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Current Issue

July - August, 2017

Vol. 16 Issue 4

On the cover: The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for Study of the Liver and the Canadian Association for the Study of the Liver



  • Fighting Mortality in the Waiting List: Liver Transplantation in North America, Europe, and Asia Daniel Zamora-Valdés, Pilar Leal-Leyte, Peter T. W. Kim, Giuliano Testa Page 480-486

    Liver disease is a major cause of mortality worldwide. Liver transplantation (LT) is the most effective treatment for end stage liver disease. Available resources and social circumstances have led to different ways of implementing LT around the world. The experience with pediatric LT corroborates the hypothesis that a combination of surgical strategies can be beneficial. The goal of this manuscript is to describe the strategies used by LT centers in North America, Europe and Asia and how these strategies can be applied to reduce waitlist mortality and increase access to LT.



  • Genetic and Epigenetic Profile of Patients With Alcoholic Liver Disease Luigi Boccuto, Ludovico Abenavoli Page 490-500

    Alcoholic liver disease (ALD) is a definition encompassing a spectrum of disorders ranging from simple steatosis to cirrhosis and hepatocellular carcinoma. Excessive alcohol consumption triggers a series of metabolic reactions that affect the liver by inducing lipogenesis, increasing oxidative stress, and causing abnormal inflammatory responses. The metabolic pathways regulating lipids, reactive oxygen species (ROS), and immune system are closely related and in some cases cross-regulate each other. Therefore, it must be taken into account that major genetic and epigenetic abnormalities affecting enzymes involved in one of such pathways can play a pivotal role in ALD pathogenesis. However, recent studies have pointed out how a significant predisposition can also be determined by minor variants, such as relatively common polymorphisms, epigenetic modifications, and microRNA abnormalities. Genetic and epigenetic factors can also affect the progression of liver diseases, promoting fibrogenesis, cirrhosis, and ultimately hepatocellular carcinoma. It is noteworthy that some of these factors, such as some of the cytokines involved in the abnormal inflammatory responses, are shared with non-alcoholic liver disease, while other factors are unique to ALD. The study of the genetic and epigenetic components involved in the liver damages caused by alcohol is crucial to identify individuals with high risk of developing ALD, design personalized protocols for prevention and/or treatment, and select the best molecular targets for new therapies.


Clinical Studies

Viral Hepatitis
  • Retinoid X Receptor α-Dependent HBV Minichromosome Remodeling and Viral Replication Yan Zhang, Song He, Jin-Jun Guo, Hong Peng, Jia-Hao Fan, Qing-Ling Li Page 501-509

    Background and aim. The HBV covalently closed circular DNA (cccDNA) is organized into a minichromosome in the nuclei of infected hepatocytes through interactions with histone and nonhistone proteins. Retinoid X receptor ? (RXR?), a liver-enriched nuclear receptor, participates in regulation of HBV replication and transcription through modulation of HBV enhancer 1 and core promoter activity. Material and methods. This study investigated RXR? involvement in HBV cccDNA epigenetic modifications. Quantitative cccDNA chromatin immunoprecipitation (ChIP) was applied to study the recruitment of RXR?, histones, and chromatin-modifying enzymes to HBV minichromosome in HepG2 cells after transfection of the linear HBV genome. Results. RXR? Was found to directly bind to HBV cccDNA; recruitment of RXR? to HBV mini-chromosome paralleled HBV replication, histone recruitment, and histone acetylation in HBVcccDNA. Moreover, RXR? overexpression or knock-down significantly increased or impaired the recruitment of the p300 acetyltransferase to cccDNAminichromosome. Conclusions. Our results confirmed the regulation of RXR? on HBV replication in vitro and demonstrated the modulation of RXR? on HBV cccDNA epigenetics. These findings provide a profound theoretical and experimental basis for late-model antiviral treatment acting on the HBV cccDNA and minichromosome.

