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November- December, 2012

Vol. 11 Issue 6

On the cover: A. Multiple hepatic masses in the left liver lobe (white arrow) with portal invasion (black arrow). B. Intrahepatic portal invasion (black arrows).

HEPATOLOGY HIGHLIGHTS

CONCISE REVIEW

  • Polycystic liver disease: a clinical review Natasha Chandok Page 819-826

    Polycystic liver disease rarely occurs in isolation as part of autosomal dominant polycystic liver disease, but more commonly, it exists as an extra-renal manifestation of autosomal dominant polycystic kidney disease. The pathogenesis of polycystic liver disease involves defects in the primary cilium of the cholangiocyte, with genetic mutations that impair key proteins integral to the complex functioning of cilia. While most patients are asymptomatic and require no intervention aside from reassurance and genetic counseling, in a minority of patients, polycystic liver disease creates a myriad of symptoms from the compressive effects of enlarged cysts, and can even cause malnutrition and liver decompensation in the severest of cases. In patients with symptomatic disease, a variety of interventional radiology or surgical techniques can be considered, including aspiration with sclerotherapy of a dominant cyst, fenestration, segmental hepatic resection, and even liver transplantation. Although there are no curative medical options for polycystic liver disease, somatostatin analogs hold promise and have shown minimal efficacy in human studies. However, further research is needed to develop more efficacious medical treatments.

  • Genomic determinants of hepatitis C virus antiviral therapy outcomes: toward individualized treatment Mauricio Venegas, Javier Brahm, Rodrigo A. Villanueva Page 827-837

    Hepatitis C virus (HCV) is an important global health problem with an estimated prevalence of more than 170 million infected individuals worldwide. Currently, the standard antiviral therapy, based on pegylated interferon alpha and ribavirin, can achieve a virological response in only nearly 50% of the patients infected with HCV genotype 1, the most widely distributed globally. During the last years, relevant data from genome- wide association studies (GWAS) about the impact and contribution of the patient genomics on viral infection outcomes has suggested the possibility that an individualized antiviral therapy can be considered. In this review, we analyze the existing information on single nucleotide polymorphisms (SNPs) of several host genes and viral factors that influence, as a whole, the outcome of the standard antiviral therapy, and that might be used to predict an individualized antiviral response. We also discuss the clinical data within the most recent context of the triple antiviral therapy.

  • Greater Celandine hepatotoxicity: a clinical review Rolf Teschke, Christian Frenzel, Xaver Glass, Johannes Schulze, Axel Eickhoff Page 838-848

    Herbal hepatotoxicity is a rare and poorly described disease because reported cases are mostly scattered and lack an appropriate causality assessment. We now describe in detail the clinical picture of herbal hepatotoxicity by extracts of Greater Celandine (GC), syn. Chelidonium majus L. from the Papaveraceae family, which contain more than 20 ingredients including various biologically active isoquinoline alkaloids. For this purpose, we analyzed and reviewed published cases of 16 patients from various European countries. In all patients, herbal hepatotoxicity was of probable and highly probable causality for GC, using the original and updated scale of CIOMS (Council for International Organizations of Medical Sciences). GC associated hepatotoxicity usually has an acute clinical course exhibiting a hepatocellular pattern of injury and is correlated to an idiosyncratic reaction with its metabolic subtype. Jaundice combined with high values of serum aminotransferases was present in virtually all cases with favourable outcome despite severe clinical course. In conclusion, GC hepatotoxicity is a typical herbal hepatotoxicity with a sound causality track for GC, but there is uncertainty regarding the respective causative compound(s). The present detailed review of GC hepatotoxicity may serve as an example for clinical causality assessments of future cases of liver injury due to other herbs.

