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Current Issue

March - April, 2012

Vol. 11 Issue 2

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



  • Hepatitis B viral load and risk of HBV-related liver disease: from East to West? Soeradj Harkisoen, Joop E. Arends, Karel J. Van Erpecum, Anneke van den Hoek, Andy I.M. Hoepelman Page 164-171

    Chronic hepatitis B has a variable course in disease activity with a risk of clinical complications like liver cirrhosis and hepatocellular carcinoma. As clinical symptoms present in a late stage of the disease, identification of risk factors is important for early detection and therefore improvement of prognosis. Recently, two REVEAL-HBV studies from Taiwan have shown a positive correlation between viral load at any point in time and the development of cirrhosis and hepatocellular carcinoma. Due to differences in viral and host factors between Asians and other populations, it is unclear whether these results can be extrapolated to different populations. This manuscript will discuss viral predictors of hepatitis B related liver disease in relation to ethnic origin.

  • Transient elastography in non-alcoholic fatty liver disease Ludovico Abenavoli, Michel Beaugrand Page 172-178

    Non-alcoholic fatty liver disease (NAFLD) is a relevant issue in public health owing to its epidemiological burden. It represents the most common chronic liver disease in the general population and is expected to increase in future as a result of an ageing population. Liver biopsy is still considered the "gold standard" for distinguishing the broad range of NAFLD. However, liver biopsy is often not recommended in the NAFLD patients, because of its cost, the potential risk of bleeding and the absence of consensus regarding the histopathological criteria that firmly differentiate between the NAFLD entities. Due to the remarkable increase in the prevalence of NAFLD and the concomitant efforts in developing novel therapies, a non-invasive, simple and reproducible technique is needed in the clinical practice. Transient elastography is a non-invasive technique for liver stiffness measurement (LSM) as a function of the extent of hepatic fibrosis. This review focuses on practical issues in the use of LSM in the NAFLD patients and suggests areas for further research and development.

  • A review of drug interactions with boceprevir and telaprevir: implications for HIV and transplant patients Kyle J. Wilby, Erica D. Greanya, Jo-Ann E. Ford, Eric M. Yoshida, Nilufar Partovi Page 179-185

    Purpose. Chronic hepatitis C virus (HCV) is a major problem affecting up to 170 million people worldwide. Two protease inhibitors have recently been approved that will revolutionize treatment. Our objective was to summarize and evaluate the literature pertaining to the pharmacokinetics of boceprevir and telaprevir, in order to provide clinicians with insight into the management of actual and potential drug interactions. Summary. A standardized search using MEDLINE (1948-November 2011), EMBASE (1980-November 2011), IPA (1970-November 2011), Google, and Google Scholar that combined the search terms boceprevir, telaprevir, pharmacokinetics, drug interaction, and drug metabolism was performed. Manual reference searches of chosen articles were completed. Monographs and articles, conference proceedings, and abstracts were evaluated. Boceprevir and telaprevir are both substrates and inhibitors of cytochrome P450 3A4 and telaprevir is a substrate of p-glycoprotein. Levels of boceprevir are decreased in patients taking efavirenz but effects with other antiretrovirals are minimal or unknown. Coadministration with efavirenz may compromise telaprevir levels and should be avoided. Telaprevir may increase levels of cyclosporine, tacrolimus, atorvastatin, and amlodipine, which may expose patients to increased adverse effects. Conclusions. Significant drug-drug interactions occur with both boceprevir and telaprevir. Until studies are reported and experience is gained with these agents, clinicians will need to be careful when administering in high-risk populations and those receiving chronic therapy with interacting agents. Studies are urgently needed in HIV patients taking antiretrovirals and patients taking chronic immunosuppresion as these populations are at increased risk of experiencing clinically significant interactions.


