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Current Issue

April - June, 2008

Vol. 7 Issue 2

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

HEPATOLOGY HIGHLIGHTS

CONCISE REVIEW

  • The role of microRNAs in primary liver cancer Heike Varnholt Page 104-113

    Small RNA molecules such as microRNAs, for many years considered to be superfluous genomic material, are now known to play important regulatory roles in apoptosis, cell proliferation and differentiation, angiogenesis and thus in carcinogenesis. Primary liver carcinomas such as hepatocellular carcinomas, cholangiocarcinomas and mixed variants show a rising incidence with high mortality among affected patients but lack effective targeted therapies except the new multiple kinase inhibitor Sorafenib. This review elucidates the recent contributions of miRNA gene expression analyses to a better understanding of the complex molecular interactions in liver carcinogenesis and highlights their future promise to provide novel tools for improved diagnostics, more accurate prognostic assessment and tailored molecular therapies in liver cancer.

  • The natural course of HCV infection and the need for treatment Savino Bruno, Corinna Facciotto Page 114-119

    Nowadays, hepatitis C infection has been identified as the main cause of chronic liver disease, including cirrhosis and hepatocellular carcinoma in Western Countries. However, despite its large diffusion (with more than 150 million of people infected world-wide), the lack of symptoms during the acute phase, together with the indolent course of the disease over time, hampers the difficulties to assess the natural history of the disease, which still remains an interesting clinical dilemma.. This complexity can also be argued from the large heterogeneity of disease complication's rate observed when different methodological approaches were used (retrospective cohort studies, prospective cohort studies, retrospective-prospective cohort studies). Moreover, the progression of the disease could also be dramatically affected by many variables related to the host, the virus and the environment. Finally, in the last few years, the long–term outcome of the infected subjects, has been deeply modified by the use of efficacy antiviral therapy, as shown by the better survival observed in patients who had achieved a sustained virological response after interferon treatment.

  • Intestinal flora, probiotics, and cirrhosis Ignacio Guerrero-Hernández, Aldo Torre-Delgadillo, Florencia Vargas Vorackova, Misael Uribe Page 120-124

    Intestinal microflora constitutes a symbiotic ecosystem in permanent equilibrium, composed mainly of anaerobic bacteria. However, such equilibrium may be altered by daily conditions as drug use or pathologies interfering with intestinal physiology, generating an unfavorable environment for the organism. Besides, there are factors which may cause alterations in the intestinal wall, creating the conditions for translocation or permeation of substances or bacteria. In cirrhotic patients, there are many conditions that combine to alter the amount and populations of intestinal bacteria, as well as the functional capacity of the intestinal wall to prevent the permeation of substances and bacteria. Nowadays, numerous complications associated with cirrhosis have been identified, where such mechanisms could play an important role. There is evidence that some probiotic microorganisms could restore the microbiologic and immunologic equilibrium in the intestinal wall in cirrhotic patients and help in the treatment of complications due to cirrhosis. This article has the objective to review the interactions between intestinal flora, gut permeability, and the actual role of probiotics in the field of cirrhotic patients.

  • Hepatitis B virus and Hepatocarcinogenesis Faisal Azam, Anastasios Koulaouzidis Page 125-129

    Hepatitis B viral (HBV) infection is the commonest cause of hepatocellular carcinoma. HBV DNA is the most important predictor of hepatocarcinogenesis in HB surface antigen positive patients. We reviewed the mechanism of hepatocarcinogenesis on molecular level with a special emphasis on the role of X-protein. Hepatitis B X-protein communicates with host targets and disturbs cellular functions including cell cycle regulation, apoptosis, signalling, transcriptional regulation, encoding of cytoskeleton, cell adhesion molecules, oncogenes and tumour suppressor genes.

ORIGINAL ARTICLES

  • Black bean extract ameliorates liver fibrosis in rats with CCl4-induced injury Alberto Gabriel López Reyes, Netzahualcoyotl Arroyo-Curras, Beiman G Cano, Víctor Javier Lara-Díaz, Gustavo E Guajardo-Salinas, Jose F. Islas, Vicente Morales-Oyarvide, Luis A. Morales-Garza, Francisco Javier Galvez-Gastelum, Guillermo Grijalva, Jorge E. Moreno-Cuevas Page 130-135