ORIGINAL ARTICLES

Clinical Studies

Viral Hepatitis
  • Genotype/subgenotype distribution of hepatitis B virus among hemodialysis patients with chronical hepatitis B Murat Sayan, Cengiz Dogan Page 849-854

    Introduction. Hepatitis B virus (HBV) infection in hemodialysis (HD) patients is a major concern, but limited information exists on the HBV genotyping in patients on maintenance HD in Turkey. Aim. To investigate the genotype and subgenotype distribution of HBV in Turkish HD patients with chronic hepatitis B. Material and methods. A total of 248 HBsAg positive patients undergoing long-term HD from all regions of Turkey were included in this study. HBV genotypes were determined by phylogenetic analysis and by genotyping tools. Results. HBV DNA was detected in 94/248 (38%) of the patients. Among the study patients, genotype D of HBV was predominant (99%) and one patient (1%) was infected with genotype G. The majority (82%) of HBV genotype D branched into subgenotype D1, and also in ayw2 HBsAg subtype clusters in the phylogenetic tree. However, 10% and 8% of the strains branched into subgenotype D2 (also in ayw3 HBsAg subtype cluster) and subgenotype D3 clusters, respectively. Conclusion. In conclusion, HBV genotyping should be routinely applied to HD patients to establish a baseline. Determination of genotypes/subgenotypes of HBV may provide robust epidemiological data related to their circulation as well as their transmissibility.

  • Validation and comparison of simple noninvasive models for the prediction of liver fibrosis in chronic hepatitis C Thabata Glenda Fenili Amorim, Guilherme Jönck Staub, César Lazzarotto, André Pacheco Silva, Joice Manes, Maria da Graça Ferronato, Maria Beatriz Cacese Shiozawa, Janaína Luz Narciso-Schiavon, Esther Buzaglo Dantas-Corrêa, Leonardo de Lucca Schiavon Page 855-861

    Introduction. Although it is standard procedure in the evaluation of liver diseases, biopsy is an invasive method subject to sampling error and intra or inter-observer variability. Thus, surrogate markers of liver fibrosis have been proposed, with variable availability and accuracy. Aim. Validate and compare the performance of APRI and FIB-4 as predictors of liver fibrosis in HCV patients. Material and methods. Crosssectional study including patients with HCV-RNA (+) who underwent liver biopsy. Significant fibrosis was defined as METAVIR stage ≥ 2. The diagnostic performance of the models in predicting significant fibrosis were evaluated and compared by ROC curves. Results. The study included 119 patients, mean age 43.7 ± 10.6 years and 62% males. Significant fibrosis was identified in 41 patients. The AUROCs observed were: APRI = 0.793 ± 0.047, FIB-4 = 0.811 ± 0.045 and AST/ALT = 0.661 ± 0.055 (P = 0.054 for APRI vs. AST/ALT, and P = 0.014 for FIB-4 vs. AST/ALT). Considering classic cutoffs, the PPV and NPV for APRI and FIB-4 were, respectively, 77% and 92% and 83% and 81%. Thirteen (19%) patients were misdiagnosed by APRI and 16 (18%) by FIB-4. By restricting the indication of liver biopsy to patients with intermediate values, it could have been correctly avoided in 47% and 63% of the patients with APRI and FIB-4, respectively. Conclusion. The models APRI and FIB-4 were superior to AST/ALT ratio in the diagnosis of significant fibrosis in chronic HCV infection. Even though the overall performance of APRI and FIB-4 was similar, a higher proportion of patients may be correctly classified by FIB-4.

  • Epidemiological, clinical and laboratory features of chronic hepatitis B infection in a cohort of immigrant and Italian patients from Ferrara, Italy Carlo Contini, Lorenzo Badia, Rosario Cultrera, Anastasio Grilli, Aldo De Togni Page 862-869