Clinical Studies

Viral Hepatitis
  • Pegylated interferon-alpha2b plus ribavirin for the treatment of chronic hepatitis C virus genotype 4 infection in patients with normal serum ALT Jaber Al-Ali, Iqbal Siddique, Rosh Varghese, Fuad Hasan Page 186-193

    Background. Approximately one-third of patients with chronic hepatitis C virus infection have persistently normal liver enzymes reflected by a normal serum alanine transaminase (ALT). Data with regards the efficacy and safety of treatment in patients chronically infected with Hepatitis C virus genotype 4 and normal serum ALT are limited. Aim. To evaluate the efficacy and safety of peginterferon alfa-2b plus ribavirin combination therapy in this population. Material and methods. Twenty-two patients with chronic hepatitis C virus genotype 4 infection were enrolled in an open-labeled, uncontrolled pilot study. All patients had biopsy proven chronic hepatitis and persistently normal serum ALT levels. Patients were treated with subcutaneous peginterferon alfa-2b at a dose of 1.5 μg/kg body weight once per week plus oral ribavirin (15 mg/kg/day) for 48 weeks. Patients were followed for 24 weeks post-treatment. Results. Sixteen patients out of twenty two completed the study (9 [40.9%] females, mean age 43.8 years). The ALT level were normal in all patients, with a mean of 38.6 U/L. Sustained viral response was achieved in 13 patients (59%), 4 patients (18.1%) were non-responders and 2 patients (9%) relapsed while 1 patient had a viral breakthrough during treatment. Two patients (9%) discontinued the treatment because of adverse events. Conclusions. Combination therapy of pegylated interferon-alpha2b and ribavirin is safe and resulted in a sustained virological response in a significant number of patients with chronic Hepatitis C, genotype 4, and persistently normal serum ALT.

  • Prevalence of hepatitis A, B and C serological markers in children from western Mexico Griselda Escobedo Meléndez, Nora A. Fierro, Sonia Roman, Monserrat Maldonado-González, Eloy Zepeda-Carrillo, Arturo Panduro Page 194-201

    Introduction. Viral hepatitis in children is a major public health problem worldwide. Aim. To evaluate the prevalence of serological markers for hepatitis A, B and C infections in Mexican children diagnosed with hepatitis during a five-year period. Material and methods. A total of 31,818 children admitted to a tertiary level hospital in Mexico from 2005 to 2009 were evaluated for hepatitis. Results. Hepatitis was found in 215 (0.7%) of the children. Serum samples from hepatitis-positive children were screened for anti-HAV IgM, HBsAg, total anti-HBc and anti-HCV. HAV was the leading cause of viral hepatitis (81%), followed by HBV and HCV (3.1 and 2%, respectively), whereas no serological marker was observed in 13.9% of the analyzed samples. Furthermore, when children were categorized by age, a significant increase in anti-HAV detection was observed in school-aged children (7-11 years old) (p < 0.001) and a reduction in adolescents (12-15 years old). Conclusion. In conclusion, hepatitis A is the most prevalent viral hepatitis infection detected in children, followed by HBV and HCV. In addition, the high percentage of hepatitis infections without a known etiological agent and the serological test limitations require the detection of occult HBV, HCV and hepatitis E infections. The age-dependent vulnerability of groups with HAV infections emphasizes the importance of HAV vaccination in young children in Mexico.

  • Serum N-glycomic markers in combination with panels improves the diagnosis of chronic hepatitis B Ying Qu, Chun Fang Gao, Kun Zhou, Yun Peng Zha, Ming Yi-Xu, Lun Gen Lu Page 202-212

