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Background/aims: This study was performed to evaluate any improvement in the nutritional state and clinical symptoms in patients with liver failure and advanced cirrhosis after consumption of a liver diet with restricted energy and protein, in combination with a branched chain amino acids (BCAA)-enriched elemental diet., Methodology: A BCAA-enriched elemental diet, in combination with a liver diet, characterized by restricted energy and protein, was administered in divided meals to 20 patients with liver failure associated with ascites or hepatic encephalopathy for 4 weeks., Results: The symptom of ascites abated as a result of increased total serum protein and albumin levels after the nutritional intervention in comparison with baseline levels. Ammonia levels were slightly increased without exacerbating hepatic encephalopathy, and the protein nutrition state consequently improved., Conclusions: Divided meals of a BCAA-enriched elemental diet combined with a liver diet improved the nutritional state and clinical symptoms of patients with liver failure.

Background/aims: To observe the clinical safety of bioartificial liver supporting system constructed by human hepatoma cell line., Methodology: Seventeen patients with liver failure were treated with C3A-cell-constructed bioartificial liver supporting system, contrasting the difference of biochemical results and imaging data with 9 patients treated with non-bioartificial liver during 5-year treatment., Results: 11 cases of Treatment Group survived at 3 months' follow-up, among whom 2 cases underwent hepatic transplantation. 9 cases without hepatic transplantation survived in 5-year follow-up, and 1 of them was found to occur focal liver lesion at the 5th years, and had hepatic lobectomy. Pathological prompt: hepatocellular carcinoma with moderate differentiation. Totally 4 patients in Control Group survived after 3 months' follow-up, including 1 patient of hepatic transplantation. All the 3 patients without hepatic transplantation survived the last 5-year follow-up, with basically normal biochemical indicators and no focal liver lesion were found by imaging examination., Conclusions: It was safe to use bioartificial liver constructed by tumor cell line C3A to treat liver failure.

Background/aims: It is difficult to estimate the functional reserve of the liver required for safe hepatectomy in patients with severe chronic liver disease The aim of this study was to retrospectively construct simple model based on routine laboratory data to predict both early liver failure (ELF) and mortality from recurrence-free liver failure (MLF) as an index for late liver failure after hepatectomy., Methodology: Between 2000 and 2004, 196 consecutive patients underwent curative hepatectomy, and data from 127 minor hepatectomies were included in this study., Results: Mean survival time was [mean (SD)] 1252 (670) days after hepatectomy. ELF and MLF were observed in 29 and 13 patients, respectively. PT%, TB, and direct bilirubin (DB) were the best predictors in patients with both ELF and MLF. PT% alone was the best predictor of ELF and MLF with area under ROC curves of 0.70 and 0.81, respectively. By using a preoperative PT% of ≤ 70, we could accurately predict ELF and MLF in 77% and 87% of patients, respectively. ICG-R15 could not accurately predict both ELF and MLF for any cut-off values., Conclusions: Unlike ICG-R15, PT% is a simple noninvasive index for estimating liver functional reserve to predict both ELF and MLF.

Background/aims: The serum aspartate aminotransferase-to-platelet ratio index (APRI) is a biomarker for hepatic fibrosis. The relationship between the APRI and postoperative hepatic failure is unclear., Methodology: The risk factors for postoperative hepatic failure and the APRI were evaluated in 457 patients who underwent liver resection for HCC., Results: Nineteen patients (4.2%) experienced postoperative hepatic failure and five (1.1%) died. An increased APRI (p = 0.039), increased total bilirubin (p = 0.044), longer operation (p = 0.035) and increased intraoperative blood loss (p = 0.028) were independent risk factors in the multivariate analysis. Incidence of postoperative hepatic failure in patients with an APRI ≥ 1.57 (13/127, 10%) was significantly higher than in patients with an APRI < 1.57 (6/330,1.8%, p = 0.0002). Moreover, incidence of hepatic failure in high APRI cases with both an operation ≥ 500 min and intraoperative blood loss ≥ 1L (6/33 (18.1%)) tended to be higher than in those with lower values (7/94 (7.4%), p = 0.051)., Conclusions: Increased APRI (≥ 1.57) may be a preoperative predictor of postoperative hepatic failure. Meticulous surgery with shorter operations and reduced blood loss may reduce the incidence of postoperative hepatic failure, even in patients with a high APRI.

