Revising the upper limit of normal for levels of serum alanine aminotransferase in a Middle Eastern population with normal liver histology.

BACKGROUND: Recently, the upper limits of normal (ULN) for alanine-aminotransferase (ALT) has been recommended to be lowered to ≤ 30 U/l in men and ≤ 19 U/l in women. AIM: To evaluate the ALT concentrations in a healthy Middle Eastern population with biopsy-proven normal liver tissue. METHODS: ALT values were calculated from 175 consecutive Saudi potential living liver donors who underwent a liver biopsy as part of a stepwise pretransplant workup. RESULTS: The mean age of the 110 potential donors with normal liver histology was 27 ± 6.2 years for men and 38.6 ± 7.1 years for women. The mean body mass index (BMI) levels were 23.0 ± 3.5 kg/m(2) for men and 24.7 ± 3.25 kg/m(2) for women, and the ALT levels were higher in male patients (22.6 ± 9 vs. 16.4 U/l ± 8, p value = 0.003). Multivariate linear regression showed that BMI and sex were independent variables that were positively associated with the levels of ALT (p < 0.0001). Moreover, when we analyzed donors according to the Prati criteria, 63 (36.0 %) of the individuals were classified into this subgroup. The mean ALT concentration was 12.9 U/l ± 4.5 in women and 19.7 U/l ± 6.9 in men, and these values were significantly lower than those obtained from subjects who did not fit the Prati criteria (19.4 U/l ± 1.8, p = 0.04 for women and 29.0 U/l ± 12.1, p = <0.0001 for men). Thus, we calculated healthy ALT values of 33 IU/l for men and 22 IU/l for women. CONCLUSIONS: The ULN for ALT levels in Middle Eastern populations should be lowered, including separate values for males and females. Furthermore, metabolic parameters were shown to have a significant effect on ALT levels.

Should a Living Donor Renal Graft be Removed Due To Prolonged Delayed Function? A Case Report.

BACKGROUND Delayed graft function (DGF) is defined as failure of the transplanted kidney to function in the early -post-transplant period. DGF is a rare complication after living donor kidney transplant and is most common after deceased donor kidney transplant, probably due to prolonged warm and cold ischemia times during retrieval. Most cases of DGF resolve spontaneously within days to weeks. There are very few reported cases in the literature of DGF lasting over 4 weeks. We present a case that resolved after 55 days. The recipient subsequently achieved normal renal function. CASE REPORT Our patient was a 52-year-old man with end-stage renal disease who underwent a second living donor renal transplant. The donor was his son, with whom he had 1 antigen mismatch. Postoperative day 1, the patient developed anuria and failed to improve with fluids and diuretics. Investigations ruled out common causes of renal dysfunction (rejection, ischemia), but failed to disclose the cause of this condition. After an extended period of watchful waiting, the graft function returned, reaching normal creatinine and urine output levels. CONCLUSIONS DGF after living donor kidney transplantation is rare, and few cases lasting more than a month have been reported. Before diagnosing DGF, other causes of renal dysfunction (rejection, ischemia, medication adverse effects) must be ruled out. In the absence of these, expectant management is appropriate and full graft recovery can be expected, even with anuria and hemodialysis.

Clinical Practice Guidelines for Liver Transplantation in Saudi Arabia.

The demand for liver transplantation in the Kingdom of Saudi Arabia (KSA) is associated with the country's high burden of liver disease. Trends in the epidemiology of liver transplantation indications among recipients in KSA have changed over 20 years. Non-alcoholic steatohepatitis has eclipsed the hepatitis C virus in the country due to the effective treatment strategies for HCV. Risk factors for NASH, like type 2 diabetes mellitus, obesity, and hyperlipidemia, are becoming a major concern and a leading indication for liver transplantation in the KSA. There is also a significantly increased prevalence and incidence of genetic adult familial liver diseases in KSA. New immunosuppressive agents and preservation solutions, improved surgical capabilities, and early disease recognition and management have increased the success rate of liver transplant outcome but concerns about the side effects of immunosuppressive therapy can jeopardise long-term survival outcomes. Despite this, indications for liver transplantation continue to increase, resulting in ongoing challenges to maximize the number of potential donors and reduce patient mortality rate while expecting to get transplanted. The Saudi Center of Organ Transplant is the recognized National Organ Donation Agency for transplantation, which renders important support for procurement and allocation of organs. This guidance document aims to help healthcare providers in managing patients in the liver transplant setting.

