A novel combined systemic inflammation-based score can predict survival of intermediate-to-advanced hepatocellular carcinoma patients undergoing transarterial chemoembolization.

BACKGROUND: There is currently limited information regarding the prognostic ability of the dNLR-PNI (the combination of the derived neutrophil-to-lymphocyte ratio [dNLR] and prognostic nutritional index [PNI]) for hepatocellular carcinoma (HCC). This study aimed to assess the predictive ability of the dNLR-PNI in patients with intermediate-to-advanced HCC after transarterial chemoembolization (TACE). METHODS: A total of 761 HCC patients were enrolled in the study. The dNLR-PNI was retrospectively calculated in these patients, as follows: patients with both an elevated dNLR and a decreased PNI, as determined using the cutoffs obtained from receiver operating characteristic curve analysis, were allocated a score of 2, while patients showing one or neither of these alterations were allocated a score of 1 or 0, respectively. RESULTS: During the follow-up period, 562 patients died. Multivariate analysis suggested that elevated total bilirubin, Barcelona Clinic Liver Cancer C stage, repeated TACE, and dNLR-PNI were independently associated with unsatisfactory overall survival. The median survival times of patients with a dNLR-PNI of 0, 1, and 2 were 31.0 (95% confidence interval [CI] 22.5-39.5), 16.0 (95% CI 12.2-19.7) and 6.0 (95% CI 4.8-7.2) months, respectively (P < 0.001). CONCLUSIONS: The dNLR-PNI can predict the survival outcomes of intermediate-to-advanced HCC patients undergoing TACE, and should be further evaluated as a prognostic marker for who are to undergo TACE treatment.

Postoperative Albumin-Bilirubin Grade Change Predicts the Prognosis of Patients with Hepatitis B-Related Hepatocellular Carcinoma Within the Milan Criteria.

OBJECTIVE: Albumin-bilirubin (ALBI) grade has been validated as a simple, evidence-based, and objective prognostic tool for patients with hepatocellular carcinoma (HCC). However, minimal information is available concerning postoperative ALBI grade changes in HCC. This study aimed to investigate the prognostic value of postoperative ALBI grade changes in patients with hepatitis B virus (HBV)-related HCC within the Milan criteria after liver resection. METHODS: Patients with HBV-related HCC within the Milan criteria who underwent liver resection between 2010 and 2016 at West China Hospital were reviewed (N = 258). A change in ALBI grade was defined as first postoperative month ALBI grade-preoperative ALBI grade. If the value was >0, postoperative worsening of ALBI grade was considered; otherwise, stable ALBI grade was considered. Cox proportional hazard regression analyses were used to determine the factors that influence recurrence and survival. RESULTS: During the follow-up, 130 patients experienced recurrence and 47 patients died. Multivariate analyses revealed that postoperative worsening of ALBI grade (HR 1.541, 95% CI 1.025-2.318, P = 0.038), microvascular invasion (MVI, HR 1.802, 95% CI 1.205-2.695, P = 0.004), and multiple tumors (HR 1.676, 95% CI 1.075-2.615, P = 0.023) were associated with postoperative recurrence, whereas MVI (HR 2.737, 95% CI 1.475-5.080, P = 0.001), postoperative worsening of ALBI grade (HR 2.268, 95% CI 1.227-4.189, P = 0.009), high alpha-fetoprotein level (HR 2.055, 95% CI 1.136-3.716, P = 0.017), and transfusion (HR 2.597, 95% CI 1.395-4.834, P = 0.003) negatively influenced long-term survival. Patients with postoperative worsening of ALBI grade exhibited increased incidence of recurrence and worse long-term survival. CONCLUSION: Postoperative worsening of ALBI grade was associated with increased recurrence and poorer overall survival for patients with HBV-related HCC within the Milan criteria. We should pay attention to liver function changes in HCC patients after liver resection.

miR-203 inhibits augmented proliferation and metastasis of hepatocellular carcinoma residual in the promoted regenerating liver.

