Platelet-albumin-bilirubin score - a predictor of outcome of acute variceal bleeding in patients with cirrhosis.

BACKGROUND: The albumin-bilirubin (ALBI) score was validated as a prognostic indicator in patients with liver disease and hepatocellular carcinoma. Incorporating platelet count in the platelet-albumin-bilirubin (PALBI) score improved validity in predicting outcome of patients undergoing resection and ablation. AIM: To evaluate the PALBI score in predicting outcome of acute variceal bleeding in patients with cirrhosis. METHODS: The data of 1517 patients with cirrhosis presenting with variceal bleeding were analyzed. Child Turcotte Pugh (CTP) class, Model of End-stage Liver Disease (MELD), ALBI and PALBI scores were calculated on admission, and were correlated to the outcome of variceal bleeding. Areas under the receiving-operator characteristic curve (AUROC) were calculated for survival and rebleeding. RESULTS: Mean age was 52.6 years; 1176 were male (77.5%), 69 CTP-A (4.5%), 434 CTP-B (29.2%), 1014 CTP-C (66.8%); 306 PALBI-1 (20.2%), 285 PALBI-2 (18.8%), and 926 PALBI-3 (61.1%). Three hundred and thirty-two patients died during hospitalization (21.9%). Bleeding-related mortality occurred in 11% of CTP-B, 28% of CTP-C, in 21.8% of PALBI-2 and 34.4% of PALBI-3 patients. The AUROC for predicting survival of acute variceal bleeding was 0.668, 0.689, 0.803 and 0.871 for CTP, MELD, ALBI and PALBI scores, respectively. For predicting rebleeding the AUROC was 0.681, 0.74, 0.766 and 0.794 for CTP, MELD, ALBI and PALBI scores, respectively. CONCLUSION: PALBI score on admission is a good prognostic indicator for patients with acute variceal bleeding and predicts early mortality and rebleeding.

Validation of modified albumin-bilirubin-TNM score as a prognostic model to evaluate patients with hepatocellular carcinoma.

BACKGROUND: An ideal staging system for hepatocellular carcinoma (HCC) should rely on the hepatic reserve function and tumor burden. With the improvement in diagnostic and treatment strategies for HCC, in addition to recent treatment of viral hepatitis, finding a suitable assessment tool for hepatic reserve has become mandatory. AIM: To validate a recently proposed modified albumin-bilirubin-TNM (mALBI-T) grade as a prognostic model for patients with HCC in Egypt. METHODS: For patients diagnosed with HCC, Child-Turcotte-Pugh (CTP) score, Barcelona Clinic Liver Cancer (BCLC) stage, albumin-bilirubin (ALBI), plateltet-albumin-bilirubin (PALBI), ALBI-based BCLC, ALBI-T and mALBI-T grades were estimated. Patients were followed from time of diagnosis to date of death or date of data collection if they remained alive. Overall survival and received treatments were determined. Survival data were analyzed. RESULTS: A total of 1910 patients were included (mean age, 57 years; 1575 males). At presentation, 50.6% had CTP A, 36.1% had CTP B and 13.4 % had CTP C; 12% had ALBI grade 1, 62.3% had ALBI grade 2 and 24.7% had ALBI grade 3. Overall median survival was 13 mo; survival was better in patients with ALBI 1 than in those with ALBI 2 and 3 (28.6 vs 14 and 5.8 mo, respectively, P < 0.001). Patients with ALBI-T grades 0 and 1 had better survival than those with ALBI-T grades 2, 3, 4 and 5 (P < 0.001). The modified ALBI-T showed better stratification and significant improvement in prediction of survival. CONCLUSION: ALBI-T grade is a superior prognostic tool that selects patients with HCC who have better liver reservoir and tumor stage. mALBI-T is a better prognostic model in patients with HCC.

Change in the hepatic profile of hepatitis C virus genotype 4-infected patients with compensated cirrhosis receiving ombitasvir, paritaprevir, and ritonavir plus ribavirin: A subanalysis of the AGATE-II study.

