Efficacy of generic sofosbuvir with daclatasvir compared to sofosbuvir/ledipasvir in genotype 4 hepatitis C virus: A prospective comparison with historical control.

Background and Aim: Management of genotype 4 hepatitis C virus (HCV) has shifted to interferon-free regimens with a high sustained virological response (SVR-12), especially with NS5B/NS5A inhibitor combinations such as sofosbuvir and ledipasvir (Sof-Led). The guidelines have recommended the combination of sofosbuvir and another NS5A inhibitor, daclatasvir, to manage HCV genotypes 1-3. However, its use was extended to genotype 4 HCV based on extrapolating evidence. Our aim is to assess the efficacy of generic sofosbuvir + branded daclatasvir (Sof-Dac) compared to the Sof-Led combination in treating genotype 4 HCV. Methods: This study is an open-label, 2-period, noninferiority study that compared patients receiving a combination of generic sofosbuvir 400 mg and daclatasvir 60 mg orally daily (Group 2) prospectively to a historical control (Group 1) that included patients who received a combination of sofosbuvir/ledipasvir 400/90 mg orally daily. The primary endpoint is the proportion of patients who achieved SVR-12. Results: The study included 111 patients in the (Sof-Led) Group 1 and 109 patients (Sof-Dac) Group 2. For the primary outcome, SVR-12 was achieved in 106 (95.5%) of the patients in Group 1 versus 108 (99.1%) in Group 2 (p = 0.2). In addition, all patients who achieved SVR-12 also achieved SVR-24. Conclusion: Generic sofosbuvir combined with branded daclatasvir was safe and effective for treating genotype 4 HCV compared to Sof-Led. This combination may significantly reduce the cost burden, enabling a larger pool of treated patients. Office of research affairs at KFSHRC RAC# 2171 036.

The use of ex-vivo liver perfusion circuit in sheep model: Preliminary report.

OBJECTIVES: To describe a novel animal model for ex-vivo liver perfusion. METHODS: This study was carried out at King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia, between September 2016 and January 2019. We assembled a perfusion circuit operated by a continuous pressure-driven arterial pump with continuous portal and arterial pressure and volume measurements. We used normothermic oxygenated perfusate. The livers used were retrieved from the sheep. RESULTS: Ex-vivo continuous perfusion of the liver was achieved for up to 9 hours with stable pressure and volume in both hepatic artery and portal vein. In 4 experiments the arterial pressure was kept in a range of 48-52 mmHg with a mean of 51.75±4.31 resulting in arterial volume at steady state of 223.5±48.25 ml/minute (95% confidence level). At steady state the mean portal pressure was 16.25±1.45 mmHg with a mean volume of 854±313.75 ml/minute (95% confidence level). Bile production was observed during the perfusion period. Hemodynamic parameters were similar to the physiological parameters observed in normothermic perfusion model of the porcine liver. CONCLUSION: A normothermic oxygenated ex-vivo perfusion circuit was successfully constructed using the sheep liver. A sustainable functional circuit with physiological hemodynamic parameters was achieved. Further study on sheep model seems to be feasible.

Identification of Gene Signature as Diagnostic and Prognostic Blood Biomarker for Early Hepatocellular Carcinoma Using Integrated Cross-Species Transcriptomic and Network Analyses.

Background: Hepatocellular carcinoma (HCC) is considered the most common type of liver cancer and the fourth leading cause of cancer-related deaths in the world. Since the disease is usually diagnosed at advanced stages, it has poor prognosis. Therefore, reliable biomarkers are urgently needed for early diagnosis and prognostic assessment. Methods: We used genome-wide gene expression profiling datasets from human and rat early HCC (eHCC) samples to perform integrated genomic and network-based analyses, and discovered gene markers that are expressed in blood and conserved in both species. We then used independent gene expression profiling datasets for peripheral blood mononuclear cells (PBMCs) for eHCC patients and from The Cancer Genome Atlas (TCGA) database to estimate the diagnostic and prognostic performance of the identified gene signature. Furthermore, we performed functional enrichment, interaction networks and pathway analyses. Results: We identified 41 significant genes that are expressed in blood and conserved across species in eHCC. We used comprehensive clinical data from over 600 patients with HCC to verify the diagnostic and prognostic value of 41-gene-signature. We developed a prognostic model and a risk score using the 41-geneset that showed that a high prognostic index is linked to a worse disease outcome. Furthermore, our 41-gene signature predicted disease outcome independently of other clinical factors in multivariate regression analysis. Our data reveals a number of cancer-related pathways and hub genes, including EIF4E, H2AFX, CREB1, GSK3B, TGFBR1, and CCNA2, that may be essential for eHCC progression and confirm our gene signature's ability to detect the disease in its early stages in patients' biological fluids instead of invasive procedures and its prognostic potential. Conclusion: Our findings indicate that integrated cross-species genomic and network analysis may provide reliable markers that are associated with eHCC that may lead to better diagnosis, prognosis, and treatment options.