Hepatitis B viral infection is a global health threat, with more than 1 million deaths caused by HBV-related liver disease every year. Approximately 1% of HBV-infected patients may end up with liver failure caused by spontaneous or induced factors, and the prognosis is extremely poor. The virulence of HBV is one of the major causes of liver failure and the antiviral treatment is normally given to these patients. But it is controversial if the antiviral therapy improves short-term mortality in these patients. There are many studies shown when add the antiviral drugs (nucleotide analogs) immediately may improve the survival, but in the late-stage the survival have no significant difference. For these patients who are waiting for the liver transplantation, the nucleotide analogs are still needed to prevent the recurrence of HBV. However, after antiviral treatment cessation, the disease relapse and severe acute exacerbation of hepatitis is common, therefore long-term antiviral treatment and potent drugs with low drug resistance are recommended for the HBV-related liver failure patients.

Background/aims: Some HBV mutations have been shown to have an association with liver disease. The aim of the study was to investigate the incidence of mutations in hepatitis B virus (HBV) pre-core/basal core promoter (BCP) and reverse transcriptase (RT) regions and their relationship with disease progression in chronic HBV-infected patients., Methodology: A total of 133 patients were enrolled in this study, comprising the acute-on-chronic hepatitis B liver failure (ACLF-HBV) and chronic hepatitis B (CHB) patients. The pre-core/ BCP and RT gene fragments were amplified by high-fidelity PCR. Mutations of pre-core/BCP and RT regions were examined by direct sequencing., Results: There were no significant differences in age, the average level of ALT and course of disease between the ACLF-HBV and CHB groups. The HBeAg positive rate and average values of HBV-DNA loads of the ACLF-HBV patients were lower than that of CHB patients. In HBV pre-core/ BCP region, the point mutations T1753C (39.06% vs. 21.74%, p<0.01), A1762T (26.56% vs. 13.04%, p<0.05), G1764A (31.25% vs. 18.84%, p<0.01), G1896A (29.69% vs. 15.94%, p<0.05) and G1899 (23.44% vs. 10.14%, p<0.05) were significantly more frequent in the ACLFHBV than CHB patients. For combined mutations, A1762T+G1764A (23.43% vs. 11.59 %, p<0.05) and G1896A+ G1899A (21.88% vs. 13.04%, p<0.05) were significantly more frequent in ACLF-HBV than CHB patients. However, there were no significant differences in RT mutations between two groups., Conclusions: ACLFHBV patients had more frequent mutations in HBV precore/ BCP region than that of CHB patients. Some mutations in HBV pre-core/BCP region might be related to the aggravation of chronic HBV infection.

Background/aims: Evaluation of the urgency of the liver transplantation in individual patients may help to prioritize patients at risk of death. Consequently we undertook the search for independent prognostic factors in patients with liver cirrhosis., Methodology: The study group was composed of 219 patients with liver cirrhosis, treated in our Department, from 1996 to 2005. Patients' files were examined for details of physical findings, results of laboratory examinations, and patients' survival. Prognostic significance of 15 variables was analyzed. All prognostic factors which turned out to be statistically significant in univariate analysis were included in the Cox proportional hazard model., Results: Child-Turcotte-Pugh (CTP) score B (p<0.001; hazard ratio (HR): 13.33), CTP score C (p<0.001; HR=7.45), presence of hepato-renal syndrome (p<0.001; HR=3.54), history of esophageal bleeding (p=0.048; HR=1.63) and presence of peripheral edema (p=0.034; HR=1.61) were found to be independently associated with survival. Model of End-stage Liver Disease score, etiology of cirrhosis, sex, ascites, bacterial spontaneous peritonitis, encephalopathy, serum creatinine concentration, INR and serum bilirubin concentration were shown to be significantly associated with patients' prognosis, however not independently., Conclusions: Analysis of presence of common clinical symptoms is crucial for evaluation of patients' prognosis.

Background/aims: Thrombocytopenia and platelet function abnormalities are problems commonly found in patients with chronic liver disease (CLD). Despite lack of widespread recognition as to the clinical significance of Soluble P-selectin (sP-selectin), in that increased levels of sP-selectin have been described in patients with CLD, it has been proposed as a marker of in-vivo platelet activation. The study's aim was to determine whether levels of sP-selectin in patients with CLD increase in accordance with the degree of liver failure, the likelihood of CLD patients with high sP-selectin levels being more prone to thrombosis, as well as investigating the coagulation and fibrinolytic parameters related to the sP-selectin., Methodology: This study was comprised of two groups: 40 patients with cirrhosis and portal hypertension (28 males and 12 females); and a control group of 10 healthy volunteers (6 males and 4 females). In both groups, biochemical parameters, sP-selectin, coagulation and fibrinolytic activity levels were measured and a Doppler ultrasound was performed., Results: Plasma sP-selectin levels were found to be higher in the patients compared to those of the control group (p < 0.01), while at the same time significant differences were observed with respect to the stage of disease. Patients with low platelet counts were found to have higher sP-selectin levels than those with normal platelet counts (p < 0.01). Seven patients (17.5%) were seen to have portal vein thrombosis upon doppler ultrasound examination, while sP-selectin levels were significantly lower in those patients with thrombosis than those without (p < 0.05). It was our finding that sP-selectin levels inversely correlated with anti thrombin III., Conclusions: In conclusion, sP-selectin levels related to the degree of liver disease and thrombosis are seen together with low platelet and sP-selectin levels in patients with cirrhosis.