Liver resection is still the most commonly used therapeutic treatment for hepatocellular carcinoma (HCC), and liver regeneration promotes HCC growth in the regenerating liver. The high recurrence/metastasis of HCC is the main cause of death for HCC patients after liver resection. However, how the augmented growth and metastasis of residual HCC induced by the promoted liver regeneration following liver resection can be abolished remains unclear. In this study, a rat model with liver cirrhosis and diffused HCC was established by administration of diethylnitrosamine. Recombinant miR-203 adenovirus was administered to induce hepatic miR-203 overexpression and 30% partial hepatectomy (PH) followed. The effect of miR-203 on the proliferation, invasion and metastasis of the residual HCC in the remnant cirrhotic liver with promoted regeneration was investigated. We found that the basic spontaneous regeneration of the non-tumorous liver by 30% PH promoted proliferation, invasion and lung metastasis of the hepatic residual HCC. miR-203 overexpression further promoted the regeneration of the non-tumorous liver by upregulating Ki67 expression and enhancing IL-6/SOCS3/STAT3 pro-proliferative signals. Importantly, miR-203 overexpression markedly inhibited the proliferation, invasion and metastasis of hepatic residual HCC through suppressing expression of Ki67, CAPNS1 and lung metastasis. Moreover, it was found that miR-203 overexpression reversed the epithelial-mesenchymal transition induced by hepatectomy through targeting IL-1ß, Snail1 and Twist1. In conclusion, our results suggested that miR-203 overexpression inhibited the augmented proliferation and lung metastasis of the residual HCC induced by the promoted liver regeneration following PH partly by regulating epithelial-mesenchymal transition.

MicroRNA-203 promotes liver regeneration after partial hepatectomy in cirrhotic rats.

BACKGROUND: Liver resection or partial hepatectomy (PH) is still the most commonly used therapeutic option for hepatocellular carcinoma (HCC) at present. However, the impaired regenerative ability induced by the accompanied liver cirrhosis is an important risk factor of posthepatectomy liver failure, and posthepatectomy liver failure is a feared complication that accounts for up to 75% of mortality after extensive liver resection. MicroRNA(miR)-203 is a tumor suppressor of HCC and may act as a positive intermediary in A20-enhanced interleukin (IL-6)/signal transducer and activator of transcription 3 (STAT3) pro-proliferative signals, which may promote liver regeneration after PH. However, its direct pro-proliferative effect on cirrhotic liver after hepatectomy is unknown. MATERIALS AND METHODS: Liver cirrhosis was induced by intraperitoneal injection of 50% CCl4-olive oil solution in adult male Wistar rat. Rats with liver cirrhosis received portal vein injection of physiological saline, miR-203 lentivirus, or control empty lentivirus, and then 70% PH was performed under ether anesthesia 7 d later. Liver samples were harvested at 0, 24, 36, and 72 h after 70% PH. Hepatic expressions of cyclin D1 and Ki67 were checked to evaluate the liver regenerative ability. Hepatic expressions of IL-6, suppressor of cytokine signaling 3 (SOCS3), and phospho-STAT3 were also tested to clarify the mechanisms of miR-203 in liver regeneration. RESULTS: The regeneration of miR-203 overexpression cirrhotic liver after 70% PH was enhanced and peaked at 24 and 36 h after 70% PH. The cyclin D1-positive liver cells/high-power field (HPF) in miR-203 overexpression liver markedly increased at 24 and 36 h after 70% PH compared with 0-h samples. When comparing with the control groups, cyclin D1-positive liver cells/HPF in miR-203 overexpression liver were also significantly increased at 24 and 36 h after 70% PH. A similar result of the Ki67-positive liver cells/HPF was achieved at 36 h after 70% PH. The hepatic expression of IL-6 showed a rising tendency after 70% PH, and the levels of IL-6 are significantly higher in miR-203 overexpression livers. Hepatic expression of SOCS3 was negatively expressed with hepatic miR-203 expression level, and the reduced expression of SOCS3 facilitated the phosphorylation of STAT3. CONCLUSIONS: By targeting SOCS3 and then enhancing proliferating IL-6/STAT3 signaling pathway, hepatic overexpression of miR-203 can facilitate the initiation of liver regeneration and enhance the potency of liver regeneration after 70% PH in cirrhotic rat. Together with the tumor suppressive effect on HCC, miR-203 would be an ideal candidate for promoting liver regeneration in HCC patients undergoing liver resection without the risk of tumorigenesis or cancer recurrence.

Alpha fetoprotein changes predict hepatocellular carcinoma survival beyond the Milan criteria after hepatectomy.

