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September - October, 2018

Vol. 17 Issue 5

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

EDITORIALS

OPINIONS

  • Adherence to Appropriate Nutrition in Acute Alcoholic Hepatitis is Low Judy A. Trieu, Mohammad Bilal, Briana Lewis, Eric Gou, Lindsay Sonstein, Sreeram Parupudi Page 752-755

    Malnutrition is a common cause of impeding recovery in patients with acute alcoholic hepatitis (AAH). Previous reports have shown that appropriate nutritional supplementation reduce short and long-term mortality in patients with AAH. Despite these clear recommendations, the element of nutrition in AAH is often neglected. We designed a quality improvement project to evaluate and improve compliance with appropriate nutrition in patients presenting with AAH at our institution. Patients admitted with AAH between December 2015 to December 2016 were included. Our primary outcome was compliance with appropriate nutrition. Secondary outcomes included nutrition consultation and hepatology consultation. A total of fifty-four patients were included. Nine of the 53 patients (17%) received high calorie and high protein diets. Hepatology was consulted in 72% (38/53) of the patients, and 21% (8/38) of these patients received appropriate nutrition as compared to only 8.3% (1/12) in whom hepatology was not consulted. Nutrition was consulted in 55% (29/53) of these patients and 67% (19/28) of those patients received appropriate nutrition. In conclusion, our compliance of appropriate nutrition in AAH is low. Our initial investigation suggests that hepatology and nutrition consultation improved compliance with appropriate nutrition. The next step will be to implement protocolized care for appropriate nutrition in AAH by incorporating consultation of hepatology and nutrition services, assess the effect on adherence to appropriate nutrition, and determine the impact on patient outcomes.

VIEWPOINTS

CONCISE REVIEW

  • Controversies in Early Liver Transplantation for Severe Alcoholic Hepatitis Tiffany Wu, Timothy R. Morgan, Andrew S. Klein, Michael L. Volk, Sammy Saab, Vinay Sundaram Page 759-768

    Alcoholic hepatitis (AH) is a condition of acute liver inflammation in the setting of heavy alcohol use that is often managed with corticosteroids in severe cases. Among non-responders to steroids, however, prognosis is poor with up to 75% mortality within 6 months after treatment failure. Early liver transplantation (LT) can achieve an acceptable short-term survival, and initial studies have demonstrated 3-year survival rates of up to 84%. However, the practice of early LT in severe AH remains controversial with concerns over the 6-month rule of sobriety and risk of alcohol relapse post-transplant. Proponents of LT advocate for better understanding of alcohol use as a disorder rather than self-inflicted cause of illness, aim to redefine the misguided application of the 6-month rule, and point out similar relapse rates among patients with early LT and those with greater than 6 months abstinence before transplant. Opponents of LT emphasize the correlation between alcohol relapse and graft failure and mortality, public resistance and potential for distrust among donors, and arguments that transplant centers need to establish improved models to predict relapse and standardize candidate selection criteria across centers. Here we review recent literature on this controversy and provide recommendations for moving forward to consensus.

ORIGINAL ARTICLES

  • Salidroside and Curcumin Formula Prevents Liver Injury in Nonalcoholic Fatty Liver Disease in Rats Hong-Shan Li, Hao Ying, Zhe-Yun He Page 769-778

