Clinics in diagnostic imaging (115). Extraluminal biliary tree obstruction due to compression by pancreatic head tumour.

A 58-year-old Chinese woman presented initially with obstructive jaundice. Initial ultrasonography showed gallstones, calculus in common bile duct, and obstructed biliary system. Endoscopic retrograde cholangiopancreatography showed an extrinsic compression at common bile duct, and subsequent computed tomography scan showed a mass in the head of the pancreas. Endoscopical ultrasonography revealed masses in the gallbladder and pancreas. An exploratory laparotomy confirmed gallbladder cancer with spread to pancreas, segment IV of the liver, and regional lymph nodes. The patient was treated palliatively with metallic biliary stent for biliary drainage.

Long-term results of liver transplant in patients with chronic viral hepatitis-related liver disease in Singapore.

INTRODUCTION: Liver disease from chronic hepatitis B (CHB) and C (CHC) constitutes 57 percent of adult liver transplant in Singapore. Their long-term results post-transplant may be affected by recurrence of the viral illness. This study aims to evaluate the long-term results and survival in patients transplanted for CHB- and CHC-related liver disease. METHODS: Patients transplanted for CHB- and CHC-related disease from 1990 until March 2004, which included decompensated cirrhosis and hepatocellular carcinoma (HCC), were reviewed and analysed. RESULTS: 25 patients were transplanted for CHB-related liver disease, with mean follow-up of 153 +/- 25 weeks. Two- and four-year survival rates were 75 percent and 69 percent, respectively. Hepatitis B recurrence from YMDD mutants occurred in five patients, and four were treated successfully with adefovir dipivoxil, with resolution in transaminases and/or improvement in histology. One patient became non-compliant with follow-up and medications, and died 173 weeks post-transplant from reactivation of the wild-type hepatitis B virus. Nine patients were transplanted for CHC-related liver disease, with mean follow-up of 188 +/- 40 weeks, and two- and four-year survival rates of 89 percent and 76 percent, respectively. Two patients developed hepatitis C recurrence and were treated with interferon and ribavarin. One responded with sustained response but the other remained viraemic and died of HCC recurrence two years post-transplant. CONCLUSION: Long-term results from CHB- and CHC-related liver diseases were satisfactory and comparable to major transplant centres in the USA and Europe. Recurrence of viral hepatitis post-transplant is controllable with current antiviral therapy.

MELD may not be the better system for organ allocation in liver transplantation patients in Singapore.

INTRODUCTION: The Model for End-Stage Liver Disease (MELD) score is a good predictor of mortality on the liver transplant waiting list and is the current system of organ allocation in the USA. However, a higher MELD may be associated with poorer outcome post-liver transplantation. The aim of this study was to determine if MELD should be implemented as the system for organ allocation for liver transplantation in Singapore. METHODS: There were 46 adult patients who underwent primary liver transplantation at the National University Hospital, Singapore from January 1996 to December 2002. We applied the MELD score to patients who were transplanted and looked for a correlation with survival post-transplant. Patients were followed-up until the most recent visit or death. Survival analysis was performed using Cox regression and Kaplan-Meier method. RESULTS: The mean age at transplant was 52.7 (SD 2.34) years. The majority of the patients transplanted had Hepatitis B (43 percent). The median MELD score at transplantation was 17 (7-42) and the median Child's score was 11 (6-15). There was a significant correlation between pre-transplant MELD and survival at six months (p-value is 0.037, 95 percent confidence interval [CI] is 1.004-1.13) but not at one year (p-value is 0.065, 95 percent CI is 0.99-1.12). There were no differences in the pre-transplant MELD (odds-ratio [OR] 1, 95 percent CI 0.9-1) as well as survival for patients with and without Hepatitis B (OR 0.72, 95 percent CI 0.22-2.35). CONCLUSION: MELD allows livers to be allocated to the patients with the greatest medical urgency but its influence on post-transplant survival should be further clarified so that post-transplant survival is not compromised.

Referral patterns and waiting times for liver transplantation in Singapore.