In AGATE-II, treatment with ombitasvir coformulated with paritaprevir/ritonavir plus ribavirin (RBV) in Egyptians infected with hepatitis C virus genotype 4 resulted in high rates of sustained virologic response at post-treatment week 12. This subanalysis examined the effects of treatment in AGATE-II on liver biomarkers in patients with compensated cirrhosis. AGATE-II was a phase 3, open-label, partly randomized trial of ombitasvir/paritaprevir/ritonavir with weight-based RBV daily once in treatment-naive or treatment-experienced patients. Patients without cirrhosis received treatment for 12 weeks and patients with compensated cirrhosis were randomized 1:1 to the same regimen for either 12 or 24 weeks. Sixty patients with compensated cirrhosis were randomized to treatment for 12 weeks (n = 31) or 24 weeks (n = 29). In the 12-week arm, significant improvements were observed in biomarkers of liver injury (alanine aminotransferase: -53.7 U/L, P < 0.001; aspartate aminotransferase: -35.9 U/L, P < 0.001) and liver fibrosis (aspartate aminotransferase to platelet ratio index: -0.987, P < 0.001; fibrosis-4 index: -1.165, P < 0.001). Similar results were reported in the 24-week arm. Treatment with ombitasvir/paritaprevir/ritonavir plus RBV in hepatitis C virus genotype, 4-infected Egyptians with compensated cirrhosis resulted in improvements in certain biomarkers of liver synthetic function, injury, and fibrosis, independent of treatment duration.

Effectiveness of ravidasvir plus sofosbuvir in interferon-naïve and treated patients with chronic hepatitis C genotype-4.

BACKGROUND & AIMS: Although treatment of hepatitis C virus (HCV) and HCV-genotype-4 (GT4) has become very effective, it remains very expensive, and affordable options are needed, especially in limited resource countries. The aim of this study was to assess the efficacy and safety of the combination of ravidasvir (an NS5A inhibitor) and sofosbuvir to treat patients with chronic HCV-GT4 infection. METHODS: A total of 300 patients with HCV-GT4 infection were recruited in three groups: treatment-naïve patients with or without compensated Child-A cirrhosis (Group 1); interferon-experienced patients without cirrhosis (Group 2); and interferon-experienced patients with cirrhosis (Group 3). Groups 1 and 2 received ravidasvir 200 mg QD plus sofosbuvir 400 mg QD for 12 weeks and were randomized 1:1 to treatment with or without weight-based ribavirin. Group 3 patients received ravidasvir plus sofosbuvir with ribavirin and were randomized 1:1 to a treatment duration of 12 weeks or 16 weeks. The primary endpoint was sustained virologic response at 12 weeks post-treatment (SVR12). RESULTS: A total of 298 patients were enrolled: 149 in Group 1, 79 in Group 2 and 70 in Group 3. SVR12 was achieved in 95.3% of all patients who started the study, including 98% of patients without cirrhosis and 91% of patients with cirrhosis, whether treatment-naïve or interferon-experienced. Ribavirin intake and history of previous interferon therapy did not affect SVR12 rates. No virologic breakthroughs were observed and the study treatment was well tolerated. CONCLUSIONS: Treatment with ravidasvir plus sofosbuvir, with or without ribavirin, was well tolerated and associated with high sustained virologic response rate for HCV-GT4 infected patients with and without cirrhosis, regardless of previous interferon-based treatments. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT02371408. LAY SUMMARY: This study evaluated efficacy and safety of the new oral hepatitis C drug ravidasvir in combination with the approved oral drug sofosbuvir in 298 patients infected with hepatitis C type 4. Our results showed that treatment with ravidasvir plus sofosbuvir, with or without ribavirin, was well tolerated and associated with high response rate in patients with and without cirrhosis.

Hepatitis C infection in Egypt: prevalence, impact and management strategies.

Hepatitis C virus (HCV) infection is a major public health burden in Egypt, where it bears the highest prevalence rate in the world. Estimates for prevalence are based upon data reported from the 2008 and 2015 Egypt Demographic Health Surveys. In this review, we demonstrate the prevalence results of both surveys and analyze the difference in the results. The overall HCV prevalence is estimated to be declining. However, the clinical impact of chronic HCV infection is expected to grow considerably. A mathematical model shows that by increasing the rate of treatment, the expected number of patients will decline significantly in 2030. The current and expected future burden of chronic HCV infection to the Egyptian economy, including direct and indirect costs due to disability and loss of lives, has been estimated and discussed in this review. The economic burden will continue to grow, but a model shows that the introduction of highly effective therapies will result in a significant reduction in the cumulative total economic burden of HCV by 2030. In recognition of the HCV tremendous health and economic burden, the Egyptian government established the National Committee for Control of Viral Hepatitis to implement an integrated nationwide strategy to provide patient care and ensure global treatment access. This review illustrates the epidemiological and disease burden aspects of HCV in Egypt in addition to introducing the national plan and program for managing HCV, which has been successful so far in treating a large number of patients, with the aim of achieving disease control and eventual elimination in Egypt.