    Introduction and aim. Salidroside and curcumin (SC) formula could alleviate lipid deposition in high fat diet-induced nonalcoholic fatty liver disease (NAFLD). However, the mechanisms are still unknown, and the magnitude of potential therapeutic benefit remains understudied. Material and methods. The rats were treated with high fat diet for 14 weeks to induce NAFLD. The experiment was divided into control, model (NAFLD), SC formula and rosiglitazone groups (n = 7 in each group). Hematoxylin-eosin (H&E) staining was applied to detect liver morphological changes. Biochemical, metabolic indices and inflammation factors in liver tissue and serum were detected. Additionally, the activities of related enzymes were detected by enzyme-linked immunosorbent assay. Results. In the established rat model, typical lipid deposition and liver steatosis were observed. Liver triglyceride, free fatty acids, sera alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transferase, fasting insulin, fasting blood glucose and homeostasis model assessment of insulin resistance were elevated in model group. Liver malondialdehyde was significantly elevated, while superoxide dismutase was significantly decreased in model group, compared with control. Moreover, tumor necrosis factor-α and Interleukin-1 were significantly produced in model group, compared with control. As a mechanism, high fat diet decreased tissue AMP-activated protein kinase (AMPK), phosphorylated AMPK, carnitine palmitoyltransferase 1 and increased inacetyl-CoA carboxylase (ACCase), phosphorylated ACCase. Importantly, these abnormal changes caused by high fat diet were reduced by SC formula administration. Conclusion. SC formula could ameliorate the injury caused by high fat diet. The effect was likely mediated via its influence on insulin resistance, lipid peroxidation injury and AMPK signaling pathway.

  • Thyroid Function and Risk of Non-Alcoholic Fatty Liver Disease in Euthyroid Subjects Yiting Liu, Wei Wang, Xiaosong Yu, Xingshun Qi Page 779-788

    Introduction and aims. The association between thyroid function and non-alcoholic fatty liver disease (NAFLD) remained controversial. A large cross-sectional study aimed to explore the relationship in euthyroid population. Material and methods. A total of 1773 euthyroid subjects who underwent health check-up during one-year period were enrolled. NAFLD was diagnosed by ultrasound and fatty liver index (FLI). Fibrosis was estimated by BARD score. Thyroid function parameters, including thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), were recorded. Multivariate logistic regression analyses were performed to identify the independent risk factors. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results. NAFLD was diagnosed by ultrasound in 638 (35.98%) subjects and by FLI ≥ 60 in 694 (39.14%) subjects. Regardless of ultrasound or FLI, the overall analysis demonstrated that TSH and FT3 levels were significantly higher in subjects with NAFLD than subjects without NAFLD, but FT4 level was not significantly different between them. This association remained in middle-age subjects, but not elderly subjects. In the multivariate logistic regression analysis, TSH (OR = 1.108, 95%CI = 1.056-1.398, P = 0.024) and FT3 (OR = 1.258, 95%CI = 1.123-1.409, P = 0.000) levels were independently associated with the risk of NAFLD diagnosed by ultrasound; and only FT3 level (OR = 1.252, 95%CI = 1.074 - 1.460, P = 0.004) was independently associated with the risk of NAFLD estimated by FLI ≥ 60. Additionally, FT3 level (OR = 1.178, 95%CI = 1.025 - 1.354, P = 0.021) was independently associated with the risk of fibrosis estimated by BARD score ≥ 2 in NAFLD subjects. Conclusion. Among the euthyroid population, FT3 and TSH levels were positively associated with the risk of NAFLD.

  • Acoustic Radiation Force Impulse Elastography with APRI and FIB-4 to Identify Significant Liver Fibrosis in Chronic Hepatitis B Patients Cheng-Hao Tseng, Chi-Yang Chang, Lein-Ray Mo, Jaw-Town Lin, Chi-Ming Tai, Daw-Shyong Perng, Chih-Wen Lin, Yao-Chun Hsu Page 789-794

