Hepatitis B Virus DNA-Level Change is Associated With Tumor Recurrence in Patients With Resected Hepatitis B Virus Hepatocellular Carcinoma.

INTRODUCTION: To investigate the significance of perioperative hepatitis B virus (HBV) DNA changes for predicting recurrence in patients with HBV-related hepatocellular carcinoma (HCC) undergoing liver resection (LR). METHODS: From 2013 to 2020, 241 patients with HBV-related HCC who underwent LR in five Hallym university-affiliated hospitals were enrolled. The serum HBV DNA level, together with other clinicopathological variables, was analyzed for association with HCC recurrence. RESULTS: Preoperatively, 99 patients had undetectable HBV DNA and 142 had detectable viral levels. Of those with detectable viral levels, 72 rapidly progressed to undetectable levels within 3 mo after LR (Rapid group), and 70 showed persistently detectable levels (Nonrapid group). The Rapid group had a better recurrence-free survival (RFS) rate than the Nonrapid group (1-y, 3-y RFS = 75.4%, 57.3%, versus 54.7%, 39.9%, respectively, P = 0.012). In the subgroup analysis, the Rapid group had a better RFS rate in early stages (1-y, 3-y RFS = 82.6%, 68.5%, versus 62.8%, 45.8%, respectively, P = 0.005); however, the RFS rates between the two groups were comparable in the advanced stage (1-y, 3-y RFS = 61.1%, 16.7% versus 45.5%, 22.7%, respectively, P = 0.994). Among the 142 patients with preoperatively detectable HBV DNA, persistently detectable HBV DNA within 3 mo postoperatively (hazard ratio [HR] = 1.7, P = 0.022), large tumor size (HR = 2.7, P < 0.001), multiple tumors (HR = 3.2, P < 0.001), and microvascular invasion (HR = 1.7, P = 0.028) were independent risk factors for RFS in multivariate analysis. CONCLUSIONS: Rapidly undetectable HBV DNA after LR is associated with a better prognosis for recurrence in patients with HCC. Therefore, appropriate treatment and/or screening may be necessary for patients who do not return to undetectable HBV DNA after LR.

Serum immune biomarker levels combined with hepatitis B virus infection status predict early recurrence of early-stage hepatocellular carcinoma with microvascular invasion after liver resection.

INTRODUCTION: The tumor immune response plays a vital role in cancer recurrence in patients with malignancies. We aim to clarify the risk factors for early recurrence and investigate the efficacy of blood-based biomarkers to predict the risk of early recurrence in early-stage hepatocellular carcinoma (HCC) patients with microvascular invasion (MVI) after hepatectomy. MATERIALS AND METHODS: A total of 101 cases of HCC with MVI who underwent liver resection were enrolled. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors of early recurrence. We calculated the area under the receiver operating characteristic curve to evaluate the performance of the four biomarkers identified as risk factors for early recurrence. RESULTS: Multiple logistic regression analysis indicated that complement (C)4, cluster of differentiation (CD)4+, immunoglobulin A (IgA), and hepatitis B virus (HBV) DNA of greater than 500 IU/mL were correlated with early recurrence of HCC. The area under the curve was greater for the combination model than for the HBV DNA, CD4+, IgA, or C4 models alone. CONCLUSION: Preoperative serum CD4+, C4, IgA, and HBV DNA levels were linked with early recurrence of early-stage HCC with MVI and the combination model was of considerable predictive value for the prognosis of HCC with MVI.

Immunosuppressive Drug-Resistant Armored T-Cell Receptor T Cells for Immune Therapy of HCC in Liver Transplant Patients.

