Patients with acute-on-chronic hepatitis B liver failure (HBV-ACLF) show high morbidity and mortality. Independent prognostic predictors of short-term HBV-ACLF mortality include the Child-Turcotte-Pugh (CTP) score, the model for end-stage liver disease (MELD) score, other MELD-based indices and the dynamic changes in these indices. The aims of this study were to evaluate the existing prognostic scores in a large cohort of HBV-ACLF patients and create a new predictive model. We retrospectively reviewed 392 HBV-ACLF patients from December 2008 to November 2011 and evaluated their 3-month survival. The predictive accuracy of CTP, MELD and MELD-based indices and the dynamic changes in the MELD-related scores (Δ scoring systems) upon admission and after two weeks of treatment were compared using the area under the receiver operating characteristic (ROC) curve method. Life-threatening factors and a series of bio-clinical parameters were studied by univariate and multivariate analyses. Among the existing scores, MELD had the best predictive ability. However, our new regression model provided an area under the curve of 0.930 ± 0.0161 (95% CI: 0.869 to 0.943), which was significantly larger than that obtained with the MELD score at admission and after two weeks of treatment as well as with the dynamic changes of the MELD score (0.819, 0.921, and 0.826, respectively) (Z=3.542, P=0.0004). In a large cohort of patients retrospectively reviewed for this study, our prognostic model was superior to the MELD score and is, therefore, a promising predictor of short-term survival in patients with HBV-ACLF.
Acute Disease ; Adult ; Chronic Disease ; Female ; Hepatitis B ; complications ; Humans ; Liver Failure ; etiology ; Male ; Middle Aged ; Prognosis

BACKGROUND/AIMS: Hepatitis-B-related acute-on-chronic liver failure has a poor prognosis. However, the advent of potent oral antiviral agents means that some patients can now recover with medical treatment. We aimed to identify the prognostic factors for hepatitis-B-related acute-on-chronic liver failure including the initial as well as the dynamically changing clinical parameters during admission. METHODS: Sixty-seven patients were retrospectively enrolled from 2003 to 2012 at Samsung Medical Center. The patients were classified into three categories: Recovery group (n=23), Liver transplantation group (n=28), and Death group (n=16). The Liver transplantation and Death groups were combined into an Unfavorable prognosis group. We analyzed the prognostic factors including the Model for End-Stage Liver Disease (MELD) scores determined at 3-day intervals. RESULTS: A multivariable analysis showed that the unfavorable prognostic factors were a high initial MELD score (> or =28) (odds ratio [OR] =6.64, p=0.015), moderate-to-severe ascites at admission (OR=6.71, P=0.012), and the aggravation of hepatic encephalopathy during hospitalization (> or =grade III) (OR=15.41, P=0.013). Compared with the baseline level, significant reductions in the MELD scores were observed on the 7th day after admission in the Recovery group (P=0.016). CONCLUSIONS: Dynamic changes in clinical parameters during admission are useful prognostic factors for hepatitis-B-related acute-on-chronic liver failure.
Acute-On-Chronic Liver Failure/*diagnosis/drug therapy/etiology ; Adult ; Aged ; Antibodies, Monoclonal, Murine-Derived/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Antiviral Agents/therapeutic use ; Cyclophosphamide/therapeutic use ; DNA, Viral/analysis ; Doxorubicin/therapeutic use ; Female ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*diagnosis/drug therapy ; Hospitalization ; Humans ; Liver Transplantation ; Male ; Middle Aged ; Multivariate Analysis ; Odds Ratio ; Prednisone/therapeutic use ; Prognosis ; Retrospective Studies ; Severity of Illness Index ; Vincristine/therapeutic use ; Young Adult

