Verifying the Benefits of Radical Treatment in Posttransplant Hepatocellular Carcinoma Oligo-recurrence: A Propensity Score Analysis.

This study verified whether radical treatment for hepatocellular carcinoma (HCC) oligo-recurrence after liver transplantation conveys survival benefits. A retrospective study of 144 patients with posttransplant HCC recurrence was performed. Propensity score matching was performed to adjust for baseline covariates between patients who received radical and palliative treatments. The primary endpoint was postrecurrence survival. A total of 50 patients (35%) received radical treatment for recurrence, and 76 (53%) and 18 (13%) patients received palliative and supportive treatments, respectively. Compared with the radical group, patients who received palliative treatment had more early recurrences (time from transplant 17 versus 11 months; P = 0.01) and more extensive disease in terms of tumor numbers (1 versus 4; P < 0.001), size of largest tumor (1.8 versus 2.5 cm; P = 0.046), numbers of involved organs (interquartile range [IQR], 1-1 versus 1-2; P = 0.02), and alpha-fetoprotein (AFP) level (7 versus 40 ng/mL; P = 0.01). Multivariate Cox regression analysis revealed that early recurrence (time from transplant hazard ratio [HR], 1.02; 95% confidence interval [CI], 1.01-1.03; P = 0.001), larger recurrent tumor (HR, 1.12; 95% CI, 1.03-1.23; P = 0.01), liver recurrence (HR, 1.84; 95% CI, 1.17-2.90; P = 0.01), and log10 AFP level at recurrence (HR, 1.27; 95% CI, 1.07-1.52; P = 0.01) predicted poor survival. Mammalian target of rapamycin inhibitor (HR, 0.331; 95% CI, 0.213-0.548; P < 0.001) and radical treatment (HR, 0.342; 95% CI, 0.213-0.548; P < 0.001) were associated with improved survival. After 2-to-1 propensity score matching for covariates, the 50 patients who received curative treatment survived significantly longer than the 25 matched patients who received palliative treatment (median survival time, 30.9 ± 2.4 versus 19.5 ± 3.0 months; P = 0.01). Radical treatment conveys survival benefits to HCC oligo-recurrence after liver transplantation.

Hepatitis B Virus-Telomerase Reverse Transcriptase Promoter Integration Harnesses Host ELF4, Resulting in Telomerase Reverse Transcriptase Gene Transcription in Hepatocellular Carcinoma.

BACKGROUND AND AIMS: Hepatitis B virus (HBV) integrations are common in hepatocellular carcinoma (HCC). In particular, alterations of the telomerase reverse transcriptase (TERT) gene by HBV integrations are frequent; however, the molecular mechanism and functional consequence underlying TERT HBV integration are unclear. APPROACH AND RESULTS: We adopted a targeted sequencing strategy to survey HBV integrations in human HBV-associated HCCs (n = 95). HBV integration at the TERT promoter was frequent (35.8%, n = 34/95) in HCC tumors and was associated with increased TERT mRNA expression and more aggressive tumor behavior. To investigate the functional importance of various integrated HBV components, we employed different luciferase reporter constructs and found that HBV enhancer I (EnhI) was the key viral component leading to TERT activation on integration at the TERT promoter. In addition, the orientation of the HBV integration at the TERT promoter further modulated the degree of TERT transcription activation in HCC cell lines and patients' HCCs. Furthermore, we performed array-based small interfering RNA library functional screening to interrogate the potential major transcription factors that physically interacted with HBV and investigated the cis-activation of host TERT gene transcription on viral integration. We identified a molecular mechanism of TERT activation through the E74 like ETS transcription factor 4 (ELF4), which normally could drive HBV gene transcription. ELF4 bound to the chimeric HBV EnhI at the TERT promoter, resulting in telomerase activation. Stable knockdown of ELF4 significantly reduced the TERT expression and sphere-forming ability in HCC cells. CONCLUSIONS: Our results reveal a cis-activating mechanism harnessing host ELF4 and HBV integrated at the TERT promoter and uncover how TERT HBV-integrated HCCs may achieve TERT activation in hepatocarcinogenesis.