Background/aims: To determine the biochemical data that reliably predict allograft injury from acute rejection (AR) in patients with living related liver transplantation (LRLT), liver function test and histopathological characteristics of AR were compared and analyzed retrospectively., Methodology: From Aug. 1994 to Nov. 2000, 101 cases received orthotopic liver transplantation (OLT), which included 53 patients with LRLT in our series. Completed liver functions including aspartate transferase (AST), alanine transferase (ALT), bilirubin total/direct (Bil.T/D), alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) were collected with peak level when AR was diagnosed by liver biopsy. The best data of the same patients when disease free, were compared and analyzed with non-parametric Wilcoxon signed ranks test and Mann-Whitney test. All of the ARs were reversed with steroid pulse therapy, and two cases converted to FK506. No steroid-resistant rejection or chronic rejection was found in our series., Results: In the patients with LRLT, 17 episodes in 13 patients with AR were found. The incidence of histological analysis proved AR was 12.9% (13/101) in OLT and 24.5% (13/53) in LRLT respectively. Among the liver function tests, AST (p<0.0001), ALT (p<0.0001), Bil.T (p=0.001), Bil.D (p=0.001), GGT (p<0.0001), and INR (p=0.034) were the significant predictors respectively in the patients with AR episode. Once liver enzymes had elevated, the AST/ALT ratio <1.0 showed a more significant difference in AR than in those of the no rejection group (p<0.0001). ALP showed significant difference in our series. The severity of histological change was not correlated to the degree of liver enzymes elevation., Conclusions: Complete liver function tests especially AST, ALT, Bil.T/D, GGT and the ratio of AST/ALT are very sensitive tests in a group of patients receiving LRLT with AR. The severity of AR is based on the histopathologic change but is not related to the degree of liver enzymes elevation itself. Meanwhile, the outcome of acute rejection in living related liver transplantation is quite good.

Background/aims: We investigated the relationship between postoperative liver failure and serum acute-phase protein level before and after liver resection., Methodology: Thirty-four patients who underwent liver resection were prospectively included. Serum concentrations of negative (albumin, prealbumin and retinol-binding protein) and positive (orosomucoid, haptoglobin and C-reactive protein) acute-phase proteins were assayed prior to surgery (baseline) and on postoperative day 3, 12 and 45. Postoperative liver failure was defined as serum bilirubin more than 50 micromol/L or prothrombin time less than 50% on postoperative day 7. Univariate analysis was performed to compare patients who did and did not present postoperative liver failure., Results: Postoperative liver failure occurred in 8 cases and was correlated with: 1) higher negative and lower positive acute-phase protein levels (p<0.04) at baseline, 2) lower negative and lower positive acute-phase protein levels on postoperative day 3, 12 or 45 (p< or =0.05)., Conclusions: Early onset of inflammatory serum protein profile was correlated with absence of postoperative liver failure. Serum acute-phase protein could be used as predictor as well as early postoperative diagnosis marker of postoperative liver failure. Relationship between preoperative inflammation and postoperative liver failure warrants further investigations because of potential therapeutic consequences.

Background/aims: To predict the occurrence of postoperative liver failure after hepatectomy, the clinical significance of monitoring alkaline phosphatase (ALP) has been studied, and the relationship between the change of total bilirubin and the level of ALP or gamma-glutamyl transpeptidase (gamma-GTP) after hepatectomy was evaluated., Methodology: The 163 patients, who underwent hepatectomy at our institute for the past 12 years, were divided into three groups according to the postoperative events. HF consisted of 5 patients with liver failure, HB showed the postoperative high bilirubinemia (over 5mg/dL) in 13 cases and GP were 145 cases without any postoperative problems., Results: 1. The postoperative highest level of total bilirubin (T-Bil) correlated with the decreasing rate of ALP, prothrombin time (PT), total cholesterol (T-CHO) or gamma-GTP and total blood loss (p<0.01). 2. The level of ALP decreased after hepatectomy significantly and the decreasing rate was serious in HB and HF (p<0.05). 3. The recovering time to preoperative level of ALP was clearly shorter in GP than in HB and HF. 4. The level of ALP and gamma-GTP at the point where the level of T-Bil increased over 5mg/dL, was useful to distinguish between HF and HB. 5. The good correlation between postoperative level of ALP and gamma-GTP was noted. The decreasing levels of ALP and gamma-GTP were found to be critical below 80% and 55% after bisegmentectomy. Furthermore, the recovered levels of ALP and gamma-GTP were important to distinguish between HF and HB., Conclusions: Monitoring the ALP level was indicated to be useful to estimate the postoperative course of bilirubin.