BACKGROUND/AIMS: A revised classification system for renal dysfunction in patients with cirrhosis was proposed by the Acute Dialysis Quality Initiative and the International Ascites Club Working Group in 2011. The aim of this study was to determine the prevalence of renal dysfunction according to the criteria in this proposal. METHODS: The medical records of cirrhotic patients who were admitted to Konkuk University Hospital between 2006 and 2010 were reviewed retrospectively. The data obtained at first admission were collected. Acute kidney injury (AKI) and chronic kidney disease (CKD) were defined using the proposed diagnostic criteria of kidney dysfunction in cirrhosis. RESULTS: Six hundred and forty-three patients were admitted, of whom 190 (29.5%), 273 (42.5%), and 180 (28.0%) were Child-Pugh class A, B, and C, respectively. Eighty-three patients (12.9%) were diagnosed with AKI, the most common cause for which was dehydration (30 patients). Three patients had hepatorenal syndrome type 1 and 26 patients had prerenal-type AKI caused by volume deficiency after variceal bleeding. In addition, 22 patients (3.4%) were diagnosed with CKD, 1 patient with hepatorenal syndrome type 2, and 3 patients (0.5%) with AKI on CKD. CONCLUSIONS: Both AKI and CKD are common among hospitalized cirrhotic patients, and often occur simultaneously (16.8%). The most common type of renal dysfunction was AKI (12.9%). Diagnosis of type 2 hepatorenal syndrome remains difficult. A prospective cohort study is warranted to evaluate the clinical course in cirrhotic patients with renal dysfunction.
Acute Kidney Injury/*epidemiology/etiology/mortality ; Adult ; Aged ; Cohort Studies ; Female ; Hospital Mortality ; Humans ; Kidney Failure, Chronic/*epidemiology/etiology/mortality ; Liver Cirrhosis/complications/*diagnosis ; Male ; Middle Aged ; Prevalence ; Prospective Studies ; Severity of Illness Index ; Survival Rate

The aim of this study was to investigate the clinical characteristics of acute hepatitis A during a recent outbreak in Korea. Data of patients diagnosed with acute hepatitis A from 2007 to 2009 were collected from 21 tertiary hospitals retrospectively. Their demographic, clinical, and serological characteristics and their clinical outcomes were analyzed. A total of 4,218 patients (mean age 33.3 yr) were included. The median duration of admission was 9 days. The mean of the highest ALT level was 2,963 IU/L, total bilirubin was 7.3 mg/dL, prothrombin time INR was 1.3. HBsAg was positive in 3.7%, and anti-HCV positive in 0.7%. Renal insufficiency occurred in 2.7%, hepatic failure in 0.9%, relapsing hepatitis in 0.7%, and cholestatic hepatitis in 1.9% of the patients. Nineteen patients (0.45%) died or were transplanted. Complications of renal failure or prolonged cholestasis were more frequent in patients older than 30 yr. In conclusion, most patients with acute hepatitis A recover uneventfully, however, complication rates are higher in patients older than 30 yr than younger patients. Preventive strategies including universal vaccination in infants and active immunization of hepatitis A to adult population should be considered for prevention of community-wide outbreaks of hepatitis A in Korea.
Acute Disease ; Adolescent ; Adult ; Age Factors ; Aged ; Child ; Child, Preschool ; Cholestasis/epidemiology/etiology ; Demography ; Hepatitis A/complications/*diagnosis/mortality ; Humans ; Kidney Failure, Chronic/epidemiology/etiology ; Liver Transplantation ; Middle Aged ; Morbidity ; Republic of Korea ; Retrospective Studies ; Tertiary Care Centers ; Young Adult

This study was aimed to investigate the morphological, biological ,clinical and therapy features in a special case of primary gastric non-Hodgkin's lymphoma (PG-NHL) through analysis of PG-NHL patient who developed fulminating hepatitis following chemotherapy and radiotherapy and thus received liver transplantation (LT). The morphological changes of cells were analyzed by bone marrow smear, the expression and mutation of abnormal genes were detected by nested multiplex PCR, and HBV-DNA copies were detected by real-time fluorescence quantitative PCR (FQ-PCR). The results showed that at onset of disease, patient was diagnosed as primary gastric non-Hodgkin's lymphoma (PG-NHL) with HBsAg(+) and HBVDNA(-). LUGANO stage was Ia. aaIPI score was 0.The patient was treated with R-CHOP regimen (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone), rituximab maintenance treatment and radiotherapy. During the treatment, the patient has taken entecavir, 1 week later after the radiotherapy (2 months later after the chemotherapy), then the entecavir was discontinued. Six months later HBV DNA(+), the progressive acute hepatic failure (AHF) happened to the patient, who thus received phylogenetic right liver transplantation (LT). He has survived for 3 years after LT so far. The liver function of patient was normal more than 3 years after LT. The patient was checked regularly by PET-CT, and his PG-NHL continue complete remission(CR). It is concluded that the patients receiving chemotherapy or immunosuppressive therapy should be screened for HBV DNA, liver function and HBV reactivation signs. HbsAg positive patients should receive preventive antiviral therapy. After chemotherapy or immunosuppressive therapy, the patients should be given antiviral maintenance therapy, and the liver damage should receive the hepatoprotective and effective support treatment, LT is necessary and feasible to obtain long-term survival.
Hepatitis B ; complications ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; Humans ; Liver Failure, Acute ; etiology ; surgery ; Liver Transplantation ; Lymphoma, Large B-Cell, Diffuse ; blood ; surgery ; therapy ; Male ; Middle Aged