BACKGROUND: Assessing the outcomes of surgeries for hepatocellular carcinoma (HCC) patients who exceed the Milan criteria is necessary. Some studies have demonstrated that preoperative or postoperative alpha fetoprotein (AFP) can predict HCC patients' prognoses. METHODS: A total of 280 HCC patients who were positive for AFP and received curative resection were retrospectively analyzed. The patients were classified into three groups according to their preoperative and postoperative AFP levels (group A: normalized AFP; group B: AFP decreases >50%, but continued abnormality; and group C: AFP decreases <50%). Disease-free survival and overall survival rates were analyzed using the Kaplan-Meier method. The factors associated with AFP changes were evaluated by logistic regression. RESULTS: AFP dynamic changes were independently associated with disease-free survival and overall survival rates. Group A had better 3- and 5-y survivals than groups B or C (58.7% and 39.5% versus 31.3% and 14.9% versus 17.1% and 8.8%, P < 0.001). Preoperative AFP, tumor differentiation, tumor diameter, microvascular invasion, and satellite nodules remained significant risk factors that were associated with AFP changes. Furthermore, in group A, the disappearances of AFP within and beyond 8 wk resulted in similar overall survival rates (P > 0.05). Among those with HCC recurrence, the patients treated with resurgery or radiofrequency ablation achieved the best recurrence to death survivals. Those treated with transcatheter arterial chemoembolization achieved the next best survivals. CONCLUSIONS: AFP changes predicted the prognoses of patients with HCC beyond the predictions of the Milan criteria. Preoperative AFP (>400 ng/mL), tumor differentiation, tumor diameter, and satellite nodules were the risk factors related to AFP normalization. The regular follow-up and early detection of recurrent HCCs that are suitable for curative therapies, such as resurgery and radiofrequency ablation, might improve the prognoses. Other therapies, such as transcatheter arterial chemoembolization, might also be effective.

Liver resection versus liver resection plus TACE for patients with hepatocellular carcinoma beyond Milan criteria.

BACKGROUND: The recurrence of patients with hepatocellular carcinoma (HCC) beyond the Milan criteria after liver resection (LR) is common. This study aimed to clarify whether LR plus postoperative adjuvant transcatheter arterial chemoembolization (TACE) could improve the outcomes of patients with HCC beyond the Milan criteria after LR. METHODS: A total of 754 consecutive patients with HCC beyond the Milan criteria who received LR alone (n = 459) or LR + TACE (n = 295) were included. A propensity scoring matched model (PSM) was used to adjust for the baseline differences between the groups. RESULTS: The 1, 3, and 5-y recurrence-free survival (76.7%, 40.4%, and 30.8%, respectively, for the LR-alone group versus 78.3%, 50.5%, and 46.2%, respectively, for the LR + TACE group; P = 0.004) and overall survival (94.1%, 58.3%, and 36.3%, respectively, for the LR-alone group versus 95.3%, 71.3%, and 54.9%, respectively, for the LR + TACE group; P < 0.001) rates of patients who underwent LR alone were much lower than in the LR + TACE group. Multivariate Cox proportional hazards regression analysis showed that LR alone was an independent risk factor for postoperative recurrence and poor long-term survival. After one-to-one PSM, 284 patients who underwent LR alone and 284 patients who underwent LR + TACE were selected for further analyses. Similar results were observed in the PSM model. CONCLUSIONS: This study showed that LR + TACE may be beneficial for patients with HCC beyond the Milan criteria. Postoperative adjuvant TACE should be considered to patients with HCC beyond the Milan criteria.

Alvimopan combined with enhanced recovery strategy for managing postoperative ileus after open abdominal surgery: a systematic review and meta-analysis.

BACKGROUND: To assess the efficacy and safety of alvimopan in conjunction with enhanced recovery strategy, compared with this strategy alone, in management of postoperative ileus in patients undergoing open abdominal surgery. METHODS: Electronic databases were comprehensively searched for relevant randomized controlled trials. We were interested in doses of 6 and 12 mg. The efficacy end points included the time to recovery of full gastrointestinal (GI) function (a composite end point measured by the time to first toleration of solid food [SF] and the time to first passage of stool, GI-2), the recovery of upper (SF) or the lower (the time to first bowel movement, BM) GI function, and the length of hospital stay (the time to discharge order written). Safety end points included GI-related, non-GI-related, and serious adverse events. These parameters were all analyzed by RevMan 5.3 software. RESULTS: Nine randomized controlled trials involving 4075 patients were enrolled in this study. The pooled results showed that alvimopan significantly decreased the time to GI-2 recovery (6 mg, hazard ratio [HR] = 1.45, P < 0.00001; 12 mg, HR = 1.59, P < 0.00001), BM (6 mg, HR = 1.54, P < 0.00001; 12 mg, HR = 1.74, P = 0.0002), and the time to discharge order written (6 mg, HR = 1.37, P < 0.00001; 12 mg, HR = 1.34, P < 0.00001) compared with the placebo group. However, SF was significantly reduced in 6 mg group (HR = 1.23, P = 0.008) rather than 12 mg group (HR = 1.14, 95% confidence interval 1.00, 1.30, P = 0.04). The incidence of some GI-related and serious adverse events were significantly lower in the alvimopan group than the placebo group, and the dose of 12 mg was superior to 6 mg in this regard. CONCLUSIONS: Alvimopan can accelerate recovery of GI function (especially for the lower GI tract), shorten the length of hospital stay, and reduce postoperative ileus-related morbidity without compromising opioid analgesia in an enhanced recovery setting.