    Aim. The present study aimed to evaluate the changes in the serum N-glycome profiles in chronic hepatitis B (CHB) patients and to assess the role of N-glycome-derived markers in the noninvasive diagnosis of liver fibrosis. Materials and Methods. After liver biopsy for pathological grading and staging, 128 CHB patients underwent serum N-glycomic analysis using DNA sequencer-assisted fluorophore-assisted carbohydrate electrophoresis (DSA-FACE) and sensitive markers were screened. Results. Peaks 1, 2, 8 and 10 in the N-glycome profiles could, to some extents, distinguish liver fibrosis at different stages. In addition, the N-glycome-derived marker log(peak2/peak8) possessed the highest diagnostic accuracy. The areas under the receiver operating characteristic (AUROCs) curves of the log(peak2/peak8) were 0.675, 0.736 and 0.754 in the diagnosis of significant fibrosis, advanced fibrosis and early cirrhosis, respectively. In combination with some marker panels (SLFG, S index, Fibrometer, Hui, Forns, APRI and Hepascore), it showed the best diagnostic potency in distinguishing significant fibrosis (SLFG + log[peak2/peak8], AUROC = 0.813) from advanced fibrosis (SLFG + log[peak2/peak8], AUROC = 0.899) and a better diagnostic potency in the identification of early cirrhosis (S index + log[peak2/peak8], AUROC = 0.903, lower than Hui model [AUROC = 0.927]) in the validation cohort. Conclusions. N-glycomic changes are present in the serum of CHB patients with liver fibrosis, and N-glycan profiling is a noninvasive and effective tool to assess the liver fibrosis, especially in combination with serum marker panels.

Liver transplantation
  • Predictive factors of abstinence in patients undergoing liver transplantation for alcoholic liver disease José Altamirano, Ramón Bataller, Andres Cardenas, Javier Michelena, Neus Freixa, Miquel Monrás, José Ríos, Alexandre Liccioni, Juan Caballería, Antoni Gual, Anna Lligoña Page 213-221

    Introduction. Alcoholic cirrhosis is one of the most common indications for liver transplantation (LT) in western countries. A major concern about transplant patients due to alcoholic liver disease (ALD) is alcoholic recidivism. Data concerning psycho-social characteristics of patients with 6 months of abstinence at initial evaluation for LT is scarce. Objectives. The aims of this study were 1) To evaluate the psycho-social profile of a cohort of patients with alcoholic cirrhosis being evaluated for LT. 2) Determine factors associated with abstinence from alcohol at initial psycho-social evaluation for LT and 3) To evaluate the potential impact of alcohol-free beer consumption on 6-month abstinence. Material and methods. Ninety patients referred to the Alcohol Unit of the Hospital Clínic of Barcelona (January 1995-December 1996) were included. Univariate and multivariate logistic regression analyses were used to identify the factors associated with cessation in alcohol consumption and with 6-month abstinence. Results. Factors associated with cessation in alcohol consumption were awareness of alcohol toxicity (OR = 5.84, CI 1.31-26.11, p = 0.02) and family recognition (OR = 3.81, CI 1.27-11.41, p = 0.01). Cessation of alcohol consumption at knowledge of ALD (OR = 5.50, CI 1.52-19.81, p = 0.009), awareness of alcohol toxicity (OR = 2.99, CI 1.02- 9.22, p = 0.05) and family recognition (OR = 5.21, CI 1.12-24.15, p = 0.03) were the independent factors associated with 6-month abstinence previous to psycho-social evaluation for LT. Conclusion. In conclusion awareness of alcohol toxicity and family recognition are the independent factors that influence cessation in alcohol consumption and 6-month abstinence in patients evaluated for LT. The use of alcohol-free beer was associated with a higher rate of abstinence in patients without alcohol cessation.

  • Liver transplantation for autoimmune hepatitis in Peru: outcomes and recurrence Martín Padilla, Rosario Mayorga, Félix Carrasco, Tayana Bedregal, Fernando Bobadilla, Carlos Rondón, José Chaman Page 222-227