  • Occult Hepatitis C Infection Among Hemodialysis Patients: A Prevalence Study Reza Naghdi, Mitra Ranjbar, Farah Bokharaei-Salim, Hossein Keyvani, Shokoufeh Savaj, Shahrzad Ossareh, Amir Shirali, Amir H. Mohammad-Alizadeh Page 510-513

    Introduction and aim. Occult hepatitis C infection (OHCI) is the presence of HCV-RNA in the liver or peripheral blood mononuclear cells (PBMC) accompanying with negative serologic results. The aim of this study was to evaluate the prevalence of OHCI among Iranian chronic hemodialysis (HD) patients. Material and methods. In this cross sectional study 200 chronic HD patients with negative HCV antibody enrolled the study. Blood sample of patients were obtained, followed by Polymerase Chain reaction (PCR) testing for detection of HCV RNA. Patients with positive serum HCV RNA were considered as manifest hepatitis C infection (MHCI). However, patients with negative serum HCV RNA underwent further tests on PBMCs for detection of OHCI. Results. Serum HCV RNA was positive in 2 (1%) patients whom considered as MHCI, and 6 (3.03%) patients had positive PBMC HCV RNA. Conclusion. In conclusion, chronic HD patients have been considered as a high risk group for hepatitis C infection. The results of this study suggest that these patients are also at risk for OHCI. Furthermore, evaluating PBMCs to detect HCV RNA would be a sensitive diagnostic method to find OHCI patients.

  • Hepatitis C Virus Infection and Risk of Venous Thromboembolism: A Systematic Review and Meta-Analysis Karn Wijarnpreecha, Charat Thongprayoon, Panadeekarn Panjawatanan, Patompong Ungprasert Page 514-520

    Background/Objectives. Hepatitis C virus (HCV) infection is one of the leading causes of cirrhosis. As a result of chronic inflammatory response to the virus, HCV-infected patients may be at a higher risk of venous thromboembolism (VTE). However, the data on this association is unclear. This systematic review and meta-analysis was conducted with the aims to summarize all available evidence. Material and methods. A literature search was performed using MEDLINE and EMBASE from inception to April 2016. Studies that reported relative risks, odd ratios, or hazard ratios comparing the risk of VTE among HCV-infected patients vs. subjects without HCV infection were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Results. Three studies met our eligibility criteria and were included in analysis. The pooled RR of VTE in HCV-infected patients vs. subjects without HCV infection was 1.38 (95% CI, 1.08-1.77, I2 = 40%). Subgroup analysis showed that risk was increased for both pulmonary embolism (PE) and deep venous thrombosis (DVT) even though without adequate power to demonstrate statistical significance (Pooled RR of 1.34, 95% CI, 0.67-2.66 for PE and pooled RR 1.45, 95% CI, 0.93-2.77 for DVT). Conclusion. Our study demonstrated a significantly increased risk of VTE among HCV-infected patients. Further studies are required to clarify how this risk should be addressed in clinical practice.

  • Expression of Natural Killer Cell Inhibitory Receptors is Associated with Significant Liver Injury in Chronic Hepatitis C in Children Anna Mania, Mariusz Kaczmarek, Pawel Kemnitz, Magdalena Figlerowicz, Jan Sikora, Wojciech Sluzewski, Jan Zeromski Page 521-529

    Introduction and aim. Natural Killer (NK) cells play an important role in innate immune response to viral infections and their high proportion is situated in the liver. The aim of this study was to analyze possible relation between the expression of NK cell receptors and varied intensity of liver lesions in chronic hepatitis C (CHC) in children. Material and methods. Study included 105 children with CHC - 54 boys and 51 girls, age 13.62 ± 3.48 years. Blood specimens were taken at the day of the liver biopsy. Histological evaluation was performed according to METAVIR scoring system. Circulating NK cells were evaluated by flow cytometry. The results were shown as a proportion of cells expressing evaluated receptor and its' mean fluorescent intensity (MFI). Results. In 58 children with CHC (55.2%) significant liver fibrosis was observed ( ≥F2). Higher proportion of cells expressing CD158e inhibitory receptors was observed in the group of children with ALT > 2UNL (21.11 ± 14.60 vs. 12.22 ± 8.99%; p = 0.037). While higher proportion of cells expressing inhibitory CD158b receptor was observed in children with significant fibrosis (F ≥ 2) compared to minimal fibrosis (F < 2) - (34.14 ± 12.44 vs. 27.48 ± 8.71%; p = 0.049). Children with advanced fibrosis (F ≥ 3) had higher MFI of NK cell CD 158b receptor than children with fibrosis scored F < 3 - (5344.20 ± 3407.49 vs. 2979.67 ± 1190.64; p = 0.049). Proportion of NK cells expressing CD158b was found a predictor of significant fibrosis in univariate analysis - [OR 1.065; 95%CI (1.07-1.15); p = 0.046]. Conclusions. Higher proportion of NK cells expressing inhibitory CD158b and CD158e receptors is associated with significant liver injury.