Microvascular invasion patterns affect survival in hepatocellular carcinoma patients after second hepatectomy.

BACKGROUND: Microvascular invasion (MVI) is an important risk factor for survival of patients with hepatocellular carcinoma (HCC) after hepatectomy. However, its impact on patients with recurrent HCC who receive a second hepatectomy is unknown. METHODS: We enrolled 167 patients with HCC who underwent a second hepatectomy because of intrahepatic recurrences. We compared the patients' demographic, tumor, and pathologic characteristics with 766 cases of original hepatectomy. We analyzed the possible risk factors for survival after the first and second hepatectomies and the influence of different MVI patterns on patients' survival after the second hepatectomy. RESULTS: The median overall survival was comparable between the first and second hepatectomy groups, 34 (3-84) mo versus 27 (3-57) mo, P = 0.09. For patients who underwent a first hepatectomy, the presence of macro-VI or MVI, an early recurrence pattern, and a total tumor diameter >5 cm were independent risk factors. For survival after the second hepatectomy, MVI patterns that were positive-positive or negative-positive and a total recurrent tumor diameter >5 cm were significant risk factors for survival. CONCLUSIONS: A second hepatectomy provides satisfying survival for patients with intrahepatic recurrence of HCC after the initial operation. Different MVI patterns affect survival after the second hepatectomy. Because MVI represents the biological behavior of HCC, we place a high premium on the clinical value of MVI after each hepatectomy.

Hepatic Arterial Buffer Response Maintains the Homeostasis of Graft Hemodynamics in Patient Receiving Living Donor Liver Transplantation.

BACKGROUND: In living donor liver transplantation (LDLT), the hepatic hemodynamics plays important roles in graft regeneration, and the hepatic blood inflows are associated with graft size. However, the data of interplay between the hepatic arterial buffer response (HABR) and graft-to-recipient weight ratio (GRWR) in clinical LDLT are lacking. AIMS: To identify the effect of the HABR on the hepatic hemodynamics and recovery of graft function and to evaluate the safe lower limit of the GRWR in carefully selected recipients. METHODS: Portal venous and hepatic arterial blood flow was measured in recipients with ultrasonography, and the graft functional recovery, various complications, and survive states after LDLT were compared. RESULTS: In total, 246 consecutive patients underwent LDLT with right lobe grafts. In total, 26 had a GRWR < 0.7 % (A), 29 had a GRWR between 0.7 and 0.8 % (B), and 181 had a GRWR > 0.8 % (C). For small-for-size syndrome, there was no significant difference (P = 0.176). Graft survival rates at 1, 3, and 5 year were not different (P = 0.710). The portal vein flow and portal vein flow per 100 g graft weight peaks were significantly higher in the A. Hepatic arterial velocity and hepatic arterial flow decreased in all the three groups on postoperative day 1; however, the hepatic arterial flow per 100 g graft weight was close to healthy controls. CONCLUSIONS: HABR played important roles not only in the homeostasis of hepatic afferent blood supply but also in maintaining enough hepatic perfusion to the graft.

Role of microRNA in liver regeneration.

BACKGROUND: Liver regeneration is a complex process. microRNAs (miRNAs) are short, single-stranded RNAs that modify gene expression at the post-transcriptional level. Recent investigations have revealed that miRNAs are closely linked to liver regeneration. DATA SOURCES: All included studies were obtained from PubMed, Embase, the ScienceDirect databases and Web of Science, with no limitation on publication year. Only studies published in English were considered. RESULTS: We grouped studies that involved miRNA and liver regeneration into two groups: miRNAs as promoters and as inhibitors of liver regeneration. We summarized the relevant miRNAs separately from the related pathways. CONCLUSIONS: Blocking or stimulating the pathways of miRNAs in liver regeneration may be novel therapeutic strategies in future regeneration-related liver managements. We may discover additional chemotherapy targets of miRNA.

