BACKGROUND: Liver transplantation (LT) and liver resection (LR) are currently considered the standard treatment of patients with hepatocellular carcinoma (HCC). However, the outcomes of LT and LR are still inconclusive.
DATA SOURCES: MEDLINE, EMBASE, and Cochrane Library were searched for relevant studies. Surgical safety indices such as treatment-related morbidity and mortality, and efficacy indices such as overall and tumor-free survival outcomes were evaluated. Weighted mean differences and odds ratios (ORs) were calculated using a random-effects model.
RESULTS: Seventeen studies were included in this meta-analysis. LT achieved significantly higher rates of surgery-related morbidity (OR=1.47; 95% CI: 1.02-2.13) and mortality (OR=2.12; 95% CI: 1.11-4.05). Likewise, the 1-year survival rate was lower in LT (OR=0.86; 95% CI: 0.61-1.20). However, the 3- and 5-year survival rates were significantly higher in LT than in LR and the ORs were 1.12 (95% CI: 0.96-1.30) in 3 years and 1.84 (95% CI: 1.49-2.28) in 5 years. Furthermore, the tumor-free survival rate in LT was significantly higher than that in LR in 1, 3, 5 years after surgery, with the ORs of 1.72 (95% CI: 1.24-2.41), 3.75 (95% CI: 2.94-4.78) and 5.64 (95% CI: 4.35-7.31), respectively.
CONCLUSIONS: One-year morbidity and mortality are higher in LT than in LR for patients with HCC. However, long-term survival and tumor-free survival rates are higher in patients treated with LT than those treated with LR.

BACKGROUND: Originally, cava reconstruction (CR) in liver transplantation meant complete resection and reinsertion of the donor cava. Alternatively, preservation of the recipients inferior vena cava (IVC) with side-to-side anastomosis (known as "piggyback") can be performed. Here, partial clamping maintains blood flow of the IVC, which may improve cardiovascular stability, reduce blood loss and stabilize kidney function. The aim of this study was to compare both techniques with particular focus on kidney function.
METHODS: A series of 414 patients who had had adult liver transplantations (2006-2009) were included. Among them, 176 (42.5%) patients had piggyback and 238 had classical CR operation, 112 (27.1%) of the patients underwent CR accompanied with veno-venous bypass (CR-B) and 126 (30.4%) without a bypass. The choice of either technique was based on the surgeons' individual preference. Kidney function [serum creatinine, calculated glomerular filtration rate (GFR), RIFLE stages] was assessed over 14 days.
RESULTS: Lab-MELD scores were significantly higher in CR-B (22.5±11.0) than in CR (17.3±9.0) and piggyback (18.8±10.0) (P=0.008). Unexpectedly, the incidences of arterial stenoses (P=0.045) and biliary leaks (P=0.042) were significantly increased in piggyback. Preoperative serum creatinine levels were the highest in CR-B [1.45±1.17 vs 1.25±0.85 (piggyback) and 1.13±0.60 mg/dL (CR); P=0.033]. Although a worsening of postoperative kidney function was observed among all groups, this was most pronounced in CR-B [creatinine day 14: 1.67±1.40 vs 1.35±0.96 (piggyback) and 1.45±1.03 mg/dL (CR); P=0.102]. Accordingly, the proportion of patients displaying RIFLE stages ≥2 was the highest in CR/CR-B (26%/19%) when compared to piggyback (18%).
CONCLUSIONS: Piggyback revealed a shorter warm ischemic time, a reduced blood loss, and a decreased risk of acute kidney failure. Thus, piggyback is a useful technique, which should be applied in standard procedures. When piggyback is unfeasible, cava replacement, which displayed a lower incidence of vascular and biliary complications in our study, remains as a safe alternative.

