Erythropoietic protoporphyria (EPP) is an inherited disorder of the heme metabolic pathway that is characterized by accumulation of protoporphyrin in the blood, erythrocytes, and tissues, and cutaneous manifestations of photosensitivity, all resulting from abnormalities in ferrochelatase (FECH) activity due to mutations in the FECH gene. Protoporphyrin is excreted by the liver, and excess protoporphyrin leads to cholelithiasis with obstructive episodes and chronic liver disease, finally progressing to liver cirrhosis. Patients with end-stage EPP-associated liver disease require liver transplantation. We describe here a 31-year-old male patient with EPP who experienced acute-on-chronic liver failure and underwent deceased-donor liver transplantation. Surgical and postoperative care included specific shielding from exposure to ultraviolet radiation to prevent photosensitivity-associated adverse effects. The patient recovered uneventfully and was doing well 24 months after transplantation. Future prevention and treatment of liver disease are discussed in detail.
Acute Disease ; Adult ; End Stage Liver Disease/etiology/pathology/*therapy ; Ferrochelatase/genetics/metabolism ; Humans ; Liver Cirrhosis/diagnosis ; *Liver Transplantation ; Male ; Mutation ; Protoporphyria, Erythropoietic/complications/*diagnosis/pathology

BackgroundContribution of model for end-stage liver disease incorporating with serum sodium (MELD-Na) score in predicting acute kidney injury (AKI) after orthotopic liver transplantation (OLT) is yet to be identified. This study assessed the prognostic value of MELD-Na score for the development of AKI following OLT.

MethodsPreoperative and surgery-related variables of 321 adult end-stage liver disease patients who underwent OLT in Fuzhou General Hospital were collected. Postoperative AKI was defined and staged in accordance with the clinical practice guidelines developed by Kidney Disease: Improving Global Outcomes. Univariate and multivariate analysis was performed to determine the risk factors for AKI following OLT. The discriminating power of MELD/MELD-Na score on AKI outcome was evaluated by receiver operating characteristic (ROC) curve. Spearman's correlation analysis was used for identifying the correlated relationship between MELD/MELD-Na score and the severity levels of AKI.

ResultsThe prevalence of AKI following OLT was in 206 out of 321 patients (64.2%). Three risk factors for AKI post-OLT were presented, preoperative calculated MELD score (odds ratio [OR] = 1.048, P = 0.021), intraoperative volume of red cell suspension transfusion (OR = 1.001, P = 0.002), and preoperative liver cirrhosis (OR = 2.015, P = 0.012). Two areas under ROC curve (AUCs) of MELD/MELD-Na score predicting AKI were 0.688 and 0.672, respectively; the difference between two AUCs was not significant (Z = 1.952, P = 0.051). The Spearman's correlation coefficients between MELD/MELD-Na score and the severity levels of AKI were 0.406 and 0.385 (P = 0.001, 0.001), respectively.

ConclusionsWe demonstrated that preoperative MELD score, intraoperative volume of red cell suspension transfusion and preoperative liver cirrhosis were risk factors for AKI following OLT. Furthermore, we preliminarily validated that MELD score seemed to have a stronger power discriminating AKI post-OLT than that of novel MELD-Na score.

Acute Kidney Injury ; blood ; etiology ; pathology ; Adult ; End Stage Liver Disease ; blood ; etiology ; pathology ; Female ; Humans ; Liver Transplantation ; adverse effects ; Male ; Middle Aged ; Retrospective Studies ; Sodium ; blood

OBJECTIVETo investigate the changes of left ventricular structure and function in patients with liver cirrhosis and their correlation with the model for end-stage liver disease (MELD) score.

METHODSA total of 89 cirrhotic patients admitted between June, 2012 and June, 2014 and 30 healthy control subjects were enrolled in the study. According to MELD score, the cirrhotic patients were divided into 3 groups with MELD scores ≤9, between 10 and 19, and ≥20. The parameters of the left ventricle in resting state were measured using Doppler echocardiography, including left ventricular end systolic diameter (LVESD), left ventricular end diastolic diameter (LVEDD), interventricular septal thickness (IVST), left ventricular posterior wall thickness (LVPWT), left atrial diameter (LAD), ejection fraction (LVEF), cardiac output (CO), mitral flow velocity, and E wave deceleration time (DT), and evaluated their relationship with MELD score.

