Younger age and presence of macrovascular invasion were independent significant factors associated with poor disease-free survival in hepatocellular carcinoma patients undergoing living donor liver transplantation.

OBJECTIVE: Patients with hepatocellular carcinoma (HCC) exceeding the University of California, San Francisco (UCSF) criteria are normally rejected for cadaveric liver transplants. However, whether they should be allowed to undergo living donor liver transplantation (LDLT) has been controversial. We reviewed the outcome of patients with advanced HCC who underwent LDLT at our center. METHODS: From April 2002 to May 2011, 176 patients underwent LDLT at our center; of these, 77 (44%) had HCC at the explant liver. Patient overall survival and recurrence-free survival (RFS) was analyzed using Kaplan-Meier method. Multivariate analysis was performed by Cox analysis. RESULTS: Age was 56±1 (56, 29-71) years; 62 (80.5%) were male; Model for End-stage Liver Disease Score was 11±1 (9, 6-36), alpha fetoprotein (AFP) was 3683±2019 (69, 3-139,591) ng/L; maximum tumor size was 4.5 (0.5-15) cm. Number or tumor nodules was 5 (1-10), and 32 (42%) had macrovascular invasion diagnosed pretransplant. Eleven (14%) were within UCSF criteria. After follow-up of 953±90 (744, 2-2989) days, 53 (69%) were alive and 48 (62%) were recurrence-free. One-, 3- and 5-year overall survival (OS) and recurrence-free survival (RFS) were 80%, 70%, and 57% and 80%, 65%, and 48%, respectively. Five-year OS and RFS for those within UCSF criteria were both 78% versus 55% and 46% outside UCSF criteria (P=not significant). At multivariate analysis, high AFP, younger age, and macrovascular invasion were associated with both poor RFS. CONCLUSION: In HCC patients exceeding UCSF criteria, a reasonable 5-year overall survival of 55% post-LDLT can be obtained. Patients with HCC exceeding the UCSF criteria, especially in the older age group with no portal vein invasion and lower AFP level, should be actively considered for LDLT.

Pretransplant Model for End-stage Liver Disease score has no impact on posttransplant survival in living donor liver transplantation.

BACKGROUND: A high Model For End-stage Liver Disease (MELD) score≥25 has been reported to be associated with increased posttransplant mortality and morbidity among patients undergoing living donor liver transplantation (LDLT). We reviewed the results of patients undergoing LDLT at our transplant center for decompensated cirrhosis to determine whether a high MELD impacted posttransplant survival. METHODS: From April 2002 to May 2011, 86-176 patients (49%) who underwent LDLT at our center had the indication of decompensated cirrhosis without hepatocellular carcinoma. Data were expressed in mean values±standard error of the means (range). Patients survival rates were analyzed using Kaplan-Meier method. RESULTS: Among the 86 patients with decompensated cirrhosis: Age was 49±2 (1-68) years and 60 (70%) were of male gender. The causes in 25 (29%) were hepatitis B and 25 (29%) hepatitis C as well as one each for hepatitis B/C and B/D coinfections: 9 (10%), alcoholic cirrhosis. MELD score was 18±1 (range=6-40). In hospital mortality was 6/86 (7%). At 1152±95 (range=7-3317) days posttransplant follow-up 64 (74%) were alive with 1-, 3-, and 5-year survival rates of 84%, 70%, and 70%, respectively. MELD scores did not differ between those who survived and those who died (17.5±8.0 versus 17.8±8.4). No difference was noted in those with MELD<25 or ≥25. In fact, the recipient with the highest MELD score (40) survived. CONCLUSION: A high MELD score had no impact on posttransplant survival among cirrhotic patients undergoing LDLT. It should be considered to be an urgent indication rather than a contraindication to LDLT.

Mimicry of acute cholecystitis from Wilson's disease.

We present a 33-year-old Chinese woman with Wilson's disease in whom ultrasonography and computed tomography showed gallbladder features suggestive of acute cholecystitis. Incongruence in liver function prompted further investigations with the final diagnosis of Wilson's disease, complicated by oedema of the gallbladder mimicking acute cholecystitis. The patient was subsequently treated nonoperatively, and is well on follow-up.

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.

Delayed bleeding after liver biopsy: a dreaded complication.

We present an unusual case of percutaneous liver biopsy complicated by delayed haemothorax in a 55-year-old Chinese man with hepatitis C cirrhosis and severe haemophilia A. The patient presented ten days after the initial liver biopsy, and was managed with prompt investigations for confirming the diagnosis, infusion of factor VIII and fresh frozen plasma, and early referral to the surgeon for consideration of surgical repair. The importance of early detection and aggressive therapy is emphasised.

Clinics in diagnostic imaging (116). Ruptured hepatocellular carcinoma.

A 37-year-old Chinese man with chronic hepatitis B, who frequently defaulted past follow-up appointments, was admitted for acute abdomen and shock. Computed tomography of the abdomen revealed a ruptured hepatocellular carcinoma involving the left lobe. After fluid resuscitation, gelfoam embolisation was performed to arrest the bleeding, followed by segmental resection of the hepatic lesion. There was aggressive recurrence following left segmental hepatectomy, and despite two courses of transarterial chemoembolisation, the patient died of local and pulmonary recurrences five months after his initial presentation. The management of hepatocellular carcinoma rupture is discussed.

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.

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 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.

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.

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.

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.

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.

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.