rate, and it remains a challenge to predict its outcomes in clinical practice. We aimed to determine the association between monocyte-to-HDL-cholesterol ratio (MHR) and short-term prognosis in HBV-DeCi patients. METHODS: A total of 145 HBV-DeCi patients were enrolled. A multivariate analysis was performed to identify predictors of mortality. The findings were validated by a receiver operating characteristic analysis using the area under the curve (AUC). RESULTS: A total of 20 (13.8%) patients had died 30 days after admission. MHR was markedly increased in the non-survivors compared with the survivors. In the multivariate analysis, MHR was identified as an independent risk factor for mortality, with a significant predictive value (AUC = 0.825; sensitivity, 90.0%; specificity, 62.4%). CONCLUSIONS: Elevated MHR is associated with increased mortality rate in HBV-DeCi patients.

Liver regeneration after performing associating liver partition and portal vein occlusion for staged hepatectomy (ALPPS) is histologically similar to that occurring after liver transplantation using a small-for-size graft.

PURPOSE: Associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) can achieve marked future liver remnant (FLR) hypertrophy but this procedure is associated with a risk of mortality due to liver failure because of an insufficient FLR functional increase, a situation comparable to small-for-size syndrome (SFSS) after living-donor liver transplantation (LDLT). METHODS: The clinical data, morphologic volume changes, and histopathologic and immunohistochemical findings in hepatocytes and bile ductules were compared between ALPPS (n = 10) and LDLT with a risk for SFSS (n = 12). RESULTS: Although the patient characteristics and short-term outcome differed between the groups, the mean hypertrophy ratios with respect to liver volume for the FLR after performing the first-stage ALPPS procedures resembled those in small-for-size grafts after similar time intervals: 1.702 ± 0.407 in ALPPS vs. 1.948 ± 0.252 in LDLT (P = 0.205). The histologic grades for sinusoidal dilation (P = 0.896), congestion (P = 0.922), vacuolar change (P = 0.964), hepatocanalicular cholestasis (P = 0.969), and ductular reaction (P = 0.728) within the FLR at the second-stage operation during ALPPS or implanted graft were all similar between the groups. CONCLUSIONS: The hepatic regenerative process may be similar in ALPPS and LDLT using a small-for-size graft. Reducing the hepatic vascular inflow that may be excessive for the FLR volume during the first stage of ALPPS might enhance the functional recovery since measures with a similar effect appear to lessen the likelihood of SFSS.

Liver failure in pregnancy: a review of 25 cases.

We retrospectively reviewed the medical records from 25 pregnant women with liver failure from May 2009 to July 2019. Data describing clinical symptoms and manifestations, routine blood analyses, coagulation, and liver and kidney function were extracted. Swansea criteria were assessed to identify variables with prognostic significance for maternal mortality. The results showed that acute fatty liver was the primary cause of liver failure and 8 (88.89%) patients died within 7 days. Swansea diagnostic criteria for assessing the severity of liver failure were consistent with Chinese guidelines and were more systematic and convenient. The incidence of postpartum haemorrhage was 76%, and the velocity of bleeding was approximately 600 mL per hour. Increased Swansea score, hepatic encephalopathy and decreased PWR were important prognostic indicators for mortality. Recovery during the 7 days postpartum period was an important determinant of maternal outcomes.Impact statementWhat is already known on this subject? Liver failure in pregnant women is a rare but potentially devastating disease with a high rate of short-term morbidity and mortality. There are limited reports about clinical predictors of maternal-foetal outcomes and the dilemmas faced in the term of delivery.What the results of this study add? The incidence of postpartum haemorrhage was 76% in pregnant women with liver failure, but the velocity of bleeding was approximately 600 mL per hour. Our study revealed the Swansea score and the ratio of hepatic encephalopathy were significantly higher and platelet-to-white blood cell ratio (PWR) was lower in women who died compared to those who survived. During treatment period, 8 (88.89%) patients died within 7 days.What the implications are of these findings for clinical practice and/or further research? Swansea score, hepatic encephalopathy and PWR were important prognostic indicators for mortality in pregnant women with liver failure. Recovery during the 7 days postpartum period was an important determinant of maternal outcomes. Our findings may prompt researchers to conduct a large multicentre study to evaluate the prognostic indicators for mortality in pregnant women with liver failure.

Development of a nomogram to predict outcome after liver resection for hepatocellular carcinoma in Child-Pugh B cirrhosis.