BACKGROUND: Preoperative absolute monocyte count in peripheral blood (AMCPB) is closely associated with prognoses in not only various malignancies but also hepatocellular carcinoma (HCC). The purpose of this study was to evaluate whether pretransplant AMCPB predicts posttransplant outcomes in patients with HCC undergoing liver transplantation (LT).
METHOD: We retrospectively analyzed relationships between clinicopathologic factors involving pretransplant AMCPB and tumor recurrence or survival in 256 patients who had undergone LT for HCC between January 2005 and April 2012.
RESULTS: ROC curve analysis showed that AMCPB >200/mm3 was a risk factor for tumor recurrence; 43 patients showed higher AMCPB (>200/mm3), whereas 213 showed lower AMCPB (≤200/mm3) at the time of LT. On multivariate analysis, pretransplant high AMCPB, positive findings in pretransplant 18F-FDG PET/CT, pathological maximal tumor size >5 cm, intrahepatic metastasis, moderately or poorly differentiated tumor and microvascular invasion were independent factors affecting recurrence-free survival. When we performed subgroup analysis based on the Milan criteria, high AMCPB was an independent factor for predicting HCC recurrence in patients with tumor beyond the Milan criteria (P=0.004), and not for patients within the criteria.
CONCLUSION: This study demonstrated that pretransplant AMCPB could predict tumor recurrence after LT for HCC, especially in patients with tumor beyond the Milan criteria.

BACKGROUND: Living donor liver transplantation (LDLT) has been widely accepted over the past decade, and hepatic dysfunction often occurs in the donor in the early stage after liver donation. The present study aimed to evaluate the effect of intra-operative cholangiography (IOC) and parenchymal resection on liver function of donors in LDLT, and to assess the role of IOC in influencing the biliary complications and improving the overall outcome.
METHODS: Data from 40 patients who had donated their right lobes for LDLT were analyzed. Total bilirubin (TB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamyl transpeptidase (GGT) at different time points were compared, and the follow-up data and the biliary complications were also analyzed.
RESULTS: The ALT and AST values were significantly increased after IOC (P<0.001) and parenchymal resection (P<0.001). However, the median values of TB, ALP and GGT were not significantly influenced by IOC (P>0.05) or parenchymal resection (P>0.05). The biochemical changes caused by IOC or parenchymal resection were not correlated with the degree of post-operative liver injury or the recovery of liver function. The liver functions of the donors after operation were stable, and none of the donors suffered from biliary stenosis or leakage during the follow-up.
CONCLUSIONS: IOC and parenchymal resection may induce a transient increase in liver enzymes of donors in LDLT, but do not affect the recovery of liver function after operation. Moreover, the routine IOC is helpful to clarify the division line of the hepatic duct, thus reducing the biliary complication rate.

BACKGROUND: Extended hemihepatectomy is usually recommended to treat large centrally located hepatocellular carcinoma (HCC). However, the morbidity and mortality are high because of the postoperative liver failure. Mesohepatectomy is seldom used because of its technical complexity. This study aimed to evaluate the short-term and long-term curative effect of mesohepatectomy.
METHODS: From January 2002 to September 2008, a total of 198 consecutive patients with centrally located HCC underwent hepatectomy in our department. According to the surgical procedures, they were divided into mesohepatectomy (group M, n=118), extended right hemihepatectomy (group RE, n=47) and extended left hemihepatectomy (group LE, n=33) groups. The surgical techniques, clinical pathological characteristics and outcomes were compared between group M, group RE and group LE.
RESULTS: The operative time of group M was significantly longer than that of the other two groups (P<0.05); however the total bilirubin on postoperative day 3 in group M was the lowest among the three groups (P<0.01). In group M, the number of the patients whose resection margin achieving 1 cm was significantly lower than that of the other two groups (P<0.05). The mortality rates in groups M, RE and LE were 2.5%, 8.5% and 3.0%, respectively (P>0.05). The morbidity rate in group M was significantly lower than that in group RE (37.3% vs 55.3%, P=0.034), but not in group LE (37.3% vs 24.2%, P=0.163). The biliary leakage tended to be more common in group M (10.2%, P>0.05). The incidence of postoperative liver failure in group M was significantly lower than that in group RE (1.7% vs 10.6%, P=0.032), but not in group LE (1.7% vs 6.1%, P=0.208). The 1-, 3- and 5-year tumor-free survival rates and the overall survival rates after mesohepatectomy were 53.4%, 30.5% and 16.9% and 67.8%, 45.5% and 28.9%, respectively.
CONCLUSIONS: Mesohepatectomy is a safe and effective technique for centrally located HCC patients. Compared with extended right hemihepatectomy, mesohepatectomy can retain residual liver volume to the maximum limit and reduce postoperative liver failure rate. But no significant advantage was found compared mesohepatectomy to extended left hemihepatectomy.