INTRODUCTION: Referral patterns, waiting times, waiting list, and mortality provide information on how effectively a transplant programme deals with referred patients. This paper aims to review these parameters in the Singapore National Liver Transplant Programme. METHODS: Data of all patients referred to the Singapore National Liver Transplant Programme since its inception were captured and outcomes were retrieved and described. RESULTS: 562 patients were referred for liver transplant evaluation from 1990-2004, consisting of 457 adults and 105 children. The main indications for referral were hepatitis B liver disease and hepatocellular carcinoma in adults, and biliary atresia in children. Most patients were of United Network of Organ Sharing (UNOS) status 3 or 4 at the time of referral. 114 (20.28 percent) patients had transplants, consisting of 66 adults (14.44 percent) and 48 (45.71 percent) children. 138 adults and ten children were rejected for transplant, mainly for the reason of being "too early". The median waiting time for adults who had transplants was 3.3 months while adults still on the waiting list had been waiting for 16.2 months. The overall waiting list mortality was 44.3 percent, being 52.5 percent in adults and 23.2 percent in children. CONCLUSION: The overall transplantation rate is low and the waiting list mortality is high as a result of low availability of organs, particularly in adults. Paediatric liver transplant appears to have been better at dealing with referred patients but this is probably due to availability of living-related liver transplant. Improvement in these may result from the Human Organ Transplant Act.

Long-term post-liver transplant complications of renal impairment and diabetes mellitus: data from Singapore.

INTRODUCTION: Patients who survive the initial post-liver transplantation period face the development of chronic diseases in the long run. We studied two important complications of liver transplantation, namely: renal impairment and diabetes mellitus. METHODS: We analysed adult patients followed-up for more than one year using data from our liver transplant clinical records. Long-term post-transplant renal impairment (RI) was defined as glomerular filtration rate (GFR) less than 60 ml/min/1.73 square metres and long-term post-transplant diabetes mellitus (DM) was defined as fasting blood glucose more than 7.8 mmol/L, that existed at least one year after liver transplantation. Pre- and post-transplant factors that could be associated with these conditions were examined. RESULTS: Altogether, 35 patients were evaluated. Mean age at transplant was 50 years. Mean duration of follow-up was 58.4 months. There was 11.4 percent of pre-transplant RI and 17.0 percent of pre-transplant DM. Prevalence of post-transplant RI was 43.5 percent at one year and 45.0 percent at four years. Long-term post-transplant RI was associated with renal impairment at six months post-transplant (p-value is 0.033). Prevalence of severe post-transplant RI (GFR is less than 30 ml/min/1.73 square metres) at four years was 5.7 percent. Prevalence of post-transplant DM was 45.5 percent at two years but declined to 5.3 percent at four years. CONCLUSION: Post-transplant renal impairment appears to be a potential long-term problem while post-transplant diabetes mellitus appears to improve with time.

Treatment of steroid-resistant acute liver transplant rejection with basiliximab.

Current rescue therapies for acute steroid-resistant rejection, such as OKT3 and high-dose tacrolimus, are not uncommonly associated with side effects that contribute to significant morbidity of the patient. Basiliximab is a chimeric monoclonal antibody that acts as an interleukin-2 receptor antagonist on the surface of activated T lymphocytes. It has until now only been used as immunoprophylaxis in adult liver transplant patients. In this report, we describe the use of Basiliximab as rescue therapy in a case of acute steroid-resistant rejection in an adult living related liver transplant recipient.

Clinics in diagnostic imaging (104): Gastric trichobezoar (or hairball).

A 56-year-old man underwent triphasic computed tomography (CT) of the abdomen as part of his work-up for liver transplantation. A mottled, rounded lesion with a dense rim was noted in the gastric lumen, which remained unchanged in appearance in the arterial, portal venous, and delayed phases of the CT. Gastroscopy performed three days later confirmed the presence of trichobezoar. The foreign body was broken down into smaller pieces by an endoscopic snare and was passed out spontaneously. The clinical presentation, radiological findings, and management of trichobezoars are discussed.

Bilirubin appears to be the only independent variable affecting mortality on liver transplant waiting list if waiting time exceeds 1 year.

BACKGROUND: The Model for End-Stage Liver Disease (MELD) score has been shown to be the best predictor of short-term mortality on the liver transplant waiting list in the United States but waiting time often exceeds 1 year in many countries. We wanted to identify the factors affecting mortality on the liver transplant waiting list in Singapore where waiting time for liver transplant exceeds 1 year. PATIENTS AND METHODS: All patients who were listed on the liver transplant waiting list in Singapore from January 1997 to December 2003 excluding those who were transplanted were analyzed. MELD was calculated according to the United Network for Organ Sharing formula. Univariate analysis was performed to identify factors affecting mortality on the waiting list and multivariate analysis by logistic regression. Categorical and continuous variables were compared with the chi-square and Mann-Whitney U tests. RESULTS: There were 48 patients in the study. We found that on univariate analysis, bilirubin, INR, MELD score, and Child's score significantly influenced mortality on the waiting list but on multivariate analysis, bilirubin was the only independent prognostic indicator of mortality on the waiting list (LR = 1.97; 95% confidence interval = 1.08 to 3.61). INR was found to be significantly correlated to bilirubin with Pearson correlation (R = 0.63, P < .001). CONCLUSION: Bilirubin is the only independent factor affecting mortality on the liver transplant waiting list where waiting time exceeds 1 year.

