Prognostic factors in patients with acute liver failure undergoing live donor liver transplantation.

Mortality from acute liver failure (ALF) is high. Live donor liver transplantation (LDLT) is the treatment of choice for ALF in Asia, because cadaveric donors are rare. We sought to review our results in ALF patients with undergoing LDLT at our center. One hundred two LDLTs were performed at our center from April 2002 to November 2007, 15 (14%) because of ALF. Mean (SEM; median, range) follow-up was 1,065 (189; 1400; 3-2046) days. Nine patients (60%) had acute exacerbation of chronic hepatitis B; and 6 (40%) had drug-induced liver injury. Age was 47 (3; 50; 27-65) years. Ten patients (67%) were men. At transplantation, laboratory values were included bilirubin, 449 (35) micromol/L; creatinine concentration, 182 (32) mmol/L. The international normalized ratio was 2.4 (0.2). The Model for End-Stage Liver Disease (MELD) score was 34 (2). Both inpatient and long-term mortality was 20% 3 of 15 patients died. The 5-year survival was 80%. Compared with survivors, patients who died had a significantly higher creatinine concentration 289 vs 155 micromol/L, international normalized ratio (3.4 vs 2.1), MELD score (47 vs 32). We conclude that despite being sick with median and mean MELD scores of 32 and 34, 80% of patients with ALF can achieve good long-term survival after LDLT.

Experience of the transplant team is an important factor for posttransplant survival in patients with hepatocellular carcinoma undergoing living-donor liver transplantation.

Living-donor liver transplantation (LDLT) is an effective treatment for patients with unresectable hepatocellular carcinoma (HCC). However, it remains controversial whether expanded listing criteria can be used for LDLT. We aimed to review results of LDLT for patients with HCC at our center. Patients with HCC were accepted for LDLT if there was no extrahepatic spread on computed tomography (CT) and positron emission tomography CT scan. Transarterial chemoembolization was performed before LDLT to control the tumors. Sirolimus or everolimus was used as part of the immunosuppressive protocol for all patients. Over the last 6 years, 35 of the 102 (34%) LDLT were performed at our center for HCC. Age (mean +/- SEM) was 55.3 +/- 1.3 years; 28 patients (80%) were men. Eight (23%) had LDLT performed in 2002 or 2003 (period 1), and 27 (77%) in 2004 to 2007 (period 2). Eleven (31%) were within and 23 (69%) were outside the Milan criteria. After 583 +/- 76 days follow-up, nine (25%) died, three of recurrent HCC. Three-year survival was significantly better in period 2 than in period 1 (90% vs 13%; P < .001). Although the 3-year survival for those within Milan criteria was better than those outside Milan criteria, the difference did not reach statistical significance (86% vs 57%; P = .26). Six (17%) had HCC recurrence, of whom five died. We concluded that reasonable medium-term survival can be obtained for patients with HCC. The experience level of the transplant team seemed to be the most important predictor of patient outcome.

Presentation of drug-induced liver injury in Singapore.

INTRODUCTION: Drug-induced liver injury (DILI) is an important clinical problem. However, although traditional Chinese medicines (TCM) are widely consumed in Asia, most cases of TCM-DILI are reported as case reports or case series. We aimed to evaluate the clinical course of DILI at an Asian tertiary liver centre. METHODS: All patients with DILI seen by one hepatologist from July 2003 to June 2004 at a local liver centre were prospectively collected and reviewed. RESULTS: 29 cases of DILI were seen by the hepatologist over the 12-month period. Median age was 51 (range 18-76) years, 20 (69 percent) were female, and 24 (83 percent) were Chinese. TCM were the commonest group of drugs implicated as 15 (52 percent) of the patients had presumed DILI from TCM, while four (14 percent) were from anti-tuberculosis drugs. 18 (62 percent) presented as hepatitic picture, seven (24 percent) as cholestatic, and four (14 percent) as mixed picture. Extrahepatic manifestations were seen only in ten percent of patients. Three (ten percent) died and one (3 percent) underwent liver transplant for liver failure. CONCLUSION: DILI is a common clinical problem with significant mortality. TCM is an important cause of DILI in Asia. Further studies on DILI from TCM or other complementary medicines are needed.

Surgery in patients with advanced liver cirrhosis: a Pandora's box.

Advanced liver cirrhosis is a relative contraindication for abdominal surgery, as such patients are likely to develop postoperative complications and mortalities. We describe two patients with liver cirrhosis who developed postoperative decompensation and expired after undergoing non-abdominal surgery. We highlight that even non-abdominal surgery could incur high mortality in patients with Child's class B or C liver cirrhosis. Surgery should be avoided in such patients unless it is absolutely necessary. If the procedure is essential and life-saving, the patient should be co-managed by a team of surgeon, anaesthesist and hepatologist. A full evaluation of the baseline liver status, preoperative optimisation, and close postoperative monitoring are required to reduce the risk of decompensation and improve survival.