Ombitasvir, paritaprevir, and ritonavir plus ribavirin for chronic hepatitis C virus genotype 4 infection in Egyptian patients with or without compensated cirrhosis (AGATE-II): a multicentre, phase 3, partly randomised open-label trial.

BACKGROUND: In Egypt, chronic hepatitis C virus (HCV) infection occurs in around 10% of the population (about 8 million individuals), and is a leading cause of liver cirrhosis, hepatocellular carcinoma, and mortality. Although HCV genotype 4 constitutes about 20% of HCV infections worldwide, the prevalence in Egypt is more than 90%. We assessed the efficacy and safety of the two direct-acting antiviral drugs ombitasvir, an NS5A inhibitor, and paritaprevir, an NS3/4A protease inhibitor dosed with ritonavir, plus ribavirin in treatment of chronic HCV infection in Egypt. METHODS: AGATE-II was a phase 3, open-label, partly randomised trial in patients with chronic HCV genotype 4 infection recruited from five academic and hepatology centres in Egypt. Patients were HCV treatment-naive or treatment-experienced with interferon-based regimens. Eligible patients were aged 18 years or older, and had been chronically infected with HCV genotype 4 for at least 6 months with a plasma HCV RNA concentration of more than 1000 IU/mL at screening. Patients without cirrhosis were assigned to receive 12 weeks of 25 mg ombitasvir, 150 mg paritaprevir, and 100 mg ritonavir orally once daily plus weight-based ribavirin. Patients with compensated cirrhosis were randomly assigned (1:1) to receive the same treatment for either 12 weeks or 24 weeks. Randomisation was stratified by previous pegylated interferon and ribavirin treatment experience using a web-based interactive response technology system and computer-generated schedules prepared by personnel from the funder's statistics department. Investigators were masked to randomisation schedules and were informed of each patient's assigned treatment by the interactive response technology system immediately after allocation. The primary endpoint was the proportion of patients with a sustained virological response (HCV RNA <15 IU/mL) 12 weeks after the last dose of study drug (SVR12). All patients who received at least one dose of study drugs were included in the primary and safety analysis. This study is registered with ClinicalTrials.gov, number NCT02247401. FINDINGS: Between Nov 4, 2014, and March 16, 2015, we screened 182 patients with HCV infection, of whom 160 were eligible for inclusion; 100 patients were assessed as not having cirrhosis and were given 12 weeks of treatment, and 60 patients assessed as having cirrhosis were randomly assigned to the 12-week treatment group (n=31) or the 24-week treatment group (n=29). 94 (94%; 95% CI 88-97) of 100 patients in the without cirrhosis group, 30 (97%; 84-99) of 31 patients in the cirrhosis 12-week treatment group, and 27 (93%; 78-98) of 29 patients in the cirrhosis 24-week treatment group achieved SVR12. The most common adverse events in patients without cirrhosis were headache (41 [41%]) and fatigue (35 [35%]). Fatigue occurred in nine (29%) patients in the cirrhosis 12-week treatment group and 11 (38%) patients in the cirrhosis 24-week treatment group, and headache occurred in nine (29%) patients in the cirrhosis 12-week treatment group and in 10 (35%) patients in the cirrhosis 24-week treatment group. Adverse events were predominantly mild or moderate in severity, and laboratory abnormalities were not clinically meaningful. No patients discontinued treatment because of an adverse event. One serious adverse event in the group without cirrhosis was attributed to study drugs by the investigators; the patient had deep venous thrombosis. INTERPRETATION: Ombitasvir, paritaprevir, and ritonavir plus ribavirin for 12 weeks achieved SVR12 in a high proportion of patients and was well tolerated in Egyptian patients with HCV genotype 4 infection with or without compensated cirrhosis. Extension of treatment to 24 weeks in patients with cirrhosis did not improve the proportion of patients achieving SVR12. A shorter duration regimen could be useful to address the significant burden of HCV genotype 4 infection in patients with compensated cirrhosis. FUNDING: AbbVie.