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.

Utility of post-liver transplantation MELD and delta MELD in predicting early and late mortality.

INTRODUCTION: The performance of early post-liver transplantation (post-LT) model for end-stage liver disease (MELD) or even its dynamic changes over time (ΔMELD) in predicting the mortality after LT is still controversial. AIM: The aim of this study was to assess the ability of absolute and ΔMELD calculated at days 7 and 30 after LT to predict 1- and 5-year mortality. PATIENTS AND METHODS: Data of 209 consecutive patients who underwent LT in two centers were reviewed. Patients who received LT for hepatocellular carcinoma were excluded, as well as those who did not survive for at least 1 month. MELD and [INCREMENT]MELD were calculated for each patient at 7 and 30 days after LT. RESULTS: One hundred fifty-six patients were included, mostly male [104 (66.7%)] with a mean age of 51.9±8.8 years. The main indications for transplantation were decompensated hepatitis C virus-related liver cirrhosis [138 (88.5%)] and hepatitis C and B virus co-infection [10 (6.4%)]. Grafts were obtained from 104 living donors and 52 deceased donors. Survival at 1 and 5 years was 89.7 and 85.9%, respectively, with a mean survival of 52.3±1.5 months. In univariate analysis, both absolute and ΔMELD at postoperative days 7 and 30 significantly predicted 1- and 5-year post-LT mortality. In multivariate analysis, MELD at postoperative day 30 was significantly associated with 1- (odds ratio: 1.24, 95% confidence interval: 1.14-1.35, P<0.0001) and 5-year mortality (odds ratio: 1.23, 95% confidence interval: 1.14-1.33, P<0.0001). The area under the curve for MELD at 30 days post-LT in the prediction of mortality was 0.823 (P=0.01) at 1 year and 0.812 (P<0.001) at 5 years. A cutoff of post-LT day 30 MELD less than 10 could predict mortality with a sensitivity and specificity of 90 and 68.1% at 1 year and 81.3 and 69.7% at 5 years, respectively. CONCLUSION: Failure of the MELD score to decline over the first postoperative month to less than 10 is a significant predictor of both early and late post-LT mortality.

Treatment of Patients With Hepatitis C Virus Infection With Ledipasvir-Sofosbuvir in the Liver Transplant Setting.

BACKGROUND: Hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma and the leading indication for liver transplantation. In the Middle East, genotype 4 HCV infection is the most common genotype. However, limited data exists on the treatment of genotype-4 in the liver transplant setting. We evaluated the safety and efficacy of ledipasvir (LDV)-sofosbuvir (SOF) in treating HCV genotype-4 infected patients with cirrhosis or postliver transplantation. METHODS: This prospective, single-arm, observational study includes cohort of patients with cirrhosis before liver transplantation (cohort A) and a cohort of postliver transplantation patients (cohort B). Patients received LDV/SOF (90-400 mg) once daily for 12 to 24 weeks with or without ribavirin (RBV). Patients with creatinine clearance below 30 were excluded. RESULTS: A total of 111 patients (61 cirrhotic; 50 postliver transplants) with HCV genotype 4 were treated in King Faisal Specialist Hospital and Research Center; 55% cohort A and 44% cohort B received RBV. Sustained virological response sustain virological response (SVR)12 was 91.8% and 86% of cohorts A and B, respectively. There were no treatment-related mortality or serious adverse effects. RBV dose reduction occurred in 25% without any treatment discontinuation. SVR12 rates in cohort A were significantly higher in patients with a viral load below 800 000 (100% vs 83.9%, P value = 0.022). Viral load did not impact SVR rates in cohort B. The use of RBV did not increase SVR12 and was associated with anemia. CONCLUSIONS: LDV/SOF without RBV is an effective and safe treatment option for patients with HCV genotype 4 infection in preliver and postliver transplant settings.