BACKGROUND & AIMS: Treatment allocation in patients with hepatocellular carcinoma (HCC) on a background of Child-Pugh B (CP-B) cirrhosis is controversial. Liver resection has been proposed in small series with acceptable outcomes, but data are limited. The aim of this study was to evaluate the outcomes of patients undergoing liver resection for HCC in CP-B cirrhosis, focusing on the surgical risks and survival. METHODS: Patients were retrospectively pooled from 14 international referral centers from 2002 to 2017. Postoperative and oncological outcomes were investigated. Prediction models for surgical risks, disease-free survival and overall survival were constructed. RESULTS: A total of 253 patients were included, of whom 57.3% of patients had a preoperative platelet count <100,000/mm3, 43.5% had preoperative ascites, and 56.9% had portal hypertension. A minor hepatectomy was most commonly performed (84.6%) and 122 (48.2%) were operated on by minimally invasive surgery (MIS). Ninety-day mortality was 4.3% with 6 patients (2.3%) dying from liver failure. One hundred and eight patients (42.7%) experienced complications, of which the most common was ascites (37.5%). Patients undergoing major hepatectomies had higher 90-day mortality (10.3% vs. 3.3%; p = 0.04) and morbidity rates (69.2% vs. 37.9%; p <0.001). Patients undergoing an open hepatectomy had higher morbidity (52.7% vs. 31.9%; p = 0.001) than those undergoing MIS. A prediction model for surgical risk was constructed (https://childb.shinyapps.io/morbidity/). The 5-year overall survival rate was 47%, and 56.9% of patients experienced recurrence. Prediction models for overall survival (https://childb.shinyapps.io/survival/) and disease-free survival (https://childb.shinyapps.io/DFsurvival/) were constructed. CONCLUSIONS: Liver resection should be considered for patients with HCC and CP-B cirrhosis after careful selection according to patient characteristics, tumor pattern and liver function, while aiming to minimize surgical stress. An estimation of the surgical risk and survival advantage may be helpful in treatment allocation, eventually improving postoperative morbidity and achieving safe oncological outcomes. LAY SUMMARY: Liver resection for hepatocellular carcinoma in advanced cirrhosis (Child-Pugh B score) is associated with a high rate of postoperative complications. However, due to the limited therapeutic alternatives in this setting, recent studies have shown promising results after accurate patient selection. In our international multicenter study, we provide 3 clinical models to predict postoperative surgical risks and long-term survival following liver resection, with the aim of improving treatment allocation and eventually clinical outcomes.

Randomized Trial of Spheroid Reservoir Bioartificial Liver in Porcine Model of Posthepatectomy Liver Failure.

Acute liver failure (ALF) is a catastrophic condition that can occur after major liver resection. The aim of this study was to determine the effects of the spheroid reservoir bio-artificial liver (SRBAL) on survival, serum chemistry, and liver regeneration in posthepatectomy ALF pigs. Wild-type large white swine (20 kg-30 kg) underwent intracranial pressure (ICP) probe placement followed by 85% hepatectomy. Computed tomography (CT) volumetrics were performed to measure the extent of resection, and at 48 hours following hepatectomy to assess regeneration of the remnant liver. Animals were randomized into three groups based on treatment delivered 24-48 hours after hepatectomy: Group1-standard medical therapy (SMT, n = 6); Group2-SMT plus bio-artificial liver treatment using no hepatocytes (0 g, n = 6); and Group3-SMT plus SRBAL treatment using 200 g of primary porcine hepatocyte spheroids (200 g, n = 6). The primary endpoint was survival to 90 hours following hepatectomy. Death equivalent was defined as unresponsive grade 4 hepatic encephalopathy or ICP greater than 20 mmHg with clinical evidence of brain herniation. All animals in both (SMT and 0 g) control groups met the death equivalent before 51 hours following hepatectomy. Five of 6 animals in the 200-g group survived to 90 hours (P < 0.01). The mean ammonia, ICP, and international normalized ratio values were significantly lower in the 200-g group. CT volumetrics demonstrated increased volume regeneration at 48 hours following hepatectomy in the 200-g group compared with the SMT (P < 0.01) and 0-g (P < 0.01) groups. Ki-67 staining showed increased positive staining at 48 hours following hepatectomy (P < 0.01). Conclusion: The SRBAL improved survival, reduced ammonia, and accelerated liver regeneration in posthepatectomy ALF. Improved survival was associated with a neuroprotective benefit of SRBAL therapy. These favorable results warrant further clinical testing of the SRBAL.

