J.I. Herrero

A randomized study comparing lamivudine monotherapy after a short course of hepatitis B immune globulin (HBIg) and lamivudine with long-term lamivudine plus HBIg in the prevention of hepatitis B virus recurrence after liver transplantation.

BACKGROUND/AIMS To compare the efficacy in preventing hepatitis B virus (HBV) recurrence of lamivudine vs. lamivudine plus hepatitis B immune globulin (HBIg) after a short course of HBIg and lamivudine in liver transplanted chronic hepatitis B patients. METHODS Forty-six patients with HBV cirrhosis received lamivudine before liver transplantation and were then randomized to receive lamivudine plus HBIg for 1 month followed by lamivudine or both drugs for 17 months. RESULTS Thirty-two patients were transplanted and 29 were randomized to receive combination therapy (15 cases) or lamivudine monotherapy (14 cases). HBV DNA was undetectable in all cases (17 induced by lamivudine therapy) at the time of liver transplantation. After 18 months of follow-up, all patients survived without HBV recurrence: hepatitis Bs antigen and HBV DNA were negative; however, HBV DNA was detected by polymerase chain reaction in four cases (three with HBIg plus lamivudine and one with lamivudine). Alanine aminotransferase levels were normal except in six cases (one HCV and two HDV coinfections). There were no drug-related adverse events. CONCLUSIONS Lamivudine monotherapy after a short course of lamivudine and HBIg is equally as efficacious in preventing HBV recurrence as HBIg plus lamivudine during the first 18 months after liver transplantation. This strategy is more economic and convenient to administer than long-term HBIg plus lamivudine.

Intrahepatic cholangiocarcinoma or mixed hepatocellular-cholangiocarcinoma in patients undergoing liver transplantation: a Spanish matched cohort multicenter study.

Objective:To evaluate the outcome of patients with hepatocellular-cholangiocarcinoma (HCC-CC) or intrahepatic cholangiocarcinoma (I-CC) on pathological examination after liver transplantation for HCC. Background:Information on the outcome of cirrhotic patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study is limited. Methods:Multicenter, retrospective, matched cohort 1:2 study. Study group: 42 patients undergoing a transplant for HCC and with a diagnosis of HCC-CC or I-CC by pathological study; and control group: 84 patients with a diagnosis of HCC. I-CC subgroup: 27 patients compared with 54 controls; HCC-CC subgroup: 15 patients compared with 30 controls. Patients were also divided according to the preoperative tumor size and number: uninodular tumors 2 cm or smaller and multinodular or uninodular tumors 2 cm or larger. Median follow-up: 51 (range, 3–142) months. Results:The 1-, 3-, and 5-year actuarial survival rate differed between the study and control groups (83%, 70%, and 60% vs 99%, 94%, and 89%, respectively; P < 0.001). Differences were found in 1-, 3-, and 5-year actuarial survival rates between the I-CC subgroup and their controls (78%, 66%, and 51% vs 100%, 98%, and 93%; P < 0.001), but no differences were observed between the HCC-CC subgroup and their controls (93%, 78%, and 78% vs 97%, 86%, and 86%; P = 0.9). Patients with uninodular tumors 2 cm or smaller in the study and control groups had similar 1-, 3-, and 5-year survival rate (92%, 83%, 62% vs 100%, 80%, 80%; P = 0.4). In contrast, patients in the study group with multinodular or uninodular tumors larger than 2 cm had worse 1-, 3-, and 5-year survival rates than their controls (80%, 66%, and 61% vs 99%, 96%, and 90%; P < 0.001). Conclusions:Patients with HCC-CC have similar survival to patients undergoing a transplant for HCC. Preoperative diagnosis of HCC-CC should not prompt the exclusion of these patients from transplant option.

“Very Early” Intrahepatic Cholangiocarcinoma in Cirrhotic Patients: Should Liver Transplantation Be Reconsidered in These Patients?

A retrospective cohort multicenter study was conducted to analyze the risk factors for tumor recurrence after liver transplantation (LT) in cirrhotic patients found to have an intrahepatic cholangiocarcinoma (iCCA) on pathology examination. We also aimed to ascertain whether there existed a subgroup of patients with single tumors ≤2 cm (“very early”) in which results after LT can be acceptable. Twenty‐nine patients comprised the study group, eight of whom had a “very early” iCCA (four of them incidentals). The risk of tumor recurrence was significantly associated with larger tumor size as well as larger tumor volume, microscopic vascular invasion and poor degree of differentiation. None of the patients in the “very early” iCCA subgroup presented tumor recurrence compared to 36.4% of those with single tumors >2 cm or multinodular tumors, p = 0.02. The 1‐, 3‐ and 5‐year actuarial survival of those in the “very early” iCCA subgroup was 100%, 73% and 73%, respectively. The present is the first multicenter attempt to ascertain the risk factors for tumor recurrence in cirrhotic patients found to have an iCCA on pathology examination. Cirrhotic patients with iCCA ≤2 cm achieved excellent 5‐year survival, and validation of these findings by other groups may change the current exclusion of such patients from transplant programs.

Efficacy of transjugular intrahepatic portosystemic shunt to prevent total portal vein thrombosis in cirrhotic patients awaiting for liver transplantation.