Dyspnoea due to plasma transfusion-related acute lung injury.

We describe an unusual case of unexpected dyspnoea following transfusion of fresh frozen plasma (FFP) in a previously-well 72-year-old woman. Our patient was scheduled for an ultrasonographically-guided liver biopsy for work-up for autoimmune hepatitis. She was given FFP to correct a prolonged prothrombin time. Shortly after the transfusion was initiated, she started coughing and became progressively dyspnoeic. Clinically, she was tachypnoeic with diffuse bilateral crepitations, and rapidly went into respiratory failure. She was intubated and placed on mechanical ventilation. Her condition improved and she was extubated by the second day, with no long-term pulmonary sequelae. A diagnosis of transfusion-related acute lung injury (TRALI) was made, based on the rapidity of onset and association with transfusion. This was confirmed by the findings of anti-human leukocyte antigen antibodies in both the patient and recipient blood. Our case highlights this important but under-recognised condition. The incidence, diagnosis and management of TRALI are also discussed.

Liver transplantation for hepatocellular carcinoma in Singapore.

INTRODUCTION: The prognosis of patients with hepatocellular carcinoma (HCC) is poor. Surgical resection offers the benefit of removal of the tumour but is associated with liver decompensation and tumour recurrence, even after successful surgery. Liver transplantation offers the benefits of complete tumour removal with prevention of both decompensation and recurrence post-operation. This paper aims to review results of liver transplantation for patients with HCC in Singapore. METHODS: All adult patients with HCC accepted on the waiting list for liver transplantation (based on the Milan criteria) from 1996 to 2004 in Singapore were reviewed. Patients' HCC were managed with either transarterial chemoembolisation or percutaneous radiofrequency ablation while they were on the waiting list. Post-transplant survival and factors associated with mortality were analysed by Cox regression analysis. RESULTS: 41 patients with HCC were accepted onto the waiting list over the nine-year period. 22 underwent transplantation and 19 did not, with a one-year survival of 91 percent versus 24 percent, respectively. (p-value is less than 0.001). Mean waiting time for transplant was 39 weeks. Post-transplant HCC recurrence was 2/22 (nine percent). Among all patients, mortality was significantly related to baseline white cell counts, prothrombin time, age, alpha-foetoprotein level, Child-Pugh score, and whether patients underwent transplant. CONCLUSION: Despite the relatively long waiting time of a mean of 39 weeks, post-transplant recurrence of HCC was relatively low at nine percent. Liver transplant is an effective treatment for patients with a HCC, with a reasonable long-term survival.

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.

Liver transplantation in Singapore 1990-2004.

INTRODUCTION: Liver transplantation is the accepted standard of care for patients with hepatocellular carcinoma, decompensated liver cirrhosis, and acute liver failure. Since the first liver transplant done in Singapore in 1990, results have been improving. We review the overall results of liver transplantation over the last 15 years. METHODS: All transplant cases from 1990 to 2004 were reviewed retrospectively. RESULTS: 100 liver transplants were performed over the last 15 years; four in the first five years and 96 in the subsequent ten years. Overall one- and five-year survival rates were 80 percent and 78 percent, respectively. 44 were paediatric transplants, of which biliary atresia was the commonest indication for paediatric transplant. 56 were adult transplants of which hepatocellular carcinoma and decompensated hepatitis B cirrhosis were the commonest indications for adult transplant. Infection remained the commonest cause of mortality. CONCLUSION: The number of transplants carried out per year was small due to the low cadaveric donation rate, but the survival of liver transplant patients was comparable to well-established liver transplant centres.

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.

Empirical treatment for the management of patients presenting with uninvestigated reflux symptoms: a prospective study in an Asian primary care population.

BACKGROUND: Data on Asian patients who present with reflux symptoms to their primary care physicians are limited. AIM: To determine whether empirical therapy without endoscopy is appropriate for patients who present to their primary care physicians with uninvestigated reflux symptoms without alarm symptoms. METHOD: Forty-seven patients presenting with uninvestigated, dominant reflux symptoms but without alarm features to their primary care physicians underwent endoscopy within 2 weeks of referral. Their endoscopic findings were compared with those of 162 primary care patients presenting with uninvestigated dominant dyspepsia. All patients, except those with ulcers, were treated with esomeprazole 20 mg b.d. for 2 weeks. Their treatment response was assessed at 2 weeks using a symptom score. RESULTS: Among patients with dominant reflux symptoms, 14 (30%) had erosive oesophagitis. No other clinically significant endoscopic findings were detected among them. In contrast, erosive oesophagitis and peptic ulcer were found in 13 (8%, P < 0.001 vs. reflux group), and 12 (7%, P = 0.06 vs. reflux group), respectively, of patients with dominant dyspepsia. Thirty-seven of forty-five (82%) of those with dominant reflux symptoms and 109 of 139 (78%; P = N.S. vs. reflux group) of those with dominant dyspepsia reported > or = 50% resolution of symptoms after esomeprazole treatment. CONCLUSIONS: Empirical proton pump inhibitor without endoscopy is reasonable for uninvestigated patients who present to primary care physicians with dominant reflux symptoms.