Combined hepatectomy and radiofrequency ablation versus TACE in improving survival of patients with unresectable BCLC stage B HCC.

BACKGROUND: Combined hepatectomy and radiofrequency ablation (RFA) provides an additional treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) who are conventionally deemed unresectable. This study aimed to analyze the outcome of this combination therapy by comparing it with transarterial chemoembolization (TACE). METHODS: We retrospectively reviewed 51 patients with unresectable BCLC stage B HCC who had received the combination therapy. We compared the survival of these patients with that of 102 patients in the TACE group (control). Prognostic factors associated with worse survival in the combination group were analyzed. RESULTS: No differences in tumor status and liver function were observed between the TACE group and combination group. The median survival time for the combination group and TACE group was 38 (6-54) and 17 (3-48) months, respectively (P<0.001). The combination group required longer hospitalization than the TACE group [8 (5-14) days vs 4 (2-9) days, P<0.001]. More than two ablations decreased the survival rate in the combination group. CONCLUSIONS: Combined hepatectomy and RFA yielded a better long-term outcome than TACE in patients with unresectable BCLC stage B HCC. Patients with a limited ablated size (≤2 cm), a limited number of ablations (≤2), and adequate surgical margin should be considered candidates for combination therapy.

Postoperative neutrophil-to-lymphocyte ratio plus platelet-to-lymphocyte ratio predicts the outcomes of hepatocellular carcinoma.

BACKGROUND: There is limited information regarding NLR-PLR (the combination of the neutrophil-to-lymphocyte ratio [NLR] and platelet-to-lymphocyte ratio [PLR]) in hepatocellular carcinoma (HCC). This study aimed to assess the predictive ability of NLR-PLR in patients with resectable hepatitis B virus-related HCC within Milan criteria after hepatectomy. METHODS: Two hundred thirty-six consecutive HCC patients were included in the study. The postoperative NLR-PLR was calculated based on the data obtained on the first postoperative month after liver resection as follows: patients with both an elevated PLR and an elevated NLR, which were detected by receiver operating characteristic curve analysis, were allocated a score of 2, and patients showing one or neither of these elevations were allocated a score of 1 or 0, respectively. RESULTS: During the follow-up period, 113 patients experienced recurrence and 41 patients died. Multivariate analyses suggested that tumor-node-metastasis stage, preoperative alpha-fetal protein, and postoperative NLR-PLR were independently associated with recurrence, whereas microvascular invasion and postoperative NLR-PLR adversely impacted the overall survival. The 5-y recurrence-free and overall survival rates of the patients with a postoperative NLR-PLR of 0, 1, or 2 were 43.6%, 35.6%, or 8.3% (P < 0.001) and 82.1%, 73.0%, or 10.5% (P < 0.001), respectively. CONCLUSIONS: The postoperative NLR-PLR predicted outcomes of hepatitis B virus-related HCC patients within Milan criteria after liver resection.

Upper abdominal shape as a risk factor of extended operation time and severe postoperative complications in HCC hepatectomy through subcostal incision.

BACKGROUND: Subcostal incision is the most widely used approach in open surgery for patients with hepatocellular carcinoma (HCC). Body shape is recognised to be a factor influencing the difficulty of surgery; however, the exact impact of the increased difficulty on the patients' operation as well as the outcome has not been analysed. In this study, we retrospectively studied the possible influence of patients' body shape, tumour burden and varied surgical methods on the operation procedure and postoperative complications. METHODS: From January 2009 to December 2013, 651 patients with HCC were included in the study. We studied the patients' sex, age, body mass index, upper abdominal body shape described by the depth-to-width ratio for the trunk at the celiac axis on CT/MRI, Child-Pugh classification, tumour burden and a different liver dissection method before the surgery and used a regression model for analysis. RESULTS: Prolonged operation time is associated with advanced tumour stage, large CA ratio, previous abdominal surgery, selective hepatic vascular occlusion and dissecting with Cavitron ultrasonic surgical aspirator rather than clamp crushing. Surgical blood loss is associated with operation time, liver function and a different liver dissection method. The incidence of severe postoperative complication was 17.5% (114/651) and was associated with larger CA ratio, Child-Pugh stage B liver function and greater blood loss. CONCLUSIONS: Large upper abdominal shape is a risk factor of both prolonged operation time and severe postoperative complication. CA ratio combined with liver function and surgical blood loss has an acceptable power to predict severe postoperative complications.