The role of graft to recipient weight ratio on enhanced recovery of the recipient after living donor liver transplantation - A systematic review of the literature and expert panel recommendations.

BACKGROUND: There continues to be debate about the lower limit of graft-to-recipient weight ratio (GRWR) for living donor liver transplant (LDLT). OBJECTIVES: To identify the lower limit of GRWR compatible with enhanced recovery after living donor liver transplant and to provide international expert panel recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, and Cochrane Central. METHODS: Systematic review following PRISMA guidelines and recommendations using the GRADE approach derived from an international expert panel. Studies assessing how GRWR affects recipient outcomes such as small for size syndrome, other complications, patient and graft survival, and length of stay were included. PROTOCOL REGISTRATION: CRD42021260794. RESULTS: Twenty articles were included in the qualitative synthesis, and all were retrospective observational studies. There was heterogeneity in the definition of study cohorts and key outcome measures such as small-for-size syndrome. Most studies lacked risk adjustment given limited single-center sample size. GRWR of ≥ .8% is associated with enhanced recovery. Recipients of grafts with GRWR < .8%, however, were found to have similar outcomes as those with ≥ .8% when appropriate consideration is made for portal flow modulation and recipient illness severity. CONCLUSIONS: GRWR ≥ .8% is often compatible with enhanced recovery, but grafts < .8% can be used in selected LDLT recipients with optimal donor-recipient selection, surgical technique, and perioperative management (Quality of Evidence; Low | Grade of Recommendation; Strong).

RSK2-inactivating mutations potentiate MAPK signaling and support cholesterol metabolism in hepatocellular carcinoma.

BACKGROUND & AIMS: Mutational profiling of patient tumors has suggested that hepatocellular carcinoma (HCC) development is mainly driven by loss-of-function mutations in tumor suppressor genes. p90 ribosomal S6 kinase 2 (RSK2) functions as a direct downstream kinase of ERK1/2 and elevated RSK2 expression has been reported to support oncogenic functions in some cancers. We investigated if RSK2 was also dysregulated by inactivating mutations in cancers including HCC. METHODS: We performed exome sequencing and targeted DNA sequencing on HBV-associated HCCs to examine recurrent RSK2 mutations. The functional significance and mechanistic consequences of RSK2 mutations were examined in natural RSK2-null HCC cells, and RSK2-knockout HCC cells. The potential downstream pathways underlying RSK2 mutations were investigated by RNA sequencing, qRT-PCR and mass spectrometry. RESULTS: We detected recurrent somatic RSK2 mutations at a rate of 6.3% in our HCC cohorts and revealed that, among many cancer types, HCC was the cancer most commonly harboring RSK2 mutations. The RSK2 mutations were inactivating and associated with a more aggressive tumor phenotype. We found that, functionally, restoring RSK2 expression in natural RSK2-null HBV-positive Hep3B cells suppressed proliferation and migration in vitro and tumorigenicity in vivo. Mechanistically, RSK2-inactivating mutations attenuated a SOS1/2-dependent negative feedback loop, leading to the activation of MAPK signaling. Of note, this RSK2 mutation-mediated MAPK upregulation rendered HCC cells more sensitive to sorafenib, a first-line multi-kinase inhibitor for advanced HCC. Furthermore, such activation of MAPK signaling enhanced cholesterol biosynthesis-related gene expression in HCC cells. CONCLUSIONS: Our findings reveal the mechanistic and functional significance of RSK2-inactivating mutations in HCC. These inactivating mutations may serve as an alternative route to activate MAPK signaling and cholesterol metabolism in HCC. LAY SUMMARY: In this study, we identified and functionally characterized RSK2-inactivating mutations in human hepatocellular carcinoma and demonstrated their association with aggressive tumor behavior. Mutations in RSK2 drive signaling pathways with known oncogenic potential, leading to enhanced cholesterol biosynthesis and potentially sensitizing tumors to sorafenib treatment.

Model for End-Stage Liver Disease With Additional Criteria to Predict Short-Term Mortality in Severe Flares of Chronic Hepatitis B.

