ALPPS Versus Portal Vein Embolization for Hepatitis-related Hepatocellular Carcinoma: A Changing Paradigm in Modulation of Future Liver Remnant Before Major Hepatectomy.

OBJECTIVE: The aim of this study was to evaluate the short- and long-term outcome of associating liver partition and portal vein ligation for staged hepatectomy (ALPPS) for hepatitis-related hepatocellular carcinoma (HCC). SUMMARY BACKGROUND DATA: ALPPS has been advocated for future liver remnant (FLR) augmentation in liver metastasis or noncirrhotic liver tumors in recent years. Data on the effect of ALPPS in chronic hepatitis or cirrhosis-related HCC remained scarce. METHODS: Data for clinicopathological details, portal hemodynamics, and oncological outcome were reviewed for ALPPS and compared with portal vein embolization (PVE). Tumor immunohistochemistry for PD-1, VEGF, and AFP was evaluated in ALPPS and compared with PVE and upfront hepatectomy (UH). RESULTS: From 2002 to 2018, 148 patients with HCC (hepatitis B: n = 136, 92.0%) underwent FLR modulation (ALPPS, n = 46; PVE: n = 102). One patient with ALPPS and 33 patients with PVE failed to proceed to resection (resection rate: 97.8% vs 67.7%, P < 0.001). Among those who had resections, 65 patients (56.5%) had cirrhosis. ALPPS induced absolute FLR volume increment by 48.8%, or FLR estimated total liver volume ratio by 12.8% over 6 days. No difference in morbidity (20.7% vs 30.4%, P = 0.159) and mortality (6.5% vs 5.8%, P = 1.000) with PVE was observed. Chronic hepatitis and intraoperative indocyanine green clearance rate ≤39.5% favored adequate FLR hypertrophy in ALPPS. Five-year overall survival for ALPPS and PVE was 46.8% and 64.1% (P = 0.234). Tumor immunohistochemical staining showed no difference in expression of PD-1, V-EGF, and AFP between ALPPS, PVE, and UH. CONCLUSIONS: ALPPS conferred a higher resection rate in hepatitis-related HCC with comparable short- and long-term oncological outcome with PVE.

Liver transplantation and hepatitis B virus infection: towards an immunoglobulin-free antiviral treatment after transplantation.

PURPOSE OF REVIEW: This article provides an update on the latest development on deploying oral nucleosides in an immunoglobulin-free regime against hepatitis B virus (HBV) recurrence after liver transplantation. RECENT FINDINGS: Entecavir and tenofovir are the two newer oral nucleosides that are associated with a low virological rebound rate at less than 2% at 5 years. As a result, they have been applied as standalone treatment against HBV recurrence after liver transplantation without immunoglobulin. Recent evidence has shown that a hepatitis B surface antigen seroclearance rate of 86% and 91% after 1 and 2 years was achievable with entecavir monotherapy. Moreover, none of the patients had histological graft damage because of HBV recurrence and an overall survival over 80% at 7 years has been reported. SUMMARY: With newer and more potent oral nucleos(t)ide (NA) available, a hepatitis B immune globulin-free regimen after liver transplantation has become safe and feasible for suppression of HBV recurrence after liver transplantation, and for avoidance of HBV-related graft complications.

Prevention and management of biliary anastomotic stricture in right-lobe living-donor liver transplantation.

Biliary strictures can be categorized according to technical factor as anastomotic or nonanastomotic strictures. Biliary anastomotic stricture is a common complication after living-donor liver transplantation, occasionally causing deaths. The two most commonly used methods for biliary anastomosis are duct-to-duct anastomosis and hepaticojejunostomy. Before presenting a description of the latest techniques of duct-to-duct anastomosis and hepaticojejunostomy, this review first relates the technique of donor right hepatectomy, as most biliary complications suffered by recipients of living-donor liver transplantation originate from donor operations. Three possible causes of biliary anastomotic stricture, namely impaired blood supply, biliary anomaly, and technical flaw, are then discussed. Lastly, the review focuses on the latest management of biliary anastomotic stricture. Treatment modalities include endoscopic retrograde cholangiography with dilatation, percutaneous transhepatic biliary drainage with dilatation, conversion of duct-to-duct anastomosis to hepaticojejunostomy, and revision hepaticojejunostomy. End-to-side versus side-to-side hepaticojejunostomy is also discussed.

Improved anterior hepatic transection for isolated hepatocellular carcinoma in the caudate.