The critical value of remnant liver volume-to-body weight ratio to estimate posthepatectomy liver failure in cirrhotic patients.

BACKGROUND: The extensive use of major hepatectomy for liver malignancies with cirrhosis increases the risk of posthepatectomy liver failure (PHLF), which is associated with a high frequency of postoperative complications, mortality, and an increased length of hospital stay. Remnant liver volume-to-body weight ratio (RLV-BWR) is more specific than the ratio of RLV-to-total liver volume (RLV-TLV) in predicting postoperative course after major hepatectomy in normal liver. Patients having normal liver with an anticipated RLV-BWR ≤0.5% are at considerable risk for hepatic dysfunction and postoperative mortality. In the present study, the critical value of RLV-BWR after liver resection in cirrhotic liver was investigated. PATIENTS AND METHODS: Thirty one patients who underwent hepatectomy for hepatocellular carcinoma in one medical treatment unit of West China Hospital from September 2012 to December 2012 were retrospectively enrolled in study. Volumetric measurements of TLV using computed tomography were obtained before hepatectomy. PHLF was diagnosed by the "50-50 criteria." The influence of RLV-TLV and RLV-BWR on the occurrence of PHLF was investigated, and the critical value of RLV-BWR was concluded. RESULTS: According to the occurrence of PHLF, the patients were retrospectively divided into PHLF group and non-PHLF group. There were no statistical differences of preoperative indicators between the two groups. The intraoperative indicators including the resected liver volume, RLV-TLV, and RLV-BWR were statistically significant (P < 0.05) between the two groups. The postoperative indicators including total bilirubin (TBIL), international normalized ratio, and peritoneal drainage fluid at the third and the fifth day after surgery were statistically significant (P < 0.05) between the two groups. Area under the receiver operating characteristic curve (ROC curve) predicted by RLV-BWR to the incidence of PHLF was 0.864 (P = 0.019) with 95% confidence interval (95% CI = 0.608-0.819), and the sensitivity and specialty rate were 70% and 95%, which were more than 50% and 70%, respectively. It suggested that the critical value of RLV-BWR (1.4%) had a certain predictive value on PHLF. Area under the receiver operating characteristic curve predicted by RLV-TLV to the incidence of PHLF was 0.568 (P = 0.628) with 95% confidence interval (95% CI = 0.376-0.747), and the sensitivity and specialty rate were 42.9% and 82.6%, respectively. The sensitivity (42.9%) <50% suggested that the critical value of RLV-TLR (51%) had a poor predictive value on PHLF. According to the curve critical value 1.4% of RLV-BWR, the patients were divided into RLV-BWR ≥1.4% group and RLV-BWR <1.4% group, and the incidence of PHLF between the two groups was statistically significant (P = 0.006). CONCLUSIONS: RLV-BWR was more specific than RLV-TLV in predicting PHLF after major hepatectomy of cirrhotic liver. Patients with an anticipated RLV-BWR <1.4% are at considerable risk for PHLF.

Neutrophil to lymphocyte ratio changes predict small hepatocellular carcinoma survival.

BACKGROUND: There is limited information available concerning the delta neutrophil to lymphocyte ratio (ΔNLR) in hepatocellular carcinoma (HCC). The present study was designed to evaluate the predictive value of dynamic change of NLR in patients who undergo curative resection for small HCC. METHODS: A retrospective cohort study was performed to analyze 189 patients with small HCC who underwent curative resection between February 2007 and March 2012. Patient data were retrieved from our prospectively maintained database. Patients were divided into two groups: group A (NLR increased, n = 80) and group B (NLR decreased, n = 109). Demographic and clinical data, overall survival (OS), and recurrence-free survival (RFS) were statistically compared and a multivariate analysis was used to identify prognostic factors. RESULTS: The 1, 3, and 5-y OS in group A was 92.7, 70.0, and 53.0%, respectively, and 96.2, 87.5, and 75.9%, respectively, for group B (P = 0.003); The corresponding 1, 3, and 5-y RFS was 58.7, 37.9, 21.8, and 81.2%, 58.5% and 53.8% for groups A and B, respectively (P <0.001). Multivariate analysis suggested that ΔNLR was an independent prognostic factor for both OS (P = 0.004, Hazard Ratio (HR) = 2.637, 95% confidence interval (CI) 1.356-5.128) and RFS (P <0.001, HR = 2.372, 95% CI 1.563-3.601). CONCLUSIONS: Increased NLR, but not high preoperative NLR or postoperative NLR, helps to predict worse OS and RFS in patients with small HCC who underwent curative resection.