    Background. Italy has recently become a land of immigration. Two hundred and fifty thousand carriers are immigrants and chronic HBV infection is the prevalent form. Considering the elevated number of foreigners resident in our province and the potential risk of transmission to local people, we retrospectively investigated the patterns of chronic hepatitis B (CHB) in 154 patients (76 foreigners, 78 Italians) observed in our Institution, with regard to demographic and clinical/laboratory characteristics. Results. The immigrants were younger (mean age 31 years) compared to Italians (51.5) and mainly came from East Europe. Regarding exposure to HBV, the intra-familial risk factor was most frequently observed in foreigners, compared to Italians (p = 0.03). Foreigners also showed a higher prevalence of HBeAg positive forms, HDV co-infection (7.9%) and abnormal ALT and/or HBV-DNA values, compared to Italians. HBeAg positivity was more associated with increased ALT (OR = 36.6, p = 0.001) than with elevated HBV viremia (OR = 6.5, p = 0.049); age was a protective factor (OR = 0.1; p = 0.014). No significant association was found between increased ALT and foreign nationality. The simultaneous presence of increased ALT and viremia was more frequent among foreigners, (OR = 7.6, p = 0,014) and increased with age (OR = 1.06, p = 0.013). Antiviral therapy was given in 7.8% of foreign citizens. Conclusion. Immigrants constitute a vulnerable population subgroup that would benefit from a more active approach regarding doctor-patient relationship for early recognition of HBV and treatment programmes.

  • Occult HBV infection among anti-HBc positive HIV-infected patients in apex referral centre, Eastern India R. Panigrahi, S. Majumder, M. Gooptu, A. Biswas, S. Datta, P.K. Chandra, A. Banerjee, S. Chakrabarti, D. Bandopadhyay, B.K. De, R. Chakravarty Page 870-875

    Background. The prevalence of occult HBV, defined by the presence of HBV DNA in individuals with antibodies to HBV core antigen and with absence of HBV surface antigen, but its clinical significance and virological features in HIV-infected patients is still unclear. Aim. To investigate the prevalence, clinical significance and molecular characterization of occult hepatitis B virus infection in ART-Naive HIV-positive individuals. Material and methods. Among the 1077 HIV-infected patients with different risk factors for HIV infection, 297 were HBsAg-ve ART-naive, of them 112 was randomly selected for the study. HBV DNA was tested by in-house PCR and quantified by qPCR. Molecular characterization was performed by sequencing the envelope and overlapping polymerase genes. Results. We found the prevalence of occult HBV to be 10.7% among a randomly selected group of HBsAg-ve/antiHBc+ve HIV-infected patients. Overall 33.9% (38 of 112) of the patients were antiHBc positive indicating exposure to HBV infection. HBV DNA was detected in 12/38 (31.5%) antiHBc positive samples and 50% of them had CD4 T cell count < 200 cells/mm3. HCV coinfection was low (2.7%). No surrogate marker for OBI could be identified. Presence of antiHBs antibodies did not rule out OBI. Liver biopsy in six cases showed varying stages of chronic hepatitis. Several mutations were detected but not the common immune escape mutant G145R. Conclusion. In conclusion the prevalence of OBI was significantly high among HIV coinfected patients, which highlights the importance of HBV DNA testing in these patients and indicates need for further prospective studies in larger cohorts to assess its clinical significance.

  • IL28B polymorphisms predict the response to chronic hepatitis C virus infection treatment in a Mexican population Laura E. Martínez-Gómez, Norberto C. Chávez-Tapia, Ana I. Burguete-García, Nancy Aguilar-Olivos, Vicente Madrid-Marina, Margarita Bahena-Román, Citlalli Orbe-Orihuela, Misael Uribe, Nahum Méndez-Sánchez Page 876-881