    Background. Liver transplantation is the only therapy for end-stage liver disease. Cirrhosis secondary to autoimmune hepatitis (AIH) is an indication in 4-6% of adult transplants. Aims. To describe the outcomes and recurrence of AIH in liver transplant patients. Material and methods. Twenty patients were retrospectively studied. Results. The female/male ratio was 3:1, the median age was 36.7 years (range, 16 to 39 years), and the median MELD score was 18.5. According to serological analysis, 19 patients were AIH type 1 and one patient was AIH type 2. AIH was associated with human leukocyte antigen (HLA) DR13+ and DR4+. The overall 5-year patient and graft survival rates were 94 and 85%, respectively. Three (15.7%) cases of recurrent AIH were diagnosed based on histological evidence. Clinical and histological features of acute and chronic rejection were present in four (20%) and three (16.6%) patients, respectively. Conclusion. AIH frequently affected young women, was the most frequent indication for liver transplantation. Rejection and recurrence were commonly associated with AIH, but did not affect patient survival. No significant relationship between HLA-DR type and recurrence was found. Rapid progression to cirrhosis should be considered in severe recurrences.

Non alcoholic fatty liver disease (NAFLD)
  • Evidence for liver injury in the setting of obstructive sleep apnea Thomas J. Byrne, James M. Parish, Virend Somers, Bashar A. Aqel, Jorge Rakela Page 228-231

    Introduction. Obstructive sleep apnea (OSA) and non-alcoholic fatty liver disease (NAFLD) are both strongly associated with obesity. Whether OSA is an independent risk factor for liver injury is uncertain. Objective. To assess the hypothesis that OSA is associated with liver injury independent of obesity. Materials and methods. We reviewed the histories of 73 consecutive patients referred to a hospital-based sleep lab because of suspected OSA. OSA was determined to be present if the apnea-hypopnea index was > 10. Obesity was defined as a BMI ≥ 30 kg/m2. Patients were included for analysis if they had aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels obtained within 60 days of sleep study. Patients with evidence of viral hepatitis, autoimmune-, metabolic- or established alcoholic-liver disease were excluded. Patients who reported alcohol intake equivalent to a dose ≥ 20 g/day were also excluded. 53 of 73 patients met study criteria. Patients were subdivided for analysis into groups meeting or not meeting OSA and obesity criteria, and having or not having elevated aminotransferase levels. Results. 35/53 patients (66%) had OSA. 31/53 (58%) patients were obese. 15 (28%) and 12 (23%) patients had elevated AST and ALT, respectively. Mean age, gender distribution, mean BMI and percentage with either diabetes or hyperlipidemia were not significantly different in those with or without OSA. Elevated ALT was found in 11/35 (31%) patients with OSA, compared to 1/18 patients without OSA (p = 0.041). Frequency of elevated AST [obese 11/31 (35%); non-obese 4/22 (18%)] or ALT [obese 10/31 (32%); non-obese 2/22 (9%)] was not significantly different in the obese and non-obese cohorts. Conclusions. OSA may be a risk factor for liver injury independent of obesity. The prevalence and nature of liver disease in the setting of OSA should be determined with larger, prospective studies. The impact of OSA treatment, if any, on liver injury should be similarly evaluated.

  • Renal and circulatory effects of large volume plasma expansion in patients with hepatorenal syndrome type 1 Andreas Umgelter, Katrin S. Wagner, Wolfgang Reindl, Peter B. Luppa, Fabian Geisler, Wolfgang Huber, Roland M. Schmid Page 232-239

    Introduction. Hepatorenal syndrome type I (HRS I) may be a consequence of circulatory dysfunction in cirrhotic patients with portal hypertension. This uncontrolled interventional pilot study examines the hemodynamic and renal effects of large volume plasma expansion in HRS I. Material and methods. 14 cirrhotic patients (8 m, 6 f, age 60 (58-65) years) with HRS I received large volume plasma expansion with up to 400 mL of 20% human albumin solution per 12 over 48 h under hemodynamic monitoring by transpulmonary thermodilution. Creatinine clearances (ClCreat) were calculated for 12-h periods. Plasma expansion was withheld if criteria of volume overload [Extravascular lung Water Index (ELWI) > 9 mL/kg or Global End-Diastolic Volume Index (GEDI) > 820 mL/m2] were met. Paracentesis was performed according to clinical necessity and treatment continued for 48 h thereafter. Serum creatinine values were observed for 12 days. Results. Patients received 1.6 (1.5-2.0) g of albumin per kg bodyweight and day for 48 to 96 h. During the treatment period, GEDVI [724 (643-751) mL/m2 vs. 565 (488-719) mL/m2; p = 0.001], cardiac index (CI) [4.9 (4.1-6.15) L/min/m2 vs. 3.9 (3.4-5.0) L /min/m2; p = 0.033], urinary output [25 (17-69) mL/h vs. 17 (8-39) mL/h; p = 0.016) and ClCreat [20 (15-47) vs. 12 (6-17); p = 0.006] increased whereas systemic vascular resistance index (SVRI), plasma renin activity (PRA) and plasma aldosterone were significantly reduced. At 48 h there were two complete responses (serum creatinine < 133 μmol/L) and on day 12, 8 patients had a complete response. Conclusion. HRS I may respond to large volume plasma expansion with or without paracentesis.