    Introduction and aim. In chronic hepatitis B (CHB) patients with equivocal indication for antiviral therapy, therapeutic decision currently depends on histopathology of the liver. We aimed to evaluate if acoustic radiation force impulse (ARFI) in conjunction with aspartate transaminase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) score could replace liver biopsy to indicate treatment for CHB. Material and methods. We prospectively enrolled 101 clinically non-cirrhotic patients whose serum alanine aminotransferase was mildly elevated (1-2 folds above the upper normal limit) despite a high viral load (HBV DNA > 2,000 IU/mL). All participants underwent liver biopsy, and measurement of ARFI, APRI and FIB-4. The ability of the markers to distinguish fibrosis ≥ METAVIR F2 was evaluated. Results. According to histopathology, liver fibrosis was METAVIR F0 in 2 (2.0%), F1 in 43 (42.6%), F2 in 34 (33.7%), F3 in 16 (15.8%), and F4 in 6 (5.9%) patients, and was correlated with ARFI (p = 0.0001), APRI (p = 0.012), and FIB-4 (p = 0.004). The six patients with cirrhosis were included for analysis, and received antiviral therapy. The C statistics of ARFI, APRI, and FIB-4 for fibrosis ≥ F2 were 0.70 (95% confidence interval [CI], 0.59-0.80), 0.62 (95% CI, 0.51-0.73), and 0.64 (0.53- 0.75), respectively. The cut-off values for 95% sensitivity and 95% specificity to identify significant fibrosis were 0.97 m/sec and 1.36 m/sec for ARFI, 0.36 and 1.0 for APRI, 0.63 and 2.22 for FIB-4, respectively. Using a combination of these 3 indices, 44 patients (43.6%) could be spared a liver biopsy procedure. Conclusions. A combination of ARFI, APRI, and FIB-4 may spare some CHB patients with equivocal indication for antiviral treatment a liver biopsy.

  • Chronic Hepatitis C Patients with Obesity: Do we Need two Operators for Accurate Evaluation of Liver Stiffness? Gamal E. Shiha, Shahira El-Etreby, Mounir Bahgat, Magdy Hamed, Mohamed El Sherbini, Elsayed A. Ghoneem, Khaled Zalata, Reham E. Soliman, Mohamed A. ElBasiouny, Nabiel NH Mikhail Page 795-801

    Introduction and aim. Transient elastography is gaining popularity as a non-invasive method for predicting liver fibrosis, but inter observer agreement and factors influencing reproducibility have not been adequately assessed. Material and methods. This cross-sectional study was conducted at Specialized Medical Hospital and the Egyptian Liver Foundation, Mansoura, Egypt. The inclusion criteria were: age older than 18 years and chronic infection by hepatitis C. The exclusion criteria were the presence of ascites, pacemaker or pregnancy. Three hundred and fifty-six patients participated in the study. Therefore, 356 pairs of exams were done by two operators on the same day. Results. The overall inter observer agreement ICC was 0.921. The correlation the two operators was excellent (Spearman's value q = 0.808, p < 0.001). Inter-observer reliability values were κ = 0.557 (p < 0.001). A not negligible discordance of fibrosis staging between operators was observed (87 cases, 24.4%). Discordance of at least one stage and for two or more stages of fibrosis occurred in 60 (16.9%) and 27 cases (7.6%) respectively. Obesity (BMI ≥ 30 kg/m2) is the main factor associated with discordance (p = 0.002). Conclusion. Although liver stiffness measurement has had an excellent correlation between the two operators, TE presented an inter-observer variability that may not be negligible.

  • Association between Repeated Praziquantel treatment and Papillary, and Intrahepatic Cholangiocarcinoma Vor Luvira, Supot Kamsa-ard, Siriporn Kamsa-ard, Varisara Luvira, Tharatip Srisuk, Ake Pugkhem, Chawalit Pairojkul, Vajarabhongsa Bhudhisawasdi Page 802-809