Liver transplantation in the Kingdom of Saudi Arabia.

The first liver transplantation (LT) in Saudi Arabia was performed in 1991; however, it was not until 1994 that the first structured LT program was launched. Until 1997, all LTs in the Kingdom of Saudi Arabia (KSA) were deceased donor liver transplantations. Programs performing LTs needed the authorization of the Saudi Center for Organ Transplantation (SCOT), which provides the essential support for organ procurement and allocation as well as regulatory support for organ transplantation in the country. Currently, there are 4 LT centers in the KSA. Three centers are in Riyadh, the capital city of KSA, and 1 is in the city of Dammam in the Eastern province. Pediatric living donor liver transplantation (LDLT) began in 1997, while the adult LDLT program started 4 years later in 2001. Currently, more than 2000 LTs have been performed by the 4 centers in the KSA. Over 50% of those were performed at King Faisal Specialist Hospital and Research Center in Riyadh. The outcomes of these transplants have been comparable with the international standards. The aim of this review is to provide an overview of LT in KSA. Liver Transplantation 23 1312-1317 2017 AASLD.

Effect of Downstaging and Bridging of Hepatocellular Carcinoma on Survival Following Liver Transplant: A Single Center Experience.

OBJECTIVES: Hepatocellular carcinoma is among the leading causes of cancer death. The Milan criteria are the first and most widely used criteria for selecting patients with hepatocellular carcinoma for a good transplant outcome. Studies have shown that patients with hepatocellular carcinoma outside the Milan criteria have good outcomes if they are successfully downstaged before transplant. We report our experience with locoregional therapy for hepatocellular carcinoma, either for bridging or for downstaging prior to transplant. MATERIALS AND METHODS: We retrospectively reviewed the electronic charts and our institutional database for adult patients diagnosed with hepatocellular carcinoma between 2001 and 2016. We recorded patient demographics, the type of transplant (living donor or deceased donor), radiologic findings, the type of locoregional intervention, and overall survival. RESULTS: A total of 642 adult liver transplants were performed during the study period (290 living donor and 352 deceased donor), of which 158 (24.6%) were conducted in patients with hepatocellular carcinoma (104 men and 54 women). Hepatocellular carcinoma was associated with hepatitis C in 80 patients (51%), hepatitis B in 44 (28%), and was cryptogenic in 13 (8%). Patients were grouped based on their radiologic staging (within Milan, within and beyond University of California, San Francisco), and subsequently described by whether they received locoregional therapy. Median survival and mortality were noted. Kaplan-Meier survival curves showed no statistically significant difference for patients within the Milan criteria, with or without locoregional therapy (P = .5). When patients within the Milan criteria were combined with patients within the University of California, San Francisco criteria, those who were downstaged from outside the latter criteria had similar survival. CONCLUSIONS: We demonstrate that carefully selected patients beyond the Milan criteria and even beyond the University of California, San Francisco criteria can be bridged and downstaged successfully for liver transplant.

Aggressive Recurrence of Primary Hepatic Epithelioid Haemangioendothelioma after Liver Transplantation.

HEHE is a rare neoplasm of vascular origin that occurs in the liver; UNOS reported a favorable outcome after liver transplantation in 110 patients with 1-year and 5-year survival of 80% and 64%. Case Report. A 40-year-old lady presented with a three-month history of right upper abdominal pain with nausea, vomiting, and significant loss of weight associated with scleral icterus and progressive abdominal distension. Examination revealed jaundice, hepatomegaly, and ascites. Serum bilirubin was 26.5 mg/dL and ALP was 552 CT. Abdomen and pelvis showed diffuse infiltrative neoplastic process of the liver with a mass effect and stretching of the hepatic and portal veins, in addition to bile duct dilatation. Viral hepatitis markers were negative and serum alpha fetoprotein was within reference range. Liver biopsy was consistent with HEHE, with positive endothelial markers (CD31, CD34, and factor VIII-related antigen). She underwent living related liver transplantation on June 2013 and was discharged after 20 days with normal liver enzymes. Four months later, she presented with diffuse disease recurrence. Liver biopsy confirmed disease recurrence; she received supportive treatment and unfortunately she died 2 weeks later. Conclusion. HEHE can have rapid and aggressive recurrence after liver transplantation.

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.

Graft-versus-Host Disease after Liver Transplantation: A Single-Center Case Series.