MELD or Sodium MELD: A Comparison of the Ability of Two Scoring Systems to Predict Outcomes After Transjugular Intrahepatic Portosystemic Shunt Placement.

OBJECTIVE. The purpose of this study was to compare the ability of the model for end-stage liver disease (MELD) and sodium MELD (MELD-Na) scoring systems to predict outcomes after transjugular intrahepatic portosystemic shunt (TIPS) placement. MATERIALS AND METHODS. Two hundred and nineteen consecutive patients who underwent TIPS placement were retrospectively reviewed. The primary outcomes were death within 30 days and 90 days after TIPS placement (30- and 90-day mortality, respectively), and secondary outcomes included death within 365 days after TIPS placement (365-day mortality), length of hospital stay, and readmission to the hospital within 30 days of TIPS placement. RESULTS. Mortality rates within 30, 90, and 365 days after TIPS placement were 2.3% (5/219), 8.2% (17/207), and 21.7% (41/189), respectively. Logistic regression showed that the MELD score predicted 30-day mortality (odds ratio [OR], 1.13; 95% CI, 1.00-1.27; p = 0.04) and trended toward predicting 90-day mortality (OR, 1.09; 95% CI, 1.00-1.18; p = 0.06), whereas the MELD-Na score did not predict 30-day mortality (OR, 1.02; 95% CI, 0.97-1.06; p = 0.51) or 90-day mortality (OR, 1.01; 95% CI, 0.98-1.15; p = 0.44). In a comparison of the ROC AUCs for MELD and MELD-Na, MELD showed improved prediction of 30-day mortality (p = 0.06) but did not significantly vary in prediction of 90- and 365-day mortality (p = 0.80 and p = 0.76, respectively). When the maximal inflection point for MELD and MELD-Na was analyzed on the basis of 90-day mortality, a score of 23 was found to be most significant for both MELD (OR, 6.6; 95% CI, 1.5-29.1; p = 0.01) and MELD-Na (OR, 3.3; 95% CI, 1.1-9.6; p = 0.03). MELD and MELD-Na both accurately predicted the length of hospital stay after TIPS placement (p = 0.005 and p = 0.01, respectively). CONCLUSION. MELD is superior to MELD-Na for predicting 30-day and, perhaps, 90-day mortality after TIPS placement. At present, decisions regarding patient selection for TIPS placement should be made on the basis of the MELD score rather than the MELD-Na score.

Prognosis of Split Liver Transplantation Compared with Whole Liver Transplantation in Adult Patients: Single-center Results under the Korean MELD Score-based Allocation Policy.

BACKGROUND: Split liver transplantation (SLT) has been occasionally performed in Korea. This study compared the incidence and prognosis of SLT with whole liver transplantation (WLT) in adult patients. METHODS: Between June 2016 and November 2019, 242 adult patients underwent a total of 256 deceased donor liver transplantation operations. SLT was performed in 7 patients (2.9%). RESULTS: The mean age of SLT donors was 29.7 ± 7.4 years, and the mean age of recipients was 55.7 ± 10.6 years, with the latter having a mean model for end-stage liver disease score of 34.6 ± 3.1. Mean split right liver graft weight was 1,228.6 ± 149.7 g and mean graft-recipient weight ratio was 1.97 ± 0.39. Of the seven SLT recipients, Korean Network for Organ Sharing (KONOS) status was one in status 1, one in status 2 and five in status 3. The graft (P = 0.72) and patient (P = 0.84) survival rates were comparable in the SLT and WLT groups. Following propensity score matching, graft (P = 0.61) and patient (P = 0.91) survival rates remained comparable in the two groups. Univariate analysis showed that pretransplant ventilator support and renal replacement therapy were significantly associated with patient survival, whereas KONOS status category and primary liver diseases were not. Multivariate analysis showed that pretransplant ventilator support was an independent risk factor for patient survival. CONCLUSION: Survival outcomes were similar in adult SLT and WLT recipients, probably due to selection of high-quality grafts and low-risk recipients. Prudent selection of donors and adult recipients for SLT may expand the liver graft pool for pediatric patients without affecting outcomes in adults undergoing SLT.

Changes in thyroid function in patients with liver failure and their clinical significance: A clinical study of non-thyroidal illness syndrome in patients with liver failure.