    Introduction. The treatment of hepatitis C virus (HCV) genotype 1 with ribavirin (RBV) and pegylated-interferon alpha (peg-IFNα) provides a low-level sustained virological response (SVR). Single nucleotide polymorphisms (SNPs) in the interleukin 28B (IL28B) gene have been identified as SVR predictors. Our aim was to establish an association between three IL28B SNPs (rs8099917, rs12979860, and rs8103142) and the peg-IFNα/RBV treatment response in a Mexican population cohort with chronic HCV. Material and methods. A cohort study was performed with 83 chronic HCV patients at the Fundación Clínica Médica Sur in Mexico City. All patients were treated with peg-IFNα and RBV. The data were analyzed by logistic regression, with adjustments for age, gender, and viral genotype, to determine any associations between the SNPs and the treatment response. Results. In the study group of 83 HCV patients, the main genotype was genotype 1 (70%, n = 58) and the overall SVR was 32.53% (n = 27). In the HCV-1 group, SVR was 27%, whereas SVR was 44% in the HCV-2 group. We found an association between rs12979860 CC and SVR in a codominant model (OR = 4.83, 95% CI = 1.12-20.8, P = 0.033). There was no statistically significant association between SVR and rs8099917 or rs8103142. rs12979860 polymorphisms of CC, CT, and TT, were present in 24%, 41%, and 35% of patients, respectively. Conclusion. A Mexican HCV-1-infected population treated with peg-IFNα and RVB had a low SVR rate, which was associated with the SNP rs12979860 (CC). SVR was not associated with the SNPs rs8099917 or rs8103142.

Liver transplantation
  • Health-related quality of life in Egyptian patients after liver transplantation Mahasen Mabrouk, Gamal Esmat, Ayman Yosry, Magdy El Serafy, Wahid Doss, Naglaa Zayed, Medhat El Sahhar, Sally Awny, Ashraf Omar Page 882-890

    Introduction-Aim. Health-Related Quality of Life (HRQOL) has become an important focus of patient care and clinical outcomes research with the improvement in patient and graft survival after liver transplantation (LT). The current study was designed to evaluate the post-transplant HRQOL profiles using the Liver Disease Quality of Life 1.0 (LDQOL 1.0) Questionnaire and demonstrate the possible effect of peri-transplant clinical covariates on these profiles. Material and methods. Participants included pre-transplant group (waiting-list patients n = 50) and post-transplant group (mean 5 ± 4 years after deceased or living donor LT n = 103) who were recruited from 3 specialized centers in Egypt. We applied the LDQOL 1.0 questionnaire; a 111-item containing the Short Form-36 version 2.0 (SF-36v2) as a generic component supplemented by 75 disease-specific items. The etiology of cirrhosis, co-morbidities, model for end-stage liver disease (MELD), Child-Pugh class and post-operative complications were analyzed. Results. All recipients had significant higher HRQOL scores than patients in waiting-list using both questionnaire components. Recipients with pre-LT MELD ≥ 15, Child-Pugh class C, history of hepatocellular carcinoma (HCC) demonstrated low HRQOL scores. Recipients without post-operative surgical complications had a statistically better HRQOL using the disease-specific, but not the SF-36v2 component. On the other hand, both components demonstrated non-significant lower scores in recipients with rejection episodes, cytomegalovirus (CMV) infection and hepatitis C recurrence had compared to those without medical complications. Conclusion. Generally HRQOL improves dramatically after LT as assessed by LDQOL questionnaire. Moreover, combined questionnaires can provide accurate information about the possible impaired HRQOL post-LT due to pre-transplant disease severity and post-operative complications.

  • Steatotic livers. Can we use them in OLTX? Outcome data from a prospective baseline liver biopsy study Mauricio Gabrielli, Fabrizio Moisan, Marcela Vidal, Ignacio Duarte, Macarena Jiménez, Guillermo Izquierdo, Pilar Domínguez, Javier Méndez, Alejandro Soza, Carlos Benítez, Rosa Pérez, Marco Arrese, Juan Guerra, _ Jarufe Page 891-898

    Introduction. Steatotic livers have been associated with greater risk of allograft dysfunction in liver transplantation. Our aim was to determinate the prevalence of steatosis in grafts from deceased donors in Chile and to assess the utility of a protocol-bench biopsy as an outcome predictor of steatotic grafts in our transplant program. Material and methods. We prospectively performed protocol-bench graft biopsies from March 2004 to January 2009. Biopsies were analyzed and classified by two independent pathologists. Steatosis severity was graded as normal from absent to < 6%; grade 1: 6-33%; grade 2: > 33-66% and grade 3: > 66%. Results. We analyzed 58 liver grafts from deceased donors. Twenty-nine grafts (50%) were steatotic; 9 of them (16%) with grade 3. Donor age (p < 0.001) and BMI over 25 kg/m2 (p = 0.012) were significantly associated with the presence of steatosis. There were two primary non-functions (PNF); both in a grade 3 steatotic graft. The 3-year overall survival was lower among recipients with macrovesicular steatotic graft (57%) than recipients with microvesicular (85%) or non-steatotic grafts (95%) (p = 0.026). Conclusion. Macrovesicular steatosis was associated with a poor outcome in this series. A protocol bench-biopsy would be useful to identify these grafts.