OBJECTIVETo investigate the clinical application, indication, timing and prognosis of blood purification (artificial liver, BP) in treatment of acute liver failure in children.

METHODArtificial liver was used to treat 30 cases of pediatric acute liver failure (PALF), who were hospitalized in pediatric intensive care unit of Bayi Children's Hospital Affiliated to Beijing Military Command General Hospital, during March 2010 to July 2013. Simple plasma exchange (PE) mode was used for PALF without complications, while PE combined with continuous veno-venous hemodiafiltration (CVVHDF) mode was used for PALF with cerebral edema and/or hepatorenal syndrome and/or serious abnormality of electrolyte and acid-base balance.

RESULTSixteen cases survived and restored hepatic function, with a survival rate of 53.3%. Single PE therapy could significantly decrease total bilirubin (TBIL) from (293.96 ± 214.52) µmol/L to (155.64 ± 140.97) µmol/L (P = 0.033), increase prothrombin time activity (PTA) from (34.50 ± 18.34) % to (60.50 ± 33.97) % (P = 0.013), while it did not significantly influence ammonia from (156.43 ± 67.23) µmol/L to (124.03 ± 62.58) µmol/L (P = 0.156) and alanine transarninase (ALT) from (752.53 ± 1 291.84) U/L to (132.00 ± 98.57) U/L (P = 0.066). PE + CVVHDF therapy could significantly ameliorate TBIL from (326.90 ± 233.85) µmol/L to (157.53 ± 125.31) µmol/L (P = 0.033), ALT from (1 476.64 ± 1 728.18) U/L to (169.38 ± 207.18) U/L (P = 0.019), ammonia from (215.83 ± 83.92) µmol/L to (141.25 ± 63.09) µmol/L (P = 0.022) and PTA from (36.68 ± 23.13)% to (71.75 ± 50.50) % (P = 0.044). Prothrombin time (PT) from (29.71 ± 17.75)s to (16.27 ± 6.38)s (P = 0.008) , ALT from (1 574.11 ± 1 775.96) U/L to (145.81 ± 113.89 ) U/L (P = 0.003) , TBIL from (233.16 ± 219.70) µmol/L to (75.19 ± 86.07) µmol/L (P = 0.012) , ammonia from (182.75 ± 90.07) µmol/L to (101.81 ± 37.14) µmol/L (P = 0.002) and PTA from (38.38 ± 20.39)% to (83.13 ± 41.68)% (P = 0.001) in survived cases significantly ameliorated after BP therapy. TBIL from (394.04 ± 192.80) µmol/L to (249.34 ± 113.97) µmol/L (P = 0.023) in died cases declined significantly after BP therapy, while alteration of PT, ALT, ammonia , and PTA had no statistical significance (P > 0.10) after BP therapy.

CONCLUSIONPE + CVVHDF therapy could significantly ameliorate not only TBIL and PTA but also ammonia and ALT compared with single PE therapy. The decline of only an index like TBIL or ALT after BP therapy could not improve the prognosis. The inconsistency between serum bilirubin and ALT levels was an important factor that suggested poor prognosis of ALF, and it might increase survival rate to use BP therapy before that inconsistency emerged.

