[Research of artificial intelligence-based clinical decision support system for primary hepatocellular carcinoma].

Objective: To apply artificial intelligence technology in clinical real-world data of patients with primary hepatocellular carcinoma, explore the precise treatment of disease and build up artificial intelligence-based clinical decision support system. Methods: A total of 5 642 patients with primary hepatocellular carcinoma admitted to West China Hospital from July 2004 to June 2016 with complete follow-up records were included in the study. A merged model composed of multiple sub-classifiers was adopted to calculate therapy recommendation coefficient, and receiver operator characteristic curve was analyzed. Survival risk and recurrence risk were predicted by DeepSurv algorithm, and Kaplan-Meier survival curves were further compared among low, middle and high risk groups. Siamese-Net was applied to find similar patients. Results: The Top-1 and Top-2 accuracy of therapy recommendation coefficient reached 82.36% and 94.13% respectively. In internal verification of West China Hospital, the above-mentioned value reached 95.10% in accordance with multi-disciplinary team results. The C-index derived from survival risk model was 0.735 (95%CI:0.70-0.77), and the difference of Kaplan-Meier in pairwise comparison was of statistical significance under log-rank test (P<0.001). Meanwhile, the C-index derived from recurrence risk model was 0.705 (95%CI:0.68-0.73), and the difference of Kaplan-Meier in pairwise comparison was of statistical significance under log-rank test (P<0.001). Conclusions: The artificial intelligence-based clinical decision support system for primary hepatocellular carcinoma has can accurately make therapy recommendation and prognosis prediction for primary hepatocellular carcinoma.

Pediatric Donor to Adult Recipients in Donation After Cardiac Death Liver Transplantation: A Single-Center Experience.

BACKGROUND: The impact of using liver allografts from donors who are younger than 14 years at the time of donation after cardiac death (DCD) liver transplantation in terms of early allograft dysfunction (EAD) and graft survival is undefined. To determine if adults undergoing DCD liver transplantation who receive a graft from a donor age younger than or equal to 13 years have similar outcomes to recipients of organs from older than 18-year-old donors. METHODS: Records from adult patients undergoing DCD liver transplantation between March 2012 and December 2015 who received whole grafts from donors after cardiac death were reviewed. Patients with donors younger than or equal to 13 years (group 1) and older than 18 years (group 2) were compared for EAD rates, hepatic artery thrombosis (HAT), and graft survival. RESULTS: Records of 60 DCD liver transplantation patients were analyzed. The 90-day and 1-year graft survival rate of both groups was 90% versus 96% (P = .427) and 80% versus 84% (P = .668), respectively. The EAD rates of groups 1 and 2 were 30% versus 34% (P = .806). The incidence of HAT was 20% in group 1 compared with 12% in group 2 (P = .610). Also, 0.7% < graft to recipient weight ratio (GRWR) <0.8% was also usable for pediatric donor to adult recipients. CONCLUSIONS: Whole liver grafts from donors younger than or equal to 13 years can potentially be used in selected size-matched (GRWR >0.7%) DCD adult recipients.

Health-Related Quality of Life and Psychological Distress in Patients With Early-Stage Hepatocellular Carcinoma After Hepatic Resection or Transplantation.

BACKGROUND: The aim of our study was to compare the post-operative health-related quality of life in patients with small hepatocellular carcinoma (HCC; within the Milan criteria) after liver resection or liver transplantation. METHODS: From August 2000 to December 2010, 207 patients were diagnosed with early HCC within the Milan criteria. We divided these patients into 2 groups according to their curative schedule: the liver transplantation group (n = 95) and the liver resection group (n = 110). We compared the baseline characteristics of these 2 groups of patients, after which we focused on comparing the post-operative health-related quality of life (HRQOL) and psychological outcome in these 2 groups. RESULTS: The demographics of the patients in the 2 groups were similar, and there were no significant differences except for higher family income in the transplantation group (P = .002).With long-term follow-up, there were no significant differences in the 8 domains of the HRQOL and the 9 domains of the psychological outcome measure between the 2 groups. Both the transplantation and resection groups exhibited good outcomes in both HRQOL and psychological outcome measures. CONCLUSIONS: Several years after operation, early-stage HCC patients who underwent liver transplantation or resection had similar long-term HRQOL and psychological outcomes.