BACKGROUND: Acute liver failure (ALF) is an acute severe deterioration of liver function with high mortality. Early and accurate prognostic assessment of patients with ALF is critically important. Although the model for end-stage liver disease (MELD) scores and King's College Hospital (KCH) criteria are well-accepted as predictive tools, their accuracy is unsatisfactory. The indocyanine green (ICG) clearance test (ICGR15, ICG retention rate at the 15 minutes) is a sensitive indicator of liver function. In this study, we investigated the efficacy of the ICGR15 for the short-term prognosis in patients with ALF. We compared the predictive value of ICGR15 with the MELD scores and KCH criteria.
METHODS: Sixty-nine patients who had been diagnosed with ALF were recruited retrospectively. ICGR15 had been performed by ICG pulse spectrophotometry and relevant clinical and laboratory indices were analyzed within 24 hours of diagnosis. In addition, the MELD scores and KCH criteria were calculated.
RESULTS: The three-month mortality of all patients was 47.83%. Age, serum total bilirubin and creatinine concentrations, international normalized ratio for prothrombin time, ICGR15, MELD scores and KCH criteria differed significantly between surviving and deceased patients. A positive correlation was observed between ICGR15 and MELD scores (r=0.328, P=0.006). The ICGR15-MELD model, Logit(P)=0.096×ICGR15+0.174×MELD score–9.346, was constructed by logistic regression analysis. The area under the receiver operating characteristic curve was 0.855. When set the cut-off point to -0.4684, the sensitivity was 87.90% and specificity, 72.20%. The area under the receiver operating characteristic curve of the ICGR15-MELD model (0.855) was significantly higher than that of the ICGR15 (0.793), MELD scores (0.776) and KCH criteria (0.659). Based on this cut-off value, the patients were divided into two groups. The mortality was 74.36% in the first group (ICGR15-MELD≥-0.4686) and 13.33% in the second group (ICGR15-MELD<-0.4686), with a significant difference between the two groups (χ2=25.307, P=0.000).
CONCLUSION: The ICGR15-MELD model is superior to the ICGR15, MELD scores, and KCH criteria in predicting the short-term prognosis of patients with ALF.

BACKGROUND: Currently, no documentation is available regarding Chinese children with acute liver failure (ALF). This study was undertaken to investigate etiologies and outcomes of Chinese children with ALF.
METHODS: We retrospectively enrolled 32 pediatric patients with ALF admitted in five hospitals in different areas of China from January 2007 to December 2012. The coagulation indices, serum creatinine, serum lactate dehydrogenase, blood ammonia and prothrombin activity were analyzed; the relationship between these indices and mortality was evaluated by multivariate analysis.
RESULTS: The most common causes of Chinese children with ALF were indeterminate etiology (15/32), drug toxicity (8/32), and acute cytomegalovirus hepatitis (6/32). Only 1 patient (3.13%) received liver transplantation and the spontaneous mortality of Chinese children with ALF was 58.06% (18/31). Patients who eventually died had higher baseline levels of international normalized ratio (P=0.01), serum creatinine (P=0.04), serum lactate dehydrogenase (P=0.01), blood ammonia (P<0.01) and lower prothrombin activity (P=0.01) than those who survived. Multivariate analysis showed that the entry blood ammonia  was the only independent factor significantly associated with mortality (odds ratio=1.069, 95% confidence interval 1.023-1.117, P<0.01) and it had a sensitivity of 94.74%, a specificity of 84.62% and an accuracy of 90.63% for predicting the death. Based on the established model, with an increase of blood ammonia level, the risk of mortality would increase by 6.9%.
CONCLUSIONS: The indeterminate causes predominated in the etiologies of ALF in Chinese children. The spontaneous mortality of pediatric patients with ALF was high, whereas the proportion of patients undergoing liver transplantation was significantly low. Entry blood ammonia was a reliable predictor for the death of pediatric patients with ALF.