BACKGROUND: Non-thyroidal illness syndrome (NTIS) develops in a large proportion of critically ill patients and is associated with high risk for death. We aimed to investigate the correlation between NTIS and liver failure, and the short-term mortality of patients with these conditions. METHODS: The clinical data of 87 patients with liver failure were collected retrospectively, 73 of them were randomly selected for an observational study and to establish prognostic models, and 14 for model validation. Another 73 sex- and age-matched patients with mild chronic hepatitis were randomly selected as a control group. Serum free triiodothyronine (FT3), free thyroxine (FT4), and thyroid-stimulating hormone (TSH) were measured. The clinical characteristics of patients with liver failure and NTIS were analyzed. The follow-up of patients lasted for 3 months. Additionally, the values for predicting short-term mortality of model for end-stage liver disease (MELD), Child-Turcotte-Pugh (CTP), chronic liver failure-sequential organ failure assessment (CLIF-SOFA) scores, FT3-MELD model, and FT3 were evaluated. RESULTS: The observation group had significantly lower FT3 (2.79 ± 0.71 vs. 4.43 ± 0.75 pmol/L, P < 0.001) and TSH [0.618 (0.186-1.185) vs. 1.800 (1.570-2.590) mIU/L, P < 0.001], and higher FT4 (19.51 ± 6.26 vs. 14.47 ± 2.19 pmol/L, P <0.001) than the control group. NTIS was diagnosed in 49 of the patients with liver failure (67.12%). In the observation group, patients with NTIS had a higher mortality rate than those without (63.27% vs. 25.00%, P = 0.002). Across the whole cohort, the 3-month mortality was 50.68%. The international normalized ratios (INR) were 2.40 ± 1.41 in survivors and 3.53 ± 1.81 in deaths (P = 0.004), the creatinine (Cr) concentrations were 73.27 ± 36.94 µmol/L and 117.08 ± 87.98 µmol/L (P = 0.008), the FT3 concentrations were 3.13 ± 0.59 pmol/L and 2.47 ± 0.68 pmol/L (P < 0.001), the MELD scores were 22.19 ± 6.64 and 29.57 ± 7.99 (P < 0.001), the CTP scores were 10.67 ± 1.53 and 11.78 ± 1.25 (P = 0.001), and the CLIF-SOFA scores were 8.42 ± 1.68 and 10.16 ± 2.03 (P < 0.001), respectively. FT3 was negatively correlated with MELD score (r = -0.430, P < 0.001). An FT3-MELD model was established by subjecting FT3 concentration and MELD score to logistic regression analysis using the following formula: Logit(P) = -1.337 × FT3+0.114 × MELD+0.880. The area under the receiver operating characteristic (ROC) curve was 0.827 and the optimal cut-off value was 0.4523. The corresponding sensitivity and specificity were 67.6% and 91.7%. The areas under the ROC curve for FT3 concentration, MELD score, CTP score, and CLIF-SOFA score were 0.809, 0.779, 0.699, and 0.737, respectively. CONCLUSIONS: Patients with liver failure often develop NTIS. FT3-MELD score perform better than CTP and CLIF-SOFA scores in predicting mortality in patients with liver failure. Thus, the FT3-MELD model could be of great value for the evaluation of the short-term mortality of such patients.

[Research progress of prewarning parameters of pre-hepatic failure].

Liver failure is a common clinical syndrome of severe liver disease, with high short-term mortality. Although there is currently no standardized and unified diagnostic criteria for pre-hepatic failure in the world, so the proposal of its concept is of great significance to further improve the prewarning of liver failure. This article reviews the prewarning parameters of the risk of liver failure related from the perspectives of etiologies, clinical laboratory tests and pathogenesis, and thereby aims to help clinicians improve their understanding of early diagnosis of liver failure and promote related research to further reduce the mortality rate of patients with liver failure.

Combined Systemic Disruption of MET and Epidermal Growth Factor Receptor Signaling Causes Liver Failure in Normal Mice.