[Valproic acid activates autophagy in multiple myeloma cell lines RPMI8226 and U266].

OBJECTIVE: To investigate the effects of valproic acid (VPA) on autophagy in multiple myeloma (MM) cell lines RPMI8226 and U266. METHODS: The method of dye acridine orange (AO) was used for observing morphological changes of autophagy under fluorescence microscope; The cell proliferation inhibition was measured by MTT assay; Cells apoptosis was evaluated by flow cytometry; Autophagy-related factors LC3, Beclin1 expressions changes were detected by real-time quantitative PCR (Real-time PCR) and western blot assay. RESULTS: AO stainings as dispersively brownish red vesicles were observed both in the control and chloroquine groups, while a lot of brownish red acidic vesicles in clusters were seen in rapamycin and VPA groups. The growths of RPMI8226 and U266 cells were suppressed by VPA treatment in a dose-and time-dependent manner, after treatment with VPA for 24 h, the IC50 were (12.03 ± 0.23) mmol/L for RPMI8226 cells and (10.16 ± 0.37) mmol/L for U266 cells respectively; Poptotie cells of RPMI8226 and U266 increased in a time-dependent manner after exposure to VPA. Real-time PCR and Western blot results of RPMI8226 and U266 cells showed that gradually increased LC3, Beclin1 mRNA and protein expressions with LC3 Ⅰ to LC3 Ⅱ conversion rate after increasing the concentration of VPA and prolonging duration of action of VPA. CONCLUSIONS: The results reveal disclosed the basal level of autophagy in MM cells, VPA as a autophagy activator may be one of its actions on the treatment of MM.

[Living donor liver transplantation for the treatment complicated hepatic cystic echinococcosis: first case report from China].

OBJECTIVE: To report the first clinical experience of living donor liver transplantation(LDLT) in patient with complicated hepatic cystic echinococcosis in China. METHODS: First Affiliated Hospital of Xinjiang Medical University successfully implemented LDLT in the treatment of one patient with complicated hepatic cystic echinococcosis after four times liver surgery and secondary congestive cirrhosis on May 9, 2015. The clinical data of the patient has been retrospectively analyzed. RESULTS: LDLT procedure was successfully performed in a patient with four previous liver intervention due to his recurrence. The patient was lack of right lobe, while with significant hypertrophy in left lobe. The reoccurred lesion compressed the retrohepatic vena cava, left hepatic vein, portal vein, that led to the stricture of retrohepatic vena cava, left hepatic vein orifice. The phlebography displayed remarkable stricture in retrohepatic vena cava and rich collateral circulation by which the venous blood flow back to the right atrium via paravertebral vein. The orifice of left hepatic vein shaped as hair-like so that the stenting was impossibly. After the multi-disciplinary team discussion, the liver transplantation was proposed, while the autotransplantation was considered as first line option, and with the backup of living related donor. The laparotomy showed the hugely enlarged liver with nodular changes. The frozen section was tested twice and showed as spotty necrosis with pseudo-lobe formation. Although the enlarged left lobe about 2 000 g weight, the liver colored as grey with cotton-like texture, the plan for autotransplantation was abandoned regarding the high risk for post-operative liver failure. Therefore, LDLT was performed. The donor was her brother who donated right lobe with 685 g weight. The operation time was 1 005 min with anhepatic time 335 min. Total of 12 units red blood cell suspension was transfused. The coagulating function was back to normal in 3 days after operation. The patient was discharged at 30 days after operation, while the routine blood test and biochemical markers had back to normal levels. The patient had taken tacrolimus and methylprednisolone with normal life. The liver functions of transplanted liver were normal in 90 days after surgery. The patient was able to self-activity and regular outpatient follow-up. CONCLUSION: Hepatic CE is an infectious disease, and liver transplantation could be the last choice for complicated case, especially in combination with severe complications, like Budd-Chiari syndrome.