BACKGROUND: Graft versus host disease (GVHD) is a rare complication following liver transplantation (LT) and has high mortality. We describe our single-center experience with 6 cases of GVHD diagnosed over a period of 14 years in a total of 604 liver transplant recipients--283 deceased donor liver transplants (DDLT) and 321 living-related liver transplants (LDLT). CASE REPORT: We report a case series of 6 patients with acute GVHD after liver transplantation from May 2001 to December 2014. Five cases were males; age 51-67 years (average 61). The time from transplantation until clinical presentation of GVHD ranged from 36 to 140 days, with average duration of 72 days. All cases had diarrhea and pancytopenia, 4 out of 5 presented with erythematous skin rashes, and 2 had cytomegalovirus colitis. GVHD was confirmed by skin biopsies, engraftment profile from bone marrow biopsy, and sigmoid colon biopsy. Treatment strategies included use of corticosteroids in 4 cases, stopping immunosuppression in 1 case, and no treatment in 1 case with mild disease. Five patients died between 18 to 65 days from clinical presentation (average 43 days) and 1 patient with mild GVHD is doing well 290 days after clinical presentation. CONCLUSIONS: GVHD is a rare complication after liver transplantation that needs a high index of suspicion in patients who develop rash, diarrhea, or sever pancytopenia. There is no consensus on the best treatment regimen and mortality remains high.

An analysis of outcomes of liver retransplant in adults: 12-year's single-center experience.

OBJECTIVES: Liver retransplant is the only therapeutic option for irreversible liver graft failure. Its incidence varies between 5% and 22% worldwide. Liver retransplant - despite some recent improvement - is associated with significantly poorer outcome compared with the primary transplant. The purpose of this study was to assess the outcome of liver retransplant compared with primary liver transplant, compare the outcome of early and late liver retransplant, and to evaluate the outcome of liver retransplant within different predictive index categories. MATERIALS AND METHODS: We retrospectively reviewed adult patients who had liver retransplant from May 2001 to December 2013. Patients were divided into 2 groups: group A (early liver retransplant), retransplant within 30 days; and group B (late liver retransplant), retransplant > 30 days after primary liver transplant. RESULTS: After 460 primary adult liver transplants, 17 liver retransplants (3.7%) were performed in 16 adults. Mean patient survival after liver retransplant was 29.5 ± 31.9 months. The 1-, 3-, and 5-year patient survival was 68.8%, 51.6%, and 38.7%. Mean graft survival following liver retransplant was 27.9 ± 32.1 months, and 1-, 3-, and 5-year graft survival was 51.5%, 34.3%, and 22.9%. Patient and graft survival was significantly better in group B than group A at 1 year and 3 years. There were 9 liver retransplants (52.9%) with predictive index category IV; 7 retransplants (41.2%) with predictive index category III; and 1 retransplant (5.9%) with predictive index category II. Patient survival was significantly higher for predictive index category III than IV at 1 year and 3 years. CONCLUSIONS: Patient and graft survival are lower after liver retransplant than primary liver transplant. Graft and patient survival are better in late than early liver retransplant and in predictive index category III than IV.

Passing loop technique for portal inflow modulation in liver recipients with partial portal vein thrombosis: a case report.

Refinements of surgical techniques in liver transplant during the last 10 years have offered more successful outcomes for recipients with portal vein thrombosis. Patency of the portal vein after a thrombectomy can be neither adequately evaluated, nor objectively assessed; therefore, we suggest that rerouting part of the portal flow through a "passing loop," with or without augmenting the portal flow, may be a salvage procedure, when there is a possible postoperative rethrombosis of the portal vein.

Liver transplant in Budd-Chiari syndrome: a single-center experience in Saudi Arabia.