  • Racial Disparities in Hepatitis C Treatment Eligibility Omar T. Sims, David E. Pollio, Barry A. Hong, Carol S. North Page 530-537

    Background. Hepatitis C (HCV) is more prevalent in African Americans than in any other racial group in the United States. However, African Americans are more likely to be deemed ineligible for HCV treatment than non-African Americans. There has been limited research into the origins of racial disparities in HCV treatment eligibility. Aim. The purpose of this study was to compare medical and non-medical characteristics commonly assessed in clinical practice that could potentially contribute to HCV treatment ineligibility disparities between African American and non-African American patients. Material and methods. Patients with confirmed HCV RNA considering treatment (n = 309) were recruited from university-affiliated and VA liver and infectious disease clinics. Results. African Americans and non-African Americans did not differ in prevalence of lifetime and current psychiatric disorders and risky behaviors, and HCV knowledge. HCV clinical characteristics were similar between both groups in terms of HCV exposure history, number of months aware of HCV diagnosis, stage of fibrosis, and HCV virologic levels. African Americans did have higher proportions of diabetes, renal disease, and bleeding ulcer. Conclusions. No clinical evidence was found to indicate that African Americans should be more often deemed ineligible for HCV treatment than other racial groups. Diabetes and renal disease do not fully explain the HCV treatment ineligibility racial disparity, because HCV patients with these conditions are priority patients for HCV treatment because of their greater risk for cirrhosis, steatosis, and hepatocellular carcinoma. The findings suggest that an underlying contributor to the HCV treatment eligibility disparity disfavoring African Americans could be racial discrimination.

Non alcoholic fatty liver disease (NAFLD)
  • Meta-Analysis of Randomized Controlled Trials of Pharmacologic Agents in Non-alcoholic Steatohepatitis Adnan Said, Ahmed Akhter Page 538-547

    Background. Currently, there is no standardized treatment regimen for non-alcoholic steatohepatitis. Aim. We performed a metaanalysis of high quality randomized controlled trials that evaluated treatment response to metformin, thiazolidinediones (TZDs), and vitamin E in adult patients with non-alcoholic steatohepatitis. Outcome measures were improvement in liver histology, biochemical, and anthropometric measures. Material and methods. Nine trials met inclusion criteria (3 with TZD, 3 with Metformin, 2 with Vitamin E and 1 with both TZD and Vitamin E.). Results. With metformin, weighted liver histologic scores for steatosis, ballooning, and fibrosis did not demonstrate significant improvement and lobular inflammation worsened significantly (weighted mean increase 0.21, 95% CI 0.11 to 0.31, P < 0.0001). The liver histology score including steatosis (OR 3.51, 95% CI 2.14 to 5.78) and lobular inflammation (OR 2.65, 95% CI 1.69 to 4.15) improved with TZDs. Hepatic fibrosis (OR 1.58, 95% CI 0.98 to 2.54) and ballooning scores (OR 1.84, 95% CI 0.94 to 3.58) did not demonstrate significant improvement. With Vitamin E, weighted liver histologic scores for steatosis (weighted mean decrease -0.60, 95% CI -0.85 to -0.35, P < 0.0001), lobular inflammation (weighted mean decrease - 0.40, 95% CI -0.61 to -0.20, P = 0.0001) and ballooning (weighted mean decrease -0.30, 95% CI -0.54 to -0.07, P = 0.01) demonstrated significant improvement compared to placebo. Fibrosis did not significantly change. Conclusion. In patients with NASH, TZDs and Vitamin E improve liver histologic scores but metformin does not. Insulin resistance also improves with both TZDs and metformin. Fibrosis does not improve with any of the agents.