Response to transarterial chemoembolization as a selection criterion for resection of hepatocellular carcinomas.

BACKGROUND: Liver resection for intermediate (Barcelona Clinic Liver Cancer (BCLC) stage B) hepatocellular carcinoma (HCC) remains controversial. This study attempted to demonstrate the effectiveness of preresection transarterial chemoembolization (TACE) as a selection criterion for BCLC-B HCC. METHODS: The study included patients with BCLC-B HCC who underwent liver resection after TACE. The tumour response to TACE was evaluated according to the modified Response Evaluation Criteria in Solid Tumours (mRECIST). Patients with a complete or partial response comprised the responder group, whereas those with stable or progressive disease were classified as non-responders. RESULTS: A total of 242 patients were included. After between one and eight sessions of TACE, 141 patients were included in the responder group: 37 patients (15·3 per cent) who achieved a complete response and 104 who had a partial response. The cumulative 1-, 3- and 5-year overall survival rates were 97·2, 88·7 and 75·2 per cent respectively in the responder group, compared with 90·1, 67·3 and 53·5 per cent among 101 non-responders (P < 0·001). Tumour-free survival rates were also better among responders than non-responders (P < 0·001). In multivariable analysis, independent predictors of overall and tumour-free survival were response to TACE and microvascular invasion (all P < 0·001). CONCLUSION: mRECIST may represent selection criterion for intermediate HCC for surgical treatment.

Hepatocellular Carcinoma Patients May Benefit From Postoperative Huaier Aqueous Extract After Liver Transplantation.

BACKGROUND: Liver transplantation has been the first choice for most early- or intermediate-stage hepatocellular carcinoma (HCC) cases. However, postoperative anti-HCC therapies remain controversial. In this study, we aimed to evaluate the safety and efficacy of Huaier aqueous extract (Jinke), when used as an adjuvant postoperative anti-HCC therapy. METHODS: We retrospectively collected the clinical and follow-up data of HCC patients who underwent liver transplantation at our center. We divided them into 2 groups: a control liver transplantation group and a Huaier treatment group. The baseline characteristics, tumor characteristics, intraoperative data, postoperative recovery, long-term overall survival rate, and tumor-free survival rate were compared between the 2 groups. RESULTS: Fifty-three patients were included in our study, including 28 patients who underwent postoperative Huaier therapy and 25 patients who underwent liver transplantation without postoperative Huaier therapy. The baseline and tumor characteristics were similar between the 2 groups. None of the patients in the Huaier group experienced any severe adverse events. The long-term predictive overall survival was similar between the 2 groups (P = .202). However, the Huaier group had a higher predictive tumor-free survival rate than the control group (P = .029). And the 10- and 30-month predictive tumor recurrence rates were 17.9% and 35.7% in the Huaier group, which were significantly lower than those in the control group (60% and 64%; P < .05). CONCLUSIONS: HCC patients may benefit from Huaier therapy after liver transplantation, but a longer follow-up time and larger cohort study may be necessary to be sure.

De Novo Malignancies After Liver Transplantation With 14 Cases at a Single Center.