Adolescent ; Bilirubin ; blood ; Biomarkers ; blood ; Brain Edema ; etiology ; therapy ; Child ; Child, Preschool ; Female ; Hemodiafiltration ; methods ; Heparin ; pharmacology ; Hepatorenal Syndrome ; etiology ; therapy ; Humans ; Infant ; Liver Failure, Acute ; blood ; complications ; mortality ; therapy ; Liver Function Tests ; Male ; Plasma Exchange ; Prothrombin Time ; Survival Rate ; Treatment Outcome

OBJECTIVETo compare the clinical values of the model for end-stage liver disease (MELD)-Na scoring system and the Child-Turcotte-Pugh (CTP) scoring system for predicting the short-term prognosis of acute-on-chronic hepatitis B liver failure.

METHODSA total of 339 patients with acute-on-chronic hepatitis B liver failure and admitted to the Eighth People's Hospital of Guangzhou and Nanfang Hospital of Southern Medical University between January 2010 and December 2012 were included in this retrospective analysis. The short-term predictive values of MELD-Na and CTP scores were compared for this patient population.

RESULTSThe mean MELD-Na score in the advanced stage of liver failure was significantly higher than those in the early and middle stages, respectively (both P less than 0.01). The mean MELD-Na score in the middle stage of liver failure was also significantly higher than that in the early stage (P less than 0.01). In contrast, the mean CTP scores for the three stages of liver failure were not significantly different (all P more than 0.05). The MELD-Na score showed a stronger correlation with the stage of liver failure (rs =0.485, P less than 0.01) than did the CTP score (rs =0.306, P less than 0.01). The short-term mortality rates were significantly different for the three stages of liver failure (P less than 0.01). The mean MELD-Na score of the death group was significantly higher than that of the survival group (P less than 0.01). The CTP scores, however, were not significantly different between the death and survival groups (P more than 0.05).The short-term mortality rate of liver failure was significantly higher for patients with increased scores for the MELD-Na and CTP systems (both P less than 0.01). The areas under the curve of the MELD-Na and CTP scores were 0.813 and 0.823, respectively. The MELD-Na and CTP score have similar predictive values (P more than 0.05).

CONCLUSIONThe MELD-Na scoring system is slightly superior to the CTP scoring system for predicting short-term prognosis of acute-on-chronic hepatitis B liver failure.The predictive value may improve for both the MELD-Na score and the CTP score when combined with expert clinical practice and experience.

Acute-On-Chronic Liver Failure ; etiology ; Hepatitis B ; Hepatitis B, Chronic ; complications ; Humans ; Prognosis ; Retrospective Studies ; Sodium

PURPOSE: Due to the seroepidemiological shift in hepatitis A (HA), its severity, mortality, and complications have increased in recent years. Thus, the aim of this study was to identify predictive factors associated with poor prognosis among patients with HA. MATERIALS AND METHODS: A total of 304 patients with HA admitted to our institution between July 2009 and June 2011 were enrolled consecutively. Patients with complications defined as acute liver failure (ALF) were evaluated, and mortality was defined as death or liver transplantation. RESULTS: The mean age of patients (204 males, 100 females) was 32 years. Eighteen (5.9%) patients had progressed to ALF. Of the patients with ALF, 10 patients (3.3%) showed spontaneous survival while 8 (2.6%) died or underwent liver transplantation. Multivariate regression analysis showed that Model for End-Stage Liver Disease (MELD) and systemic inflammatory response syndrome (SIRS) scores were significant predictive factors of ALF. Based on receiver operating characteristics (ROC) analysis, a MELD > or =23.5 was significantly more predictive than a SIRS score > or =3 (area under the ROC: 0.940 vs. 0.742, respectively). In addition, of patients with a MELD score > or =23.5, King's College Hospital criteria (KCC) and SIRS scores were predictive factors associated with death/transplantation in multivariate analysis. CONCLUSION: MELD and SIRS scores > or =23.5 and > or =3, respectively, appeared to be related to ALF development. In addition, KCC and SIRS scores > or =3 were valuable in predicting mortality of patients with a MELD > or =23.5.
Adult ; Female ; Hepatitis A/*complications ; Humans ; Liver Failure, Acute/*etiology/*mortality/pathology ; Male ; Multivariate Analysis ; Prognosis ; Prospective Studies ; ROC Curve ; Systemic Inflammatory Response Syndrome/complications