Liver transplantation
  • Isolated Intrapulmonary Vascular Dilatations and the Risk of Developing Hepatopulmonary Syndrome in Liver Transplant Candidates Manuel Mendizabal, David S. Goldberg, Federico Piñero, Diego T. Arufe, María José de la Fuente, Pablo Testa, Matías Coronel, Sergio Baratta, Luis G. Podestá, Michael B. Fallon, Marcelo O. Silva Page 548-554

    Background. The natural history of intrapulmonary vascular dilations (IPVD) and their impact on patient outcomes in the setting of portal hypertension has only been described in small series. Aims. To assess the development of hepatopulmonary s?ndrome (HPS) in patients with isolated IPVD and to evaluate outcomes of IPVD and HPS among patients evaluated for liver transplantation (LT). Material and methods. Data from a prospective cohort of patients evaluated for LT with standardized screening for HPS were analyzed. IPVDs were defined as the presence of microbubbles in the left atrium > 3 cycles following right atrial opacification. HPS was defined as the presence of IPVD and hypoxemia (Alveolar-arterial gradient ? 15 mmHg) in the absence of concomitant cardiopulmonary disease. Results. A total of 104 patients with negative contrast-enhanced echocardiogram (CE) were compared to 63 patients with IPVD and 63 patients with HPS. Only four patients were categorized as ?severe? HPS based on degree of hipoxemia (defined as PaO2 < 60 mmHg). Twenty IPVD patients were followed with ABG over a mean duration of 21 months (range 9-43), of whom 7 (35%) subsequently met HPS criteria. Overall unadjusted survival from the time of LT evaluation using multi-state survival models that accounted for pre- and post-LT time was not statistically different among the three groups (negative CE, IPVD, and HPS; p > 0.5). Conclusions. Patients with IPVD appear to have a substantial risk of developing oxygenation impairment over time and progress to HPS. In our cohort, survival in patients with HPS and isolated IPVD is not different when compared to those without IPVDs.

Hepatobiliary Malignancies
  • Independent Predictors of Mortality and Resource Utilization in Viral Hepatitis Related Hepatocellular Carcinoma Pegah Golabi, Thomas Jeffers, Zahra Younoszai, Munkhzul Otgonsuren, Mehmet Sayiner, Alita Mishra, Chapy Venkatesan, Zobair M. Younossi Page 555-564

    Introduction. Hepatitis B (HBV) and C viruses (HCV) are important causes of hepatocellular carcinoma (HCC). Our aim was to assess mortality and resource utilization of patients with HCC-related to HBV and HCV. Material and methods. National Cancer Institute's Surveillance, Epidemiology and End Results (SEER)-Medicare linked database (2001-2009) was used. Medicare claims included patient demographic information, diagnoses, treatment, procedures, ICD-9 codes, service dates, payments, coverage status, survival data, carrier claims, and Medicare Provider Analysis and Review (MEDPAR) data. HCC related to HBV/HCV and non-cancer controls with HBV/HCV were included. Pair-wise comparisons were made by t-tests and chi-square tests. Logistic regression models to estimate odds ratios (ORs) with 95% confidence intervals (CIs) were used. Results. We included 2,711 cases of HCC (518 HBV, 2,193 HCV-related) and 5,130 non-cancer controls (1,321 HBV, 3,809 HCV). Between 2001-2009, HCC cases related to HBV and HCV increased. Compared to controls, HBV and HCV patients with HCC were older, more likely to be male (73.2% vs 48.9% and 57.1% vs. 50.5%), die within one-year (49.3% vs. 20.3% and 52.2% vs. 19.2%), have decompensated cirrhosis (44.8% vs. 6.9% and 53.9% vs. 10.4%) and have higher inpatient ($60.471 vs. $47.223 and $56.033 vs. $41.005) and outpatient charges ($3,840 vs. $3,328 and $3,251 vs. $2,096) (all P < 0.05). In two separate multivariate analyses, independent predictors of one-year mortality were older age, being male and the presence of decompensated cirrhosis. Conclusions. The rate of viral hepatitis-related HCC is increasing. Mortality and resource utilization related to HBV and HCV-related HCC is substantial.