    Introduction and aim. The carcinogenesis of tubular and papillary cholangiocarcinoma (CCA) differ. The available epidemiologic studies about risk factors for CCA do not differentiate between the tubular and papillary type. The current study investigated the relationship between the number of repeated use of Praziquantel (PZQ) treatments and each type of CCA. Material and methods. This was a hospital-based, matched, case-control study of patients admitted to Srinagarind Hospital, Khon Kaen University. The patients were 210 pathologically-confirmed cases of CCA, while the controls were 840 subjects diagnosed with other diseases. The 4 controls were individually matched with each case by sex, age, and date of admission. The cases were classified according to location (intrahepatic vs. extrahepatic) and cell type (papillary vs. tubular). Multivariable conditional logistic regression was used for the analysis. Results. After adjusting for confounders, there were statistically significant associations between intrahepatic and papillary CCA and repeated use of PZQ treatment. The respective odds of developing intrahepatic CCA for those who used PZQ once, twice, or more was 1.54 (95%CI:0.92-2.55 ), 2.28 (95%CI:0.91-5.73), and 4.21 (95%CI:1.61-11.05). The respective odds of developing papillary CCA for those who used PZQ once, twice, or more was 1.45 (95%CI:0.80-2.63), 2.96 (95%CI:1.06-8.24), and 3.24 (95%CI:1.09-9.66). There was no association between number of uses of PZQ treatment and developing extrahepatic or tubular CCA. Conclusion. The current study found an association between papillary and intrahepatic CCA and repeated use of PZQ treatment. We suggest further study on the risk factors for papillary and tubular CCA should be performed separately.

  • A Head CT is Unnecessary in the Initial Evaluation of A Cirrhotic Patient with Recurrent Hepatic Encephalopathy Sumit Kumar, Ronak Modi, Bhavik M. Bhandari, David A. Sass, Kenneth D. Rothstein Page 810-814

    Introduction and aim. The evaluation to determine the cause of hepatic encephalopathy consists primarily of laboratory testing to rule out infections and metabolic causes. Despite lack of evidence, it is a common practice amongst clinicians to obtain a head CT as part of their initial evaluation in a cirrhotic presenting with recurrent episodes of hepatic encephalopathy. Material and methods. Medical records of all cirrhotic adults admitted to a tertiary care hospital from 2007 to 2010 with hepatic encephalopathy were reviewed. Results. In 67 patients, there were 147 episodes of hepatic encephalopathy where a head CT was performed. Six CTs had intracranial findings explaining hepatic encephalopathy. Two patients had focal neurologic findings on physical exam with no history of trauma, one had a history of trauma with no focal neurologic deficits and two had both a history of trauma and focal neurologic findings. Only one case revealed an intracranial hemorrhage with neither a preceding history of trauma nor positive neurological signs. The overall prevalence of intracranial findings in hepatic encephalopathy was 4% (6/147) and 0.6% (1/142) in the absence of trauma or focal neurologic findings. Laboratory and clinical variables including mean levels of ammonia, sodium, creatinine, bilirubin, albumin, platelet count, INR, encephalopathy grade and MELD score did not have a statistically significant impact on head CT findings (P > .05). Conclusion. In conclusion, the yield of a head CT in determining the cause of change in mental status is extremely low in patients with cirrhosis who present with recurrent hepatic encephalopathy.

  • Multicenter Experience using Ledipasvir/Sofosbuvir ± RBV to Treat HCV GT 1 Relapsers after Simeprevir and Sofosbuvir Treatment Bashar Aqel, Michael Leise, Hugo E. Vargas, Kymberly D. Watt, Andrew P. Keaveny, Nan Zhang, Surakit Pungpapong Page 815-821

    Introduction and aim. Approximately 10%-15% of patients with hepatitis C genotype 1 (HCV GT1) experience virological relapse after all-oral antiviral regimen using simeprevir (SMV) and sofosbuvir (SOF). The efficacy and safety of treating such relapsers using ledipasvir/sofosbuvir (LDV/SOF) with/without ribavirin (RBV) has been limited. Objective. Report the virological response and safety of LDV/SOF with/without RBV for 12-24 weeks in treating HCV GT1 relapsers after SMV + SOF. Material and methods. Patients treated with standardized clinical protocol utilizing LDV/SOF with/without RBV at three transplant centers were retrospectively reviewed. Results. Forty-five patients (29% post-LT, 82% male, 13% non-white, 73% subtype 1a, 86% IL28B CT/TT, 78% F3-4) started LDV/SOF with/without RBV at a median of 22 weeks (range 7-55 weeks) after the last dose of SMV+SOF treatment. Thirty-seven patients received LDV/SOF for 24 weeks (24/37 patients with RBV) and eight patients received LDV/SOF for 12 weeks (5/8 patients with RBV). RBV dose was adjusted for renal function. Sixteen patients who were RBV-ineligible received LDV/SOF without RBV for 12 or 24 weeks. SVR 12 was achieved in 96% (43/45) of patients. Baseline viral load, RBV use, or GT1 subtype did not impact SVR 12. Minimal adverse events were reported in those without RBV; 45% of patients who received RBV developed significant anemia requiring RBV dose reduction and/or discontinuation. In LT recipients, minimal immunosuppression dose adjustments were required and no biopsy-proven acute rejection occurred. Conclusions. Treatment with LDV/SOF with/without RBV for 12-24 weeks was very well tolerated and resulted in high SVR 12 rates (96%) in HCV GT1 relapsers to SMV + SOF treatment.