OBJECTIVE: To analyze the clinical characteristics, risk factors, and prevention of de novo malignant tumors after liver transplantation. METHODS: Fourteen patients who underwent liver transplantation were identified as having de novo malignancies. The clinical characteristics and survival of these patients were retrospectively reviewed. RESULTS: Fourteen cases of de novo malignancies after liver transplantation occurred for an incidence rate of 1.94% (14/722), including 11 men (78.6%, mean age, 48 y) and 3 women (21.4%, mean age, 50 y). The mean period from transplantation to cancer diagnosis was 55 ± 35 months. The distribution of tumor histologic types included colon cancer, lung cancer, esophageal cancer, nasopharyngeal cancer, liver cancer, parotid carcinoma, bone cancer, post-transplantation lymphoproliferative disorder, stomach cancer, bladder cancer, and laryngeal cancer. Twelve cases (85.7%) had hepatitis B. Five patients (35.7%) underwent operations, and the other 9 patients underwent chemotherapy or radiotherapy. During a mean follow-up period of 37 ± 26 months after the diagnosis of de novo malignancy, 8 patients (57.1%) died, with only 1 dying of causes not related to the de novo malignancy. The survival analysis showed 1-, 5-, and 7-year survival rates of 85.7%, 71.4%, and 42.9%, respectively. CONCLUSIONS: De novo malignancies after organ transplantation have been suggested to be a major cause of late mortality. De novo malignancy after orthotopic liver transplantation was found to be related to smoking, sex, and low immune function due to immunosuppressive agents. Solid tumors should be removed, and the patient should receive chemotherapy or radiotherapy as early as possible. Early diagnosis and treatment are very important for improving the prognosis.

Radiofrequency ablation versus surgical resection for small unifocal hepatocellular carcinomas.

We aimed to compare the effectiveness and safety of hepatic resection and radiofrequency ablation (RFA) for small hepatocellular carcinomas (HCCs) less than 5 cm in diameter. A total of 289 patients were diagnosed with a small HCC (a single tumor no larger than 5 cm). Among these patients, 133 underwent hepatic resection, and 156 received RFA. Demographic data, intraoperative data, post-operative recovery data, and the baseline characteristics of the 2 groups of patients were compared. The incidence of post-operative complications; 1-, 3-, and 5-year survival rates; and tumor recurrence were determined. No statistically significant differences in the baseline characteristics were noted between the 2 groups. By contrast, operation time (P = 0.003), intraoperative blood loss (P = 0.000), and the length of post-operative hospital stay (P = 0.000) were significantly lower in the RFA group compared with the surgical resection group. The 2 groups displayed similar post-operative complication rates (12% or 16/133 in the liver resection group vs. 8.3% or 13/156 in the RFA group, P = 0.395). The 1-, 3-, and 5-year overall survival rates of the patients in the liver resection group were 88.7%, 78.2%, and 66.2%, respectively, whereas the rates in the RFA group were 90.4%, 76.3%, and 66.0%, respectively (P = 0.722). The 1-, 3-, and 5-year tumor-free survival rates of patients in the resection group were 87.2%, 69.9%, and 58.6%, respectively, whereas the rates in the RFA group were 85.9%, 66.0%, and 54.5%, respectively (P = 0.327). In addition, among HCC patients receiving RFA, patients with tumors no greater than 3 cm in diameter exhibited no significant differences regarding overall survival and tumor-free survival rates compared with patients with tumors 3 to 5 cm in diameter (all P > 0.05). RFA is an effective and safe treatment option for small HCCs and may be a preferred choice for HCC patients with small lesions.

Immediate radical therapy or conservative treatments when meeting the Milan criteria for advanced HCC patients after successful TACE.

BACKGROUND AND AIMS: Many advanced hepatocellular carcinoma (HCC) cases can be successfully downstaged into the Milan criteria; however, immediate radical therapy cannot be applied to all such patients for various reasons. Of the patients who are not eligible for immediate radical therapy, some accept repeated downstaging therapies and some undergo persistent observation. The aim of the present study was to compare long-term survival between these two groups of patients. PATIENTS AND METHODS: Between August 2003 and October 2008, 156 HCC patients successfully received downstaging therapy resulting in compliance with the Milan criteria. Of those, 98 cases accepted radical therapies, including liver transplantation (LT), resection, or radiofrequency ablation (RFA) (group 1), and 58 cases underwent repeated transcatheter arterial chemoembolization (TACE) or persistent observation (group 2). The baseline characteristics, demographic data, downstaging protocol, and information on long-term outcomes were collected and compared. RESULTS: No significant differences were observed in the patient demographic data, downstaging protocols, or tumor characteristics between the two groups. The 1-, 3-, and 5-year overall survival rates were 92.9, 82.7, and 78.6 %, respectively, in group 1, whereas these rates were 82.8, 65.5, and 48.3 %, respectively, in group 2 (P = 0.046). Among the 58 patients in group 2, the 1-, 3-, and 5-year overall survival rates were 92.3, 65.4, and 46.2 %, respectively, in the repeated TACE group, and 81.3, 65.6, and 50 %, respectively, in the persistent observation group (P = 0.783). CONCLUSION: Immediate radical therapy should be the first choice for advanced HCC patients who undergo successful TACE, and repeated TACE is unnecessary.