BACKGROUND AND AIMS: HBV-specific T-cell receptor (HBV-TCR) engineered T cells have the potential for treating HCC relapses after liver transplantation, but their efficacy can be hampered by the concomitant immunosuppressive treatment required to prevent graft rejection. Our aim is to molecularly engineer TCR-T cells that could retain their polyfunctionality in such patients while minimizing the associated risk of organ rejection. APPROACH AND RESULTS: We first analyzed how immunosuppressive drugs can interfere with the in vivo function of TCR-T cells in liver transplanted patients with HBV-HCC recurrence receiving HBV-TCR T cells and in vitro in the presence of clinically relevant concentrations of immunosuppressive tacrolimus (TAC) and mycophenolate mofetil (MMF). Immunosuppressive Drug Resistant Armored TCR-T cells of desired specificity (HBV or Epstein-Barr virus) were then engineered by concomitantly electroporating mRNA encoding specific TCRs and mutated variants of calcineurin B (CnB) and inosine-5'-monophosphate dehydrogenase (IMPDH), and their function was assessed through intracellular cytokine staining and cytotoxicity assays in the presence of TAC and MMF. Liver transplanted HBV-HCC patients receiving different immunosuppressant drugs exhibited varying levels of activated (CD39+ Ki67+ ) peripheral blood mononuclear cells after HBV-TCR T-cell infusions that positively correlate with clinical efficacy. In vitro experiments with TAC and MMF showed a potent inhibition of TCR-T cell polyfunctionality. This inhibition can be effectively negated by the transient overexpression of mutated variants of CnB and IMPDH. Importantly, the resistance only lasted for 3-5 days, after which sensitivity was restored. CONCLUSIONS: We engineered TCR-T cells of desired specificities that transiently escape the immunosuppressive effects of TAC and MMF. This finding has important clinical applications for the treatment of HBV-HCC relapses and other pathologies occurring in organ transplanted patients.

Predictors of portal vein thrombosis after laparoscopic splenectomy and azygoportal disconnection in hepatitis B cirrhosis: a prospective study.

BACKGROUND: The thrombosis of the main and intrahepatic branches of the portal vein (TMIP) is potentially lethal and deemed a common complication following laparoscopic splenectomy and azygoportal disconnection (LSD) in patients with cirrhosis and portal hypertension (PH). The predictors of TMIP after LSD remain unclear. The aim of this prospective study was to explore the predictive and risk factors for TMIP after LSD in cirrhotic patients with PH caused only by hepatitis B virus. METHODS: From September 2014 to March 2017, we enrolled 115 patients with hepatitis B cirrhosis and PH who successfully underwent LSD. Patients were subdivided into a TMIP group and a non-TMIP group. Univariate and multivariate logistic regression analysis was conducted on 24 items of demographic and preoperative data, to explore the risk factors of TMIP. RESULTS: Twenty-nine (25.22%) patients developed TMIP on postoperative day (POD) 7 and 26 (22.81%) patients developed TMIP on POD 30. From POD 7 to POD 30, 12 patients who did not have TMIP at POD 7 were newly diagnosed with TMIP, with portal vein diameter 15.05 ± 2.58 mm. Another 14 patients in whom TMIP had resolved had portal vein diameter 14.02 ± 1.76 mm. Univariate analysis and multivariate logistic regression revealed that portal vein diameter ≥ 13 mm [relative risk (RR) 5.533, 95% confidence interval (CI) 1.222-25.042; P = 0.026] and portal vein diameter ≥ 15 mm (RR 3.636, 95% CI 1.466-9.021; P = 0.005) were significant independent risk factors for TMIP on POD 7 and 30, respectively. CONCLUSION: Portal vein diameter ≥ 13 mm and ≥ 15 mm were significant independent predictors for TMIP after LSD in patients with hepatitis B cirrhosis and PH on POD 7 and POD 30, respectively. TRIAL REGISTRATION: We registered our research at https://www. CLINICALTRIALS: gov/ . The name of research registered is "Warfarin Prevents Portal Vein Thrombosis in Patients After Laparoscopic Splenectomy and Azygoportal Disconnection." The trial registration identifier at clinicaltrials.gov is NCT02247414.

Novel postoperative nomograms for predicting individual prognoses of hepatitis B-related hepatocellular carcinoma with cirrhosis.