Primary graft dysfunction after liver transplantation.

BACKGROUND: Primary graft dysfunction (PGD) causes complications in liver transplantation, which result in poor prognosis. Recipients who develop PGD usually experience a longer intensive care unit and hospital stay and have higher mortality and graft loss rates compared with those without graft dysfunction. However, because of the lack of universally accepted definition, early diagnosis of graft dysfunction is difficult. Additionally, numerous factors affect the allograft function after transplantation, making the prediction of PGD more difficult. The present review was to analyze the literature available on PGD and to propose a definition. DATA SOURCE: A search of PubMed (up to the end of 2012) for English-language articles relevant to PGD was performed to clarify the characteristics, risk factors, and possible treatments or interventions for PGD. RESULTS: There is no pathological diagnostic standard; many documented definitions of PGD are different. Many factors, such as donor status, procurement and transplant process and recipient illness may affect the function of graft, and ischemia-reperfusion injury is considered the direct cause. Potential managements which are helpful to improve graft function were investigated. Some of them are promising. CONCLUSIONS: Our analyses suggested that the definition of PGD should include one or more of the following variables: (1) bilirubin ≥ 10 mg/dL on postoperative day 7; (2) international normalized ratio ≥ 1.6 on postoperative day 7; and (3) alanine aminotransferase or aspartate aminotransferase >2000 IU/L within 7 postoperative days. Reducing risk factors may decrease the incidence of PGD. A majority of the recipients could recover from PGD; however, when the graft progresses into primary non-function, the patients need to be treated with re-transplantation.

Genetic variants of p21 and p27 and hepatocellular cancer risk in a Chinese Han population: a case-control study.

The p21 (Cip1/CDKN1A) and p27 (Kip1/CDKN1B) are members of the Cip/Kip family of cyclin-dependent kinase inhibitors, which can arrest cell proliferation and serve as tumour suppressors. We hypothesized that genetic variants in p21 and p27 may modify individual susceptibility to hepatocellular carcinoma (HCC). To test this hypothesis, we evaluated the associations of the polymorphisms of Ser31Arg and C+20T in p21 and C-79T and Gly109Val in p27, as well as their combinations, with HCC risk in a case-control study of 476 HCC cases and 526 cancer-free controls in a Chinese population. The matrix-assisted laser desorption ionisation time-of-flight (MALDI-TOF) mass spectrometry method was performed to detect these polymorphisms. We found that the variant genotypes of p21 Ser31Arg and p27 C-79T were individually associated with a significantly increased risk of HCC, but no associations were observed for other variant genotypes. Moreover, the combined variant genotypes of the four loci were associated with a significantly increased HCC risk (adjusted OR = 2.24, 95% CI = 1.72, 2.91 among subjects carrying 3 or more variant alleles), especially among HbsAg-positive individuals (adjusted OR = 3.09, 95% CI = 1.86, 5.14). Furthermore, the combined variant genotypes of the four loci (carrying three or more variant alleles) increased a 1.93-fold (95% CI = 1.20, 3.09) and 1.76-fold (95% CI = 1.17, 2.64) risk of HCC among smokers and nonsmokers. The variant genotypes of the two genes in this study have negative correlation with the clinicopathologicals observed. These results suggest that p21 polymorphisms individually or in combination with p27 polymorphisms increases risk of HCC, particularly among HbsAg-positive individuals.

Zinc finger protein A20 inhibits maturation of dendritic cells resident in rat liver allograft.