  • Olfactory Function is Affected in Patients with Cirrhosis Depending on the Severity of Hepatic Encephalopathy Clemens Heiser, Bernhard Haller, Maximilian Sohn, Benedikt Hofauer, Andreas Knopf, Tobias Mühling, Jessica Freiherr, Martin Bender, Maximilian Tiller, Anna Schmidt, Wolfgang Schepp, Felix Gundling Page 822-829

    Introduction and aim. Olfactory functions are altered to a variable degree by chronic liver disease. Few studies including only small populations of patients emphasized the possibility of hepatic encephalopathy (HE) influencing olfactory nervous tasks. So far, no study has explicitly focused on olfactory function depending on the severity of HE as assessed by objective diagnostic procedures. Thus we performed a study using the "Sniffin' Sticks" test system, critical flicker-fusion frequency (CFF) and clinical West Haven criteria. Material and methods. 54 cirrhotic patients with liver cirrhosis were included. Furthermore, 43 adult volunteers participating as a non-cirrhotic control group. Olfactory testing was performed using the "Sniffin' Stick" test battery (Burghart Medizintechnik, Wedel, Germany) which renders a widely-used tool both in clinical and research settings for the assessment of olfactory threshold, odor identification and discrimination. Several complications of cirrhosis were diagnosed by reference methods. Statistical analysis of cirrhosis-associated complications and their relation to olfactory function was performed. Assessment of HE and classification of different stages were performed according to clinical criteria (West- Haven criteria) and according to CFF, which was determined using a portable analyzer. Results. Olfactory function was significantly reduced in cirrhotic patients (in 61.1%) compared to controls (p < 0.001). Among cirrhotics patients, the prevalence of olfactory deficits (hyposmia, anosmia) increased with the severity of HE as assessed by CFF and clinical criteria (p = 0.008 and p = 0.097, respectively). No correlation was observed between olfactory deficits and severity of liver disease as assessed by Child-Pugh-Score, etiology of cirrhosis and complications of cirrhosis such as ascites and portal venous hypertension. Conclusions. Olfactory testing serves as a screening tool for HE and may facilitate grading of HE-severity.

  • Low Fibrinogen Levels are Associated with Bleeding After Varices Ligation in Thrombocytopenic Cirrhotic Patients Edoardo G. Giannini, Elisa Giambruno, Mattteo Brunacci, Maria Corina Plaz Torres, Manuele Furnari, Giorgia Bodini, Patrizia Zentilin, Vincenzo Savarino Page 830-835