Successful listing of patients for liver transplant was related to participation of referring doctor in the transplant program.

INTRODUCTION: Experience with liver transplantation is limited in many parts of Asia. Therefore, patients from nontransplant centers may not be referred in a timely fashion for transplants. Our aim was to evaluate the pattern of referral for liver transplantation and their outcomes in Singapore. METHODS: Consecutive patients referred from 1990 to 2001 were reviewed. Patients from any hospital in Singapore (or the region) could be referred to the program. They were discussed at the weekly meetings. Appropriate patients were placed on the waiting list. "Pending" indicated that the disease was early or there were unsettled medical or social issues. Unsuitable patients were "rejected" for transplant. RESULTS: There were 385 patients referred over a 12-year period. Hepatitis B cirrhosis and hepatocellular carcinoma (HCC) were the most common indications among adults, whereas biliary atresia was the most common for children. Pediatric patients were more likely than adult patients to be listed for transplant (53/76 vs 106/309, P < .001). Patients referred by regular attendees of the program were more likely to be accepted than nonattendees (38% vs 25%, P = .04). "Disease too early", "advanced HCC", and "refusal by family members" were the most common reasons for rejection. CONCLUSION: Members of the Liver Transplant Program were more likely to refer suitable patients for transplant at the appropriate time. Better interaction between gastroenterologists inside and outside the transplant program would help to improve the timing of referrals for liver transplantation, and hence, patient survival.

Adefovir dipivoxil as the rescue therapy for lamivudine-resistant hepatitis B post liver transplant.

INTRODUCTION: Complications of hepatitis B virus (HBV) infection are among the most common indications for liver transplant in many parts of Asia. However, none of the current posttransplant hepatitis B prophylaxis strategies, namely, lamivudine, hepatitis B immunoglobulin monotherapy, or combination therapy, is ideal. Our aim was to evaluate the use of adefovir dipivoxil (ADV) as a rescue therapy for posttransplant HBV patients who developed lamivudine resistance. METHODS: Twenty-two consecutive patients with HBV-related liver disease, who underwent first liver transplants from 1995 to 2002, received HBV prophylaxis with indefinite lamivudine with substitution of ADV for patients who developed drug resistance and clinical deterioration, defined as persistent elevation of transaminases or histologic deterioration. RESULTS: Sixteen patients (73%) were alive at their last follow-up and six (38%) had developed hepatitis B recurrence at a median of 46 (range 9 to 74) months posttransplant. Two with persistently normal transaminases and normal liver histology at 3 and 42 months postrecurrence have been continued on lamivudine. Four showed clinical deterioration and received ADV for a median of 24 months; all displayed normalization of transaminases and a 2 to 5 log drop in HBV DNA titers. Three had paired biopsies before and after substitution of ADV with two showing improvement and one stable appearance. The median serum creatinine value increased slightly from 126 to 138 micromol/L (P = 0.72). CONCLUSION: ADV is an effective rescue therapy for patients with lamivudine-resistant hepatitis B post-liver transplant. Further studies are needed to ascertain the optimal posttransplant hepatitis B prophylaxis.

Renal impairment and diabetes mellitus after liver transplant.

INTRODUCTION: One of the major concerns in liver transplant patients who survive past 1 year posttransplant is the development of chronic diseases. AIM: We studied two important clinical conditions that can have a chronic course-renal impairment and diabetes mellitus-among long-term liver transplant survivors. METHODS: All adult patients transplanted and followed for at least 1 year were evaluated for clinical status, blood tests, and imaging studies. The occurrence and development of renal impairment, defined as a serum creatinine above 125 micromol/L or creatinine clearance less than 75 mL/min, or diabetes mellitus were evaluated for contributing factors. RESULTS: The 35 evaluated patients of mean age at transplant of 50 years had a mean follow-up duration of 45 months. The incidence of posttransplant renal impairment was 22.8% at 1 year and 47.6% at 3 years. This disorder was associated with pretransplant renal impairment and with a diagnosis of diabetes. Posttransplant diabetes mellitus was observed in 48.6% with 41.1% resolving over time. CONCLUSION: Posttransplant renal impairment appears to be a potential long-term problem. Although this relates to pretransplant conditions, longer follow-up is required to examine whether posttransplant factors contribute to its progression.