BACKGROUND: Ron receptor tyrosine kinase signaling in macrophages, including Kupffer cells and alveolar macrophages, suppresses endotoxin-induced proinflammatory cytokine/chemokine production. Further, we have also identified genes from Ron replete and Ron deplete livers that were differentially expressed during the progression of liver inflammation associated with acute liver failure in mice by microarray analyses. While important genes and signaling pathways have been identified downstream of Ron signaling during progression of inflammation by this approach, the precise role that Ron receptor plays in regulating the transcriptional landscape in macrophages, and particular in isolated Kupffer cells, has still not been investigated.
METHODS: Kupffer cells were isolated from wild-type (TK+/+) and Ron tyrosine kinase deficient (TK-/-) mice. Ex vivo, the cells were treated with lipopolysaccharide (LPS) in the presence or absence of the Ron ligand, hepatocyte growth factor-like protein (HGFL). Microarray and qRT-PCR analyses were utilized to identify alterations in gene expression between genotypes.
RESULTS: Microarray analyses identified genes expressed differentially in TK+/+ and TK-/- Kupffer cells basally as well as after HGFL and LPS treatment. Interestingly, our studies identified Mefv, a gene that codes for the anti-inflammatory protein pyrin, as an HGFL-stimulated Ron-dependent gene. Moreover, lipocalin 2, a proinflammatory gene, which is induced by LPS, was significantly suppressed by HGFL treatment. Microarray results were validated by qRT-PCR studies on Kupffer cells treated with LPS and HGFL.
CONCLUSION: The studies herein suggest a novel mechanism whereby HGFL-induced Ron receptor activation promotes the expression of anti-inflammatory genes while inhibiting genes involved in inflammation with a net effect of diminished inflammation in macrophages.

BACKGROUND: Cancer relapse, associated with increased drug resistance and rate of metastasis, often follows completion of chemotherapy but the cancer escape mechanisms are still incompletely understood. Percutaneous ethanol injection (PEI) has been used for treating hepatocellular carcinoma (HCC) for decades, while the recurrence after PEI treatment remains a major limitation. Recent evidence mounted that cancer cells could survive from chemical induced apoptosis, suggesting a potential route through which cancer relapse may occur. This study focuses on the consequence of HepG2 recovery from ethanol-induced apoptotic event.
METHODS: The model of HepG2 recovery from ethanol-induced apoptotic event was established by live cell imaging, BrdU assay and Western blotting. MTT assay, wound healing assay and invasion assay were used to investigate the behavior of HepG2 after recovery.
RESULTS: HepG2 cells could recover from ethanol-induced apoptosis. These cells changed their behaviors such as drug resistance, mobility and invasiveness. On average, the recovered HepG2 cell clones were found to be 46% more resistant to ethanol and 84% higher in mobility. The recovered clones became 58.2% more sensitive to 5-fluorouracil.
CONCLUSIONS: HepG2 cells can recover from ethanol-induced apoptotic event. These cells became more resistant to ethanol and more invasive. Although the recovered cell clones were more resistant to ethanol, they became more sensitive to 5-fluorouracil treatment.

BACKGROUND: Some patients with colorectal carcinoma have liver metastases (LMs) which cannot be detected by conventional imaging. This study aimed to assess whether hepatic perfusion changes induced by micrometastases can be detected by perfusion computed tomography (CT).
METHODS: LMs were produced in rats by injecting carcinoma cells into the portal vein. Perfusion CT was performed at microscopic (day 10), interval (day 17), and macroscopic stage (day 34). Perfusion parameters were computed using a dual-input one-compartmental model.
RESULTS: Micro and macro LMs presented a mean diameter of 0.5 and 2.6 mm, respectively. Compared to controls, LMs at interval (1.1 mm) and macroscopic stage induced significant perfusion changes: a decrease of 42% (P=0.004) and 41% (P=0.029) in hepatic transit time and an increase of 292% (P=0.073) and 240% (P=0.001) in portal delay, respectively.
CONCLUSIONS: LMs with a mean diameter between 1.1 and 2.6 mm induced significant hepatic perfusion changes, detected by CT. Such detection may help to select patients and propose chemotherapy at the time of primary tumor resection.