    Introduction and Aim. EVBL is a procedure frequently performed in cirrhotic patients for primary prophylaxis of bleeding. Patients with cirrhosis display various degrees of alteration of common coagulation parameters, and it is not known whether these alterations may predict post-EVBL bleeding. To evaluate factors predictive of post-endoscopic variceal band ligation (EVBL) bleeding in cirrhotic patients with thrombocytopenia. Material and methods. We included 109 patients with cirrhosis undergoing EVBL for primary prophylaxis of variceal bleeding. Common coagulation parameters (INR, fibrinogen levels) and complete haemogram were obtained in all patients and evaluated subdividing patients in bleeders and non bleeders following EVBL. Results. The incidence of post-EVBL bleeding was 5.5% (6 patients). INR and platelet counts, considered as continuous or dichotomous variables according to common cut-offs (i.e., INR > 1.5, platelet count < 50 x 109/L) were not predictors of post-EVBL bleeding. Patients who bled had significantly lower fibrinogen levels [146 mg/dL (98 - 262) vs. 230 mg/dL (104 - 638), P = 0.009], and no other biochemical or clinical predictors of bleeding were identified. A fibrinogen cut-off of 179 mg/dL had 98.6% negative predictive value for bleeding. Conclusion. Low fibrinogen levels are associated with an increased risk of bleeding following prophylactic EVBL in cirrhotic patients, and might be used to stratify patients' risk. However, due to their preliminary nature, these findings need to be confirmed in larger populations.

  • Serum Electrolyte Levels and Outcomes in Patients Hospitalized with Hepatic Encephalopathy Ali A. Alsaad, Fernando F. Stancampiano, William C. Palmer, April M. Henry, Jillian K. Jackson, Michael G. Heckman, Nancy N. Diehl, Andrew P. Keaveny Page 836-842

    Introduction and aims. Serum electrolyte derangements are common in patients with decompensated cirrhosis hospitalized for hepatic encephalopathy. There are limited data describing the association between electrolyte levels and outcomes in hepatic encephalopathy. We assessed the association between initial serum electrolyte values and outcomes in patients with hepatic encephalopathy. Material and methods. A total of 385 consecutive patients hospitalized with encephalopathy were included in the study. Baseline electrolyte levels (sodium, potassium, chloride, bicarbonate, calcium and phosphorus) were measured at the time of admission and assessed for association with outcomes, which included survival, admission to the intensive care unit, requirement for mechanical ventilation, and length of hospital stay. P-values ≤ 0.0083 were considered significant after adjustment for multiple testing. Results. In unadjusted analysis, significant associations were identified regarding both bicarbonate and phosphorus (admission to intensive care unit), and calcium (mechanical ventilation); however these findings weakened and no longer approached statistical significance when adjusting for confounding variables. No other significant associations between serum electrolyte measurements and outcomes were observed. Conclusions. Our findings suggest that in patients hospitalized with encephalopathy, serum electrolyte measurements are not strong predictors of patient outcome.

  • NEK2 Promotes Hepatoma Metastasis and Serves as Biomarker for High Recurrence Risk after Hepatic Resection Yu-Ying Chang, Chia-Jui Yen, Shih-Huang Chan, Yi-Wen Chou, Yun-Ping Lee, Ching-Yu Bao, Chien-Jung Huang, Wenya Huang Page 843-856

    Introduction and aim. Developing reliable biomarkers for hepatocellular carcinoma (HCC) patients who are at a high risk of recurrence after curative hepatic resection is very important for determining subsequent therapeutic strategies. We investigated the role of the cell cycle factor NIMA-related kinase 2 (NEK2) in HCC progression in hepatoma cells and post-surgery patients. Material and methods. The effects of NEK2 on proliferation, invasion and migration of hepatoma HuH7 and SK-Hep1 cells were evaluated. In a post-surgery HCC cohort (N = 97), the Nek2 induction levels in the tumors were examined with real-time RT-PCR analysis, and the results were analyzed for their correlations with recurrence. Results. NEK2 promoted G1 to S phase cell cycle progression by causing increases in cyclin D1 and AKT phosphorylation and decreases in the cyclin-dependent kinase inhibitor p27, indicating that NEK2 plays an important role during interphase in addition to its previously identified role in M phase. NEK2 also enhanced the proliferation, migration and invasion of hepatoma cells and regulated the expression of E-cadherin and MMP9. The Nek2 mRNA levels in the tumors were highly correlated with recurrence rates in the post-surgery HCC patients. Combined evaluation of the tumor AJCC stage and the Nek2 level can serve as a reliable method for predicting the relative risk of HCC recurrence in these patients. Conclusions. NEK2 plays a significant role in cell cycle progression in the inter- and M-phases. NEK2 enhances HCC metastasis and is correlated with recurrence and thus can potentially serve a promising high-risk biomarker for HCC.