Intraoperative "no go" donor hepatectomy in living donor liver transplantation.

BACKGROUND AND OBJECTIVE: Although there are many reports on donor safety, there are few concerning aborted donations. We sought to analyze the "no go" donor hepatectomies in our liver transplantation center over 10 years' experience. METHODS: Among 290 living donors brought to the operating room for liver graft harvest from March 2002 to April 2012, we examined the reasons to abandon the procedure, comparing their data with those of successful donors. RESULTS: The donor operation was aborted in 5 cases various for reasons. The main reason for the abandonment of the operation process was poor liver quality: in single cases there was: poor liver quality due to a massive cirrhotic nodule observed by laparoscopy; serious steatosis of the liver, indicated by an intraoperative biopsy; and an unsuitable biliary anatomy, including 4 branches with 2 small ones. In another case, a biliary duct variation in the intraoperative cholangiogram showed a narrow crotch of the left and right ducts. In the 5th case, the donor would have been left with only a small remaining left lobe (<30%) if the right lobe had been harvested. All 5 donors proceeded to accept a right lobe hepatectomy. Comparison with the 285 successful donors showed no significant differences in preoperative demographic data. All 5 donors recovered without complication and were in good condition over long-term follow-up. CONCLUSIONS: A low rate of "no go" donor hepatectomy can be achieved. There was no short- or long-term harm to the living donor owing to abandonment of the procedure.

Prediction factors of postoperative hyperbilirubinemia in living right lobe donor: a single-center analysis of 210 cases.

BACKGROUND: Hyperbilirubinemia in living liver donor is very common, but the causes are still unclear. AIMS: We sought to clarify the risk factors and predictors of nonobstructive hyperbilirubinemia among living donors. METHODS: We divided 210 consecutive right liver lobe donors into two groups according to the peak total bilirubin postoperatively. We collected data on preoperative, intraoperative, and postoperative biochemical measurements retrospectively, performing multivariate logistic regression analysis adjusting for potential confounders of the risk of hyperbilirubinemia. RESULTS: There were significant differences between the two groups in donor age, body mass index, operative time, blood loss, macrovescicular steatosis, allogeneic blood transfusion rate, intensive care unit stay, hospital stay and Clavien score after donation (P < .05). Age, graft/donor weight, operative time, and blood loss were significantly associated with the risk of hyperbilirubinemia upon logistic regression analysis. CONCLUSION: Hyperbilirubinemia, one type of hepatic dysfunction after a living donor procedure, was associated with multiple independent risk factors.

Identification of the novel allele HLA-A*33:22 by sequence-based typing in a Chinese individual.

The novel A*33:22 differs from A*33:03:01 by two nucleotides at position 12(A>G)and 19(T>G)of exon 3.

A novel allele HLA-B*51:63 was identified by sequence-based typing in a Chinese individual.

The novel B*51:63 is identical to B*51:01:01 with an exception of one base substitution at position 76 (A > C) of exon 3 resulting in codon #116 changed from TAC (Tyr) to TCC (Ser).

New prognostic model for adult-to-adult living donor liver transplant recipients.