INTRODUCTION Complete portal vein thrombosis (PVT) may complicate orthotopic liver transplantation (OLT), increasing its technical difficulty and the transfusion requirements and as well as affecting survival in some cases. Transjugular intrahepatic portosystemic shunt (TIPS) prevents total portal vein occlusion in patients with partial PVT. OBJECTIVE We aimed to assess the efficacy and safety of TIPS to prevent total portal vein occlusion among patients listed for OLT. PATIENTS AND METHODS We analyzed the clinical records of 15 consecutive patients with partial PVT who underwent TIPS before OLT. The control group consisted of 8 transplanted patients without TIPS but partial PVT diagnosed before OLT. Portal vein patency at surgery, ischemia time, and transfusion requirements during OLT, and survival thereafter were compared between both groups. The main complications were also compared: mortality after TIPS (from TIPS placement to OLT), intraoperative technical complications, and technical complications during the 6 months after OLT. RESULTS Clinical characteristics at the time of OLT were similar between the groups. No relevant complications were observed after TIPS; all patients underwent transplantation. One- and 5-year actuarial survival rates were similar in both groups (92% and 85% in TIPS-group versus 100 and 75% in the control group, respectively). No differences in transfusion requirement, duration of ischemia, and frequency of technical complications during and after OLT were observed between the groups. The portal vein was patent at surgery in all TIPS patients and 4 of 8 (50%) in the control group (P = .008). CONCLUSION TIPS may prevent PVT in liver transplantation candidates with partial PVT.

Conversion from calcineurin inhibitors to mycophenolate mofetil in liver transplant recipients with diabetes mellitus.

Diabetes mellitus, a frequent metabolic complication in liver transplant recipients, may be produced by the diabetogenic effect of calcineurin inhibitors cyclosporine and tacrolimus. The aim of this study was to investigate the safety and metabolic effects of a gradual switch from cyclosporine or tacrolimus to mycophenolate mofetil among 12 diabetic liver transplant recipients. One patient was withdrawn from the study due to gastrointestinal side effects. Of the 11 remaining patients, cyclosporine or tacrolimus was completely withdrawn in five patients. Two patients developed suspected acute rejection episodes that were controlled by increasing the tacrolimus dosage. Glycosylated hemoglobin A1C and C-peptide levels were significantly lower at 3 and 6 months after the initiation of mycophenolate mofetil (P<.03 in all cases). Furthermore, urea and uric acid levels were significantly reduced after the change of treatment. In conclusion, a switch from cyclosporine/tacrolimus to mycophenolate mofetil may produce beneficial metabolic effects in diabetic liver transplant recipients, but poses a risk of graft rejection.

Subsequent Nonmelanoma Skin Cancer after Liver Transplantation

BACKGROUND Liver transplant recipients have a high risk of developing nonmelanoma skin cancer (NMSC). Some develop multiple NMSC. METHODS Patients with a follow-up of >1 year have been prospectively followed to detect NMSC. We studied the risk of developing >1 NMSC. RESULTS After a follow-up of 2658 patient-years (mean, 8.5 years per patient), 59/312 (19%) patients were diagnosed with NMSC. Twenty-five had >1 NMSC. The 5-year risk of developing 1 NMSC, >1 NMSC, and a subsequent NMSC (a new NMSC after a first one) were 15%, 5.5%, and 46.5%, respectively. Age >60 years and transplantation for hepatocellular carcinoma were independently associated with a higher risk of developing >1 NMSC. CONCLUSION NMSC are frequent complications after liver transplantation and they may show a high rate of recurrence. Older age and hepatocellular carcinoma were related to the development of multiple NMSC.

Hepatitis B virus quasispecies evolution after liver transplantation in patients under long‐term lamivudine prophylaxis with or without hepatitis B immune globulin

To investigate an optimal long‐term prophylactic strategy for prevention of hepatitis B virus (HBV) recurrence after liver transplantation, we conducted a randomized study of 29 transplant recipients receiving a short course of hepatitis B immune globulin (HBIg) + lamivudine (LAM), followed by randomization to long‐term prophylaxis with LAM with or without HBIg.

Is Liver Biopsy Necessary in the Evaluation of a Living Donor for Liver Transplantation

BACKGROUND The role of liver biopsy in the evaluation of a candidate for living liver donation is controversial. Some authors suggest doing it routinely, but others do it only in selected cases. The aim of this work was to evaluate the usefulness of protocol liver biopsy in the evaluation of candidates for living liver donation. METHODS Ninety potential candidates for living liver donation were evaluated. In 46 cases donation was contraindicated without the need of liver biopsy. In the remaining 44 candidates, liver biopsy was done on a protocol basis. The usefulness of protocol biopsy was compared with the use of biopsy according to the recommendations of the Vancouver Forum. RESULTS Fifteen of the 44 biopsies were indicated according to the recommendations of the Vancouver Forum. Twelve of them were normal, and 3 had liver steatosis or steatohepatitis. Of the 29 biopsies done per protocol, 28 were normal and 1 showed liver steatosis. Donation was contraindicated according to liver biopsy findings in 3 of the 15 patients with liver biopsy done according to the Vancouver Forum recommendations and in none of the 29 patients with biopsy done per protocol (P = .034). CONCLUSIONS Protocol liver biopsy has a limited utility in the evaluation of the candidates for living liver donation.