BACKGROUND AND AIMS: The prognosis in severe acute flares of chronic hepatitis B (AFOCHB) is often unclear. The current study aimed to establish the predictive value using the Model for End-Stage Liver Disease (MELD) score for short-term mortality for severe AFOCHB. APPROACH AND RESULTS: Patients with severe AFOCHB with bilirubin > 50 µmol/L, alanine aminotransferase > 10× upper limit of normal, and international normalized ratio > 1.5 were included. All patients were commenced on entecavir and/or tenofovir. Laboratory results and MELD scores were pooled to calculate mortality at four time points (days 7, 14, 21, and 28). A total of 240 patients were included. Median hepatitis B virus DNA was 7.77 log IU/mL (range, 4.11-10.06), and 49 (20.4%) were hepatitis B e antigen-positive. The 7, 14, 21, and 28-day survival was 96.7%, 88.5%, 79.5%, and 72.8%, respectively. Using pooled results derived from 4,201 blood samples, the area under the receiver operating curve for the MELD score to predict day 7, 14, 21, and 28 mortality was 0.909, 0.892, 0.883, and 0.871, respectively. For MELD ≤ 28, mortality at day 28 was low (<25%) compared with > 50% mortality for MELD ≥ 32. For MELD = 28-32, higher day-28 mortality was observed for four criteria: age ≥52 years, alanine aminotransferase > 217 U/L, platelets < 127, and abnormal baseline imaging (all P < 0.001). In this MELD bracket, the 28-day mortality was 0%, 12.1%, 23.8%, 59.4%, and 78.8% for the presence of zero, one, two, three, and four criteria, respectively. CONCLUSIONS: MELD score at any time points can accurately predict the short-term mortality. Patients with MELD ≥ 28 should be worked up for liver transplantation, and those with MELD = 28-32 with three to four at-risk criteria, or MELD ≥ 32 should be listed.

Liver transplantation using hepatitis B core positive grafts with antiviral monotherapy prophylaxis.

BACKGROUND & AIMS: The impact of hepatitis B core antibody (anti-HBc) positive liver grafts on survival and the risk of de novo hepatitis B virus (HBV) infection after liver transplantation (LT) remain controversial. Therefore, we aimed to analyze this risk and the associated outcomes in a large cohort of patients. METHODS: This was a retrospective study that included all adults who underwent LT at Queen Mary Hospital, Hong Kong, between 2000 and 2015. Data were retrieved from a prospectively collected database. Antiviral monotherapy prophylaxis was given for patients receiving grafts from anti-HBc positive donors. RESULTS: A total of 964 LTs were performed during the study period, with 416 (43.2%) anti-HBc positive and 548 (56.8%) anti-HBc negative donors. The median follow-up time was 7.8 years. Perioperative outcomes (hospital mortality, complications, primary nonfunction and delayed graft function) were similar between the 2 groups. The 1-, 5- and 10-year graft survival rates were comparable in anti-HBc positive (93.3%, 85.3% and 76.8%) and anti-HBc negative groups (92.5%, 82.9% and 78.4%, p = 0.944). The 1-, 5- and 10-year patient survival rates in anti-HBc positive group were 94.2%, 87% and 79% and were similar to the anti-HBc negative group (93.5%, 84% and 79.7%, p = 0.712). One-hundred and eight HBsAg negative recipients received anti-HBc positive grafts, of whom 64 received lamivudine and 44 entecavir monotherapy prophylaxis. The risk of de novo HBV was 3/108 (2.8%) and all occurred in the lamivudine era. There were 659 HBsAg-positive patients and 308 (46.7%) received anti-HBc positive grafts. The risk of HBV recurrence was similar between the 2 groups. Donor anti-HBc status did not impact on long-term patient and graft survival, or the risk of hepatocellular carcinoma recurrence after LT. CONCLUSIONS: De novo HBV was exceedingly rare especially with entecavir prophylaxis. Anti-HBc positive grafts did not impact on perioperative and long-term outcomes after transplant. LAY SUMMARY: The risk of de novo hepatitis B infection after liver transplantation was rare when using hepatitis B core positive liver grafts with entecavir monotherapy prophylaxis. Hepatitis B core antibody status did not impact on perioperative and long-term outcomes after liver transplantation. This provides support for the clinical use of hepatitis B core positive liver grafts when required.