BACKGROUND: One of the best treatments for isolated hepatocellular carcinoma in the caudate lobe is major hepatectomy with caudate lobectomy, but it is not suitable for patients with poor liver function reserve. Isolated caudate lobectomy, which is a very difficult operation, is thus an alternative option. METHODS: Here we report an isolated caudate lobectomy with an anterior approach in the treatment of a large hepatocellular carcinoma with underlying cirrhosis, with focus on the technical aspects. RESULTS: In the operation, both the left and right lobes of the liver were mobilized. Hepatotomy was done along the round ligament where parenchymal transection was minimal. After exposure of the left and middle hepatic veins and the hilar plate, the caudate lobe and the tumor were resected en bloc with a 5-mm margin. CONCLUSION: Isolated caudate lobectomy can be performed safely with this anterior approach on patients with poor liver function reserve.

Samaritan donor interchange in living donor liver transplantation.

BACKGROUND: In order to overcome ABO blood group incompatibility, paired donor interchange has been practised in living donor liver transplantation. Liver transplantations using grafts donated by Samaritan living donors have been performed in Europe, North America, South Korea, and Hong Kong. Such practice is clearly on strong biological grounds although social and psychological implications could be far-reaching. Local experience has been satisfactory but is still limited. As few centers have this arrangement, its safety and viability are still being assessed under a clinical trial setting. METHODS: Here we report a donor interchange involving an ABO-compatible pair with a universal donor and an ABO-incompatible pair with a universal recipient. This matching was not only a variation but also an extension of the donor interchange scheme. RESULTS: The four operations (two donor hepatectomies and two recipient operations) were successful. All the two donors and the two recipients recovered well. Such donor interchange further supports the altruistic principle of organ donation in contrast to exchange for a gain. CONCLUSIONS: Samaritan donor interchange certainly taxes further the ethical challenge of donor interchange. Although this practice has obvious biological advantages, such advantages have to be weighed against the potential increase in potential psychological risks to the subjects in the interchange. Further ethical and clinical evaluations of local and overseas experiences of donor interchange should guide future clinical practice in utilizing this potential organ source for transplantation.

Technical considerations for radical resection of a primary leiomyosarcoma of the vena cava.

BACKGROUND: Radical resection provides the best hope for cure in leiomyosarcoma of the inferior vena cava (IVC). Multi-visceral resection is often indicated by extensive tumour involvement. This report describes the technical challenges encountered during resection of a retrohepatic IVC leiomyosarcoma. METHODS: Computed tomography showed an IVC leiomyosarcoma measuring 7.8 × 10.0 × 19.3 cm in a 41-year-old patient. The tumour reached the confluence of the hepatic veins, displacing the caudate lobe anteriorly and extending towards the IVC bifurcation inferiorly. En bloc resection of the IVC tumour with a right hepatic and caudate lobectomy, and a right nephrectomy was performed. RESULTS: Subsequent to a Cattel manoeuvre, the operative procedures carried out can be broadly categorized in four major steps: (i) mobilization of the infrahepatic IVC and tumour; (ii) mobilization of the suprahepatic IVC from diaphragmatic attachments; (iii) right hepatectomy with complete caudate lobe resection, and (iv) en bloc resection of the IVC tumour. This approach allowed the entire length of tumour-bearing IVC to be freed from the retroperitoneum and avoided the risk for iatrogenic tumour rupture during dissection at the retrohepatic IVC. Reconstruction of the IVC was not performed in the presence of venous collaterals. CONCLUSIONS: Experience in liver resection and transplantation, and appreciation of the hepatocaval anatomy facilitate the safe and radical resection of retrohepatic IVC leiomyosarcoma.

Hepatic venoplasty in living-donor liver transplantation using right lobe graft with middle hepatic vein.

Inclusion of the middle hepatic vein in a right lobe graft from a living-donor may improve venous drainage and avoid graft dysfunction, but reconstruction of the middle hepatic vein is technically difficult. We developed a hepatic venoplasty technique, which was applied in eight consecutive right lobe liver transplantations. The right and middle hepatic veins of the graft were joined together to form a triangular cuff for a single anastomosis to the recipient's inferior vena cava. Hepatic venoplasty was successful in all cases, and no interposition graft was required. Venovenous bypass was not used. All grafts showed immediate function, and no hepatic venous outflow obstruction was observed. There was no reoperation and the graft survival rate was 100%. This hepatic venoplasty technique can be applied systemically as a standard one in right lobe liver graft with the middle hepatic vein to simplify the recipient hepatectomy and to obviate venous outflow obstruction.

Use of liver stiffness measurement for liver resection surgery: correlation with indocyanine green clearance testing and post-operative outcome.