Adult-to-adult living donor liver transplantation (A-A LDLT) is an effective therapeutic modality to treat patients with end-stage liver disease. The aims of this study were to identify recipient characteristics of A-A LDLT seeking to determine variables that affected patient survival. We retrospectively examined a cohort of 154 consecutive A-A LDLT recipients with end-stage liver disease in our center over 4 years. All donors volunteered to give their partial livers with written consent. There were no organs from prisoners and no prisoner subjects. The overall survivals at 1, 2, 3, 6, 12, 24, 36, and 48 months were 93.5%, 90.9%, 88.9%, 86.3%, 80%, 65.6%, 63.8%, and 63.8%, respectively. About 31 pre- and intraoperative factors were analyzed to identify correlations with posttransplant survival using the Cox proportional-hazards regression model. Recipient age, serum creatinine concentration, intraoperative blood loss, and graft-to-recipient weight ratio were significant predictors of survival after transplantation. The prognostic index model, which was calculated by combining these four prognostic values with their regression coefficients, showed a c-statistic of 0.706 (95% confidence interval [CI] = 0.621-0.792) compared with the Model for End-stage Liver Disease value of 0.546 (95% CI = 0.350-0.558). There was a significant difference between the predictions achieved with the two models (P = .012). In conclusion, selecting younger recipients, better pretransplant renal condition, reduced intraoperative blood loss, and graft-to-recipient size match appeared to be advantageous to achieve better survivals among patients undergoing A-A LDLT.

Dual grafts live donor liver transplantation for acute-on-chronic hepatitis B liver failure.

OBJECTIVE: This study reports the preliminary experience of dual grafts living donor liver transplantation (LDLT) for patients with acute-on-chronic liver failure (AoCLF) caused by hepatitis B. METHODS: Two patients who demonstrated acute-on-chronic hepatitis B liver failure and portal hypertension with Model for End-Stage Liver Disease (MELD) scores of 42 and 37, respectively, underwent dual LDLT grafts including one right lobe without a middle hepatic vein and one left lobe because the graft-to-recipient body weight ratio of the right lobe grafts were 0.53% and 0.66%. The donors and the recipients have been followed for over 1 year. RESULTS: Mortality and operative complications were not observed in the donors or recipients. At present, the donors and recipients have returned to their daily routine. No prisoners or organs from prisoners were used to obtain these data. CONCLUSION: Dual LDLT grafts including one right lobe without the middle hepatic vein and one left lobe may be a possible therapeutic option for subjects with acute-on-chronic hepatitis B-induced liver failure.

A new HLA-B*15 variant, B*15:144, identified by sequence-based typing in a Chinese individual.

A novel human leukocyte antigen-B allele, officially named B*15:144 allele, the previous designation B*9544 allele, was found in a potential Chinese bone marrow donor when direct sequence-based typing was carried out. The novel B*15:144 is identical to B*15:02:01 with the exception of two base substitution at position 195 (C>T), 196 (T>G) of exon 3 resulting in codon #156 changed from CTG (Leu) to TGG (Trp).

Early postoperative care of liver transplantation for infants with biliary atresia during pediatric intensive care unit stay.

SUBJECT: The aim of this study was to present our institutional experience with the pediatric intensive care unit (PICU) stays of liver recipients to understand prevention of complications. METHODS: This retrospective review included 22 infants who weighed 8.8 kg or less and underwent 23 transplantations. No grafts were from executed prisoners. We summarized the diagnosis, evaluation, medicine usage, and therapeutic intervention associated with subjects experiencing complications of rejection episodes, surgery, or infection during their ICU stay. RESULTS: There was one perioperative death from primary graft nonfunction. The most common postoperative complications were infections, gastrointestinal bleeding, and vascular complications. Rejection episodes occurred among 25% of patients. The most common isolated pathogenic bacteria was Staphylococcus epidermidis. Median initial ICU stay was 10 days. Mean requirement for artificial ventilation was 37.6 hour. Mean times of use of dobutamine, prostaglandin E1, and dopamine was 3.3, 7.5, and 8.8 days, respectively. Parenteral nutrition was started at a mean of 12 hours and oral food intake at a mean of 72 hours. CONCLUSIONS: Although challenging, orthotopic liver transplantation (OLT) in small infants can be successfully performed with meticulous surgical technique and keen postoperative surveillance.