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.

Real Life Treatment of Hepatocellular Carcinoma: Impact of Deviation from Guidelines for Recommended Therapy.

BACKGROUND: Real life management of hepatocellular carcinoma occasionally deviates from guidelines for recommended therapy. AIMS: To evaluate how frequent this deviation happens in our center and assess its impact on outcome. MATERIALS AND METHODS: The treatment of 770 patients (87% males, mean age 57.8 years) was analyzed and the effect of deviation on outcome over 36 months was examined. RESULTS: Of Barcelona Clinic liver cancer stages 0 and A patients, 65.8% received resection, ablation, liver transplantation or transarterial chemoembolisation for unresectable tumors more than 5 cm in diameter, and 34.2% received treatment recommended for later stages. Of stage B patients, 62.2% received recommended therapy, 34.3% of patients received supportive therapy or sorafenib and 3.5% received upward treatment stage migration. Among stage C patients, 7.6% received sorafenib, and most (79.2%) were given supportive care. Deviation from recommended therapy occurred in 34.2%, 37.7%, and 92.4% in stages 0-A, B and C. Survival of stage 0-A patients who received downwards treatment stage migration was lower than those who received recommended treatment (p <0.001). Upward treatment stage migration in stages B, C and D did not improve survival compared to those who received recommended treatment. CONCLUSIONS: Deviation from recommended therapy had a negative impact on survival in Barcelona Clinic liver cancer stage A patients.

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.

Normal liver stiffness: A study in living donors with normal liver histology.

AIM: To define the normal range of liver stiffness (LS) values using transient elastography in living-related liver transplantation candidate donors with normal liver histology. METHODS: LS was measured using Fibroscan in 50 (16 women, 34 men) healthy potential donors (mean age 28.4 ± 5.9 years) who were being evaluated for liver donation for their relatives at the National Liver Institute, Menoufeya University, Egypt. All potential donors had normal liver tests and were negative for hepatitis B or C virus infection. Abdominal ultrasounds showed normal findings. None of the subjects had diabetes, hypertension, renal impairment, heart disease, or body mass index > 30 kg/m(2). All subjects had normal liver histology upon liver biopsy. They all donated the right lobe of their liver with successful outcomes. RESULTS: The mean LS was 4.3 ± 1.2 kPa (range: 1.8-7.1 kPa). The 5(th) and 95(th) percentiles of normal LS were 2.6 kPa and 6.8 kPa, respectively, with a median of 4 kPa; the interquartile range was 0.6 ± 0.4. LS measurements were not significantly different between men and women (4.4 ± 1.1 kPa vs 3.9 ± 1.3 kPa) and did not correlate with age. However, stiffness values were significantly lower in subjects with a body mass index < 26 kg/m(2) compared to those with an index ≥ 26 kg/m(2) (4.0 ± 1.1 kPa vs 4.6 ± 1.2 kPa; P <0.05). There were no differences in hospital stay or postoperative bilirubin, albumin,alanine and aspartate transaminases, or creatinine levels (at discharge) between donors with livers stiffness ≤ 4 kPa and those with stiffness > 4 kPa. CONCLUSION: Healthy donors with normal liver histology have a median LS of 4 kPa. Stiffness values are elevated relative to increase in body mass index.

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.

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.

Treatment of genotype 4 hepatitis C recurring after liver transplantation using a combination of pegylated interferon alfa-2a and ribavirin.

BACKGROUND: Hepatitis C virus (HCV) recurrence after liver transplantation (LT) is universal and tends to be more aggressive. Data on post-transplant HCV genotype 4 treatment is scarce. The aim of this study is to assess the safety and efficacy of pegylated interferon alpha-2a (PEG-IFN) in combination with ribavirin in the treatment of recurrent HCV genotype 4 after LT. METHODS: Twenty-five patients infected with HCV genotype 4 were treated with PEG-IFN alpha-2a at a dose of 180 µg/week in addition to 800 mg/day of ribavirin (the dose was adjusted within the tolerated range of 400-1,200 mg). Pretreatment liver biopsies were obtained from all patients. Biochemical and virological markers were assessed before, during, and after treatment. RESULTS: Twenty-two patients (88%) achieved an early virological response (EVR) (12 patients tested negative for HCV-RNA). Fifteen (60%) and 14 patients (56%) achieved an end of treatment virological response (ETVR) and a sustained virological response (SVR), respectively. Five patients had advanced pretreatment liver fibrosis. Pretreatment ALT was elevated in 24 patients (96%). The most common adverse effects were flu-like symptoms and cytopenia. Eighteen patients (72%) required erythropoietin alpha and/or granulocyte-colony stimulating factor as a supportive measure. One patient developed severe rejection complicated by sepsis, renal failure, and death. Other adverse effects included depression, mild rejection, impotence, itching, and vitiligo. CONCLUSIONS: Post-transplant treatment with pegylated interferon alpha-2a and ribavirin achieved SVR in 56% of liver transplant recipients with chronic HCV genotype 4 infection. The combination was relatively safe and exhibited a low rate of treatment withdrawal.