Acute-on-chronic liver failure (ACLF) is an increasingly recognized distinct disease entity encompassing an acute deterioration of liver function in patients with chronic liver disease. Although there are no widely accepted diagnostic criteria for ACLF, the Asia.Pacific Association for the Study of the Liver (APASL) and the American Association for the Study of Liver Disease and the European Association for the Study of the Liver (AASLD/EASL) consensus definitions are commonly used. It is obvious that the APASL and the AASLD/EASL definitions are based on fundamentally different features. Two different definitions in two different parts of the world hamper the comparability of studies. Recently, the EASL-Chronic Liver Failure Consortium proposed new diagnostic criteria for ACLF based on analyses of patients with organ failure. There are areas of uncertainty in defining ACLF, such as heterogeneity of ACLF, ambiguity in qualifying underlying liver disease, argument for infection or sepsis as a precipitating event, etc. Although the exact pathogenesis of ACLF remains to be elucidated, alteration of host response to injury, infection, and unregulated inflammation play important roles. The predisposition, infection/inflammation, response, organ failure (PIRO) concept used for sepsis might be useful in describing the pathophysiology and clinical categories for ACLF. Treatment strategies are limited to organ support but better understanding of the pathophysiology is likely to lead to discovery of novel biomarkers and therapeutic strategies in the future.
Chronic Disease ; Echocardiography ; Humans ; Liver Cirrhosis/complications ; Liver Failure/diagnosis/etiology/*pathology/prevention & control ; Liver Failure, Acute/diagnosis/etiology/*pathology/prevention & control ; Liver Transplantation ; Sepsis/complications

OBJECTIVETo establish an accurate new rat model of hyperammonemia-induced liver injury for use in studies of the molecular mechanisms underlying acute liver failure (ALF).

METHODSTwenty-six Sprague-Dawley rats were administered D-galactosamine (400 mg/kg) and endotoxin (50 mug/kg) via intraperitoneal injection to induce ALF and sacrificed at 12 h post-injection (ALF-12 group, n = 10) or 24 h post-injection (ALF-24 group, n = 16). Ten rats administered physiological saline served as the control group. In addition, 20 rats were given serial oral administrations of 10% NH4Cl solution (10 ml/kg, every 8 hrs) to establish the hyperammonemia-induced liver injury model; an additional 20 rats were prepared in parallel to serve as the ALF control group (n = 10; D-galactosamine at 800 mg/kg every 6 d for 30 days) and the physiological saline control group (n = 10). Serum samples were collected from each mouse and used to detect markers of liver function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alpha-fetal protein (AFP), and gamma-glutamyltransferase (GGT), as well as blood ammonia (BA) level and prothrombin time activity (PT-A). Affects on liver histology was assessed by hematoxylin and eosin staining of resected liver tissues, and on apoptosis by TUNEL assay and calculating the apoptotic index (AI).

RESULTSALF rats showed elevated levels of ALT (1202.51+/-282.00 U/L), AST (1560.14+/-298.98 U/L), and BA (165.9+/-23.6 mumol/L) as early as 6 hrs after model establishment; these levels peaked at 12 hrs after model establishment (ALT: 774.40+/-207.65 U/L; AST: 967.60+/-121.94 U/L; BA: 143.4+/-18.1 mumol/L; P less than 0.05). No significant variations were detected in the levels of AFP (except for the ALF-24 group) or GGT. Liver tissues of the ALF-12 and ALF-24 groups showed large or diffuse hemorrhagic necroses with sinusoidal congestion or spotty bleeding, as well as increased AI. Hyperammonemia-induced liver injury rats showed elevated levels of ALT and BA as early as 6 hrs after model establishment. Similar to the ALF rats, AFP and GGT were unaffected and AI increased. However, in contrast to the ALF rats, the liver tissues of the hyperammonemia-induced liver injury rats showed no signs of hepatocyte swelling, necrosis, or inflammatory cell invasion.

CONCLUSIONALF rats and hyperammonemia-induced liver injury rats have elevated BA and marked hepatocyte necrosis. Given that reducing the level of ammonemia can improve the animal's biochemistry indexes, it is likely that hyperammonemia plays a role in acute liver injury or ALF consequent to repeated injury. The pathogenic mechanisms of repeated injury may involve promotion of hepatocyte apoptosis in conjunction with inhibition of cellular regeneration.

Animals ; Disease Models, Animal ; Hyperammonemia ; complications ; Liver Failure, Acute ; etiology ; Male ; Rats ; Rats, Sprague-Dawley