BACKGROUND: Liver cirrhosis is a well-known risk factor for carcinogenesis of hepatocellular carcinoma (HCC). The aim of the present study was to construct individual prognostic models for HCC with cirrhosis. METHODS: The clinical differences between HCC patients with and without cirrhosis were compared using a large cohort of 1003 cases. The patients with cirrhosis were randomly divided into a training cohort and a validation cohort in a ratio of 2:1. Univariate and multivariate analyses were performed to reveal the independent risk factors for recurrence-free survival (RFS) and overall survival (OS) in HCC patients with cirrhosis. These factors were subsequently used to construct nomograms. RESULTS: Multivariate analyses revealed that five clinical variables (hepatitis B e antigen (HBeAg) positivity, alpha-fetoprotein (AFP) level, tumour diameter, microvascular invasion (MVI), and satellite lesions) and seven variables (HBeAg positivity, AFP level, tumour diameter, MVI, satellite lesions, gamma-glutamyl transpeptidase level, and histological differentiation) were significantly associated with RFS and OS, respectively. The C-indices of the nomograms for RFS and OS were 0.739 (P < 0.001) and 0.789 (P < 0.001), respectively, in the training cohort, and 0.752 (P < 0.001) and 0.813 (P < 0.001), respectively, in the validation cohort. The C-indices of the nomograms were significantly higher than those of conventional staging systems (P < 0.001). The calibration plots showed optimal consistence between the nomogram-predicted and observed prognoses. CONCLUSIONS: The nomograms developed in the present study showed good performance in predicting the prognoses of HCC patients with hepatitis B virus-associated cirrhosis.

A Stepwise Evaluation of Hepatitis B Virus-Related Acute-on-Chronic Liver Failure to Optimize the Indication for Urgent Liver Transplantation.

BACKGROUND: Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is a dynamic but reversible disease. AIM: We aimed to clarify whether the change in Chinese Group on the Study of Severe Hepatitis B-ACLF (COSSH-ACLF) grade in HBV-ACLF patients can be used to predict prognosis, and to explore the appropriate conditions for performing urgent liver transplantation. METHODS: We assessed the COSSH-ACLF grades of HBV-ACLF patients at different time points from June 2013 to May 2019 at Huashan Hospital in Shanghai, China, and analyzed the relationship between the change in grade and patient prognosis. RESULTS: A total of 207 HBV-ACLF patients were enrolled, of which 79 underwent urgent liver transplantation. Their COSSH-ACLF grades were calculated at diagnosis, 3-7 days after diagnosis, and on the final day. Most of the final ACLF grades were consistent with their corresponding grades at days 3-7 after diagnosis (62.5%), while only 44.5% were in accordance with the initial grades at diagnosis. In patients who had a poor prognosis (initial ACLF-3 and ACLF-2 or -3 at days 3-7), the 28-day survival rate was 93.3% in those who underwent transplantation and 6.8% in those who did not (P < 0.0001). However, in patients who had a good prognosis (ACLF-0 or ACLF-1 at days 3-7), the 28-day survival rate was 100% in transplanted patients and 91.5% in non-transplanted patients (P = 0.236). CONCLUSIONS: Reevaluation of the COSSH-ACLF grade 3-7 days after diagnosis could potentially show an indication for urgent liver transplantation.

Liver transplantation in acute liver failure due to Hepatitis B. Two clinical cases.

Hepatitis B virus (HBV) related acute liver failure (ALF) is uncommon in our region, and there is limited HBV literature regarding the optimal management of these cases. In this article, we report two clinical cases of young men who have sex with men (MSM), both developed severe acute hepatitis caused by HBV, progressed to ALF and afterward required liver transplantation. Antiviral post-transplant treatment included entecavir without Hepatitis B Immunoglobulin (HBIG), and immunosuppression therapy with steroids, tacrolimus, and mycophenolate. Serologic follow-up showed early Hepatitis B surface Antigen (HBsAg) seroconversion, undetectable HBV viral load, and positive Anti-HBs titers. During later follow-up, Anti-HBs titers gradually fell (<10mUI/L after six months), with normal liver function. DISCUSSION: In cases of HBV-related ALF, the liver develops a robust immune response, leading to, an early undetectable viral load and seroconversion, with loss of HBsAg, and the appearance of Anti-HBs as a result of the inflammatory response. The management varies depending on whether this is a de novo acute infection or a reactivation of a previous chronic infection. In both cases, the use of antiviral therapy is recommended, with entecavir or tenofovir, among others, but the use of specific HBIG is supported only in ALF related to chronic HBV infection. The optimal length of the antiviral therapy after liver transplantation is still under discussion. CONCLUSION: These cases of HBV related ALF with an early HBsAg seroconversion demonstrates the relevance of requesting IgM antibody against hepatitis B core antigen (anti-HBc IgM) for the etiological study of ALF with negative HBsAg. Usage of HBIG does not seem essential during the post-transplantation period in these cases.