BACKGROUND: Acute liver failure (ALF) is a serious clinical syndrome with high mortality. Sodium butyrate has been shown to alleviate organ injury in a wide variety of preclinical models of critical diseases. The aim of this study was to investigate the protective effect of sodium butyrate on ALF in rats.
METHODS: All rats were randomly divided into control, model and sodium butyrate treatment groups. Except the control group, the rats were induced ALF animal model by subcutaneous injection of human serum albumin+ D-galactosamine+lipopolysaccharide. After induction of ALF, the rats in the treatment group received sodium butyrate (500 mg/kg) at 12-hour or 24-hour time point. Fourty-eight hours after ALF induction, the animals were sacrificed and samples were harvested. Serum endotoxin, high mobility group box-1 (HMGB1), liver function parameters, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) were measured. The expression of HMGB1 and nuclear factor-kappa B (NF-κB) p65 protein in liver tissue was detected by Western blotting. The histological changes of liver and intestine were examined. The survival duration was also observed.
RESULTS: Serum endotoxin, alanine aminotransferase, HMGB1, TNF-α and IFN-γ were significantly increased and the liver histology showed more severe histopathological injury in the model group compared with the control group (P<0.05). Compared to the model group, sodium butyrate treatment significantly improved the histopathological changes in the liver and intestine, reduced serum endotoxin and inflammatory cytokines, suppressed HMGB1 and NF-кB p65 proteins in liver tissue, and prolonged the survival duration regardless of treatment at 12 hours or 24 hours after induction of ALF (P<0.05).
CONCLUSIONS: Sodium butyrate protected the liver from toxin-induced ALF in rats. The mechanisms may be due to direct hepatoprotection and decreased intestinal permeability.

BACKGROUND: In low-risk patients with acute cholecystitis who did not respond to nonoperative treatment, we prospectively compared treatment with emergency laparoscopic cholecystectomy or percutaneous transhepatic cholecystostomy followed by delayed cholecystectomy.
METHODS: In 91 patients (American Society of Anesthesiologists class I or II) who had symptoms of acute cholecystitis ≥72 hours at hospital admission and who did not respond to nonoperative treatment (48 hours), 48 patients were treated with emergency laparoscopic cholecystectomy and 43 patients were treated with delayed cholecystectomy at ≥4 weeks after insertion of a percutaneous transhepatic cholecystostomy catheter. After initial treatment, the patients were followed up for 23 months on average (range 7-29).
RESULT: Compared with the patients who had emergency laparoscopic cholecystectomy, the patients who were treated with percutaneous transhepatic cholecystostomy and delayed cholecystectomy had a lower frequency of conversion to open surgery [19 (40%) vs 8 (19%); P=0.029], a frequency of intraoperative bleeding ≥100 mL [16 (33%) vs 4 (9%); P=0.006], a mean postoperative hospital stay (5.3±3.3 vs 3.0±2.4 days; P=0.001), and a frequency of complications [17 (35%) vs 4 (9%); P=0.003].
CONCLUSION: In patients with acute cholecystitis who presented to the hospital ≥72 hours after symptom onset and did not respond to nonoperative treatment for 48 hours, percutaneous transhepatic cholecystostomy with delayed laparoscopic cholecystectomy produced better outcomes and fewer complications than emergency laparoscopic cholecystectomy.