Validated nomogram for the prediction of disease-free survival after hepatectomy for hepatocellular carcinoma within the Milan criteria: individualizing a surveillance strategy.

OBJECTIVE: We sought to develop a nomogram for the prediction of tumor recurrence after resection of hepatocellular carcinoma (HCC) within the Milan criteria. METHOD: Consecutive HCC patients admitted for hepatectomy between 1994 and 2014 were enrolled in this study. Patients were excluded if they had recurrent HCC or tumors beyond the Milan criteria. Patients were randomized and assigned to the derivation and validation sets in a 1:1 ratio. Independent factors for disease-free survival were identified using the Cox regression model. A nomogram was derived and validated with the receiver-operating characteristic (ROC) and calibration curves. RESULTS: There were 617 eligible patients included in the analysis. The median age was 59 years, 481 were male, and 87.8% of the patients were hepatitis B virus carriers. The median follow-up was 68.7 months. The 5-year overall survival rate was 73.3% and HCC recurrence was detected in 55% of the patients. In the derivation set, a nomogram was constructed based on the seven independent factors for disease-free survival: age, alpha-fetoprotein, preoperative prothrombin time, magnitude of hepatectomy, postoperative complication, number of tumor nodules, and presence of microvascular invasion. A satisfactory discrimination ability was observed in both the derivation and validation sets (c-stat 0.672 and 0.665, respectively). The calibration plot yielded agreement between the predicted and observed outcomes, using the derived nomogram. CONCLUSION: A validated nomogram quantifies the risk of recurrence after hepatectomy for HCC within the Milan criteria, and assists with the planning of individual postoperative surveillance protocols.

Defining Optimal Surgical Treatment for Recurrent Hepatocellular Carcinoma: A Propensity Score Matched Analysis.

Salvage liver transplantation (sLT) and repeated resection (RR) are effective treatments for recurrent hepatocellular carcinoma (HCC), and comparisons of the oncological outcomes between these 2 modalities were scarce. Consecutive patients admitted for either sLT or RR for recurrent HCC were recruited. All patients in the present series received either prior hepatectomy, ablative therapy, or both before RR or sLT. Patient demographic, perioperative, and outcome data were analyzed. A survival analysis was performed after propensity score matching. There were 277 eligible patients recruited, and 67 and 210 of them underwent sLT and RR, respectively. Significant differences in preoperative hemoglobin, albumin, Model of End-Stage Liver Disease (MELD) score, and tumor number were found between the sLT and RR groups. After 1:3 propensity score matching, there were 36 sLT and 108 RR patients for comparison. The median age, MELD, alpha fetoprotein, and tumor size and number of the matched population were 57 years, 7.5, 16 ng/mL, 2.5 cm, and 1, respectively. There was no difference in the hospital mortality and complication rate (Clavien IIIa or above) between the groups. The recurrence rate after RR was significantly higher than for the patients who received sLT (72.2% versus 27.8%; P < 0.001). Following RR, 3 patients received liver transplantation for further recurrence, and 54.6% of the patients developed nontransplantable recurrence. The 5-year disease-free survival (DFS) and overall survival (OS) were both superior in the sLT group (DFS, 71.6% versus 32.8%, P < 0.001; OS, 72.8% versus 48.3%, P = 0.007). In conclusion, sLT is superior to RR for treatment of recurrent HCC in terms of DFS and OS. The high rate of nontransplantable recurrence after reresection underscores the importance of timely sLT.

Efficacy of endoscopic self-expandable metal stent placement versus surgical bypass for inoperable pancreatic cancer-related malignant biliary obstruction: a propensity score-matched analysis.