  • The prevalence and clinical characteristics of glucose metabolism disorders in patients with liver cirrhosis. A prospective study Diego García-Compeán, Joel Omar Jáquez-Quintana, Fernando Javier Lavalle-González, Erick Reyes-Cabello, José Alberto González-González, Linda Elsa Muñoz Espinosa, Genaro Vazquez-Elizondo, Jesús Zacarías Villarreal-Pérez, Héctor J. Maldonado-Garza Page 240-248

    Aims. To define the prevalence and clinical characteristics of glucose metabolism disorders (GMD) in patients with compensated liver cirrhosis (LC). Material and methods. Fasting plasma glucose (FPG) levels were measured to 130 patients with clinically stable LC. Oral glucose tolerance tests (OGTT) and fasting plasma insulin determinations were performed to patients with normal FPG. Insulin resistance (IR) was calculated with HOMA2-IR index. GMD were classified according to FPG and OGTT tests results and to the chronologic relation between diagnosis of diabetes mellitus (DM) and LC as follows: type-2 DM (T2DM), hepatogenous diabetes (HD) and impaired glucose tolerance. Patients from all groups were compared. Results. The prevalence of GMD were as follows: T2DM in 25 patients (19.2%, 95% CI 12.5-25.9), HD in 28 (21.5%, 95% CI 14.5-28.5) and IGT in 36 (38.5%, 95% CI 30.1-46.7). The total of patients with GMD was 79.2% (95% CI 72.3-86.1). In 41% of cases GMD were subclinical and 48.7% of patients had IR. Patients with T2DM had a higher number of variables with significant differences compared with the other groups (more marked compared to the patients without GMD). The only differences between the patients with T2DM and HD were hypercreatininemia: 1.14 ± 0.53 vs. 0.84 ± 0.22 mg/dL (p = 0.005) and family history of DM: 8 (32%) vs. 2 (7%) (p = 0.02). Conclusion. Almost 80% of patients with compensated LC had GMD. Half of them were subclinical. The patients with T2DM had marked clinical differences compared to patients from the other groups, particularly renal impairment.

  • A comparison study of local injection and radiofrequency ablation therapy for traumatic portal vein injure guided by contrast-enhanced ultrasonography Yukun Luo, Qiang Liu, Ziyu Jiao, Rong Wu, Jie Tang, Faqin Lv Page 249-256

    Background. To compare local injection of hemostatic agents and radiofrequency (RF)-assisted hemostasis in the management of bleeding from the portal vein with varying diameters and blood flow velocities. Material and methods. Sixteen Bama pigs were used. Laparotomy was performed to expose the liver and inner diameters and blood flow velocities of the pre-injured portal vein in the hepatic segments and subsegments were measured. Vascular injuries in the portal vein were produced (4 in each pig). The pigs were randomly divided into two groups and local injection of hemostatic agents was performed in one group and RF-assisted hemostasis in the other, both techniques monitored by contrast-enhanced ultrasonography (CEUS). Time to hemostasis was measured, and the extent of liver injury was determined 2 h after treatment. Results. In the local injection group, the rates of successful hemostasis were 100, 88.9, and 50% with portal veins with inner diameters of < 1 mm, 1-2 mm, and 2-3 mm, respectively, and the maximum time to achieve hemostasis was 24.0 ± 7.2 s. Hemostasis was not successful when the diameter was > 3 mm. In the RF-assisted group, hemostasis was successfully at all sites regardless of vessel diameter; however, the maximum time to achieve hemostasis was 156.8 ± 31.2 s. Injury to surrounding tissue was significantly greater in the RF-assisted group. Conclusion. Both methods can achieve hemostasis with small diameter portal vein injuries; however, RF-assisted hemostasis is necessary for larger vessels, though it is associated with greater damage to surrounding tissue.