BACKGROUND: Liver stiffness measurement (LSM) using transient elastography has recently become available for the assessment of liver fibrosis. Whether LSM can predict the functional liver reserve in patients undergoing liver resection is not certain. AIM: To correlate liver stiffness measurement (LSM) with indocyanine green (ICG) clearance test and liver biochemistry, and to determine its usefulness in predicting postoperative outcomes in patients undergoing liver resection. PATIENTS AND METHODS: Transient elastography and ICG clearance test were performed pre-operatively in 44 patients with hepatocellular carcinoma. The LSM and ICG retention rate at 15 minutes (R15) were correlated with pre-operative factors and post-operative outcomes. RESULTS: There was significant correlation between ICG R15 and LSM. In patients with LSM ≥11 kPa vs <11 kPa, there was significantly higher ICG R15 (17.1% vs 10.0% respectively, p = 0.025). For patients with ICG R15≥10% compared to those <10%, there was significantly higher LSM (12.0 vs 7.6 kPa respectively, p = 0.015). Twenty-eight patients proceeded to resection. There was a significant correlation between LSM and the peak INR after liver resection (r = 0.426, p = 0.024). There was a significant correlation between ICG R15 and the post-operative peak AST level (r = -0.414, p = 0.029) and peak ALT level (r = -0.568, p = 0.002). The operative time was a significant independent factor associated with post-operative complications and peak INR. CONCLUSION: LSM correlated well with ICG R15 in patients undergoing liver resection, and predicted early post-operative complications. Addition of LSM to ICG R15 testing may provide better prognostic information for patients undergoing resection.

Liver transplantation for hepatocellular carcinoma in Asia.

Hepatocellular carcinoma (HCC) is a leading cause of cancer death, particularly in Asia where the major etiology, chronic hepatitis B virus infection, is endemic. The tumor frequently develops in a background of cirrhosis, and liver transplantation offers a chance to cure both the tumor and the underlying cirrhosis. The Milan criteria based on tumor size and number as an estimate of tumor burden are conventionally the gold standard in determining eligibility for transplantation, and the outcome is excellent. The shortage of organs from deceased donors has curtailed the adoption of extended criteria and led to the problems of long waiting times and dropouts. Several measures have been taken to tackle these issues, including prioritization of patients with HCC, use of pretransplant adjuvant treatment to prevent tumor progression, and living donor liver transplantation (LDLT). With a high incidence of HCC and a low organ donation rate, Asia has developed a distinctive pattern of indication and strategy in the application of liver transplantation. Over the last decade, the number of liver transplants in Asia has increased rapidly, by 10-fold, largely as a result of the development of LDLT. The proportion of patients who undergo liver transplantation for HCC is increasing and HCC comprises one third of the indication for liver transplantation in Asia. LDLT is the dominant strategy, accounting for 96% of the liver transplants for HCC. Many transplant programs accept patients beyond the Milan criteria, and the reported 3-year survival rate is about 60%. With the promotion of organ donation, better quantification of the benefit of LDLT for extended indications, and identification of predictors for survival, the practice of liver transplantation for HCC in Asia will continue to evolve.

Implications for management of Mycobacterium tuberculosis infection in adult-to-adult live donor liver transplantation.

BACKGROUND: Mycobacterium tuberculosis (TB) infection is a serious opportunistic infection especially in live donor liver transplantation (LDLT). Hepatotoxicity of antituberculous agents and hazardous drug interaction with immunosuppressants may render the graft more susceptible to injury. AIM OF STUDY: To review our experience of management of TB infection in liver transplant recipients including LDLT. PATIENTS AND METHODS: A total of 397 liver transplantations were performed in the University of Hong Kong Medical Centre from January 1991 to December 2004. Eight patients (2.0%) developed TB infection after transplantation (LDLT: n=6, DDLT: n=2) and their clinical courses were reviewed. RESULT: The mean time of developing TB infection after liver transplantation was 9 months (range 4-20 months). Anti-TB treatment was administered for a mean duration of 12.7 months (11-18 months). None of our patients developed antituberculous drug-induced hepatotoxicity or had unwanted drug interaction. With a mean follow-up of 65 months (range 18-102 months), one patient died due to the recurrence of hepatocellular carcinoma. CONCLUSION: High index of suspicion for TB infection should be warranted for a history of cough and fever after liver transplantation. No notable difference was observed in the natural history and management of TB infection between LDLT and DDLT. The use of antituberculous drugs is safe in liver transplant recipients provided that liver function is closely monitored and the dosage of immunosuppressants is adjusted accordingly.