  • Fast Morphological Gallbladder Changes Triggered by a Hypercholesterolemic Diet Alberto López-Reyes, Denise Clavijo-Cornejo, Javier Fernández-Torres, Daniel Medina-Luna, Erendida G. Estrada-Villaseñor, Luis E. Gómez-Quiroz, Marwin Gutiérrez, Julio Granados, Gilberto Vargas-Alarcón, Carlos Pineda, Hiram García, Luis A. Morales-Garza, María C. Gutiérrez-Ruiz, Karina Martínez-Flores Page 857-863

    Introduction and aim. Obesity is a worldwide epidemic problem, described as a risk factor for hepatic diseases, such as non-alcoholic fatty liver disease and other pathologies related to development of cholesterol crystals and cholesterol gallbladder stones. It has been reported that cholesterol overload may cause hepatic damage; however, little is known about the effects of an acute hypercholesterolemic diet on the gallbladder. The aim of this manuscript was to evaluate the impact of a cholesterol-rich diet on the gallbladder. Material and methods. The study included ten eight-week-old C57BL6 male mice, which were divided into two study groups and fed different diets for 48 h: a hypercholesterolemic diet and a balanced Chow diet. After 48 h, the mice were analyzed by US with a Siemens Acuson Antares equipment. Mice were subsequently sacrificed to carry out a cholesterol analysis with a Refloton System (Roche), a crystal analysis with a Carl Zeiss microscope with polarized light, and a histological analysis with Hematoxylin-eosin staining. Results. The hypercholesterolemic diet induced an increase in gallbladder size and total cholesterol content in the bile, along with important histological changes. Conclusion. Cholesterol overloads not only trigger hepatic damage, but also affect the gallbladder significantly.

  • Peer-to-Peer Sessions in Primary Care to Improve the Hepatitis B Detection Rate in Seville, Spain María Ángeles Otero, Chang-Hai Liu, Javier Ampuero, Rocío Llorca, Manuel Vargas, Julio Vargas-Romero, Manuel Romero-Gomez Page 864-870

    Introduction and aim. The detection of hepatitis B virus (HBV) depends on primary care center activity. The present study aims to investigate the impact of peer-to-peer sessions with hepatologists on hepatitis B screening efficacy in primary care centers. Material and methods. Peer-to-peer one-hour sessions were scheduled to improve the screening program for HBV in Seville, Spain. The sessions were focused on who should be tested for HBV and how positive cases should be referred. Fourteen out of 26 health care centers were selected to participate in peer-to-peer sessions. The centers were classified according to how many sessions they held (no sessions, one session or more than one session). Results. Over a five-year period, HBV screening was performed in 32 203 people. In Seville, the prevalence of HBsAg was 0.87% (283/32 203). The detection rates for new HBsAg-positive cases were 7.1, 16.9 and 21.3 cases/10⁵ population/year in non-session, one-time session and more than one session centers, respectively (p < 0.05). The rate of patients who effectively visited centers as outpatients was significantly higher after peer-to-peer sessions-86/94 (91%) for one session and 81/89 (91%) for two session centers vs. 16/27 (67%) for non-session centers (p = 0.002). The only independent predictor of patient referral was peer-to-peer sessions (OR, 1.925 [95% CI, 1.002-3.699]; p < 0.05). Conclusions. Peer-to-peer sessions in primary care centers increased HBV detection and visitation rates.