Successful treatment of severe COVID-19 pneumonia in a liver transplant recipient.

Coronavirus disease 2019 (COVID-19) pandemic spreads rapidly and may be an increasing challenge for transplant community. Clinical data on COVID-19 infection in transplant population is very limited. Herein we presented the clinical course and outcome of a 50-year-old male post liver transplantation who contracted COVID-19, with subsequent infection of his wife. The process of illness was representative. A therapeutic regime with temporary immunosuppression withdrawal and systemic low-dose corticosteroid as principle was involved in the management of the patient which made him recover from severe COVID-19 pneumonia.

Clinical characteristics and immunosuppressant management of coronavirus disease 2019 in solid organ transplant recipients.

Over 1 000 000 cases of coronavirus disease 2019 (COVID-19) have been confirmed since the worldwide outbreak began. Not enough data on infected solid organ transplant (SOT) recipients are available, especially data about the management of immunosuppressants. We report two cases of COVID-19 in two transplant recipients, with different treatments and prognoses. The first patient received liver transplantation due to hepatitis B virus-related hepatocellular carcinoma and was confirmed to have COVID-19 9 days later. Following a treatment regimen consisting of discontinued immunosuppressant use and low-dose methylprednisolone-based therapy, the patient developed acute rejection but eventually recovered. The other patient had undergone a renal transplant from a living-related donor 17 years ago, and was admitted to the hospital because of persistent fever. This patient was also diagnosed with COVID-19. His treatment regimen consisted of reduced immunosuppressant use. No signs of rejection were observed during the regimen. In the end, the patient successfully recovered from COVID-19. These effectively treated cases can provide a basis for immunosuppressant management of COVID-19-positive SOT recipients.

Fatal outcome in a liver transplant recipient with COVID-19.

Liver injury is common in patients with COVID-19, but little is known about its clinical presentation and severity in the context of liver transplant. We describe a case of COVID-19 in a patient who underwent transplant 3 years ago for hepatocellular carcinoma. The patient came to clinic with symptoms of respiratory disease; pharyngeal swabs for severe acute respiratory syndrome coronavirus 2 were positive. His disease progressed rapidly from mild to critical illness and was complicated by several nosocomial infections and multiorgan failure. Despite multiple invasive procedures and rescue therapies, he died from the disease. The management of COVID-19 in the posttransplant setting presents complex challenges, emphasizing the importance of strict prevention strategies.

Prevention and treatment of temporal lobe epilepsy: lessons from hepatitis B story!

Temporal lobe epilepsy (TLE) is the most common type of drug-resistant epilepsy and hippocampal sclerosis (HS) is the most common pathological substrate of TLE. Considering the significant consequences of uncontrolled seizures (e.g. increased morbidity and mortality), epilepsy prevention remains a necessity that potentially could save many lives. Human herpes virus-6 (HHV-6) has been linked to TLE in humans. The relationship between HHV-6 and HS-TLE could be attributed to a neuro-inflammatory cascade triggered by the infection, involving direct neuronal damage and production of several pro-inflammatory cytokines under certain conditions that are still incompletely understood. Hepatitis B virus (HBV) infection is another chronic viral infection with a life-long latency. HBV infection is linked to various clinical conditions, including liver cirrhosis. There are currently three ways to fight HBV infection and its consequences; primary prevention (by vaccination), secondary prevention (by drug therapy), and tertiary prevention (by liver transplantation). Considering the similarities between the natural histories of HHV-6 and HBV infections, and also the successful strategies which are currently available to fight HBV infection and its long-term consequences, here, we propose three strategies to fight HHV-6 and its possible long-term consequence (i.e. HS-TLE): Primary prevention: by developing vaccines to prevent HHV-6 infection; Secondary prevention: by considering trials of antiviral drugs to treat HHV-6 infection, when it happens in the childhood to hopefully prevent its long-term consequences; and, Tertiary prevention: by stem cell therapy for drug-resistant epilepsy.