Study of adiponectin in chronic liver disease and cholestasis.

PURPOSE: Adiponectin is an adipocytokine suggested to have a hepatoprotective effect. To date, little information is available in the literature regarding changes in serum adiponectin levels in cirrhosis and cholestasis and the associated metabolic disturbances. In order to elucidate the role of adiponectin in chronic liver disease our aim was to determine serum adiponectin in patients with different grades of cirrhosis and cholestasis and to correlate it with markers of liver injury, inflammation and cholestasis. We also aimed to correlate adiponectin with markers of metabolic syndrome such as body mass index and insulin resistance. METHODS: Forty patients with cirrhosis; 30 patients with cirrhosis and cholestasis; and 20 matched controls were studied. They were subjected to clinical assessment, laboratory investigations: serum bilirubin, ALT, AST, alkaline phosphatase, GGT, albumin, C-reactive protein, prothrombin activity, fasting blood sugar, insulin. HOMA index was calculated. Abdominal ultrasonography and upper GI endoscopy were performed. RESULTS: Adiponectin was elevated in patients with cirrhosis and cirrhosis/cholestasis and was significantly higher in Child A and B. Adiponectin showed correlation with liver cell injury, marker of inflammation, synthetic liver function and markers of cholestasis. Adiponectin did not correlate with complications of cirrhosis as ascites and esophageal varices nor did it correlate with BMI or HOMA. CONCLUSIONS: Adiponectin is elevated in cirrhosis and shows correlation with degree of hepatocellular injury and cholestasis. Finally, adiponectin levels in cirrhosis do not correlate with parameters of body composition or metabolism but exclusively with reduced liver function.

Moral and ethical issues in living-donor liver transplant in Egypt.

OBJECTIVES: Since brain-death criteria are not accepted in Egypt, only organs acquired from living donors can be used for transplant. Our objective was to highlight the ethical issues raised by living-donor liver transplant. MATERIALS AND METHODS: The study was conducted by reviewing publications from centers performing living-donor liver transplant in Egypt and by consulting with a group of experts in the fields of liver transplantation, clinical ethics, and religious scholarship. RESULTS: The first successful living-donor liver transplant in Egypt was performed at the National Liver Institute in 1991; however, this program did not continue because of poor early results. In August 2002, transplants began at Dar-Al-Foaud Hospital; since then, almost 500 cases of living-donor liver transplant have been performed at 9 centers. Although the donor risk is estimated to be low, 2 donors died (0.4%). The ethical principle that best applies to living-donor liver transplant is primum non nocere (first, not to harm), as the donor derives emotional benefit fromdonation and the opportunity to save a life. It is important to stress that the alternative to living-donor liver transplant in Egypt is not deceased-donor liver transplant. There are no doubts that this is a beneficial procedure for the recipient with acceptable risks to the donor. CONCLUSIONS: It is ethically appropriate to perform liver transplant using living donors.

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.

Liver transplant for hepatocellular carcinoma: experience in a Saudi population.