MET and epidermal growth factor receptor (EGFR) tyrosine kinases are crucial for liver regeneration and normal hepatocyte function. Recently, we demonstrated that in mice, combined inhibition of these two signaling pathways abolished liver regeneration after hepatectomy, with subsequent hepatic failure and death at 15 to 18 days after resection. Morbidity was associated with distinct and specific alterations in important downstream signaling pathways that led to decreased hepatocyte volume, reduced proliferation, and shutdown of many essential hepatocyte functions, such as fatty acid synthesis, urea cycle, and mitochondrial functions. Herein, we explore the role of MET and EGFR signaling in resting mouse livers that are not subjected to hepatectomy. Mice with combined disruption of MET and EGFR signaling were noticeably sick by 10 days and died at 12 to 14 days. Mice with combined disruption of MET and EGFR signaling mice showed decreased liver/body weight ratios, increased apoptosis in nonparenchymal cells, impaired liver metabolic functions, and activation of distinct downstream signaling pathways related to inflammation, cell death, and survival. The present study demonstrates that, in addition to controlling the regenerative response, MET and EGFR synergistically control baseline liver homeostasis in normal mice in such a way that their combined disruption leads to liver failure and death.

Outcomes after multiple courses of granulocyte colony-stimulating factor and growth hormone in decompensated cirrhosis: A randomized trial.

Decompensated cirrhosis (DC) carries a high mortality. Liver transplantation (LT) is the treatment of choice; however, the limited availability of donor organs has resulted in high waitlist mortality. The present study investigated the impact of multiple courses of granulocyte-colony stimulating factor (G-CSF) with or without growth hormone (GH) in these patients. Sixty-five patients with DC were randomized to standard medical therapy (SMT) plus G-CSF 3 monthly plus GH daily (group A; n = 23) or SMT plus G-CSF (group B; n = 21) or SMT alone (group C; n = 21). The primary outcome was transplant-free survival (TFS) at 12 months. Secondary outcomes were mobilization of CD34+ cells at day 6 and improvement in clinical scores, liver stiffness, nutrition, episodes of infection, and quality of life (QOL) at 12 months. There was significantly better 12-month TFS in groups A and B than in group C (P = 0.001). At day 6 of therapy, CD34+ cells increased in groups A and B compared to baseline (P < 0.001). There was a significant decrease in clinical scores, improvement in nutrition, better control of ascites, reduction in liver stiffness, lesser infection episodes, and improvement in QOL scores in groups A and B at 12 months as compared to baseline (P < 0.05). The therapies were well tolerated. CONCLUSION: Multiple courses of G-CSF improved 12-month TFS, mobilized hematopoietic stem cells, improved disease severity scores, nutrition, fibrosis, QOL scores, ascites control, reduced infections, and the need for LT in patients with DC. However, the use of GH was not found to have any additional benefit. (Hepatology 2017).

Incidence, predictors and prognosis of genotype 4 hepatitis E related liver failure: A tertiary nested case-control study.

BACKGROUND/AIMS: Hepatitis E virus (HEV) infection has been recognized an important insult of acute or acute-on-chronic liver failure (A(C)LF). This study aimed to identify the incidence, predictors and outcomes of A(C)LF in patients with hepatitis E. METHODS: All patients diagnosed of hepatitis E between 2012 and 2018 in the tertiary hospital were retrospectively and consecutively analysed. Patients with hepatitis E who developed A(C)LF were enrolled as cases (HEV-LF) and controls were randomly selected from those who did not develop liver failure with 1:3 ratio in the same cohort. RESULTS: Eight hundred and nine patients were diagnosed with hepatitis E, among which 80 were identified with HEV-related liver failure (HEV-LF) with HEV as the solely acute aetiology of A(C)LF. Sequencing of HEV genome showed genotype (GT) 4 strains in all available serum samples. Hepatitis E patients with cirrhosis underwent higher risk to develop liver failure, compared to non-cirrhotic patients. Hydrothorax, respiratory infections, lower γ-glutamyl transferase, higher lactate dehydrogenase and alpha-foetoprotein were found to be independent predictors of A(C)LF in patients with hepatitis E. The 28-day and 90-day mortality for HEV-LF was 12.86% and 30.36% respectively. Renal injury and lower triglyceride were independent factors associated with 28-day mortality. Lower alanine aminotransferase and higher International normalized ratio were independent predictors of 90-day mortality. CONCLUSIONS: Patients with GT4 hepatitis E are at high risk to develop A(C)LF. Different CLD status impacted the incidence of HEV-LF distinctively. The identified variables shall help to identify HEV patients with high risk for developing liver failure and the risk for death.

Controlled attenuation parameter does not predict hepatic decompensation in patients with advanced chronic liver disease.