Development and validation of a new tumor-based gene signature predicting prognosis of HBV/HCV-included resected hepatocellular carcinoma patients.

BACKGROUND: Due to the phenotypic and molecular diversity of hepatocellular carcinomas (HCC), it is still a challenge to determine patients' prognosis. We aim to identify new prognostic markers for resected HCC patients. METHODS: 274 patients were retrospectively identified and samples collected from Zhongshan hospital, Fudan University. We analyzed the gene expression patterns of tumors and compared expression patterns with patient survival times. We identified a "9-gene signature" associated with survival by using the coefficient and regression formula of multivariate Cox model. This molecular signature was then validated in three patients cohorts from internal cohort (n = 69), TCGA (n = 369) and GEO dataset (n = 80). RESULTS: We identified 9-gene signature consisting of ZC2HC1A, MARCKSL1, PTGS1, CDKN2B, CLEC10A, PRDX3, PRKCH, MPEG1 and LMO2. The 9-gene signature was used, combined with clinical parameters, to fit a multivariable Cox model to the training cohort (concordance index, ci = 0.85), which was successfully validated (ci = 0.86 for internal cohort; ci = 0.78 for in silico cohort). The signature showed improved performance compared with clinical parameters alone (ci = 0.70). Furthermore, the signature predicted patient prognosis than previous gene signatures more accurately. It was also used to stratify early-stage, HBV or HCV-infected patients into low and high-risk groups, leading to significant differences in survival in training and validation (P < 0.001). CONCLUSIONS: The 9-gene signature, in which four were upregulated (ZC2HC1A, MARCKSL1, PTGS1, CDKN2B) and five (CLEC10A, PRDX3, PRKCH, MPEG1, LMO2) were downregulated in HCC with poor prognosis, stratified HCC patients into low and high risk group significantly in different clinical settings, including receiving adjuvant transarterial chemoembolization and especially in early stage disease. This new signature should be validated in prospective studies to stratify patients in clinical decisions.

How to improve long-term outcome after liver transplantation?

The outcome of liver transplantation has markedly improved in the last 3 decades. Although early post-transplantation outcomes have improved over time, this is not true of the long-term outcome. The majority of late deaths are not related to graft dysfunction, and with the advent of new antiviral agents, recurrence of hepatitis B and hepatitis C after transplantation may no longer represent a source of graft loss and patient's death in the long term. The complications of metabolic syndrome may represent an increasing source of morbidity and mortality after transplantation. This study discusses these modifiable factors associated with late mortality to improve the long-term results of transplantation.

Short and Long-Term Postoperative Complications Following Total Joint Arthroplasty in Patients With Human Immunodeficiency Virus, Hepatitis B, or Hepatitis C.

INTRODUCTION: Due to advancement in treatment against human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV), the prevalence of this patient population electing to undergo total joint arthroplasty (TJA) is increasing. Current literature is scarce and conflicting especially when evaluating long-term surgical complications. The purpose of this study is to assess the postoperative medical and surgical complications following TJA in these patient populations. METHODS: Using a nationwide database between 2005 and 2012, 4 cohorts were created: patients with HIV, HCV, HBV, and HIV and HBV or HCV who underwent TJA. Cohorts were matched to a control group by age, gender, and Charlson Comorbidity Index. Thirty-day and 90-day medical complications and 90-day and 2-year surgical complications were evaluated using odds ratios with 95% confidence intervals. RESULTS: Following TJA, patients with HCV or HBV had increased risk of pneumonia, sepsis, joint infection, and revision surgery at 90 days and 2 years. Patients with HIV did not have increased risk of infection at 90 days and 2 years but did have increased risk of revision at 90 days (odds ratio 3.21, 95% confidence interval 1.31-7.84) following total hip arthroplasty. CONCLUSIONS: Patients with HIV, HBV, or HCV have an overall increased risk of postoperative medical and surgical complications following TJA. Patients with HBV or HCV are at risk of more complications than patients with HIV especially for infection within 90 days after TJA. Patients with HIV are at risk of mechanical complications but do not appear to be at significant risk for infection following total hip arthroplasty.