Utility of the Health Belief Model in predicting compliance of screening in patients with chronic hepatitis B.

BACKGROUND: Regular surveillance is recommended for patients with chronic hepatitis B, to select candidates for anti-viral therapy and detect early complications. However, factors that determine compliance are not well studied. AIM: To determine the utility of the Health Belief Model in explaining non-compliance, among a group of chronic hepatitis B patients for screening. METHODS: A total of 192 chronic hepatitis B patients who responded to advertisement for free screening took part in a telephonic interview study. Subjects were asked about the five constructs of the Health Belief Model, and factors associated with recent screening were analysed. RESULTS: The mean age of the subjects was 42.1 +/- 0.7 years; 77% white male, and 97% Chinese. About 108 patients (56%) had recent screening. At multivariate analysis, only the ability to remember date of follow-up (OR: 4.37; 95% CI: 2.07-9.17) and the perception of having to wait a long time for venepuncture (OR: 0.38; 95% CI: 0.19-0.79) were significantly associated with recent screening. CONCLUSION: Future public health measures should include improving the logistics of follow-up procedures and providing reminders for screening to improve compliance.

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.

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.

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.

Clinics in diagnostic imaging (105): Sigmoid volvulus causing intestinal obstruction, with successful endoscopic decompression.

An 89-year-old woman was admitted for intestinal obstruction. Her abdominal radiograph showed typical features of sigmoid volvulus. Decompression was done successfully through careful flexible sigmoidoscopy with minimum air insufflation. The patient's symptoms were relieved and she was discharged two days post-procedure. No recurrence was noted at extended follow-up. Rapid diagnosis and early decompression are key to optimal management of sigmoid volvulus.

Tuberculosis post-liver transplantation: a rare but complicated disease.

INTRODUCTION: Tuberculosis is a rare but serious complication after transplantation. We report a case and discuss its presentation and management. CLINICAL PICTURE: A 60-year-old Indonesian male presented initially with fever, acute confusion and rapidly progressive right upper lobe pneumonia 3.5 months post-liver transplant, and was diagnosed with pulmonary tuberculosis by positive sputum smear for acid-fast bacilli and tuberculosis culture. TREATMENT/OUTCOME: Standard anti-tuberculosis therapy was administered but was complicated by interaction with cyclosporine and drug-induced cholestasis. CONCLUSION: A high level of suspicion, prompt antituberculosis treatment and close follow-up are essential in management of post-transplant tuberculosis.

Prophylactic lamivudine prevents hepatitis B reactivation in chemotherapy patients.

BACKGROUND: Chronic hepatitis B virus carriers receiving chemotherapy develop a high hepatitis B virus reactivation rate (38-53%) with a high mortality (37-60%). Few studies have characterized the efficacy of lamivudine in the treatment of chemotherapy-induced hepatitis B virus reactivation. AIM: To determine whether lamivudine prophylaxis reduces chemotherapy-induced hepatitis B virus reactivation and mortality. METHODS: The medical records of all hepatitis B surface antigen-positive patients with malignancy treated with chemotherapy since 1995 at the National University Hospital of Singapore were identified, and divided into those who received lamivudine prophylaxis before chemotherapy (P) and those who did not (NP). The parameters examined included gender, age, malignancy type, steroid usage, number of chemotherapy courses and regimens, follow-up duration and hepatitis B virus status. The outcome measures were hepatitis B virus reactivation (abrupt rise of serum alanine aminotransferase to > 200 IU/L) and reactivation death. Patients with primary hepatoma or liver metastasis were excluded. RESULTS: Thirty-five patients were identified: 16 in the P group and 19 in the NP group. The baseline characteristics of the two groups were similar. Seven of the 19 patients in the NP group and none of the 16 patients in the P group developed reactivation (36.8% vs. 0%, P=0.009). Six of the seven patients in the NP group who developed reactivation received lamivudine at that time, but five died (mortality, 71.4%), whilst no patient in the P group died from reactivation (P=0.064). CONCLUSIONS: Prophylactic lamivudine appears to prevent hepatitis B virus reactivation and its associated mortality in patients treated with chemotherapy. This should be confirmed with prospective studies.

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.