BACKGROUND AND AIMS: We explored the difference in treatment efficacy of endoscopic self-expendable metal stent (SEMS) and surgical bypass (SB) in the management of malignant biliary obstruction (MBO) secondary to pancreatic cancer. METHOD: A retrospective analysis was conducted using consecutive patients who were admitted from 2008 to 2016 receiving either endoscopic SEMS or SB. Diagnosis other than pancreatic cancer and SEMS placement as a pre-operative drainage before Whipple's operation was excluded. Propensity score (PS) matching was performed to eliminate the confounding effect of heterogeneity between patients from two treatment groups. The rate of early, late treatment-related events, readmission and re-intervention, the duration of hospitalization, and the cost of treatment were compared. RESULTS: There were 98 patients undergoing endoscopic SEMS or SB in the study period. The median age was 68.5 years and 52% of the patients had metastatic disease with median survival of 6 months. After 1:1 PS matching, 30 patients from each group were analyzed. The hospital stay was significantly longer in the SB group (13 vs. 5 days, P < 0.001) with a trend of higher rate of early treatment-related events (24.1 vs. 6.7%, P = 0.113). None of the patients in SB group developed recurrent biliary obstruction. Higher readmission rate (36.7 vs. 3.3%, P = 0.004) and re-intervention rate (36.7 vs. 10%, P = 0.033) were found in the SEMS group. The 3-, 6-, and 9-month re-intervention rates for endoscopic SEMS and SB group were 24.9, 29.4, 45.7, and 11.2, 11.2, and 11.2%, respectively (P = 0.03). When all subsequent readmissions were taken into account, there was no significant difference in hospital stay in both groups (7.5 vs. 14 days, P = 0.359); however, the total cost of treatment in SB group was significantly higher than that in the SEMS group (13,307 vs. 7113 USD, P = 0.035). CONCLUSION: Despite being more invasive and expensive, surgical bypass provides durable relief of biliary obstruction. Endoscopic SEMS is associated with minimal procedural risks and low re-intervention rate, which are important considerations for frail patients with limited life expectancy.

Impact of Hepatitis B Carrier Status on the Outcomes of Surgical Treatment of Colorectal Liver Metastases.

BACKGROUND: Chronic hepatitis B virus (HBV) infection is associated with a lower incidence of colorectal liver metastases. We explored the impact of HBV carrier status on outcomes of surgical treatment of colorectal liver metastases. METHODS: A retrospective analysis was conducted for consecutive patients undergoing liver resection for colorectal liver metastases from 2000 to 2016. HBV carriers were matched with controls by propensity scoring. RESULTS: 304 patients with known HBV carrier status who underwent resection of colorectal liver metastases were studied. From the 21 (6.9%) hepatitis B carriers, a more prolonged prothrombin time (12.1 vs. 11.3 s, OR 1.42, p = 0.027) was observed, and fewer major resections were performed (19.0 vs. 47.3%, OR 0.262, p = 0.018). After 1:5 propensity score matching, they were compared with 105 controls with similar liver function, tumour status and receiving similar treatments. Patients with chronic hepatitis B enjoyed better median disease-free survival (15.8 vs. 9.20 month, p = 0.032). Overall survivals (50.0 vs. 43.6 month, p = 0.15) were similar. Operating time (227 vs. 240 min, OR 1.00, p = 0.33), blood loss (0.50 vs. 0.37 L, OR 1.15, p = 0.62), hospital stay (6 vs. 6 day, OR 1.02, p = 0.48), operative morbidity (9.5 vs. 16.2%, OR 0.545, p = 0.44) and mortality (0 vs. 1.0%, OR 1.62, p = 0.77) were comparable. The use of antiviral agents did not affect survival of HBV carriers. CONCLUSIONS: Chronic HBV infection confers oncological benefit to surgical treatment of colorectal liver metastases. Given satisfactory liver reserve, HBV carrier status did not affect operative morbidity or mortality.

Diagnostic and Prognostic Role of 18-FDG PET/CT in the Management of Resectable Biliary Tract Cancer.