Prognosis of Intrahepatic Cholangiocarcinomas with HBV Infection is Better than Those with Hepatolithiasis After R0 Liver Resection: A Propensity Score Matching Analysis.

BACKGROUND: The impact of different causative factors of intrahepatic cholangiocarcinoma (ICC) on disease outcome remains largely unknown. This study aimed to evaluate the prognosis of ICC patients with different pathogenic factors after hepatectomy. METHODS: Data of 731 consecutive patients undergoing R0 liver resection for ICC at The Eastern Hepatobiliary Surgery Hospital between 2004 and 2010 were analyzed. These patients were divided into the hepatitis B virus-related (HBV-ICC, n = 519), hepatolithiasis-related (stone-ICC, n = 87), HBV plus hepatolithiasis-related (HBV/stone-ICC, n = 45), and other etiologies-related (other-ICC, n = 80) ICC groups. Propensity score matching (PSM) was used to eliminate the baseline differences between these groups. RESULTS: In these four groups, the 5-year tumor recurrence and overall survival (OS) rates were 75.4, 90.3, 83.0 and 81.9%, and 32.7, 16.3, 17.7 and 22.6%, respectively. The significant differences in recurrence and OS were identified between the HBV- and stone-ICC groups (both p < 0.001). In these two groups, most of the independent prognostic predictors were similar, but tumor diameter >5 cm was demonstrated as a risk factor in the HBV-ICC patients only, and surgical margin <1 cm and human epidermal growth factor receptor 2-positive were demonstrated as risk factors in the stone-ICC patients only. With PSM, 75 patients in each of the HBV- and stone-ICC cohorts were created, and the 5-year recurrence and OS rates were 69.9 versus 88.6, and 34.6 versus 19.2%, respectively (p = 0.017, 0.027). CONCLUSION: Patients with HBV-ICC achieved better outcomes than those with stone-ICC. This prognostic difference was probably associated with biological malignant invasiveness rather than tumor stage.

Liver Retransplantation in Patients With HIV-1 Infection: An International Multicenter Cohort Study.

Liver retransplantation is performed in HIV-infected patients, although its outcome is not well known. In an international cohort study (eight countries), 37 (6%; 32 coinfected with hepatitis C virus [HCV] and five with hepatitis B virus [HBV]) of 600 HIV-infected patients who had undergone liver transplant were retransplanted. The main indications for retransplantation were vascular complications (35%), primary graft nonfunction (22%), rejection (19%), and HCV recurrence (13%). Overall, 19 patients (51%) died after retransplantation. Survival at 1, 3, and 5 years was 56%, 51%, and 51%, respectively. Among patients with HCV coinfection, HCV RNA replication status at retransplantation was the only significant prognostic factor. Patients with undetectable versus detectable HCV RNA had a survival probability of 80% versus 39% at 1 year and 80% versus 30% at 3 and 5 years (p = 0.025). Recurrence of hepatitis C was the main cause of death in the latter. Patients with HBV coinfection had survival of 80% at 1, 3, and 5 years after retransplantation. HIV infection was adequately controlled with antiretroviral therapy. In conclusion, liver retransplantation is an acceptable option for HIV-infected patients with HBV or HCV coinfection but undetectable HCV RNA. Retransplantation in patients with HCV replication should be reassessed prospectively in the era of new direct antiviral agents.

Lower rates of receiving model for end-stage liver disease exception and longer time to transplant among nonalcoholic steatohepatitis hepatocellular carcinoma.