  • Increased mortality from acute liver failure in Mexico Norberto C. Chávez-Tapia, Tonatiuh Barrientos-Gutiérrez, Carlos Manuel Guerrero-López, Jean Josue Santiago-Hernández, Nahum Méndez-Sánchez, Misael Uribe Page 257-262

    Introduction. There is significant geographic variation in the etiology and prognosis of acute liver failure (ALF). Since, little information is available for Latin America. We analyzed ALF mortality trends in Mexico. Material and methods. The rates of mortality attributable to ALF were obtained for 1998 to 2009 from the National System of Health Information in Mexico and analyzed according to date, etiology, sex, age and geographic characteristics through graphical assessment and joinpoint regression. Results. From 1998 to 2009, 2,193 ALF-related deaths were reported. A threefold increase in ALF mortality was observed during the period from 1998 to 2009 (the global mortality rate increased from 13.1 to 40.2 deaths per 10,000,000 inhabitants). The most significant increase was observed for viral etiologies after 2006, affecting people 45 years old and over. Conclusion. ALF-related deaths have increased since 2006. Although we cannot speculate on the specific causes of this increase, it may reflect improvements in the access of vulnerable populations to health care.


  • Portal vein aneurysm: is it an incidental finding only? Sameer Vyas, Divyesh Mahajan, Manavjeet Singh Sandhu, Ajay Duseja, Niranjan Khandelwal Page 263-264

    Portal vein aneurysms are uncommon incidental imaging findings. They usually do not require any treatment unless symptomatic. Contrast enhanced CT is the imaging modality of choice for depicting its morphology and extension.


  • Fulminant hepatitis during self-medication with conjugated linoleic acid Rita Nortadas, José Barata Page 265-267

    The present report describes a 63-year-old female who presented with fulminant hepatic failure requiring liver transplantation caused by a weight loss dietary supplement containing conjugated linoleic acid (CLA). Thorough investigation, including liver biopsy, revealed no other cause of hepatotoxicity. In the last few years, a considerable number of reports have been published on toxic hepatitis, associated with non-conventional products, attributed with weight-reducing properties. We emphasize the importance of taking a cautious approach when consuming herbal supplements for the purpose of weight loss, as all that is "natural" may not always be healthy. Only one report of CLA-induced toxic hepatitis is related in the medical literature.

  • Recurrent pyogenic cholangitis in a case with congenital biliary anomaly Seyfettin Köklü, Mehmet Ali Akkus, Adnan Tas, Zeliha Tufan, Yusuf Tanrikulu, Murat Kekilli, Erdem Koçak, Mehmet Alparslan Gönültas, Ömer Yimaz Page 268-271

    Recurrent pyogenic cholangitis is endemic to South-east Asia but has been very rarely reported from natives of other parts of the world. A 43-years-old woman was presented with sepsis that had a history of recurrent epigastric pain and fever attacks. Her liver tests were unremarkable suggesting any hepatobiliary diseases. Recurrent pyogenic cholangitis and congenital extrahepatic biliary anomaly have been diagnosed after serial diagnostic and therapeutic procedures including endoscopic retrograde cholangiography, MRcholangiography, percutaneous transhepatic cholangiography and finally left hepatectomy. She was cured completely following surgical treatment.


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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