OBJECTIVES: Role of 18-FDG PET/CT had been well established in other more prevalent malignancies such as colorectal and lung cancer; however, this is not as well defined in cholangiocarcinoma. Literature focusing on the prognostic values of preoperative PET/CT for resectable cholangiocarcinoma is scarce. METHOD: This is a retrospective cohort of 66 consecutive patients who had received curative resection for cholangiocarcinoma from 2010 to 2015. All patients had preoperative 18-FDG PET/CT performed. Accuracy of metastatic lymph node detection of PET/CT and the prognostic value of maximum standard uptake value (SUV-max) was explored. RESULTS: There were 38 male and 28 female recruited, and the median age was 66. Intrahepatic cholangiocarcinoma (ICC) constituted the majority (59.1%) of the cases, followed by hilar cholangiocarcinoma (22.8%), gallbladder cancer (13.6%) and common bile duct cancer (4.5%). The 3-year disease-free survival (DFS) and overall survival (OS) of the whole population were 27.1 and 39.2%, respectively. The median follow-up duration was 27 months. The accuracy of PET/CT in metastatic lymph node detection was 72.7% (P = 0.005, 95% CI 0.583-0.871) and 81.8% (P = 0.011, 95% CI 0.635-0.990) in whole population and ICC subgroup analysis, respectively. SUV-max was shown by multivariate analysis to be an independent factor for DFS (P = 0.007 OR 1.16, 95% CI 1.04-1.29) and OS (P = 0.012 OR 1.145, 95% CI 1.030-1.273) after resection. SUV-max of 8 was shown to be a discriminant cut-off for poor oncological outcomes in patients with early cholangiocarcinoma (TNM stage I or II) after curative resection (3-year DFS: 21.2 vs. 63.2%, P = 0.004, and 3-year OS: 29 vs. 74% P = 0.048, respectively). CONCLUSION: PET/CT is a reliable imaging modality for metastatic lymph node detection in cholangiocarcinoma. Tumour SUV-max is an independent factor for oncological outcomes in patients with resectable disease. For patients who have TNM stage I or II cholangiocarcinoma, tumour SUV-max over 8 is associated with significantly inferior disease-free and overall survival even after curative resection.

SENP1 promotes hypoxia-induced cancer stemness by HIF-1α deSUMOylation and SENP1/HIF-1α positive feedback loop.

OBJECTIVE: We investigated the effect and mechanism of hypoxic microenvironment and hypoxia-inducible factors (HIFs) on hepatocellular carcinoma (HCC) cancer stemness. DESIGN: HCC cancer stemness was analysed by self-renewal ability, chemoresistance, expression of stemness-related genes and cancer stem cell (CSC) marker-positive cell population. Specific small ubiquitin-like modifier (SUMO) proteases 1 (SENP1) mRNA level was examined with quantitative PCR in human paired HCCs. Immunoprecipitation was used to examine the binding of proteins and chromatin immunoprecipitation assay to detect the binding of HIFs with hypoxia response element sequence. In vivo characterisation was performed in immunocompromised mice and stem cell frequency was analysed. RESULTS: We showed that hypoxia enhanced the stemness of HCC cells and hepatocarcinogenesis through enhancing HIF-1α deSUMOylation by SENP1 and increasing stabilisation and transcriptional activity of HIF-1α. Furthermore, we demonstrated that SENP1 is a direct target of HIF-1/2α and a previously unrecognised positive feedback loop exists between SENP1 and HIF-1α. CONCLUSIONS: Taken together, our findings suggest the significance of this positive feedback loop between HIF-1α and SENP1 in contributing to the increased cancer stemness in HCC and hepatocarcinogenesis under hypoxia. Drugs that specifically target SENP1 may offer a potential novel therapeutic approach for HCC.

Acute hepatitis E virus infection causing acute liver failure requiring living-donor liver transplantation in a non-pregnant immunocompetent woman.

We report a rare case of acute liver failure from acute hepatitis E virus (HEV) in a non-pregnant woman without comorbidities who survived after liver transplantation. The source was likely consumption of partially cooked pig liver. HEV genotype 3 is the second most common genotype causing acute hepatitis E in developed countries. Fulminant hepatitis E rarely occurs without a risk factor, as in our patient. Vigilant monitoring for chronic hepatitis E in post-transplant immunocompromised patients is needed.

The friendly incidental portal vein thrombus in liver transplantation.