  • Prevalence, Risk Factors, and Survival of Patients with Intrahepatic Cholangiocarcinoma Paulina Chinchilla-López, Nancy E. Aguilar-Olivos, Jaime García-Gómez, Karen K. Hernández-Alejandro, Fredy Chablé-Montero, Daniel Motola-Kuba, Tushar Patel, Nahum Méndez-Sánchez Page 565-568

    Purpose. To investigate the prevalence, related risk factors, and survival of intrahepatic cholangiocarcinoma in a Mexican population. Material and methods. We conducted a cross-sectional study at Medica Sur Hospital in Mexico City with approval of the local research ethics committee. We found cases by reviewing all clinical records of in-patients between October 2005 and January 2016 who had been diagnosed with malignant liver tumors. Clinical characteristics and comorbidities were obtained to evaluate the probable risk factors and the Charlson index. The cases were staged based on the TNM staging system for bile duct tumors used by the American Joint Committee on Cancer and median patient survival rates were calculated using the Kaplan-Meier method. Results. We reviewed 233 cases of hepatic cancer. Amongst these, hepatocellular carcinomas represented 19.3% (n = 45), followed by intrahepatic cholangiocarcinomas, which accounted for 7.7% (n = 18). The median age of patients with intrahepatic cholangiocarcinoma was 63 years, and most of them presented with cholestasis and intrahepatic biliary ductal dilation. Unfortunately, 89% (n = 16) of them were in an advanced stage and 80% had multicentric tumors. Median survival was 286 days among patients with advanced stage tumors (25th-75th interquartile range, 174-645 days). No correlation was found between the presence of comorbidities defined by the Charlson index, and survival. We evaluated the presence of definite and probable risk factors for the development of intrahepatic cholangiocarcinoma, that is, smoking, alcohol consumption, and primary sclerosing cholangitis. Discussion. We found an overall prevalence of intrahepatic cholangiocarcinoma of 7.7%; unfortunately, these patients were diagnosed at advanced stages. Smoking and primary sclerosing cholangitis were the positive risk factors for its development in this population.

Autoimmune, Cholestatic and Biliary Disease
  • Sensitivity and Specificity of Biochemical Tests for Diagnosis of Intrahepatic Cholestasis of Pregnancy Kondrackiene Jurate, Zalinkevicius Rimantas, Sumskiene Jolanta, Gintautas Vladas, Kupcinskas Limas Page 569-573

    Background and aim. Intrahepatic cholestasis of pregnancy (ICP) is linked with increased risk of fetal complications. An accurate diagnostic test is needed to diagnose this disorder on time. We aimed to assess sensitivity and specificity of laboratory tests used for diagnosis of intrahepatic cholestasis of pregnancy and determine more reliable cut-off values of transaminases. Material and methods. Sixty one symptomatic patients with ICP and 29 healthy pregnant women were included in the retrospective analysis. Results. ICP patients had higher total bile acids (TBA) levels than healthy women (32 vs. 6; P < 0.0001) due to increase in cholic acid (CA) and chenodeoxycholic acid (CDCA). CA/CDCA ratio was significantly higher in ICP patients compared to healthy pregnant women (1.13 vs. 0.68; P < 0.00002). TBA, CA, CDCA and CA/CDCA ratio demonstrate the following sensitivity (94%, 96%, 89%, 71.9%) and specificity (63%, 63%, 59%, 79.3%, respectively) for ICP diagnosis. Lowering cut-off values for ALT (31 U/L) and AST (30 U/L) resulted only in minimal increase of sensitivity to 92.2% vs. 90.1% for ALT and to 92.2%, vs. 90.6% for AST. Conclusion. The present study did not reveal any single specific and sensitive marker for reliable diagnosis of ICP. Establishment of lower cut-off values for transaminases activity might only minimally increase the accuracy of diagnosing ICP.