Hepatocellular Carcinoma (HCC)
  • Evaluation of the C3435T polymorphism in the MDR1 gene in patients with hepatocellular carcinoma Vanessa Dido Baldissera, Angelo Alves de Mattos, Gabriela Perdomo Coral, Fernanda Branco de Araujo, Claudio Augusto Marroni, Ajácio Bandeira de Mello Brandão, Paulo Roberto Ott Fontes, Carlos Thadeu Schmidt Cerski, Antonio Atalibio Hartmann, Nélson Alexandre Kretzmann Filho Page 899-906

    Introduction. Considering the high prevalence of liver tumors and the impact on patient survival, a greater understanding of the biological behavior of those tumors if of great importance. The multidrug resistance gene (MDR1) may present as single nucleotide polymorphism (SNP) which can affect the expression and activity of P-glycoprotein (Pgp), and high expression of Pgp has been associated with a worse prognosis in affected patients. Objective. To correlate the C3435T polymorphism in the MDR1 gene with the immunohistochemical expression of Pgp. Material and methods. A total of 67 samples from patients with diagnosis of hepatocellular carcinoma (HCC), collected in the period from 2000 to 2009, were analyzed. The polymorphism in the MDR1 gene was determined by the technique of allele-specific real time PCR using TaqMan assay, and the expression of protein Pgp was evaluated by immunohistochemistry. Results. Among the samples evaluated, 56 (83.6%) were from male patients and 11 (16.4%) from females. Mean age was 60.6 years (± 8.8), ranging from 37 to 85 years. The etiology of the HCC was related to hepatitis C virus infection (HCV) in 31 (46.3%) of cases, followed by hepatitis C virus infection + alcohol in 24 cases (35.8%), alcohol in 4 cases (6)%, hepatitis B virus (HBV) in 4 cases (6%) and other factors in 4 cases (6%). Liver transplantation was performed in 48 cases (71.6%) and hepatectomia in 19 cases (28.4%). The genotypes CC, CT and TT showed frequencies of 25.4%, 41.8% and 32.8%, respectively, and the allele frequencies were 46.3% for allele C and 53.7% for allele T. The expression of Pgp in over 75% of the cells was significantly more frequent in tumor tissue. On the other hand, a low expression of Pgp, in less than 25% of the cells, was significantly more frequent in non-tumor tissue. The Pgp expression in more than 50% of tumor cells of individuals with genotypes CC, CT and TT was 15.7%, 51.0% and 33.3%, respectively, and was significantly higher when in the presence of allele T (p = 0.002). Conclusion. The presence of the polymorphic allele T is related to increased expression of Pgp protein in patients with HCC.

Miscellaneous
  • Response to different therapeutic approaches in Wilson disease. A long-term follow up study Beatriz Rodríguez, Juan Burguera, Marina Berenguer Page 907-914