Recurrence of hepatitis C virus genotype-4 infection following orthotopic liver transplantation: natural history and predictors of outcome.

BACKGROUND AND OBJECTIVES: There are few reports on hepatitis C virus genotype 4 (HCV-4) recurrences after orthotopic liver transplantation (OLT). Therefore, we undertook a study to determine the epidemiological, clinical and virological characteristics of patients with biopsy-proven recurrent HCV infection and analyzed the factors that influence recurrent disease severity. We also compared disease recurrence and outcomes between HCV-4 and other genotypes. PATIENTS AND METHODS: All patients who underwent OLT (locally or abroad) for HCV related hepatic cirrrhosis from 1991 to 2006 and had recurrent HCV infection were identified. Clinical, laboratory and pathological data before and after OLT were collected and analyzed. RESULTS: Of 116 patients who underwent OLT for hepatitis C, 46 (39.7%) patients satisfied the criteria of recurrrent hepatitis C. Twenty-nine (63%) patients were infected with HCV genotype 4. Mean (SD) for age was 54.9 (10.9) years. Nineteen of the HCV genotype 4 patients (65.5%) were males, 21 (72.4%) received deceased donor grafts, and 7 (24.1%) developed > or =1 acute rejection episodes. Pathologically, 7 (24.1%) and 4 (13.8%) patients had inflammation grade 3-4 and fibrosis stage 3-4, respectively. Follow-up biopsy in 9 (31%) HCV genotype 4 patients showed stable, worse and improved fibrosis stage in 5, 2 and 2 patients, respectively. Of the 7 patients in the recurrent HCV group who died, 6 were infected with genotype 4 and 4 of them died of HCV-related disease. CONCLUSION: This analysis suggests that HCV recurrence following OLT in HCV-4 patients is not significantly different from its recurrence for other genotypes.

Adult Living Donor Liver Re-Transplant Following Late Pediatric Liver Transplant Failure: A Case Report.

BACKGROUND Re-transplant of a late failing living donor liver graft using another graft from another living donor is a rare occurrence and is associated with high mortality due to the complexity of the procedure. There are only a few such case series reported in the literature, mainly from South Asia and Japan, where living donor liver transplant is commonly performed, and there are no such reports from Western countries. CASE REPORT This is a case of living donor liver re-transplant for a 28-year-old recipient whose graft failed 14 years after his primary living donor transplant for primary sclerosing cholangitis. The second transplant was a right-lobe graft obtained from a living donor. The presence of portal vein thrombosis in the setting of high Model for End-Stage Liver Disease (MELD) score added to the complexity of the case. The procedure was concluded successfully with an uneventful post-operative course. The patient was discharged 3 weeks after the procedure. One-year follow-up showed a normally functioning graft. CONCLUSIONS Successfully re-transplanting a patient with a failing living donor liver graft from a living donor is possible if sufficient surgical expertise is available and the risk and benefit are carefully considered. This is especially important in countries where a cadaveric graft is difficult to obtain due to organ scarcity.

A ruptured graft hematoma in the second day after deceased donor liver transplantation: a case report and review.