  • Non-neoplastic Portal Vein Thrombosis in HCV Cirrhosis Patients: Is it an Immuno-Inflammatory Disorder? Mona A. Abu El- Makarem, Atef F. El-Akad, Moustafa M. Elian, Tahra M. Sherif, Ragaa A. El-shaheed, Aliaa S. Abd EL Fatah, Douaa M. Sayed, Rania M. Bakry, Aisha M. Mahmoud Page 574-583

    Background and aims. Portal vein thrombosis (PVT) is a critical complication in cirrhotic patients. We explored the role of the activated factor VII-antithrombin (FVIIa-AT) complex and enhanced monocytic tissue factor (TF) expression in the development and prediction of non-neoplastic PVT in cirrhotic patients. Material and methods. A total of 30 HCV-cirrhosis patients were included in our study. They were compared to 35 cirrhotic patients without PVT, 15 non-cirrhotic patients with PVT, and 15 healthy controls. The plasma level of the FVIIa-AT complexes was analyzed by ELISA. MIF CD142, CD86, and HLA-DR on monocytes (CD14) were determined by flow cytometry. Results. Compared with cirrhotic patients without PVT, cirrhotic patients with PVT had comparable plasma values of FVIIa, AT, and the FVIIa-AT complex. However, they had significantly lower values compared to non-cirrhotic patients with PVT and healthy controls. Cirrhotic patients with PVT had increased monocytic TF expression (MIF CD142) compared to non-PVT cirrhotic patients and healthy controls [86.5 (93.5) vs. 18 (32.0) and 11.0 (6.0), respectively; p < 0.001 for each]. However, cirrhosis PVT could not be distinguished from non-cirrhosis PVT. The area under the ROC curve of MIF CD142 was 0.759 (0.641- 0.876; p = 0.000) at an optimal cut-off value of 45, which yielded a sensitivity of 60% and a specificity of 77.1%, as well as a PPV and NPV of 69.2% for each. Conclusion. Enhanced expression of monocytic TF may have a role in the development and prediction of non-neoplastic PVT in HCV-cirrhosis patients. Large multicenter studies are necessary to validate our results.

  • Relative Adrenal Insufficiency is Associated with the Clinical Outcome in Patients with Stable Decompensated Cirrhosis Evangelos Cholongitas, Ioannis Goulis, Eirini Pagkalidou, Anna B. Haidich, Apostolos K.A. Karagiannis, Theodora Nakouti, Chrysoula Pipili, Theodora Oikonomou, Spyros Gerou, Evangelos Akriviadis Page 584-590

    Background. The clinical impact of relative adrenal insufficiency (AI) on patients with stable decompensated cirrhosis (DeCi) has not been yet elucidated. Aim. Explore the association between AI and outcome [death or liver transplantation (LT)] in patients with DeCi. Material and methods. Patients with DeCi presenting no active complication have been included. Clinical and laboratory data, including serum levels of corticosteroid-binding globulin (CBG), interleukin (IL)-1b, IL-6 and tumor necrosis factor (TNFα) were recorded in each participant. Salivary cortisol (SC) and serum total cortisol (STC) were assessed at (T0) and 1 h (T60) after intravenous injection of 250 μg corticotropin. Results. 113 consecutive patients were totally tested. Median SC was 3.9 ng/mL and 15.5 ng/mL and median STC was 10.7 μg/dL and 22.7 μg/dL at T0 and T60 respectively. The patients with AI [group 1, n = 34 (30%)] had significantly lower systolic blood pressure (106 ± 12 vs. 113 ± 13 mmHg, p = 0.05), serum sodium (133 ± 7 vs. 137 ± 12 mEq/L, p = 0.04), HDL (29.9 ± 14 vs. 38.6 ± 18 mg/dL, p = 0.034) and albumin (2.7 ± 0.5 vs. 3.1 ± 0.5 g/dL, p = 0.002), but higher direct bilirubin (median: 1.6 vs. 0.8 mg/dL, p = 0.029) compared to those without AI [group 2, n = 79 (70%)]. Moreover, group 1 patients presented more frequently past history of spontaneous bacterial peritonitis (SBP) [10/34 (29.4%) vs. 6/79 (7.5%), p = 0.002]. AI was significantly associated with death [HR = 2.65, 95% C.I.: 1.55 - 4.52, p = 0.003 over a follow up period of 12 (6-48) months.] Conclusions. The presence of AI in patients with stable DeCi predispose to obvious clinical implications since it is associated with circulatory dysfunction, previous history of SBP and worse survival.