Receiving Model for End-Stage Liver Disease (MELD) exception status for hepatocellular carcinoma (HCC) improves wait-list survival and probability of liver transplantation (LT). We aim to evaluate etiology-specific disparities in MELD exception, LT wait-list times, and post-LT outcomes among patients with HCC listed for LT. Using United Network for Organ Sharing 2004-2013 data, we evaluated adults (age > 18 years) with HCC secondary to hepatitis C virus (HCV), nonalcoholic steatohepatitis (NASH), alcoholic cirrhosis (EtOH), hepatitis B virus (HBV), combined EtOH/HCV, and combined HBV/HCV. Multivariate regression models evaluated etiology-specific odds of active exception, probability of receiving LT, and post-LT survival. In total, 10,887 HCC patients were listed for LT from 2004 to 2013. Compared with HCV-HCC patients (86.8%), patients with NASH-HCC (67.7%), and EtOH-HCC (64.4%) had a lower proportion with active MELD exception (P < 0.001). On multivariate regression, NASH-HCC and EtOH-HCC patients had significantly lower odds of active MELD exception compared with HCV-HCC (NASH-HCC-odds ratio [OR], 0.73; 95% confidence interval [CI], 0.58-0.93; P = 0.01; EtOH-HCC-OR, 0.72; 95% CI, 0.59-0.89; P = 0.002). Compared with HCV-HCC patients, NASH-HCC (HR, 0.83; 95% CI 0.76-0.90; P < 0.001), EtOH-HCC (HR, 0.88; 95% CI 0.81-0.96; P = 0.002), and EtOH/HCV-HCC (HR, 0.92; 95% CI 0.85-0.99; P = 0.03) were less likely to receive LT if they had active exception. Without active exception, these discrepancies were more significant (NASH-HCC-HR, 0.22; 95% CI, 0.18-0.27; P < 0.001; EtOH-HCC-HR, 0.22; 95% CI, 0.18-0.26; P < 0.001; EtOH/HCV-HCC-HR, 0.26; 95% CI, 0.22-0.32; P < 0.001). In conclusion, among US adults with HCC listed for LT, patients with NASH-HCC, EtOH-HCC, and EtOH/HCV-HCC were significantly less likely to have active MELD exception compared with HCV-HCC, and those without active exception had a lower likelihood of receiving LT. More research is needed to explore why NASH-HCC patients were less likely to have active MELD exception. Liver Transplantation 22 1356-1366 2016 AASLD.

[Effect of umbilical cord mesenchymal stem cell transplantation on immune function and prognosis of patients with decompensated hepatitis B cirrhosis].

Objective: To investigate the effect of human umbilical cord mesenchymal stem cells (hUCMSCs) on the immune function and prognosis of patients with decompensated hepatitis B cirrhosis. Methods: A total of 65 patients with decompensated hepatitis B cirrhosis were divided into observation group and control group. The patients in the observation group were given intervention (via the proper hepatic artery or the portal vein) and intravenous infusion of 4×108 hUCMSCs in two doses, as well as the same basic treatment as in the control group. The patients in the control group were given conventional medical treatment. ELISA as used to measure the serum levels of interleukin-6 (IL-6), tumor necrosis factor-α (TNFα), interleukin-10 (IL-10), and transforming growth factor-ß (TGFß) in the observation group before surgery and at 1 week after surgery, as well as the serum levels of IL-6, TNFα, IL-10, and TGFß in the control group on admission and at 1 week after admission. Flow cytometry was used to measure the percentage of lymphocyte subsets in the observation group before surgery and at 1 week after surgery, as well as that in the control group on admission and at 1 week after admission. In addition, the patients' prognosis and major complications during hospitalization were observed in both groups, and the patients were followed up for 24 weeks to record the number of deaths. The t-test was used for comparison of continuous data, and the chi-square test was used for comparison of categorical data which were expressed as percentages. Results: At 1 week after the transplantation of hUCMSCs, compared with the control group, the observation group had significant reductions in the serum levels of IL-6 and TNFα and significant increases in the serum levels of IL-10 and TGFß (all P < 0.001), as well as significant increases in the percentages of T4 cells and Treg cells and significant reductions in the percentages of T8 cells and B cells (all P < 0.05). There were no significant differences in the changes in T3 cells and natural killer cells between the two groups (P > 0.05). Compared with the control group, the observation group had a significantly lower probability of progression to liver failure (6.45% vs 14.71%, P = 0.017). Conclusion: In the treatment of patients with decompensated hepatitis B cirrhosis, transplantation of UCMSCs can inhibit the proliferation of T cells and B cells and the differentiation of T8 cells, upregulate Treg cells, promote the secretion of immunosuppressive cytokines, and reduce the production of inflammatory cytokines. Therefore, it can alleviate liver inflammatory response and liver cell damage and reduce the probability of hepatic failure.

Postoperative Outcomes for Patients with Non-B Non-C Hepatocellular Carcinoma: A Subgroup Analysis of Patients with a History of Hepatitis B Infection.