BACKGROUND: Ruptured liver after transplant is a rare complication. It can lead to graft or patient loss. Few reports are available in literature. CASE REPORT: A 58 y old male patient underwent a deceased donor liver transplant due to hepatitis B virus related cirrhosis. The donor was a 38 y old trauma victim. There were no obvious injuries involving the liver during organ recovery but multiple petechiae appeared on the surface of the right lobe after preservative solution infusion. The transplant procedure was uneventful. The patient recovered quickly. On the second day the patient developed severe hypotension and laparotomy showed a deep laceration in the right lobe separating the anterior and posterior sectors. Massive blood transfusion was needed. Homeostasis was extremely dif fi cult and partial right lobe resection needed to control bleeding. The patient recovered and was discharged two weeks after the transplant. CONCLUSIONS: Hematomas secondary to interventional procedures may be treated conservatively but spontaneous hematomas mostly will need surgery. The presence of petechiae on the surface of the graft may indicate a high energy injury and the possibility of intrahepatic hematoma that may rupture after implantation.

Risk factors for biliary complications after living-donor liver transplant: a single-center experience.

OBJECTIVES: Biliary complications remain a major concern in living-donor liver transplant. They can lead to patient and graft loss. In this study, we retrospectively analyzed patients' records to identify factors that increase the frequency of biliary complications in living-donor liver transplant with an aim toward decreasing this frequency. MATERIALS AND METHODS: We performed 53 living-donor liver transplants between November 2002 and September 2007. Five cases were excluded because of graft or patient loss within 2 weeks resulting in 48 cases available for analysis. The effect of the following variables on the frequency of biliary complications was analyzed: recipient age, liver lobe used, number of graft bile ducts, number of biliary anastomoses, type of biliary anastomosis, and bile duct diameter 4 mm or smaller. RESULTS: Biliary complications were seen in 14 cases (29.1%). These included 9 biliary strictures, 3 bile leaks, and 2 bile leaks eventually healing as biliary strictures. The presence of more than 1 graft bile duct increased the frequency of biliary complications (P = .03). The other variables did not have a statistically significant effect on the frequency of biliary complications. CONCLUSIONS: The rate of complications in our experience is comparable to that already published. The presence of more than 1 bile duct in the graft is a risk factor for biliary complications in living-donor liver transplant. A review of the data suggests additional risk factors.

Experience with 122 consecutive liver transplant procedures at King Faisal Specialist Hospital and Research Center.

BACKGROUND: Saudi Arabia is a leading country in the Middle East in the field of deceased-donor liver transplantation (DDLT) and living-donor liver transplantation (LDLT). We present out experience with DDLT and LDLT at King Faisal Specialist Hospital and Research Center (KFSHRC) for the period from April 2001 to January 2007. PATIENTS AND METHODS: We performed 122 LT procedures (77 DDLTs and 45 LDLTs) in 118 patients (4 re-transplants) during this period of time. RESULTS: The number of adult and pediatric procedures was 107 and 11, respectively. The overall male/female ratio was 66/52 and the median age of patients was 43 years (range, 2-63 years). In the DDLT group, the median operating time was 8 hours (range, 4-19), the median blood transfusion was 6 units (range, 0-40), and the median hospital stay was 13 days (range, 6-183). In the DDLT group, after a mean follow-up period of 760 days (range, 2-2085), the overall patient and graft survival rate was 86%. In the LDLT group, the median operating time was 11 hours (range, 7-17), the median blood transfusion was 4 units (range, 0-65), and the median hospital stay was 15 days (range, 7-127). In the LDLT group, and after a mean follow-up period of 685 days (range, 26- 1540), the overall patient and graft survival rates were 90% and 80%, respectively with no significant difference in patient and graft survivals between groups. Biliary complications were significantly higher in LDLT compared to DDLT (P<0.05). Vascular complications were also significantly higher in LDLT compared DDLT (P<0.05). CONCLUSIONS: Both DDLT and LDLT are being successfully performed at KFSHRC with early experience indicating a higher rate of biliary and vascular complications in the LDLT group.

The impact of metabolic syndrome and prevalent liver disease on living donor liver transplantation: a pressing need to expand the pool.