    We assessed the anti-fibrotic effects of methanolic black bean extract antioxidants in a carbon tetrachloride (CCl4) liver injury model in rats. Experimentally intoxicated animals received CCl4 for eight weeks, the reference and test groups received daily intragastric quercetin or daily intragastric black bean extract. Liver fibrosis was assessed and quantified using morphometric analysis. Expression of fibrosis related genes was measured by real time RT-PCR. Qualitative and quantitative histological analysis showed that administration of 70 mg/kg b.w. of black bean extract reduced hepatic fibrosis index by 18% compared to positive controls (P 0.006), as a result of a decrease in type I (44.3% less, P 0.03) and type IV (68.9% less, P 0.049) collagen gene expression compared to CCl4-injured and Quercetin treated rats. In conclusion, we provide evidence that this methanol black bean extract ameliorates liver fibrosis and types I and IV collagen gene expression, in the animal model used. Practical applications: The compounds contained in this black bean extract exhibited strong antifibrotic effects in the CCl4 chronic liver injury model used; considering that this compounds are contained in a leguminous that has been used in human diet for a long time, their toxic potential should be very low, and this characteristic should favor their potential use in some other chronic or degenerative states that include an increase in inflammation and oxidative burst in their pathogenesis. Another possible application of this kind of extract could be its use as an antimicrobial or even antiparasitic therapeutic agent, although it is purely speculative.

  • Influence of extrahepatic viral infection on the natural history of hepatitis C María Inés Barría, Jorge Vera-Otarola, Úrsula León, Valeska Vollrath, Delphine Marsac, Arnoldo Riquelme, Marcelo López-Lastra, Alejandro Soza Page 136-143

    HCV is primarily hepatotropic, but there is mounting evidence pointing to infection and replication of extrahepatic sites. Here we evaluated the occurrence of HCV infection of peripheral blood mononuclear cells (PBMC) and explored the possible association between viral extrahepatic infection and the natural history of the disease. Forty seven Chilean, HCV infected, treatment naïve patients were included in the study. HCV RNA was isolated from plasma and PBMC and subsequently reverse transcribed, amplified and sequenced. Most patients harbored HCV 1b genotype and the most common route of infection showed to be blood transfusion. HCV RNA was readily detected in PBMCs of 34 out of the 47 patients (72%). We report that HCV sequences found in PBMC differ from those in plasma of the same subjects strongly suggesting HCV compartmentalization. In addition, we found that patients with detectable HCV RNA in PBMC had a tendency for being more likely cirrhotic [OR 3.8 (95% CI: 0.98 to 14)]. In conclusion, this study provides further arguments for the existence of HCV infection of extrahepatic sites and suggests that extrahepatic infection could be a factor influencing the natural history of the disease.

  • Genotyping of hepatitis C virus (HCV) in infected patients from Northeast Mexico Ana María Rivas-Estilla, Paula Cordero-Pérez, Karina del Carmen Trujillo-Murillo, Javier Ramos-Jiménez, Carlos Chen-López, María de L Garza-Rodríguez, Ángel Ramírez-Gutiérrez, Linda Muñoz Espinosa Page 144-147

    Information about HCV genotypes in infected patients from different regions of Mexico is limited. Objective: To determine the prevalence of HCV genotypes in a group of HCV infected patients who attended a third level Hospital in Northeast of Mexico. Methods: Genotyping analysis was performed using the InnoLiPAHCV genotype assay in 147 patients (65 males and 82 females, mean age 44 ± 12 years) with positive anti- HCV antibodies and detectable HCV-RNA levels. Results: Infected individuals were more likely to be female (56%). Histological data showed that 63% of the patients had chronic hepatitis, while the remainder presented cirrhosis (37%). The most frequent HCV genotype was 1 (73%). We found the following distribution: genotype 1 (2.7%), 1a (28.6%), 1b (37.4%), 1a/1b (4.1%), 2a (1.4%), 2b (8.8%), 2c (0.7%), 2a/2c (2.7%), 3 (2%), 3a (10.2%), 4 (0.7%) and 4c (0.7%). The most frequent associated risk factor was blood transfusion (72.5%). Conclusion: Prevalence of HCV genotypes in the Northeast of Mexico is similar to those reported previously in other Mexican regions and the most frequent risk factor continues being blood transfusion.

  • Impact of diabetes mellitus on outcome of HCC Deepak N. Amarapurkar, Nikhil D. Patel, Praful M. Kamani Page 148-151