RESULTSCompared with the control subjects, the cirrhotic patients showed significantly increased LVESD, LVEDD, IVST, LAD, CO and DT but reduced VE/VA ratio (P<0.05 or 0.01). The values of LVESD, LVEDD, IVST, LAD and DT increased gradually with MELD scores (P<0.05 or 0.01). VE/VA ratio was higher in patients with MELD score of 10-19 than in those with MELD score ≤9, and decreased significantly in those with MELD score ≥20. Of the cirrhotic patients, 55% were found to have left atrial enlargement and 44% had a VE/VA ratio ≤1; left atrial enlargement and a VE/VA ratio below 1 were more common in patients with a MELD score ≥20 than in those with lower MELD scores. The LAD, LVEDD and DT were positively correlated with MELD scores (r=0.208, 0.319 and 0.197, respectively; P<0.05 or 0.01).

CONCLUSIONSThe patients with liver cirrhosis can have cardiac function deficiency manifested mainly by left ventricular diastolic dysfunction in positive correlation with the severity of liver disease.

Cardiac Output ; Case-Control Studies ; End Stage Liver Disease ; physiopathology ; Heart Atria ; pathology ; Heart Ventricles ; physiopathology ; Humans ; Liver Cirrhosis ; physiopathology ; Severity of Illness Index ; Ventricular Function, Left

Prognosis is an essential part of the baseline assessment of any disease. For predicting prognosis of end-stage liver disease, many prognostic models were proposed. Child-Pugh score has been the reference for assessing the prognosis of cirrhosis for about three decades in end-stage liver disease. Despite of several limitations, recent large systematic review showed that Child-Pugh score was still robust predictors and it's components (bilirubin, albumin and prothrombin time) were followed by Child-Pugh score. Recently, Model for end-stage liver disease (MELD) score emerged as a "modern" alternative to Child-Pugh score. The MELD score has been an important role to accurately predict the severity of liver disease and effectively assess the risk of mortality. Due to several weakness of MELD score, new modified MELD scores (MELD-Na, Delta MELD) have been developed and validated. This review summarizes the current knowledge about the prognostic factors in end-stage liver disease, focusing on the role of Child-Pugh and MELD score.
Bilirubin/blood ; Creatinine/blood ; End Stage Liver Disease/*diagnosis/*mortality/pathology ; Humans ; International Normalized Ratio ; Prognosis ; Severity of Illness Index ; Survival Rate

Liver fibrosis is a slow, insidious process involving accumulation of extracellular matrix protein in the liver. The stage of liver fibrosis in chronic liver disease (CLD) determines overall morbidity and mortality; the higher the stage, the worse the prognosis. Noninvasive composite scores can be used to determine whether patients with CLD have significant or advanced fibrosis. Patients with low composite scores can be safely followed up in primary care with periodic reassessment. Those with higher scores should be referred to a specialist. As the epidemic of diabetes mellitus, obesity and non-alcoholic fatty liver diseases is rising, CLD is becoming more prevalent. Easy-to-use fibrosis assessment composite scores can identify patients with minimal or advanced fibrosis, and should be an integral part of decision-making. Patients with cirrhosis, high composite scores, chronic hepatitis B with elevated alanine aminotransferase and aspartate aminotransferase, or deranged liver panel of uncertain aetiology should be referred to a specialist.
Alanine Transaminase ; blood ; Aspartate Aminotransferases ; blood ; Decision Making ; End Stage Liver Disease ; complications ; diagnosis ; therapy ; Hepatitis B ; complications ; Humans ; Liver ; pathology ; Liver Cirrhosis ; complications ; diagnosis ; therapy ; Non-alcoholic Fatty Liver Disease ; complications ; diagnosis ; therapy ; Prognosis ; Referral and Consultation ; Treatment Outcome

OBJECTIVETo investigate the efficacy of hematopoietic stem cell (HSC) transplantation via the hepatic artery vs. the portal vein for end-stage liver disease (ESLD).