OBJECTIVES: We present our experience with deceased-donor liver transplant and living-donor liver transplant for hepatocellular carcinoma. Between 2001 and 2007, we transplanted 133 organs (84 deceased-donor liver transplants, 49 living-donor liver transplants) in 126 patients (4 retransplants). Twenty-three patients had hepatocellular carcinoma (14 deceased-donor liver transplants and 9 living-donor liver transplants). MATERIALS AND METHODS: The medical records of these patients were reviewed for recipient clinical, biochemical, and imaging characteristics. Slides of explants were assessed. Overall survival and tumor recurrence states were determined. All characteristics were tested for their prognostic significance. RESULTS: The median age of the patients was 55 years and the median Mayo End-stage Liver Disease score was 16. The alpha-fetoprotein was >or= 400 ng/mL in 4 patients. Histopathology revealed incidental cholangiocarcinoma in 2 patients and a hepatoblastoma in 1. The mean tumor size was 4 cm; the mean number of lesions was 2. Most tumors were graded as well or moderately differentiated; 4 were poorly differentiated. Gross macrovascular invasion was seen in 2 patients, while microvascular invasion was seen in 9. After a mean follow-up of 736 days, overall patient and graft survival rates were 80.9% and 76.2%; overall disease-free patient and graft survival rates were 76.2% and 71.4%. Two patients died of primary graft nonfunction within 1 week of the transplant. Three had tumor recurrence at 10, 13, and 18 months after transplant; 2 of these occurred in patients with cholangiocarcinoma. Two of these 3 died from an advanced tumor within few months. Significant risk factors for recurrence were gross major vessel invasion, microvascular invasion, tumor size, poor histologic differentiation, and absence of pretransplant tumor control therapy. The latter 2, in addition to Mayo End-stage Liver Disease score and preoperative alpha-fetoprotein, were independent predictors of mortality. CONCLUSIONS: In our small experience, deceased-donor liver transplant and living-donor liver transplant for hepatocellular carcinoma showed good long-term outcomes. Liver transplant for hepatocellular carcinoma accompanying cholangiocarcinoma had a poor outcome with late tumor recurrence. Use of marginal donors in patients with hepatocellular carcinoma might compromise the outcome in these patients.

Gene deletion of glutathione S-transferase M1 and T1 and risk factors of hepatocellular carcinoma in Egyptian patients.

Genetic polymorphic forms of glutathione-S-transferase (GST) were found to be associated with risk for various malignancies. The present study was undertaken to evaluate the risks-associated with GSTT1 and GSTM1 gene polymorphisms and hepatitis virus-related hepatocellular carcinoma (HCC) in an Egyptian population. Sixty patients diagnosed with HCC were subdivided into 3 groups: group I, 31 patients with HCC and HCV-related cirrhosis; group II, 19 patients with HCC and HBV- related cirrhosis and group III, 10 patients with HCC and cirrhosis of non-viral aetiology. Fifty cirrhotic patients without HCC were also included as a control group. Patients and controls were subjected to thorough history taking and clinical examination, liver function tests, hepatitis viral markers, anti-Bilharzial antibodies and serum alpha fetoprotein levels. Rectal snip for the diagnosis of active Bilharziasis, abdominal ultra-sonography and CT abdomen were performed for patients as well as liver biopsy when indicated. GSTM1 and GSTT1 were tested in peripheral blood mononuclear cells by PCR. GSTM1 gene deletion (null genotype) was observed in 56.7% of HCC patients and in 38% of the control group (P < 0.05). The GSTT1 null genotype was detected in 41.7% of the HCC patients compared to 22% of control patients (P < 0.05). The double genes null of GSTM1 and GSTT1 was detected in 10% of all HCC patients and in 2% of the control cases (P < 0.05). Comparison between the subgroups of HCC revealed that the GSTM1 null genotype was detected in 67.7% of group I, 47.4% of group II and 40% of group III cases, with a significant increase in group I compared to other HCC subgroups (P < 0.001). In addition, the GSTT1 null gene was observed in 35.5% of group I, 57.9% of group II, and 30% of group III, with a significant increase in group II (P < 0.01). In conclusion, our findings suggest that GSTM1 and GSTT1 polymorphisms appear to be associated with a modest increase in the risk of HCC in Egyptian patients. Studies with a larger sample size are still required to confirm the results and to explore the association with risk factors other than HCV and HBV in this population.

Spontaneous bacterial empyema in liver cirrhosis: an underdiagnosed pleural complication.

Spontaneous bacterial empyema, defined as spontaneous infection of the pleural fluid, represents a distinct complication of hepatic hydrothorax with a different pathogenesis, clinical course and treatment strategy from those of empyema secondary to pneumonia. Nearly 40% of episodes of spontaneous empyema are not associated with spontaneous bacterial peritonitis (SBP) or even ascites. The condition portends a poor prognosis, and is frequently under-diagnosed. This article reviews the pathogenesis, diagnosis and management of spontaneous bacterial empyema.