    Background: Diabetes mellitus (DM) is recently identified risk factor for development and progression of chronic liver disease as well as hepatocellular carcinoma (HCC). We planned a prospective analysis to identify impact of DM in Indian patients with HCC. Methods: During last 10 years, 160 consecutive patients of HCC were evaluated. Demographic profile like age of presentation, clinical features, etiology of HCC, tumor size at presentation, management and ultimate outcome was compared diabetic with non-diabetic HCC patients. Results: During last 10 years, 160 consecutive patients of HCC were evaluated (Mean age = 59.6 ± 12.9 years, sex ratio (M: F) = 5.4: 1). Etiology for HCC were hepatitis B in 45 (28.2%), hepatitis C in 18 (11.3%), alcohol in 27 (16.8%), alcohol with hepatitis B in 12 (7.5%), alcohol with hepatitis C in 1 (0.6%), non-alcoholic steatohepatitis in 4 (2.5%) and cryptogenic in 53 (33.2%) patients. Patients of HCC with DM (group-A, n =46, age = 62.6 ± 9.5 years, sex (M: F) = 6.6:1) were compared with patient of HCC without DM (group-B, n =114, age = 66.7 ± 13.7 years, sex (M: F) = 5.4:1). Duration of diabetes in group-A was 7.6 ± 3.2 years. Patients in group-A had more advanced HCC (size of lesion > 5 cm and >3 lesions of 3 cm or more diameter, portal vein thrombosis or intra-hepatic bile duct involvement) than group-B [34 (73.9%) vs 72 (54.3%)]. Mortality with in one year was significantly more in group-A compared to group-B [36 (78.2%) vs 56 (49.1%)]. Conclusion: DM is associated with more advanced lesion and poor outcome in patient with HCC.

  • Prevalence of hepatitis B and C seropositivity in a Nigerian cohort of HIV-infected patients Jesse A. Otegbayo, Babafemi O Taiwo, Titilola S Akingbola, Georgina N. Odaibo, Kayode S. Adedapo, Sudhir Penugonda, Isaac F. Adewole, David O. Olaleye, Rob Murphy, Phyllis Kanki Page 152-156

    Introduction: The clinical and public health implications of the convergence of the human immunodeficiency virus (HIV) epidemic and chronic viral hepatitis in sub-Saharan Africa are poorly understood. This study was designed to determine the seroprevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV), and the impact of co-infection on baseline serum alanine transaminase (ALT), CD4+ T lymphocyte (CD4) count, and plasma HIV-RNA (viral load) in a cohort of HIV-infected Nigerians. Methods: A retrospective study was conducted, on eligible treatment-naive patients who presented between August 2004 and February 2007 to the University College Hospital (UCH), Ibadan, Nigeria. Demographic data and pre-treatment laboratory results (hepatitis B surface antigen (HBsAg), HCV antibodies (anti-HCV), ALT, CD4 count and viral load) were retrieved from the medical records. Fisher's exact, two sample t-tests, and the Wilcoxon rank sum tests were used to compare groups. A logistic regression model was fitted to explore characteristics associated with co-infection status. Results: A total of 1779 HIV-infected patients (male: female ratio, 1:2) met inclusion criteria. HBsAg was present in 11.9%, anti- HCV in 4.8% and both markers in 1%. HBsAg was more common among males than females (15.4% vs 10.1%, respectively p = 0.001) while anti-HCV was detected in a similar proportion of males and females (5.3% versus 4.6%, respectively p = 0.559). HIV-infected patients with anti-HCV alone had a lower mean baseline CD4 count compared to those without anti- HCV or HBsAg (197 cells/mm3 vs 247 cells/mm3, respectively p = 0.008). Serum ALT was higher among patients with HBsAg compared to those without HBsAg or anti-HCV (43 International Units (IU) vs. 39 IU, respectively p = 0.015). Male gender was associated with HBV co-infection on logistic regression (OR1.786; 95% CI, 1.306-2.443; p < 0.005). Conclusion: More HIV-infected females than males presented for care in this cohort. We identified a relatively high prevalence of HBV and HCV co-infection in general, and a higher rate of HBV co-infection among males than females. Pre-treatment CD4 count was significantly lower among those with HCV co-infection, while ALT was slightly higher among those with HBV co-infection. Triple infection with HIV, HBV and HCV was present in a small but significant proportion of patients. These findings underscore the importance of testing for HBV and HCV in all HIV-infected persons in our setting.

EDITORIAL

IMAGES IN HEPATOLOGY

CASE REPORTS

  • Fanconi - Bickel Syndrome - two cases report Norberto Sotelo, Ramiro García, René Tostado, Nagasharmila Dhanakotti Page 163-167

    A one year eight month old male child and his nine month old female sibling were presented with Growth retardation, abdominal distension, doll-like faces, hepatomegaly, phosphaturia, proximal renal tubular dysfunction. The elder sibling also presented with glucosuria, hyperglycemia, hypoinsulinemia. The younger one later presented with galactosemia. Biopsy of liver on these two patients revealed the accumulation of glycogen in hepatocytes.