BACKGROUND AND AIMS: Organ shortage has been the ongoing obstacle to expanding liver transplantation worldwide. Living donor liver transplantation (LDLT) is hoped to improve this shortage. The aim of the present study is to analyze the impact of metabolic syndrome and prevalent liver disease on living donations. METHODS: From July 2007 to May 2012, 1065 potential living donors were evaluated according to a stepwise evaluation protocol. The age of the worked-up donors ranged from 18 to 45 years. RESULTS: Only 190 (18%) were accepted for donation, and 875 (82%) were rejected. In total, 265 (24.9%) potential donors were excluded because of either diabetes or a body mass index >28. Some potential donors were excluded at initial screening because of incompatible blood groups (115; 10.8%), social reasons (40; 3.8%), or elevated liver enzymes (9; 1%). Eighty-five (8%) donors were excluded because of positive hepatitis serology. Steatosis resulted in the exclusion of 84 (8%) donors. In addition, 80 (7.5%) potential donors were rejected because of variations in biliary anatomy, and 20 (2%) were rejected because of aberrant vascular anatomy. Rejection due to biliary-related aberrancy decreased significantly in the second half of our program (11 vs. 4%, p = 0.001). In total, 110 (10.3%) potential donors were rejected because of insufficient remnant volume (<30%) as determined by CT volumetry, whereas 24 (2.2%) were rejected because of a graft-to-recipient body weight ratio less than 0.8%. CONCLUSION: Metabolic syndrome and viral hepatitis negatively impacted our living donor pool. Expanding the donor pool requires the implementation of new strategies.

Liver transplantation for hepatitis B virus: Decreasing indication and changing trends.

AIM: To evaluate the indication and outcome of hepatitis B virus (HBV)-related liver transplantation (LT) in the era of newer antiviral agents. METHODS: We collected data on all patients who underwent transplantation at King Faisal Specialist Hospital and Research Center. These data included demographic, perioperative and long-term postoperative follow-up data including viral serological markers, HBV DNA, and repeated liver imaging. Between January 1990 and January 2012, 133 patients (106 males and 27 females) underwent LT for HBV-related cirrhosis at our center. All patients were followed up frequently during the first year following transplantation, according to our standard protocol; follow-up visits occurred every 3-6 mo thereafter. Breakthrough infection was defined as re-emergence of HBV-DNA or hepatitis B surface antigen (HBsAg) while on treatment. Five patients transplanted prior to 1992 did not receive immediate posttransplant anti-HBV prophylaxis; all other patients were treated with HBIG and at least one nucleos(t)ide analog. RESULTS: One hundred and thirty-three patients underwent LT for HBV and were followed for a median of 82 mo (range: 1-274). The rates of post-LT survival and HBV recurrence during the follow-up period were 89% and 11%, respectively. The following factors were associated with disease recurrence: younger age (44.3 ± 16.2 years vs 51.4 ± 9.9 years, P = 0.02), positive pretransplant hepatitis B e antigen (HBeAg) (60% vs 14%, P < 0.0001), detectable pretransplant HBV DNA (60% vs 27%, P = 0.03), positive posttransplant HBsAg (80% vs 4%, P < 0.0001) and positive posttransplant HBeAg (27% vs 1%, P < 0.0001). Forty-four (33%) patients had hepatocellular carcinoma (HCC). In the first (pre-2007) group, HBV was the second leading indication for LT after hepatitis C virus infection. A total of 64 transplants were performed, including 46 (72%) for decompensated HBV cirrhosis, 12 (19%) for decompensated cirrhosis complicated by HCC and 6 (10%) for compensated cirrhosis complicated by HCC. In the second group, nonalcoholic steatohepatitis surpassed HBV as the second leading indication for LT. A total of 69 HBV related transplants were performed, including 43 (62%) for decompensated HBV cirrhosis, 7 (10%) for decompensated cirrhosis complicated by HCC and 19 (27.5%) for compensated cirrhosis complicated by HCC. There was a significant (P = 0.007) increase in the number of transplants for compensated cirrhosis complicated by HCC. CONCLUSION: The use of potent anti-HBV agents has led to a changing trend in the indications for LT. HBV is currently the third leading indication for LT in this hyperendemic area.