OBJECTIVES: If they do not respond to other treatments, patients with Budd-Chiari syndrome are potential candidates for a liver transplant. Timing for transplant is controversial; however, before other systems deteriorate, early intervention in relatively stable patient may improve the outcome and survival of these patients. MATERIALS AND METHODS: Six patients (2 women and 4 men) had Budd-Chiari syndrome (1.2%) among 475 patients who had undergone a liver transplant at our center between 2001 and 2012. Imaging modalities including duplex ultrasound, abdominal computed tomography angiography, and hematologic evaluation were part of our routine diagnostic work-up. Although we perform mostly living-donor liver transplants, these patients received a liver transplant from a deceased donor, because there was not enough evidence to justify a living-donor liver transplant. We thought that not replacing the caval vein might negatively influence the outcome. Postoperatively, these recipients were started on a heparin infusion and triple therapy immunosuppression; only then was warfarin introduced as long-term anticoagulant. RESULTS: Two patients died, 1 from uncontrollable bleeding and disseminated intravascular coagulopathy, and the other died in the intensive care unit after 5 months because of multiorgan failure and sepsis. One patient had portal vein thrombosis 9 months after the liver transplant; the other patient needed a liver retransplant after 5 years owing to liver failure, secondary to chronic rejection. Graft survival rate was 75%, and patient survival rate was 66.6%. CONCLUSIONS: This is the first article from Saudi Arabia to describe the outcome of a liver transplant in this subgroup of patients with Budd-Chiari syndrome. Treatment of Budd-Chiari syndrome follows a therapeutic algorithm that should start with anticoagulation and may end up with liver transplant; however, it should be considered early if other treatments fail.

Liver transplantation in Wilson's disease: Single center experience from Saudi Arabia.

AIM: To determine liver transplantation outcomes in Wilson's disease (WD) patients, focusing on neurological manifestations. METHODS: This retrospective study assessed data from 16 WD patients (nine males, 56%) who had liver transplants between 1991 and 2007. Survival, graft function, and neurological complications were assessed during a follow-up period of up to 15 years. In addition, each patient's medical record was reviewed in detail to find the type of Wilson's disease (hepatic or hepatic plus neurological WD), indication for liver transplantation, use of chelating agents prior to transplantation, immediate and long term complications following transplantation, the donor details, and the pathology of explanted liver. RESULTS: End-stage liver disease was the indication for transplantation in all 16 WD patients. Four patients displayed WD-related neurological symptoms in addition to liver disease. Living-related liver transplantation was done in three cases. One patient died on postoperative day 6 due to primary graft non-function. One-year post liver transplant survival was 94%. Neurological manifestations of all four patients disappeared during their follow-up. Four patients developed acute cellular rejection, but all responded to treatment. One patient developed chronic ductopenic rejection after 15 years post-transplantation and their graft failed; this patient is currently waiting for re-transplantation. Fourteen patients (88%) are still living. The long-term average survival is currently 10.5 years, with a current median survival of 8 years. Long-term graft survival is currently 81%. CONCLUSION: Short- and long-term survival in WD patient liver transplantation was excellent, and neurological and psychological WD manifestations disappeared during long-term follow-up.

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.

Coincidental occurrence of hepatocellular carcinoma and cholangiocarcinoma (collision tumors) after liver transplantation: a case report.

Coincidental occurrence of hepatocellular carcinoma (HCC) and cholangiocarcinoma, known as "collision tumors", within a cirrhotic liver is rare. Herein, we report a case of liver transplantation (LT) in a patient with such collision tumors. Our patient was a 56-year-old woman with hepatitis C virus-related cirrhosis and 2 focal hepatic lesions, measuring 1.5 and 3 cm, in the liver segments 8 and 5, respectively. The lesion on segment 8 showed the typical radiological characteristics of HCC; however, the lesion in segment 5 showed an atypical vascular pattern and was closely associated with the inferior vena cava. Serum alpha-fetoprotein level was normal and serum carbohydrate antigen 19-9 (CA19-9) level was slightly elevated (63 U/mL); the extrahepatic spread of HCC was ruled out. The patient underwent an uneventful deceased-donor LT. Histopathological examination of the explant confirmed that the lesion on segment 8 was an HCC, but surprisingly, the lesion on segment 5 was found to be a cholangiocarcinoma. Six months after LT, the serum CA19-9 level was markedly elevated (255 U/mL), and the patient began experiencing abdominal pain. Magnetic resonance imaging showed enlarged hilar and paraaortic lymph nodes that were suggestive of metastases; histopathological analysis using ultrasound (US)-guided biopsy confirmed recurrent cholangiocarcinoma. Unfortunately, the patient died because of tumor recurrence 9 months after LT.Collision tumor resulting from the co-existence HCC and cholangiocarcinoma in a cirrhotic liver is rare and has a negative impact on the outcome of LT. Atypical vascular pattern and elevated serum CA19-9 levels are suggestive of such tumors; patients with these findings should undergo a targeted biopsy to rule out the coincidental occurrence of HCC and cholangiocarcinoma.