METHODSPatients with hepatic decompensation were prospectively recruited from September 2010 to September 2012 to receive HSC transplantation via the hepatic artery or the portal vein. Liver function was examined at 3, 6, and 12 months after transplantation. Liver biopsy Results were analyzed using the Knodell score.

RESULTSEighty patients (58 males and 22 females) were enrolled in the study. The Child-Pugh score was grade B in 69 cases, and grade C in the remaining 11 cases. HSC transplantation was performed via the portal vein in 36 patients and via the hepatic artery in 44 patients. ALT levels decreased while serum albumin levels increased significantly in both groups at 6 and 12 months after HSC transplantation (P<0.05 compared with pre-transplantation levels). Total bilirubin levels decreased significantly in both groups at 3, 6, and 12 months after HSC transplantation (P<0.05 compared with pre-transplantation levels). Additionally, prothrombin time decreased in both groups at 12 months after HSC transplantation (P<0.05 compared with pre-transplantation level). There were no significant differences in ALT, total bilirubin and prothrombin time between the two groups either before or after transplantation. Moreover, Knodell score decreased significantly at 6 and 12 months. Histological examination showed that liver cell edema, degeneration, necrosis, and inflammation were significantly relieved at 3, 6, and 12 months after transplantation. The incidence of portal vein thrombosis, upper gastrointestinal bleeding, and hepatic encephalopathy were 1.25%, 3.75%, and 2.5% respectively. The one-year survival rate was 100%.

CONCLUSIONSAutologous HSC transplantation improves liver function and histology in ESLD patients. The administration route of HSC has no significant impact on the efficacy of transplantation.

Adult ; Aged ; Disease-Free Survival ; End Stage Liver Disease ; pathology ; therapy ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Hepatic Artery ; Humans ; Infusions, Intra-Arterial ; Infusions, Intravenous ; Liver Function Tests ; Male ; Middle Aged ; Portal Vein ; Prospective Studies ; Treatment Outcome

OBJECTIVETo investigate the dynamics and clinical significance of serum hepatitis B virus (HBV) DNA levels during the terminal phase of acute-on-chronic liver failure (ACLF) with different hepatitis B e antigen (HBeAg) status.

METHODSOne-hundred-and-seven patients with terminal ACLF were tested for HBeAg status by electrochemiluminescence immunoassay and serum HBV DNA levels by real-time PCR at three chronological time ranges, representing increasing severity of disease phases prior to death (day 0): 29-56 d, 15-28 d, and 0-14 d.

RESULTSIn the 37 HBeAg(+) patients, HBV DNA levels at above-mentioned phases were 6.10+/-1.63, 5.61+/-1.50, and 5.29+/-1.96 log10 copies/mL. In the 70 anti-HBe(+) patients, HBV DNA levels were 4.63+/-1.82, 5.81+/-1.78, and 4.93+/-1.73 log10 copies/mL. Phase to phase comparisons revealed that the HBV DNA level in the HBeAg(+) group was significantly higher than that in the anti-HBe(+) group at 29-56 d (P less than 0.05), and that 15-28 d and 0-14 d were not significantly different (P more than 0.05). Intragroup comparisons of phases revealed no significant differences in the HBeAg(+) group (P more than 0.05), but a significant difference between 15-28 d and 0-14 d (P less than 0.05) for the anti-HBe(+) group.

CONCLUSIONSerum levels of HBV DNA in patients with HBeAg positivity are higher than those in patients with anti-HBe positivity as the disease phase of ACLF nears fatality. Following the deterioration to liver failure, the HBV DNA load in HBeAg(+) patients remains stable while that in anti-HBe(+) patients decreases.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; DNA, Viral ; blood ; End Stage Liver Disease ; blood ; virology ; Female ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; pathology ; Humans ; Liver Failure, Acute ; blood ; virology ; Male ; Middle Aged ; Viral Load ; Young Adult