De novo malignancies after liver transplantation: a single-center experience.

BACKGROUND AND OBJECTIVES: The recipients of liver transplantation (LT) are subjected to lifelong immunosuppression with its many drawbacks. De novo and recurrent malignancy in transplant recipients are attributed to attenuation of immunosurveillance. In the present study, we present our experience with de novo malignancies encountered after both deceased and living donor liver transplantations. DESIGN AND SETTING: Retrospective study of patients referred to LT center between April 2001 and January 2010. PATIENTS AND METHODS: Various data were collected including type of malignancy and histopathologic features, immunosuppression regimen, and patient survival. RESULTS: Of 248 LT procedures performed in 238 patients (10 retransplants), 8 patients (3.4%) developed de novo post-LT malignancies. De novo malignancies included post-LT lymphoproliferative disorders (PTLD) in 5 patients who were all Epstein-Barr virus (EBV) positive, and who were treated successfully with anti-CD20 monoclonal antibody therapy, reduction of immunosuppression, and control of EBV activity; urinary bladder cancer in 1 patient who was treated with radical surgical resection and chemotherapy but died of bone and lung metastasis within 1 year of diagnosis; endometrial carcinoma in 1 patient who was treated with radical surgical resection; and Kaposi sarcoma in 1 patient who was successfully treated with surgical excision and reduction of immunosuppression. CONCLUSION: EBV-associated PTLD is the most frequently encountered de novo malignancy after LT and is easily treatable by chemotherapy and reduction of immunosuppression.

Liver transplantation in patients with hepatocellular carcinoma: a single-center experience.

OBJECTIVES: Liver transplantation has become one of the best treatment options for early hepatocellular carcinoma in cirrhosis. We sought to study the results of liver transplantation in patients with hepatocellular carcinoma and to evaluate the outcome of the patients. MATERIALS AND METHODS: The medical records of 256 recipients who underwent a liver transplantation from April 2001 to January 2010 were reviewed. One hundred seventy-six patients received their livers from deceased donors, and 80 received their livers from living donors. Fifty-two patients underwent liver transplantation for hepatocellular carcinoma. RESULTS: From April 2001 until now, 52 patients (20.3%) underwent liver transplantation for hepatocellular carcinoma. Eighteen patients (34.6%) were performed from living-related donors, and 34 (65.4%) were from deceased donors. The patients were 37 males and 15 females (median, 55 years old; age range, 5 through 68 years). Model for end-stage liver disease score ranged from 6 to 40 with a median of 14. All patients were within the Milan criteria by the preoperative evaluation. Hospital stay ranged from 6 to 338 days with a median 14 days. Operating time ranged from 4 to 15 hours with a median 7.5 hours. Blood transfusion ranged from 0 to 19 units median 5 units. Thirty-four complications occurred in 23 patients (44.2%). Recurrence of hepatocellular carcinoma in 7 patients (13.5%), of which recurrent cholangiocarcinoma was diagnosed in 3 (5.7%), accidentally discovered in the explant. One deceased donor had hepatitis B core antibody positive. One explant showed macrovascular invasion. Sixteen patients died, 7 of 52 (13.5%) from hepatocellular carcinoma recurrence, including the 3 cases of accidental discovery of cholangiocarcinoma (5.7%). CONCLUSIONS: Apart from the common complications that can occur with any transplantation, liver transplantation remains the most-promising solution for patients with hepatocellular carcinoma among the available ones, and represents a cornerstone in managing hepatocellular carcinoma. It is the only acceptable option for complete eradication of both the disease and the predisposing factor.