BACKGROUND & AIMS: Assessment of hepatic steatosis by transient elastography (TE)-based controlled attenuation parameter (CAP) might predict hepatic decompensation. Therefore, we aimed to evaluate the prognostic value of CAP in patients with compensated advanced chronic liver disease (cACLD) and decompensated cirrhosis (DC). METHODS: A total of 430 patients who underwent TE (liver stiffness ≥10 kPa) and CAP measurements were included in this retrospective analysis. Half of patients (n = 189) underwent simultaneous HVPG measurement. In cACLD patients, first hepatic decompensation was defined by new onset of ascites, hepatic encephalopathy or variceal bleeding. In patients with DC, the following events were considered as further hepatic decompensation: requirement of paracentesis, admission for/development of grade 3/4 hepatic encephalopathy, variceal (re-)bleeding or liver-related death. RESULTS: First hepatic decompensation occurred in 25 of 292 (9%) cACLD patients, while 46 of 138 (33%) DC patients developed further hepatic decompensation during a median follow-up of 22 and 12 months respectively. CAP was not predictive of first (cACLD; per 10 dB/m; hazard ratio [HR]: 0.97, 95% confidence interval [95% CI]: 0.91-1.03, P = 0.321) or further hepatic decompensation (DC; HR: 0.99, 95% CI: 0.94-1.03, P = 0.554) in adjusted analysis. Using the well-established CAP cut-off of ≥248 dB/m for hepatic steatosis, the incidence of first (cACLD; P = 0.065) and further hepatic decompensation (DC; P = 0.578) was similar in patients with hepatic steatosis or without. Serum albumin levels (per mg/dL; HR: 0.83, 95% CI: 0.77-0.89, P < 0.001) and MELD-Na (per point; HR: 1.15, 95% CI: 1.04-1.28, P = 0.006) in cACLD and MELD-Na (per point; HR: 1.12, 95% CI: 1.05-1.19, P < 0.0001) in DC patients were the only parameters independently associated with first and further hepatic decompensation, respectively. CONCLUSION: Controlled attenuation parameter does not predict the development of first (cACLD)/further (DC) hepatic decompensation, while serum albumin levels and MELD-Na are of prognostic value.

Liver Graft-Versus-Host Disease is associated with poor survival among allogeneic hematopoietic stem cell transplant recipients.

Liver Graft-versus-host disease (GVHD) is common in patients with post-transplant liver dysfunction following allogeneic hematopoietic stem cell transplantation (AHSCT). Oftentimes, the diagnosis is made clinically, and liver biopsy is deferred. Our objective was to evaluate the risk factors and clinical outcomes of liver GVHD among patients who developed post-transplant liver dysfunction. Additionally, we evaluated the feasibility of liver biopsy in this population. We compared outcomes between liver GVHD and a "non-liver GVHD" group, which consisted of other etiologies of post-transplant liver dysfunction. Between January 2003 and December 2010, 249 patients developed post-transplant liver dysfunction following AHSCT: 124 patients developed liver GVHD and 125 were in the "non-liver GVHD" group. The incidence of acute and chronic liver GVHD at one year was 15.7% and 31.0%, respectively. The competing risk analysis revealed full intensity conditioning regimen (Hazard ratio [HR], 1.76; P = .008) and related donor (HR, 1.68; P = .004) as independent risk factors for liver GVHD. The time-varying covariate Cox regression analysis with competing risk event, demonstrated that liver GVHD was independently associated with higher non-relapse mortality, and adverse relapse-free and overall survival. A total of 112 liver biopsies were performed in 100 patients. No major complications were observed. Liver biopsy confirmed prebiopsy hypotheses in 49% of cases, and led to treatment modification in 49% of patients. Our study shows that liver GVHD is associated with adverse survival. Liver biopsy is safe and often helps directing care in this setting.

Impact of diabetes on the risk of serious liver events and liver-related deaths in people living with HIV and hepatitis C co-infection: data from the ICONA Foundation Cohort Study.