    Background and aims. There are certain areas of uncertainty regarding the best therapeutic approach in patients diagnosed with Wilson Disease (WD). Our aim was to assess treatment response to different therapies in a cohort of WD patients followed in a single center. Material and methods. This is an observational, descriptive study in which clinical, laboratory and imaging data are reviewed in a series of 20 WD patients with a median follow-up of 14 years. Type of presentation, treatment used, biochemical and copper homeostasis parameters were elicited. Results. Median age at diagnosis was 22 years. The most frequent form of presentation was hepatic (n = 10, 50%; mean age: 21.5 years), followed by neurological (25%; mean age: 34.5 years) and mixed (15%). The initial treatment in both symptomatic and asymptomatic patients at diagnosis was d-penicillamine in 90% and Zinc (Zn) in 10%, respectively. Patients who were maintained on d-penicillamine for the whole period had complete biochemical normalization (baseline ALT: 220 IU/l; last follow up 38 IU/l). In contrast, patients in whom d-penicillamine was switched to Zn, irrespective of the cause, did not show a complete biochemical remission (baseline ALT: 100 IU/l vs. 66 IU/l at last follow-up). Conclusions. Treatment was found to be effective in most cases regardless of the drug used. However, side effects were common in those treated with d-penicillamine agents, and required switching to zinc. Therapy with zinc was well tolerated and appeared to have a good efficacy. However, in 33%, a complete normalization of liver enzymes was never reached.

  • Prognostic factors associated with in-hospital mortality in patients with spontaneous bacterial peritonitis Maiara Isabel Musskopf, Fabricio Pimentel Fonseca, Jeferson Gass, Ângelo Zambam De Mattos, Jorge Alberto John, Ajácio Bandeira de Mello Brandão Page 915-920

    Introduction. Spontaneous bacterial peritonitis (SBP) is associated with a high in-hospital mortality rate ranging from 20-40%. The model for end-stage liver disease (MELD) has been suggested as a predictor of inhospital mortality in patients with SBP. However, the accuracy of the MELD has been questioned, and the integrated MELD (iMELD) score, which incorporates age and serum sodium to the previous model, has been proposed to improve prognostic accuracy. The iMELD has not yet been evaluated in patients with SBP. Aim. To evaluate the accuracy of iMELD and MELD scores in predicting in-hospital mortality in patients with SBP and to identify other prognostic factors of mortality in this group of patients. Results. Of 40 patients analyzed, 65% were male, 50% had hepatitis C, and 27.5% had hepatocellular carcinoma. Mean age was 55.6 years; 25.7% were classified as Child-Pugh class B, and 74.3% as class C. Mean scores were 46.0 and 19.9 for iMELD and MELD, respectively. In-hospital mortality was 40%. Univariate analysis showed that total bilirubin, creatinine, MELD and iMELD scores were significantly associated with in-hospital mortality. The prognostic accuracy was 80% and 77% for iMELD and MELD scores, respectively. Conclusion. In conclusion, bilirubin, creatinine, MELD and iMELD were predictors of in-hospital mortality in cirrhotic patients with SPB. iMELD was slightly more accurate than MELD in this group of patients.

  • Splenectomy in cirrhosis with hypersplenism: improvement in cytopenias, child’s status and institution of specific treatment for hepatitis C with success Saurabh Kedia, Rohit Goyal, Vivek Mangla, Ajay Kumar, Shalimar S., Prasenjit Das, Sujoy Pal, Peush Sahni, Subrat K. Acharya Page 921-929

    Introduction. Hypersplenism in cirrhosis is not infrequent and may compromise with quality of life and therapy. Splenectomy is a therapeutic option, but information on results of splenectomy is scarce. Material and methods. Consecutive patients with cirrhosis who underwent splenectomy between 2001-2010 were included in the study. Safety, efficacy of splenectomy and subsequent influence on therapy were evaluated. Results. Thirty three patients (mean age 30.9 ± 11.6 years, 19 men, viral 48.5%, autoimmune 15.1%, cryptogenic 36.4%) underwent splenectomy. Twenty were Child's A, 13 Child's B. Twenty patients had > 6 months follow up. Common indications were inability to treat with interferon, transfusion-dependent anemia, recurrent mucosal bleeds, and large spleen compromising quality of life. Median hospital stay was 7 (4-24) days. There was no splenectomy related mortality. Twenty three (70%) patients had post-operative complications, most commonly infections. Two patients required percutaneous drainage of post-operative collections, and 1 needed re-exploration for intra-abdominal bleed. Subsequent to splenectomy platelet count (44,000 to 151,000/mm3, p < 0.01) and TLC (2,500 to 13,400/mm3, p < 0.01) had sustained increase in all patients except one. Five HCV cirrhotics completed interferon and ribavirin therapy, 4 achieved sustained viral response. The quality of life improved and there was no recurrence of infections, mucosal bleed or anemia requiring transfusions in any patient. In patients on long term follow up (median duration 27 months), the median Child's score improved from 6 at baseline to 5 at follow up (p < 0.05). Conclusions. Splenectomy was safe and effective in patients with cirrhosis, and improved therapeutic options as well as Child's score.