  • Symptoms of Daytime Sleepiness and Sleep Apnea in Liver Cirrhosis Patients Al Enezi Abdullah, Fares AL-Jahdali, Anwar E. Ahmed, Nahid Shirbini, AL-Harbi Abdullah, Baharoon Salim, Yosra Z. Ali, Aljumah Abdulrahman, Mohd Khan, Abdullah Khaleid, AL-Jahdali Hamdan Page 591-598

    Background/propose. Sleep disturbance and excessive daytime sleepiness (EDS) have been reported in patients with hepatic cirrhosis with no hepatic encephalopathy (HE). The objective of this study was to evaluate daytime sleepiness and risk of obstructive sleep apnea (OSA) among liver cirrhosis patients. Material and methods. A cross-sectional study was conducted at King Abdulaziz Medical City (KAMC)-Riyadh over a period of six months, using a structured questionnaire that investigated: 1) Sleep patterns and daytime sleepiness using the Epworth Sleeping Scale (ESS), and 2) The risk for sleep apnea using the Berlin Questionnaire (BQ). We enrolled patients with a confirmed diagnosis of liver cirrhosis who were being followed at the hepatology and pre-liver transplant clinics. Results. We enrolled 200 patients with liver cirrhosis, 57.5% of whom were male. The mean age was 60 (± SD 12.2). The reported prevalence of EDS, OSA, and both EDS and OSA were 29.5%, 42.9%, and 13.6%, respectively. The prevalence of EDS was higher in patients with Hepatitis-C and patients with DM, who experienced short sleep duration. We did not find any association between the severity of liver disease and EDS or OSA as measured by Child-Pugh scores (CPS). Conclusions. The risk of OSA and EDS is high among liver cirrhosis patients. Those patients with cirrhosis secondary to Hepatitis C are at higher risk of EDS and OSA. Both EDS and OSA affect patients designated as CPS Class A more frequently than patients designated as CPS Class B.

  • Hepatic Echinococcosis with Thoracic Involvement. Clinical Characteristics of a Prospective Series of Cases Carlos Manterola, Tamara Otzen Page 599-606

    Introduction. Thoracic involvement (TIHE) is one of the evolutionary complications of hepatic echinococcosis (HE). Aim. The aim of this study was to describe the clinical characteristics and postoperative morbidity (POM) of a series of patients with TIHE treated surgically. Material and methods. Series of cases of patients treated for TIHE between 2000 and 2014 in the Hospital Regional and Clínica Mayor in Temuco, Chile, with a minimum 12-month follow-up. The outcome variable was “development of POM”. Descriptive statistics were used. Results. The series was composed of 37 patients with a mean age of 53.2 ± 47.4 years (51.4% female). Mean cyst diameter was 19.4 ± 15.5 cm, and 75.7% of the lesions were located in the right hepatic lobe. The most frequent surgical technique used for the cyst was subtotal pericystectomy (56.8%); the residual cavity was treated by capitonnage (27.0%) or omentoplasty (21.6%), and a phrenoplasty with or without prosthetic material was performed for the TIHE. Mean hospital stay was 6.0 ± 5.7 days and follow-up was 61.4 ± 79.9 months; a mortality rate of 2.7% (one patient) and a POM of 24.3% (9 patients) were verified. Conclusion. TIHE is an uncommon evolutionary complication of HE associated with significant POM rate.

Basic studies

  • Hepatoprotective Effect of Curcumin on Hepatocellular Carcinoma Through Autophagic and Apoptic Pathways Ahmed M. Elmansi, Amro A. El-Karef, Mamdouh M. El-Shishtawy, Laila A. Eissa Page 607-618