To investigate the association between diabetes and HCV infection in persons living with HIV and to determine the impact of diabetes on the occurrence of serious liver events (SLEs) and liver-related deaths (LRDs) among HIV/HCV-co-infected patients. Patients were included if they had at least one follow-up visit. In a cross-sectional analysis among all HIV patients, we have investigated the association between diabetes and HCV infection. A further longitudinal analysis was performed in the population of HIV/HCV-co-infected free from SLE with FIB-4 index < 3.25 at baseline, using the following endpoints: (A) first event between SLE and LRD; (B) liver fibrosis progression defined as the first of two consecutive FIB-4 > 3.25; (C) first event between SLE, LRD, and liver fibrosis progression. Data from 15,571 HIV patients were analyzed: 2944 (18.9%) were HCV-Ab positive, and 739 (4.7%) presented a diagnosis of diabetes at their last follow-up. Among HIV/HCV-co-infected population, 107 patients had a diagnosis of diabetes. Viremic HCV-co-infected patients had 3-fold risk of diabetes onset than HCV-uninfected patients. On HIV/HCV-co-infected population, 85 SLEs/LRDs occurred over 20,410 person-years of follow-up (PYFU), for an incidence rate of 4.2/1000 PYFU (95%CI 3.4-5.2). Diabetic patients had 3-fold risk of pooled SLE and LRD than patients without diabetes. Furthermore, viremic HCV infection was independently associated with a higher risk of SLE/LRD (aIRR 3.35 [95%CI 1.14-9.83]). In HIV-infected patients, viremic HCV co-infection is a strong predictor of diabetes. Among HIV/HCV-co-infected population, diabetic patients showed an increased risk of SLE/LRD compared with those without diabetes.

Postoperative Liver Failure Criteria for Predicting Mortality after Major Hepatectomy with Extrahepatic Bile Duct Resection.

BACKGROUND: Post-hepatectomy liver failure (PHLF) is a serious complication after major hepatectomy with extrahepatic bile duct resection (Hx with EBDR) that may cause severe morbidity and even death. The purpose of this study was to compare several criteria systems as predictors of PHLF-related mortality following Hx with EBDR for perihilar cholangiocarcinoma (PHCC). METHODS: The study cohort consisted of 222 patients who underwent Hx with EBDR for PHCC. We compared several criteria systems, including previously established criteria (the International Study Group of Liver Surgery (ISGLS) criterion; and the "50-50" criterion), and our institution's novel systems "Max T-Bili" defined as total bilirubin (T-Bili) >7.3 mg/dL during post-operative days (POD) 1-7, and the "3-4-50" criterion, defined as total bilirubin >4 mg/dL and prothrombin time <50% on POD #3. RESULTS: Thirteen patients (5.8%) died from PHLF-related causes. The 3-4-50 criterion showed high positive predictive values (39.1%), the 3-4-50, Max T-Bili, and 50-50 criterion showed high accuracies (91.7, 86.9, and 90.5%, respectively) and varying sensitivities (69.2, 69.2, and 38.5% respectively). CONCLUSIONS: The 3-4-50, Max T-Bili, and 50-50 criterion were all useful for predicting PHLF-related mortality after Hx with EBDR for PHCC.

Survival and predictors of outcome among patients with decompensated liver disease in a non-liver transplant intensive care unit. Pessimism is historical and unjustified.

BACKGROUND: Recent literature emanating from the United Kingdom and United States has reported decreasing mortality rates in patients with decompensated cirrhosis and organ failures presenting to the intensive care unit (ICU). AIM: To determine if there were comparable outcomes in a single-centre non-transplant unit in Australia. METHODS: A retrospective observational study was conducted in a tertiary, non-liver transplant unit in Sydney, Australia. Admission data and mortality outcomes were collected from patients with cirrhosis non-electively admitted to ICU between 2013 and 2017. Liver-specific and general intensive care scoring tools were also assessed for their discriminative ability to predict short-term prognostic outcomes. RESULTS: Sixty-three patients were admitted with decompensated liver disease who fulfilled the inclusion criteria. The overall hospital mortality was 37% (95% CI: 0.26-0.49). There was no difference in survival based on aetiology of liver disease (P = 0.96) but a significant difference was found based on the presenting diagnosis, with greater survival among patients diagnosed with hepatic encephalopathy on ICU admission (P = 0.02). There was 4% mortality in patients with no organ failure and 52% mortality in those with ≥3 organs in failure (P < 0.001). The ICU prognostic Sequential Organ Failure Assessment score was the better discriminative tool in predicting short-term outcomes when compared to liver prognostic scores. CONCLUSION: The outcomes of this single-centre Australian study align with current overseas literature. These results reinforce and expand on limited local evidence, corroborating the former universal prognostic pessimism towards cirrhotic patients with organ failure as unwarranted.