BACKGROUND: Recent international multidisciplinary consultation proposed the use of local (sterile or infected pancreatic necrosis) and/or systemic determinants (organ failure) in the stratification of acute pancreatitis. The present study was to validate the moderate severity category by international multidisciplinary consultation definitions.
METHODS: Ninety-two consecutive patients with severe acute pancreatitis (according to the 1992 Atlanta classification) were classified into (i) moderate acute pancreatitis group with the presence of sterile (peri-) pancreatic necrosis and/or transient organ failure; and (ii) severe/critical acute pancreatitis group with the presence of sterile or infected pancreatic necrosis and/or persistent organ failure. Demographic and clinical outcomes were compared between the two groups.
RESULTS: Compared with the severe/critical group (n=59), the moderate group (n=33) had lower clinical and computerized tomographic scores (both P<0.05). They also had a lower incidence of pancreatic necrosis (45.5% vs 71.2%, P=0.015), infection (9.1% vs 37.3%, P=0.004), ICU admission (0% vs 27.1%, P=0.001), and shorter hospital stay (15±5 vs 27±12 days; P<0.001). A subgroup analysis showed that the moderate group also had significantly lower ICU admission rates, shorter hospital stay and lower rate of infection compared with the severe group (n=51). No patients died in the moderate group but 7 patients died in the severe/critical group (4 for severe group).
CONCLUSIONS: Our data suggest that the definition of moderate acute pancreatitis, as suggested by the international multidisciplinary consultation as sterile (peri-) pancreatic necrosis and/or transient organ failure, is an accurate category of acute pancreatitis.

Liver transplantation for autoimmune hepatitis (AIH) is usually successful with excellent long-term outcomes, but primary disease may recur. The recurrence of AIH is a significant cause of graft loss. This study was to analyze the effect of splenectomy in preventing AIH relapse. The clinical courses of 12 patients who had transplantation for AIH were analyzed retrospectively. All patients were subjected to transplantation for end-stage liver disease caused by chronic AIH. Based on the duration of immunosuppressive treatment before liver transplantation, simultaneous splenectomy was performed in ten patients. Two patients underwent liver transplantation without splenectomy, one of them developed recurrent AIH and died from graft failure caused by AIH relapse. However, no episode of AIH recurrence was observed in patients who had undergone simultaneous splenectomy. Splenectomy might be an option to prevent AIH relapse in some patients with high risk factors.

To the Editor:
 We read with great interest the recent paper by Baran and colleagues,[1] published in the journal of Hepatobiliary Pancreatic Diseases International. The authors presented nails abnormalities in a 65-year-old woman with cryptogenic cirrhosis and hepatocellular carcinoma and described them as Terry's nails. Whether they were Terry's nails remains controversial, at least far away from the typical Terry's nails. Thus we have several comments with respect to the photograph. 
First, fully developed Terry's nails exhibit a ground-glass-like opacity of almost the entire nail bed. The condition is bilaterally symmetrical, with a tendency to be more marked in the thumb and forefinger (Fig. A).[2] However, the white discoloration of proximal nails is inhomogenous in their images, and red nail bed is noted in all left fingernails and in forefinger and little finger of right hand. 
Second, another classical presentation of Terry's nails is a distal thin brown to pink transverse band of 0.5-2.0 mm in width (Fig. A).[2] Although the authors described a zone of normal pink at the distal edge of the nails, only forefinger, middle and ring finger of right hand in their images have a pink transverse band with fuzzy boundaries in width of 4-6 mm and occupy 20% to 40% of the nail length. These abnormalities need to differentiate from half-and-half nails, which are typically seen in chronic renal failure, as well as in cirrhotic patients with severe hypoalbuminemia.[3] 
Nail abnormalities can be a revealing sign of a systemic disease including liver cirrhosis. The most common nail abnormality in patients with liver cirrhosis is Terry's nails. Terry's toenails also can occur in cirrhotic patients (Fig. B). Classical presentation of Terry's nails or toenails included a distal thin brown to pink transverse band of 0.5-2.0 mm in width, white nail bed, and absence of the lunula.[2, 4] Although Terry's nails are only a visual diagnosis and validated diagnostic criteria are absent, and some patients with Terry's fingernails show inhomogeneous changes in all nails in a random fashion,[5] the readers of the journal would be happier with a more classical presentation of this condition.