Background/aims: Hepatic failure after hepatic resection is a lethal complication. Various factors affecting the occurrence of hepatic failure were examined., Methodology: The subjects were 315 patients who underwent hepatic resection for hepatocellular carcinoma during the 11-year period between 1985 and 1995. Univariate analyses of 14 variables were performed among living and dead patients after hepatic resection. With the significant prognostic variables obtained in the multivariate analysis, the predicted probability of death (PPD) was calculated for each patient., Results: There were 291 survivors and 24 patients with post-operative liver failure. Among the factors showing statistical or near significance in the univariate analysis, KICG and blood loss were disclosed to be factors independently correlating with survival. PPD was calculated for each patient according to the following equation: PPD = 1/Exp(1.6766 - 0.0004394 x blood loss + 16.69 x KICG) + 1. Assessing the goodness-of-fit model by Hosmer-Lemeshow test indicated the model seemed to fit quite well., Conclusions: Minimizing the blood loss during hepatic resection is important to avoid post-operative liver failure. Careful hemostatic procedure is necessary for patients with unexpected massive blood loss during hepatic resection so as to prevent post-operative bleeding.

Background/aims: To clarify a correlation between serum alkaline phosphatase (ALP) levels and liver function and regeneration after major hepatectomy., Methodology: Post-operative changes in serum ALP levels were retrospectively examined in 91 non-cirrhotic patients with biliary tract carcinoma who underwent right hepatic lobectomy or more extensive liver resection. In addition, changes in liver volume after resection were assessed in 31 patients who underwent computed tomography before surgery and within 1 month after resection., Results: Serum ALP levels reached its nadir on post-operative day 1, followed by a gradual increase until post-operative day 28. In patients with post-hepatectomy liver failure (n = 32), serum ALP levels were significantly lower on days 1, 7, 10, 14, 21, and 28 after resection than in those without such failure (n = 59). Unexpectedly, the volumetric study of the liver showed no significant difference between the two groups in the remnant liver volume after resection., Conclusions: Serum ALP levels can function as an indicator of liver function after hepatectomy, but not reflect morphological regeneration of the liver. Thus, increased ALP levels after hepatectomy may not reflect the cellular proliferation process itself.

Background/aims: We investigated whether or not hepatocyte growth factor increases in portal serum via an endocrine mode after partial hepatectomy in humans., Methodology: Portal blood was sampled through a catheter inserted through the umbilical vein to the portal trunk during surgery in 17 patients. Serum human hepatocyte growth factor levels were determined by enzyme-linked immunosorbent assay., Results: Human hepatocyte growth factor levels were higher in portal than in peripheral serum throughout the study. Portal and peripheral serum human hepatocyte growth factor levels without complications increased rapidly and reached a maximum level 1 day after partial hepatectomy. The maximal level of portal and peripheral serum human hepatocyte growth factor was 1.20 and 1.00 ng/ml, respectively. In the case of hepatic failure after partial hepatectomy, portal and peripheral serum human hepatocyte growth factor levels markedly increased and reached 9.31 ng/ml and 6.78 ng/ml 2 days before death, respectively., Conclusions: These results suggest that hepatocyte growth factor increases in portal serum via an endocrine mode after partial hepatectomy in humans. Furthermore, measurement of the portal and peripheral serum human hepatocyte growth factor levels may be useful for the clinical evaluation of patients with post-operative hepatic failure.

A 55 year-old man was admitted with massive ascites. Although the laboratory data on admission were compatible with hepatic cirrhosis and remarkable esophageal varices were observed during endoscopy, the imaging findings such as computed tomography and ultrasonographic examination did not confirm hepatic cirrhosis. The patient had no history of alcohol abuse, blood transfusions or acute hepatitis. Serological markers related to viral and autoimmune hepatitis were all negative. Seven years ago, the patient had undergone an operation for colon cancer and has been taking tegafur since then for a total of 55 months. Tegafur was suspected as the causative agent for the liver dysfunction of this patient and the administration of tegafur was stopped. His laboratory data improved gradually and the ascites vanished. The first liver biopsy performed 6 months after discontinuation of tegafur still revealed chronic active hepatitis. However, at the liver biopsy performed 18 months after withdrawal of tegafur, inflammatory activity had subsided and the third liver biopsy, performed 34 months thereafter, revealed further improvement of the pathological changes that had occurred in the liver. We therefore conclude that the administration of tegafur may have caused chronic active liver injury with portal hypertension manifested as ascites and esophageal varices.