BACKGROUND/AIMS: This retrospective study assessed the clinical outcome of a transjugular intrahepatic portosystemic shunt (TIPS) procedure for managing portal hypertension in Koreans with liver cirrhosis. METHODS: Between January 2003 and July 2013, 230 patients received a TIPS in 13 university-based hospitals. RESULTS: Of the 229 (99.6%) patients who successfully underwent TIPS placement, 142 received a TIPS for variceal bleeding, 84 for refractory ascites, and 3 for other indications. The follow-up period was 24.9+/-30.2 months (mean+/-SD), 74.7% of the stents were covered, and the primary patency rate at the 1-year follow-up was 78.7%. Hemorrhage occurred in 30 (21.1%) patients during follow-up; of these, 28 (93.3%) cases of rebleeding were associated with stent dysfunction. Fifty-four (23.6%) patients developed new hepatic encephalopathy, and most of these patients were successfully managed conservatively. The cumulative survival rates at 1, 6, 12, and 24 months were 87.5%, 75.0%, 66.8%, and 57.5%, respectively. A high Model for End-Stage Liver Disease (MELD) score was significantly associated with the risk of death within the first month after receiving a TIPS (P=0.018). Old age (P<0.001), indication for a TIPS (ascites vs. bleeding, P=0.005), low serum albumin (P<0.001), and high MELD score (P=0.006) were associated with overall mortality. CONCLUSIONS: A high MELD score was found to be significantly associated with early and overall mortality rate in TIPS patients. Determining the appropriate indication is warranted to improve survival in these patients.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; End Stage Liver Disease/pathology ; Female ; Follow-Up Studies ; Hemorrhage/etiology ; Hepatic Encephalopathy/etiology ; Hospitals, University ; Humans ; Hypertension, Portal/*diagnosis/mortality/surgery ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Odds Ratio ; *Portasystemic Shunt, Transjugular Intrahepatic ; Republic of Korea ; Retrospective Studies ; Risk Factors ; Severity of Illness Index ; Survival Rate ; Treatment Outcome ; Young Adult

Recently, suppressor of cytokine signaling-3 (SOCS3) has been shown to be an inducible endogenous negative regulator of Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway which is relevant in inflammatory response, while its functions in acute liver failure and HBV-induced acute-on-chronic liver failure (HBV-ACLF) have not been fully elucidated. In this study, we explored the role of SOCS3 in the development of mouse hepatitis virus strain 3 (MHV-3)-induced acute liver failure and its expression in liver and peripheral blood mononuclear cells (PBMCs) of patients with HBV-ACLF. Inflammation-related gene expression was detected by real-time PCR, immunohistochemistry and Western blotting. The correlation between SOCS3 level and liver injury was studied. Our results showed that the SOCS3 expression was significantly elevated in both the liver tissue and PBMCs from patients with HBV-ACLF compared to mild chronic hepatitis B (CHB). Moreover, a time course study showed that SOCS3 level was increased remarkably in the liver of BALB/cJ mice at 72 h post-infection. Pro-inflammatory cytokines, interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α, were also increased significantly at 72 h post-infection. There was a close correlation between hepatic SOCS3 level and IL-6, and the severity of liver injury defined by alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, respectively. These data suggested that SOCS3 may play a pivotal role in the pathogenesis of MHV-3-induced acute liver failure and HBV-ACLF.
Adult ; Alanine Transaminase ; blood ; Animals ; Aspartate Aminotransferases ; blood ; Blotting, Western ; End Stage Liver Disease ; genetics ; pathology ; virology ; Female ; Gene Expression ; Hepatitis, Viral, Animal ; genetics ; pathology ; virology ; Host-Pathogen Interactions ; Humans ; Interleukin-1beta ; genetics ; metabolism ; Interleukin-6 ; genetics ; metabolism ; Leukocytes, Mononuclear ; metabolism ; virology ; Liver Failure, Acute ; genetics ; pathology ; virology ; Male ; Mice, Inbred BALB C ; Middle Aged ; Murine hepatitis virus ; physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Severity of Illness Index ; Suppressor of Cytokine Signaling 3 Protein ; Suppressor of Cytokine Signaling Proteins ; blood ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; genetics ; metabolism ; Young Adult