    Background and rationale. Microtubule-associated protein light chain 3-II (LC3-II), and Sequestosome-1 (SQSTM1) are proteins that can be used as markers for autophagic pathway. Bcl-2 protein is reported to be inversely correlated with apoptosis. We aimed to investigate the effects of curcumin on liver inflammation and fibrosis up to the first dysplastic stage of Hepatocellular carcinoma (HCC) induced by Thioacetamide (TAA) in rats and to clarify the effects of curcumin on LC3-II, SQSTM1, and Bcl-2. Male Sprague-Dawley rats were randomized into four groups: Control group, TAA group, Curcumin low-dose group, and Curcumin highdose group. The last three groups received TAA 200 mg/kg i.p. twice weekly for 18 weeks. Oxidative stress markers as hepatic malondialdehyde (MDA) concentration and superoxide dismutase (SOD) activity were measured by colorimetric methods. Hepatic SQSTM1 concentration was measured by ELISA, and gene expression levels of Bcl-2, and LC3-II were measured by RT-PCR. We also investigated the in vitro effect of curcumin on HepG2 cells viability through MTT assay, and the involvement of autophagy in this effect. Results. Curcumin increased the survival percent in rats, decreased -fetoprotein (AFP) concentration, and serum aspartate aminotransferase (AST) activity, and increased serum albumin concentration. Curcumin also significantly reduced oxidative stress in liver, inhibited apoptosis, and induced autophagy. In vitro, curcumin (50 μM) decreased HepG2 cells viabilityand the concentration of SQSTM1. Conclusions. Curcumin leads to protection against TAA induced HCC up to the first dysplastic stage through activating autophagic pathway and inhibiting apoptosis. Also, the antioxidant activity of curcumin almost prevents liver fibrosis.


  • The Role of TIPS in patients with Refractory Ascites and Portal Vein Thrombosis Paulina Chinchilla-López, Nashla Hamdan-Pérez, Jorge Guerrero-Ixtlahuac, Beatriz Barranco-Fragoso, Nahum Méndez-Sánchez Page 619-620

    Portal vein thrombosis (PVT) is one of the most common vascular disorders of the liver; its importance relies because of its significant morbidity and mortality. Large cohorts have reported a global PVT prevalence of 1%, but in some risk groups can be up to a 26%.1 The incidence of PVT in cirrhosis is less clearly defined, but reported as 16% by Amitrano, et al.2 in a group of patients with Liver Disease (LD) followed prospectively. Transjugular intrahepatic portosystemic shunt (TIPS) is commonly performed for refractory ascites, refractory variceal bleeding, hepatic hydrothorax, and Budd-Chiari syndrome. We report a case to emphasize the role of TIPS in patient with refractory acute and portal vein thrombosis.


  • Two Cases of Primary Hepatic Neuroendocrine Tumors and a Review of the Current Literature Matthew R. DeLuzio, Andrea L. Barbieri, Gary Israel, Sukru Emre Page 621-629

    Neuroendocrine tumors comprise approximately 1-2% of all gastrointestinal tumors, and while the liver is the most common site for metastasis of these tumors, primary hepatic neuroendocrine tumors are very rare entities. Since first being reported in 1958, there have been less than 150 cases reported in the literature. Because of the infrequent occurrence of these tumors, the pool of data available for analysis regarding these tumors is small. As such, the medical community must rely on the publication of case report data to further enlarge this data pool, with the hopes of eventually having enough data to draw meaningful, statistically significant conclusions with regard to diagnosis and management of these rare tumors. We have encountered two patients at our institution within the last year with primary hepatic neuroendocrine tumors. We present their cases in this manuscript in an effort to contribute to the available data on the disease. We also provide a concise review of the literature available to date regarding primary hepatic neuroendocrine tumors.

  • A Case Report of Hepatocellular Carcinoma 5 Years After HBsAg Loss in Chronic Hepatitis Delta: How Long Surveillance is Required? Laura Escolà-Vergé, Mar Riveiro-Barciela, Maria Buti Page 630-632

    Background. Hepatitis delta virus infection occurs as acute co-infection or as superinfection in patients with preexisting chronic hepatitis B. Chronic hepatitis delta leads to more severe disease than chronic hepatitis B, with more rapid progression of fibrosis and increased risk of hepatocelullar carcinoma. Case report. We report a case of hepatocelullar carcinoma 5 years after spontaneous clearance of Hepatitis B surface antigen in a patient with previous chronic hepatitis delta. He had been diagnosed with acute hepatitis delta superinfection 30 years ago which evolved to chronic delta infection and subsequently development of liver cirrhosis. Despite no specific antiviral treatment, he lost HBsAg persistently with later regression of cirrhosis. Conclusions. In patients with cirrhosis due to chronic hepatitis delta who cleared HBsAg with improvement of liver fibrosis by non invasive techniques, it remains unknown how long hepatocelullar carcinoma surveillance has to be maintained.


The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for the Study of the Liver and the Canadian Association for the Study of the Liver

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