Basic studies

  • Bile acids content in brain of common duct ligated rats Valeria Tripodi, Mario Contin, Maria Alejandra Fernández, Abraham Lemberg Page 930-934

    Introduction. Cholestasis leads to liver cell death, fibrosis, cirrhosis, and eventually liver failure. Bile duct ligated rats constitute an interesting model to study the mechanism of cholestasis, and its action on several organs and tissues, including the brain. Aim. To analyze brain bile acids individually in ligated rats to evaluate if its profile is altered towards a more toxic condition in cholestasis. Material and methods. Male Wistar rats were used and separated in two groups: bile duct ligated rats and sham operated rats (n = 5 in each group). Bile acid profile was assessed in brain homogenates. Alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase determinations, bilirubin and ammonia plasma concentration were also measured in both groups. Results. Although the total amount of bile acids in control animal brains showed a higher concentration than in bile duct ligated rats, the bile acid profile in this group was found more toxic composition than in controls. Lithocholic acid was present in brain in higher concentration (87.4 % of total brain bile acids) in ligated rats and absent in controls. Alkaline phosphatase, bilirubin and ammonia were significantly higher in bile duct ligated rats than in control group. Conclusion. It was found a toxic brain bile acid profile during hepatic cholestasis which could be one of the explanations of hepatic encephalopathy observed in cholestatic diseases.

  • Protective role of standardized Feronia limonia stem bark methanolic extract against carbon tetrachloride induced hepatotoxicity Mahendra Jain, Rakhee Kapadia, Ravirajsinh Navalsinh Jadeja, Menaka Chanu Thounaojam, Ranjitsinh Vijaysinh Devkar, Shri Hari Mishra Page 935-943

    Objective. This study evaluates hepatoprotective potential of Feronia limonia stem bark (FSB) extracts and fractions using experimental models. Materials and methods. Activity levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and cell viability were evaluated in HepG2 cells treated with carbon tetrachloride (CCl4) in presence or absence of FL extracts or fractions. Also, plasma markers of hepatic damage, hepatic antioxidants, lipid peroxidation and histopathological alterations were assessed in rats treated with CCl4 alone or in combination with 200 or 400 mg/kg bodyweight (BW) of FSB-7 or 25 mg/kg BW of silymarin. Results. In vitro co-supplementation of FSB extracts or fractions recorded varying degree of hepatoprotective potentials. Also, pre-supplementation of FSB methanolic extract (FSB-7) followed by CCl4 treatment significantly prevented hepatic damage and depletion of cellular antioxidants. Also, CCl4+ FSB-7 group showed minimal distortion in the histoarchitecture of liver and results were comparable to that of CCl4+ silymarin treated rats. Conclusion. This inventory is the first scientific report on hepatoprotective potential of FSB methanolic extract.

EDITORIAL

IMAGES IN HEPATOLOGY

CASE REPORTS

  • Porphyria cutanea tarda in an HCV-positive liver transplant patient: a case report Adriano M. Pellicelli, Aldo Morrone, Luca Barbieri, Arnaldo Andreoli Page 951-954