Persistent thrombocytopenia in liver transplant patients.

INTRODUCTION: The occurrence of thrombocytopenia in the perioperative period after a liver transplant is not uncommon. However, there are few studies on persistent thrombocytopenia during the longer follow up period of patients after liver transplantation. We examined the prevalence of and contributing factors to persistent thrombocytopenia beyond 1 year post-liver transplantation. METHODS: We analyzed adult patients followed for at least 1 year posttransplant with full blood counts and abdominal scans, as well as clinical notes. RESULTS: The 35 patients of mean age at transplant of 50 years and showed a mean follow-up of about 4 years showed a prevalence of persistent thrombocytopenia at 12 months of 54% and at 3 years of 25%. Factors that were associated with persistent thrombocytopenia were pretransplant variceal bleeding, splenomegaly, and thrombocytopenia at 3 and 6 months posttransplant. After multivariate analysis only the latter represented independent factors for persistent thrombocytopenia at 1 and 3 years posttransplant, respectively. CONCLUSION: Persistent thrombocytopenia improved over time posttransplant; no bleeding problem was observed among the affected cases.

Revealing the cause of cryptogenic cirrhosis by posttransplant liver biopsy.

INTRODUCTION: Because of the tendency for preexisting diseases to recur following liver transplantation, studying the course of patients who were transplanted for their cryptogenic cirrhosis may reveal features of the original cause. We examined the clinicopathological posttransplant progression of patients transplanted due to cryptogenic cirrhosis with emphasis on the detection of posttransplant steatosis and steatohepatitis. METHODS: The data on all patients transplanted for cryptogenic cirrhosis and their routine 1-year posttransplant liver biopsies were compared to a control group of a randomized sample of patients transplanted for other indications matched for length of follow-up. The posttransplant histological diagnosis was based on the latest available biopsy. RESULTS: Among 1710 patients, 39 present with cryptogenic etiology survived at least 1 year after transplantation. The control group consisted of 78 patients. The mean ages of the two groups were 50.7 and 49.3 years and the mean follow-up periods 6.2 and 5.7 years, both of which were similar. There was a significantly greater prevalence of posttransplant steatosis and steatohepatitis among the cryptogenic group (37.5 vs 16.7%, P = .048). The difference in patients with at least moderate steatosis was more pronounced (18.8 vs 3.3%, P = .035). Half of these cases progressed to fibrosis and cirrhosis after 48 months. CONCLUSIONS: This study found a greater incidence of allograft steatosis and steatohepatitis among patients transplanted for cryptogenic cirrhosis compared with a control group. A significant proportion of these patients developed a picture resembling nonalcoholic steatohepatitis, which progressed to fibrosis and cirrhosis.

The MELD score may help to determine optimum time for liver transplantation.

BACKGROUND: The model for end-stage liver disease (MELD) score is a good predictor of mortality on the waiting list and short-term survival post liver transplantation. AIM: Our aim was to determine if there is a pretransplant MELD score beyond which liver transplantation is prohibitive. PATIENTS AND METHODS: Forty-six adult patients underwent primary liver transplantation from January 1996 to December 2002. Patients followed to the most recent visit or death underwent survival analysis using Cox regression and Kaplan Meier methods. RESULTS: There was a significant correlation between the pretransplant MELD score and survival at 6 months posttransplant (P=.037 95% CI: 1.004-1.13). Patients with pretransplant MELD score greater than or equal to 32 showed significantly greater mortality compared with those less than 32 (HR 9.18, 95%CI=1.16-72.44). CONCLUSION: Pretransplant MELD may help to determine the optimum time for liver transplantation.

Endoscopic banding ligation treatment for bleeding oesophageal varices.

Endoscopic variceal ligation (EVL) is a promising new method for controlling actively bleeding oesophageal varices as well as for their eradication. Compared to conventional endoscopic injection sclerotherapy, EVL has a lower rebleeding rate, fewer complications and can achieve faster variceal obliteration. Disadvantages of EVL include overtube trauma and possibly longer procedure time. However, recent development of newer devices such as the multiple banding ligator may overcome these shortcomings and improve results.