Applicability of histidine-tryptophan-ketoglutarate solution in right lobe adult-to-adult live donor liver transplantation.

In a consecutive series of 60 right lobe adult-to-adult live donor liver transplantations (ALDLTs), safety and efficacy of the University of Wisconsin (UW) and histidine-tryptophan-ketoglutarate (HTK) solution were evaluated. The first 30 liver grafts were perfused with UW solution and the subsequent 30 by HTK solution. Donor and recipient characteristics of both groups were comparable. All liver graft implantations were performed with cross-clamping of the inferior vena cava (IVC) and without veno-venous bypass. Main outcome measures were posttransplantation liver biochemistry, prothrombin time, and recipient morbidity, as well as graft and recipient survival. There were no significant differences of the outcome measures between the 2 groups. The low potassium content of the HTK solution nonetheless offered logistic advantages. In 25 of the 30 recipients of the HTK group, portal vein anastomosis was performed with a clamp on the donor portal vein while the clamps on the IVC were already released. This shortened the period during which the IVC was being cross-clamped. HTK solution was as safe and effective as a cold storage solution as UW solution in ALDLT. Its low potassium content has advantage of earlier restoration of patency of the IVC and thus hemodynamic stability. The cost of using HTK solution was also lower.

Randomized controlled trial of transarterial lipiodol chemoembolization for unresectable hepatocellular carcinoma.

This randomized, controlled trial assessed the efficacy of transarterial Lipiodol (Lipiodol Ultrafluide, Laboratoire Guerbet, Aulnay-Sous-Bois, France) chemoembolization in patients with unresectable hepatocellular carcinoma. From March 1996 to October 1997, 80 out of 279 Asian patients with newly diagnosed unresectable hepatocellular carcinoma fulfilled the entry criteria and randomly were assigned to treatment with chemoembolization using a variable dose of an emulsion of cisplatin in Lipiodol and gelatin-sponge particles injected through the hepatic artery (chemoembolization group, 40 patients) or symptomatic treatment (control group, 40 patients). One patient assigned to the control group secondarily was excluded because of unrecognized systemic metastasis. Chemoembolization was repeated every 2 to 3 months unless there was evidence of contraindications or progressive disease. Survival was the main end point. The chemoembolization group received a total of 192 courses of chemoembolization with a median of 4.5 (range, 1-15) courses per patient. Chemoembolization resulted in a marked tumor response, and the actuarial survival was significantly better in the chemoembolization group (1 year, 57%; 2 years, 31%; 3 years, 26%) than in the control group (1 year, 32%; 2 years, 11%; 3 years, 3%; P =.002). When adjustments for baseline variables that were prognostic on univariate analysis were made with a multivariate Cox model, the survival benefit of chemoembolization remained significant (relative risk of death, 0.49; 95% CI, 0.29-0.81; P =.006). Although death from liver failure was more frequent in patients who received chemoembolization, the liver functions of the survivors were not significantly different. In conclusion, in Asian patients with unresectable hepatocellular carcinoma, transarterial Lipiodol chemoembolization significantly improves survival and is an effective form of treatment.

Safety and outcome of hepatitis B core antibody-positive donors in right-lobe living donor liver transplantation.

We studied the safety of right-lobe donor hepatectomy in living donors with a positive serological test result for antibody against hepatitis B core antigen (anti-HBc). Of 54 right-lobe living liver donors, serum anti-HBc was positive in 29 donors (54%) and negative in 25 donors (46%). None had a history of hepatitis and all had normal liver biochemistry test results before surgery. Surgical data, postoperative liver function, and outcome of donors were compared according to anti-HBc status. Donors positive for anti-HBc were significantly older (median age, 42 v 31 years; P <.001), but there was no difference in other demographics and liver size. Median blood loss was greater in anti-HBc-positive donors (600 v 350 mL; P =.007). Histological examination showed no difference in degree of portal fibrosis or fatty change in liver grafts. There was no significant difference in postoperative serum transaminase levels or prothrombin times; however, anti-HBc-positive donors had greater serum bilirubin levels day 6 (26 v 21 micromol/L; P =.01) and day 7 (22 v 15 micromol/L; P =.004) after surgery. Postoperative complications developed in 10 anti-HBc-positive and 6 anti-HBc-negative donors (P =.4). All donors who developed cholestasis were positive for anti-HBc, aged 45 years or older, and had mild fatty changes of the liver. Hospital stays were similar. All donors had completely normal liver function at a median follow-up of 31 months (range, 21 to 76 months). A positive serological test result for anti-HBc should not be regarded as a contraindication for right-lobe liver donation.