    between PCT and hepatitis C virus (HCV) infection is well established. Although antiviral treatment of chronic hepatitis C may improve PCT in some cases, de novo onset of PCT has been observed in patients undergoing peginterferon/ribavirin treatment. We present a rare case of a genotype 3 HCV-positive liver transplant recipient who developed PCT during antiviral treatment and discuss its probable etiopathogenesis. Case presentation. A genotype 3 HCV-positive liver transplant recipient, a 42-year-old man, was treated with peginterferon alfa-2a (180 μg/week) combined with ribavirin (1,200 mg/day) for recurrence of HCV infection after liver transplantation. He presented with hyperferritinemia but tested negative for genetic hemochromatosis (C282Y and H63D mutations). During antiviral therapy, he developed skin lesions on his hands characterized by vesicles and erosions consistent with PCT. PCT was confirmed by skin biopsy and elevated urinary uroporphyrin levels (1,469 mg/24 h). He was treated with chloroquine (200 mg) twice weekly, resulting in gradual regression of the skin lesions. Antiviral treatment was stopped after 48 weeks, and the patient achieved a sustained virological response. In conclusion, we report an extremely rare case of PCT in a genotype 3 HCV-positive liver transplant patient treated with antiviral therapy. We believe that the combination of HCV genotype 3 infection; hemolysis due to ribavirin treatment; and increased plasma levels of cytokines, such as IL-6 and TNFα, could have altered the patient's iron metabolism and thus caused PCT.

  • Spontaneous bacterial peritonitis caused by Listeria monocytogenes: a case report and literature review Cláudia Cardoso, Isabelle Cremers, Ana Paula Oliveira Page 955-957

    Spontaneous bacterial peritonitis (SBP) is a common and often serious complication of long standing ascites in the presence of advanced liver disease.1 We report a case of a 51- year-old man with alcoholic cirrhosis admitted to our department with jaundice, ascitis and lower limbs edema. A diagnosis of spontaneous bacterial peritonitis was made and empiric therapy with cefotaxime was prescribed with no response. Three days later Listeria monocytogenes was detected in peritoneal fluid culture and amoxicillin was initiated according to in vitro sensibility test. Despite adequate antibiotic therapy, the patient died one week later.

  • Dorsal root ganglionopathy in a hepatitis C patient: a case report Navya Basavaraju, Mirza Ahmad, Eoin Slattery Page 958-960

    We report an unusual clinical presentation of dorsal root ganglionopathy in a hepatitis C patient with negative cryoglobulins characterized by both motor and sensory symptoms. This mixed clinical picture in a hepatitis C patient is rare but should be considered a potential complication of HCV infection.

  • Thyroid-like cholangiocarcinoma of the liver: an unusual morphologic variant with follicular, trabecular and insular patterns Fredy Chablé-Montero, Amy Shah BS, Daniel Montante-Montes de Oca, Arturo Ángeles-Ángeles, Donald E. Henson, Jorge Albores-Saavedra Page 961-965

    We report the case of a 26-year-old woman with a 19 cm malignant hepatic neoplasm with morphological features that closely resembled a follicular thyroid carcinoma. Despite this, it was interpreted as a cholangiocarcinoma due to the absence of a primary thyroid tumor and the lack of thyroglobulin and TTF-1 immunoreactivity by the hepatic tumor. The left hepatic lobectomy specimen showed an encapsulated and multinodular gray-white mass with cystic and hemorrhagic areas. Microscopically, it displayed predominant macro and microfolicullar patterns with focal solid, trabecular and insular areas. The small and distended follicles contained a colloid-like secretion and were lined by low cuboidal cells with scant cytoplasm, round or oval hyperchromatic nuclei with fine chromatin. The solid areas, trabecular and insular structures were similar to those of follicular or papillary thyroid carcinomas. In addition, some of the neoplastic cells had clear nuclei with occasional grooves. The tumor was positive for cytokeratin (CK) 7, CK 19 and CD138, and negative for TTF-1, thyroglobulin, Hepar-1, Glypican-3, alpha-fetoprotein and neuroendocrine markers. A thyroid neoplasm was excluded clinically and by ultrasound and computed tomography. Although, the residual hepatic parenchyma was initially not cirrhotic, the patient eventually developed cryptogenic cirrhosis. The patient received adjuvant chemotherapy and died of metastatic disease 18 months after surgery. The thyroid-like pattern broadens the morphologic spectrum of cholangiocarcinoma.

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