  • Cirrhosis in Hemochromatosis: Independent Risk Factors in 368 HFE p.C282Y Homozygotes James C. Barton, Christine E. McLaren, Wen-pin Chen, Grant A. Ramm, Gregory J. Anderson, Lawrie W. Powell, V. Nathan Subramaniam, Paul C. Adams, Pradyumna D. Phatak, Lyle C. Gurrin, John D. Phillips, Charles J. Parker, Mary J. Emond, Gordon D. McLaren Page 871-879

    Introduction and aim. We sought to identify independent risk factors for cirrhosis in HFE p.C282Y homozygotes in a cross-sectional study. Material and methods. We evaluated 368 p.C282Y homozygotes who underwent liver biopsy and compared characteristics of those with and without cirrhosis. We performed multivariable logistic regression on cirrhosis with: age; sex; race/ ethnicity; diabetes; blood pints/units donated voluntarily; erythrocyte pints/units received; iron supplement use; alcohol intake, g/d; body mass index, kg/m2; swollen/tender 2nd/3rd metacarpophalangeal joints; elevated alanine aminotransferase; elevated aspartate aminotransferase; steatosis/fatty liver; iron removed by phlebotomy, g; and GNPAT p.D519G positivity. Results. Mean age of 368 participants (73.6% men) was 47 +- 13 (standard deviation) y. Cirrhosis was diagnosed in 86 participants (23.4%). Participants with cirrhosis had significantly greater mean age, proportion of men, diabetes prevalence, mean daily alcohol intake, prevalence of swollen/ tender 2nd/3rd metacarpophalangeal joints, mean serum ferritin, elevated alanine aminotransferase, elevated aspartate aminotransferase, and mean iron removed; and significantly fewer mean blood pints/units donated. GNPAT p.D519G positivity was detected in 82 of 188 participants (43.6%). In a multivariable model for cirrhosis, there were four significant positive associations: age (10-y intervals) (odds ratio 2.2 [95% confidence interval 1.5, 3.3]); diabetes (3.3; [1.1, 9.7]); alcohol intake (14 g alcohol drinks/d) (1.5 [1.2, 1.8]); and iron removed, g (1.3 [1.2, 1.4]). There was no statistical evidence of two-way interactions between these variables. Conclusion. In conclusion, cirrhosis in HFE p.C282Y homozygotes is significantly associated with age, diabetes, daily alcohol intake, and iron removed by phlebotomy, taking into account the effect of other variables.

CASE REPORTS

  • Hepatic Abscess Secondary to Stomach Perforation by a Fish Bone: a Rare Cause of Hepatic Abscess Wenxiu Yu, Hailin Yu, Jun Ling, Jiang Du, Zhijing Yin, Chengen Li, Min Zhou Page 880-883

    Gastrointestinal foreign bodies are commonly encountered in clinical practice. However, although perforation of the gastrointestinal tract by a foreign body is not unusual, the formation of a hepatic abscess as a result of the migration of a foreign body is extremely rare. Patients usually present with atypical symptoms, and the treatment of such pyogenic liver abscesses presents a challenge. Here we report a case of hepatic abscess secondary to stomach perforation by a fish bone.

  • Rare Case of Hepatic Endometriosis as an Incidental Finding: Difficult Diagnosis of a Diagnostic Dilemma Dimitrios Keramidaris, Stavros Gourgiotis, Antonella Koutela, Evgenios Mpairamidis, Christianna Oikonomou, Constantinos Villias, Alexios Rigas Page 884-887

    Endometriosis is the abnormal existence of functional uterine mucosal tissue outside the uterus. It is a usual disorder of women in reproductive age which is mainly located in the female genital tract. Hepatic endometriosis is one of the rarest disorders characterized by the presence of ectopic endometrium in the liver. It is often described as cystic mass with or without solid component. Preoperative diagnosis is difficult via cross-sectional imaging and histopathologic evaluation remains the gold standard for diagnosis. We report an asymptomatic 40-year-old female with a large cystic mass involving the left hepatic lobe. She underwent laparoscopic removal of the cyst. The diagnosis of hepatic endometriosis was established by the histopathological analysis of the surgical specimen.

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