  • Intraductal oncocytic papillary neoplasm of the liver: Case and review of a rare variant James H. Tabibian, Charles R. Lassman, Daniel J. Margolis, Carmen Landaverde, Ronald W. Busuttil, Francisco A. Durazo Page 168-173

    Intrahepatic cholangiocarcinoma (ICCA) comprises 10% of all cholangiocarcinoma (CCA). It can be divided into three macroscopic subtypes, the least common of which is characterized by intraductal growth and believed to be more amenable to good outcomes with surgical resection compared to other ICCA. Recently, the rare finding of oncocytic differentiation has been described in this subtype and termed «intraductal oncocytic papillary neoplasm» (IOPN), but it remains unclear if the presence of oncocytes confers a different tumor behavior. We present the eighth reported case of IOPN, which to our knowledge, is the first such case that, due to its location and vascular compromise, required orthotopic liver transplantation (OLT). This case adds to the little that is known about the behavior of IOPN and supports the observation that resection, or OLT when resection is not possible, is a valid treatment option.

  • Giant hydatid liver cyst. Management of residual cavity Nikolaos S. Salemis Page 174-176

    The management of the residual cavity during surgical intervention for giant hydatid liver cysts is often a challenging problem. Herein, is described the case of a 55-year-old female patient who was diagnosed with a giant hydatid cyst occupying almost the entire left lobe of the liver. After partial cystectomy, the residual cavity was managed by combination of suture obliteration with omentoplasty. The patient had an uneventful postoperative course and was discharged eight days later. The clinical presentation, diagnostic work-up and surgical management of the patient are discussed, along with a review of the literature.

  • Autoimmune hepatitis induced by the prolonged hepatitis A virus infection Fehmi Tabak, Filiz Ozdemir, Omur Tabak, Burak Erer, Veysel Tahan, Resat Ozaras Page 177-179

    Hepatitis A virus (HAV) is the most common cause of acute viral hepatitis in the world. Rarely, acute infection may persist for a long time. Autoimmune hepatitis (AIH) may provide anti-HAV IgM positivity detection for a prolonged time. On the other hand, HAV as an infectious agent may also trigger AIH. Here we presented a case which seemed like a simple acute viral hepatitis A infection at the beginning but turned out to be an AIH according to the International Autoimmune Hepatitis Group's system. A 21-year-old female was diagnosed as symptomatic acute HAV infection with anti- HAV IgM positivity and elevated aminotransferase levels. The other viral serological tests were negative. On the 6th, 12th and 18th months of the follow up, her anti-HAV IgM positivity still continued and transaminase levels were also 3 to 7 times high of the upper limit of normal. In addition, antinuclear antibody was positive. However, on the 19th month anti-HAV IgM could be detected as negative. Liver histology was prominent. The patient had a score of 16 according to the International Autoimmune Hepatitis Group's system. She was given prednisolone (10 mg/day) and azathioprine (100 mg/day). The aminotransferase levels were detected within normal ranges at the end of the first month of therapy. She was in remission during follow up for 6 years. In conclusion, prolonged HAV infection and AIH may not only trigger each other but also deteriorate the liver histology. AIH should be investigated in cases of long-lasting HAV infection in order to begin the treatment earlier. On the other hand, AIH patients should also be vaccinated for both HBV and HAV to avoid more severe diseases.

LETTER TO EDITOR

LIVER NEWS ELSEWHERE

  • Gallbladder disease in patients with primary sclerosing cholangitis Genaro Vazquez-Elizondo, Jimena Muciño-Bermejo, Nahum Méndez-Sánchez Page 182-183

    Background/Aims: Gallbladder abnormalities may be part of the spectrum in primary sclerosing cholangitis (PSC). The aim of the present study was to evaluate the occurrence and prognostic importance of gallbladder abnormalities in patients with PSC. Methods: Presence of gallbladder abnormalities was assessed in 286 patients with PSC treated at the Liver Unit, Karolinska University Hospital, Huddinge, between 1970 and 2005. Results: One or more gallbladder abnormalities were found in 41% of the patients. Gallstones were found in 25% and cholecystitis in 25%. Cholecystitis among patients with extrahepatic involvement of PSC [30% (65/214)] was significantly higher than among those with intrahepatic involvement [9% (6/70)] (P < 0.0001). A gallbladder mass lesion with a mean size of 21 (± 9) mm (S.D.) was found in 18 (6%) patients, in 56% (10/18) of whom it constituted gallbladder carcinoma. In 9 patients without a gallbladder mass lesion, histological re-evaluation disclosed epithelial dysplasia of the gallbladder. Conclusions: Gallbladder disease is common in patients with PSC. Dysplasia and carcinoma are commonly found in gallbladder epithelium, suggesting that regular examination of the gallbladder in PSC patients could be of value for early detection of a gallbladder mass lesion. Cholecystectomy is recommended when such a lesion is detected, regardless of its size. Abstract published under the permission of the Elsevier Limited.

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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