Improved outcomes have been shown in liver transplantation (LT) with portal vein thrombosis (PVT). However, PVT is still discovered incidentally during surgery despite careful preoperative imaging. Data are limited comparing the outcomes of incidental PVT with PVT diagnosed via preoperative imaging before LT. This study aims to compare the overall outcomes of patients with PVT. From 2008 to 2012, 369 patients had LT, and 58 patients with PVT were identified. They were divided into those with non-PVT (group 0; n = 311), preoperatively identified PVT (group 1; n = 28), and incidental PVT (group 2; n = 30). The demographics, characteristics, preoperative assessment, and postoperative outcomes were compared. A survival analysis was also performed. Baseline characteristics and preoperative evaluations of all 3 groups were comparable (P > 0.05) except for Model for End-Stage Liver Disease score, tumor status, platelet levels, and serum bilirubin. A multivariate analysis only showed a high serum bilirubin level to be a predictor of PVT (P = 0.004; odds ratio, 3.395; 95% confidence interval, 1.467-7.861). Postoperative outcomes were also comparable (P > 0.05). Compared to group 2, group 1 had more patients with a Yerdel classification of 3 or 4 with more extensive surgical intervention required (P = 0.02). The survival analysis in all 3 groups was comparable with 5-year survival rate of 87.4%, 84.6%, and 91.8% in group 0, 1, and 2, respectively (P = 0.66). In conclusion, recipients with PVT undergoing LT can have similar outcomes as the non-PVT patients even if PVTs were discovered incidentally. Discovery of incidental PVT only requires thrombectomy with no substantial change of treatment strategy, and the outcome is not adversely affected because most incidental PVTs are of a lower Yerdel grade. Preoperative imaging is useful to identify those with a higher Yerdel grade to allow planning of surgical strategy during transplantation.

Durability of small-for-size living donor allografts.

Our aim was to study the long-term outcomes of living donor liver transplantation using small-for-size (SFS) grafts. From July 2002 to July 2009, 233 patients received a right liver graft with a middle hepatic vein from a living donor in our center. Recipients were stratified according to the graft weight to recipient standard liver volume (GW/SLV) ratio into 4 groups: >50% (n = 89), >40% to 50% (n = 85), >35% to 40% (n = 38), and ≤ 35% (n = 21). They were compared in terms of graft survivals, biliary stricture rates, renal function in terms of estimated glomerular filtration rate (eGFR), platelet counts, and graft function in terms of serum bilirubin and international normalized ratio (INR). The 5-year graft survivals for patients with GW/SLV of >50%, >40% to 50%, >35% to 40% and ≤ 35% were 88.8%, 88.2%, 81.5%, and 81.0%, respectively. Transplantation for hepatocellular carcinoma affected graft survivals (P = 0.02), but graft size did not (P = 0.66). There were no differences in frequency of biliary stricture (21.3% versus 17.1% versus 21.1% versus 28.6%; P = 0.75). At each year after transplant, their platelet counts (P = 0.12-0.65), eGFR (P = 0.49-0.91), bilirubin (P = 0.14-0.51), and INR (P = 0.20-0.98) remained comparable. SFS grafts with GW/SLV ≤ 35% and >35% to 40% had comparable long-term outcomes with larger liver grafts. Graft size did not affect long-term graft survivals.

Clinical factors affecting rejection rates in liver transplantation.

BACKGROUND: With improvements in survival, liver transplant recipients now suffer more morbidity from long-term immunosuppression. Considerations were given to develop individualized immunosuppression based on their risk of rejection. METHOD: We retrospectively analyzed the data of 788 liver transplants performed during the period from October 1991 to December 2011 to study the relationship between acute cellular rejection (ACR) and various clinical factors. RESULTS: Multivariate analysis showed that older age (P=0.04, OR=0.982), chronic hepatitis B virus infection (P=0.005, OR= 0.574), living donor liver transplantation (P=0.02, OR=0.648) and use of interleukin-2 receptor antagonist on induction (P<0.001, OR=0.401) were associated with fewer ACRs. Patients with fulminant liver failure (P=0.004, OR=4.05) were more likely to develop moderate to severe grade ACR. CONCLUSIONS: Liver transplant recipients with older age, chronic hepatitis B virus infection, living donor liver transplantation and use of interleukin-2 receptor antagonist on induction have fewer ACR. Patients transplanted for fulminant liver failure are at higher risk of moderate to severe grade ACR. These results provide theoretical framework for developing individualized immunosuppression.