BACKGROUND: Hepatocellular carcinoma (HCC) not associated with active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, termed non-B non-C HCC (nBnC-HCC), is reportedly correlated with better survival outcomes than HBV- or HCV-related HCC. However, the nBnC-HCC population includes patients with a history of HBV infection possessing anti-hepatitis B core antibodies (HBcAb), and the oncologic significance of this finding remains unclear. METHODS: A retrospective review of the data for 562 patients who underwent curative resection for primary HCC was performed. The clinical outcomes were compared among the following four groups: HBV group (HBsAg-positive), HCV group (HCVAb-positive), HBcAb-positive nBnC-HCC group, and pure nBnC-HCC group (negative for these viral markers). RESULTS: The HBcAb-positive nBnC-HCC group showed better overall survival (OS) and recurrence-free survival (RFS) rates than the HBV, HCV, and pure nBnC-HCC groups (5-year OS 89.4 vs 68.4, 62.0, and 66.2 %; P = 0.003; 5-year RFS 53.8 vs 31.4, 28.1, and 33.6 %; P = 0.01). A multivariate analysis confirmed that a history of HBV is associated with a lower risk of OS (hazard ratio [HR] 0.23; 95 % confidence interval [CI] 0.09-0.56; P = 0.001) and RFS (HR 0.45; 95 % CI 0.27-0.73; P = 0.001). The HBcAb-positive nBnC-HCC group was associated with a higher incidence of well-differentiated HCC (33 vs 15 %; P = 0.03) and lower plasma des-gamma-carboxyprothrombin concentration (72 vs 357 mAu/mL; P = 0.047) than the pure nBnC group. CONCLUSION: The subgroup of patients with a history of HBV infection may have better survival outcomes after resection of HCC than the HBV/HCV-related or pure nBnC-HCC patients.

Efficacy and safety of basiliximab in liver transplantation for patients with hepatitis B virus-related diseases: a single centre study.

AIMS: We aim to evaluate the efficacy and safety of basiliximab in liver transplantation (LT) for patients with hepatitis B virus-related diseases. METHODS: A total of 268 patients with hepatitis B virus-related diseases undergoing LT were enrolled and divided into two groups according to the usage of basiliximab. Total survival, the survival of high-risk patients defined by the posttransplant model for predicting mortality, acute rejection rate, biochemical parameters and other follow-up data were compared between the two groups. RESULTS: Group Bas was composed of 131 patients who received basiliximab, and Group Triple enrolled the other 137 patients who did not. Between the two groups, there was no significant difference in the cumulative survival of patients without hepatocellular carcinoma (HCC) or in the cumulative survival of patients with HCC. For patients with benign end-stage liver diseases, Group Bas had more patients with a high risk of short- and medium-term mortality than Group Triple (22.81% vs. 8.85%, p = 0.017), but the survival curves of the two groups were not significantly different. The 1-year incidence of acute rejection was lower in Group Bas, although the difference was not significant (8.75% vs. 15.33%, p > 0.05). In both Group Bas and Group Triple, the level of serum creatinine (Scr) at 1 week posttransplantation was significantly lower than pretransplantation (61.00 vs. 88.50 µmol/l, p < 0.001; 61.50 vs. 74.00 µmol/l, p < 0.001; respectively). There was a significant difference in the pretransplantation Scr between the two groups (88.50 vs. 74.00 µmol/l, p = 0.005), but the values of Scr decreased to the same level 1 week (61.00 vs. 61.50 µmol/l, p > 0.05) and 4 weeks (61.00 vs. 59.00 µmol/l, p > 0.05) after transplantation. Significantly fewer recipients in Group Bas experienced hepatitis B relapse than in Group Triple (2/131 vs. 13/137, p = 0.006). CONCLUSIONS: A basiliximab-induced immunosuppressive protocol is a safe regimen that achieves similar survival without increasing the acute rejection rate for LT recipients with hepatitis B virus-related diseases. For patients with benign end-stage liver diseases, this regimen reduces medium-term mortality in high-risk patients. This regimen remarkably improves renal function in the first month after LT and is correlated with a decreased hepatitis B recurrence rate in adult patients after LT.