BACKGROUND: In organ transplant field, although viewed traditionally as instigators of organ allograft rejection, donor-derived interstitial dendritic cells (DCs), including those resident in liver, or host DCs have also been implicated in transplant tolerance in experimental models. This functional dichotomy of DC is governed by various factors, the most important of which appears to be their stage of maturation. This study was designed to examine the effect of zinc finger protein A20 on maturation of DCs resident in rat liver allograft. MATERIALS AND METHODS: Allogeneic (Dark Agouti [DA] rat to Lewis rat) liver transplantation was performed. Adenovirus carrying the full length of A20 was introduced into liver allografts by ex vivo perfusion via the portal vein during preservation (group A20), physiological saline (group PS), and empty Ad vector rAdEasy (group rAdEasy) that served as controls. Acute liver allograft rejection was assessed, and DCs resident in liver allografts were isolated on day 7 after transplantation. Nuclear factor kappa B (NF-κB)-binding activities, surface expression of costimulatory molecules (CD40, CD80, and CD86), expression of interleukin (IL) 12 messenger RNA (mRNA), and allocostimulatory capacity of DCs were measured with electrophoretic mobility shift assay, flow cytometry, reverse transcription-polymerase chain reaction, and mixed lymphocyte reaction (MLR), respectively. RESULTS: Ex vivo transfer of A20 adenovirus by portal vein infusion resulted in overexpression of A20 protein in liver allograft after transplantation. On day 7 after transplantation, histologic examination revealed a mild rejection in group A20 but a more severe rejection in group PS and group rAdEasy. DCs from group A20 liver allografts exhibited features of immature DC with detectable but very low level of NF-κB activity, IL-12 mRNA expression, and surface expression of costimulatory molecules (CD40, CD80, and CD86), whereas DCs from group rAdEasy and group PS liver allograft displayed features of mature DC with high level of NF-κB activity, IL-12 mRNA expression, and surface expression of costimulatory molecules (CD40, CD80, and CD86). DCs from group PS and group rAdEasy liver allograft were potent inducers of DNA synthesis and interferon γ production in MLR, and DCs from group A20 liver allografts induced only minimal levels of cell proliferation and interferon γ production in MLR. CONCLUSIONS: These data suggest that A20 overexpression could effectively inhibit maturation of DCs resident in liver allograft and consequently suppress acute liver allograft rejection.

Safety of living donor liver transplantation using older donors.

BACKGROUND: There is limited information concerning older donors in living donor liver transplantation (LDLT). In the present study, we attempted to clarify whether it is safe to use older donors in LDLT. METHODS: A total of 129 cases were reviewed in the present study. Donors and recipients were divided into group A (donors aged ≥ 50 y, n=21) and group B (donors aged <50 y, n=108). The pre-, intra-, and postoperative variables of the two groups were statistically compared. RESULTS: Donors' complication rates were 38.10% and 28.70% for groups A and B, respectively (P=0.719). The overall 1-, 3-, and 5-y survival rates were 90%, 80%, and 66% for group A and 86%, 83%, and 75% for group B, respectively (P=0.573). Similar Clavien III or more complication rates for recipients were observed. CONCLUSIONS: The present study suggested that LDLT using older donors had no negative influence on the outcomes of both donors and recipients.

Higher tacrolimus blood concentration is related to hyperlipidemia in living donor liver transplantation recipients.

BACKGROUND: The arrival of tacrolimus has drastically improved AALDLT recipients' survival. However, little data of tacrolimus have been reported concerning its effects on lipid metabolism for AALDLT recipients. AIM: Out aim was to investigate the relationship between tacrolimus blood concentration and lipid metabolism in AALDLT recipients. METHODS: The pre and postoperative data of 77 adult patients receiving AALDLT between 2002 and December 2007 were retrospectively reviewed. The postoperative immune suppressive regimen was prednisone with tacrolimus ± mycophenolate mofetil. Prednisone was withdrawn within the first postoperative month. Blood lipids and tacrolimus concentration were detected at the first, third, and sixth month during follow-up. Episodes of acute rejection were diagnosed based on biopsy. RESULTS: Overall prevalence of post-transplantation hyperlipidemia was 29.9% (23/77) at the sixth postoperative month. The patients were divided into two groups, the hyperlipidemia group and the ortholipidemia group. In the 23 patients with hyperlipidemia, 15 (65%) were hypercholesterolemia, five (22%) were hypertriglyceridemia, and three (13%) patients had both hypercholesterolemia and hypertriglyceridemia. In univariate analysis, only tacrolimus blood concentration at the third and sixth post-transplantation months showed significant difference (8.7 ± 2.1 vs. 6.9 ± 3.2, p = 0.013; 9.2 ± 2.7 vs. 7.3 ± 3.8, p = 0.038, respectively). In multivariate logistic analysis, only two factors appear to be risk factors, namely, tacrolimus blood concentration at the third and sixth post-transplantation months (8.7 ± 2.1 vs. 6.9 ± 3.2, p = 0.043; 9.2 ± 2.7 vs. 7.3 ± 3.8 p = 0.035, respectively). CONCLUSIONS: Higher tacrolimus blood concentration was related to hyperlipidemia at an early postoperative period. This indicates that tacrolimus blood concentration should be controlled as low as possible in the premise that there is no risk of rejection to minimize post-transplant hyperlipidemia after AALDLT.