Surgical cystogastrostomy: Is it still worthwhile?

The article by Ker et al explores the treatment of peripancreatic fluid collection (PFC). The use of percutaneous drainage, endoscopy, and surgery for managing PFC are discussed. Percutaneous drainage is noted for its low risk profile, while endoscopic cystogastrostomy is more effective due to the wider orifice of the metallic stent. Surgical cystogastrostomy is a definitive treatment with a reduced need for reintervention, especially for cases with extensive collections and significant necrosis. The choice of treatment modality should be tailored to individual patient characteristics and disease factors, considering the expertise available.

Oral nucleoside/nucleotide analogs without hepatitis B immune globulin after liver transplantation for hepatitis B.

OBJECTIVES: The long-term outcomes of oral antiviral therapy without hepatitis B immune globulin (HBIG) in prevention of reinfection with hepatitis B after liver transplantation are not known. We aimed to determine the long-term outcomes from a large population of chronic hepatitis B (CHB) liver transplant recipients using oral antiviral therapy alone. METHODS: A total of 362 consecutive CHB patients transplanted from January 2003 to May 2011 were included. None of the patients received HBIG. Viral serology, viral load, and liver biochemistry were performed at regular intervals during follow-up. RESULTS: Of the 362 patients, 176 (49%), 142 (39%), and 44 (12%) were on lamivudine (LAM), entecavir (ETV), and combination therapy (predominantly LAM+adefovir), respectively, at the time of transplant. The median follow-up length was 53 months. The rate of hepatitis B surface antigen seronegativity and hepatitis B virus (HBV) DNA suppression to undetectable levels at 8 years was 88 and 98%, respectively. The virological relapse rates (>1 log increase IU/ml) at 1, 3, 5, and 8 years was 5, 10, 13 and 16%, respectively. The virological relapse rate at 3 years for LAM, ETV, and combination group was 17, 0, and 7%, respectively (P<0.001). Forty-two patients had virological relapse, of which 36 had YMDD mutation (31 in the LAM group and 5 in the combination group). The overall 8-year survival was 83%, with no difference between the three treatment groups (P=0.94). No mortality from HBV recurrence occurred in the 362 patients. CONCLUSIONS: Oral nucleoside/nucleotide analogs without HBIG are effective in preventing graft loss secondary to hepatitis B recurrence after liver transplantation. However, new agents with a high barrier to resistance should be used to minimize drug resistance and to prevent virological rebound.

The Hong Kong consensus recommendations on the diagnosis and management of pancreatic cystic lesions.

Background: The finding of pancreatic cystic lesions (PCL) on incidental imaging is becoming increasingly common. International studies report a prevalence of 2.2-44.7% depending on the population, imaging modality and indication for imaging, and the prevalence increases with age. Patients with PCL are at risk of developing pancreatic cancer, a disease with a poor prognosis. This publication summarizes recommendations for the diagnosis and management of PCL and post-operative pancreatic exocrine insufficiency (PEI) from a group of local specialists. Methods: Clinical evidence was consolidated from narrative reviews and consensus statements formulated during two online meetings in March 2022. The expert panel included gastroenterologists, hepatobiliary surgeons, oncologists, radiologists, and endocrinologists. Results: Patients with PCL require careful investigation and follow-up due to the risk of malignant transformation of these lesions. They should undergo clinical investigation and pancreas-specific imaging to classify lesions and understand the risk profile of the patient. Where indicated, patients should undergo pancreatectomy to excise PCL. Following pancreatectomy, patients are at risk of PEI, leading to gastrointestinal dysfunction and malnutrition. Therefore, such patients should be monitored for symptoms of PEI, and promptly treated with pancreatic enzyme replacement therapy (PERT). Patients with poor response to PERT may require increases in dose, addition of a proton pump inhibitor, and/or further investigation, including tests for pancreatic function. Patients are also at risk of new-onset diabetes mellitus after pancreatectomy; they should be screened and treated with insulin if indicated. Conclusions: These statements are an accurate summary of our approach to the diagnosis and management of patients with PCL and will be of assistance to clinicians treating these patients in a similar clinical landscape.