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4. Advancing the global public health agenda for NAFLD: a consensus statement

Author

Lazarus, Jeffrey V., Mark, Henry E., Anstee, Quentin M., Arab, Juan Pablo, Batterham, Rachel L., Castera, Laurent, Cortez-Pinto, Helena, Crespo, Javier, Cusi, Kenneth, Dirac, M. Ashworth, Francque, Sven, Hickman, Ingrid J., Hocking, Samantha L., Hunyady, Bela, Idilman, Ramazan, Isakov, Vasily A., Jamal, Mohammad H., Jepsen, Peter, Iskandar, Natacha Jreige, Song, Myeong Jun, Sudhamshu, K. C., George, Jacob, Kakizaki, Satoru, Kalamitsis, George, Kanwal, Fasiha, Kao, Jia-Horng, Kaplan, Lee, Kawaguchi, Takumi, Khader, Yousef, Kim, Seung Up, Kodjoh, Nicolas, Koek, Ger, Hagström, Hannes, Koike, Kazuhiko, Komas, Narcisse Patrice, Korenjak, Marko, Kugelmas, Marcelo, Labidi, Asma, Lange, Naomi F., Lavine, Joel E., Lazo, Mariana, Lee, Nancy, Lesmana, Cosmas Rinaldi A., Huang, Terry T.-K., Liu, Chun-Jen, Long, Michelle T., Lopez-Jaramillo, Patricio, Malekzadeh, Reza, Mahtab, Mamun Al, Marchesini, Giulio, Marinho, Rui, Vázquez, Sophia E. Martínez, Mateva, Lyudmila, Nlombi, Charles Mbendi, Ismail, Mona H., Melin, Pascal, Mikolasevic, Ivana, Milovanovic, Tamara, Musso, Carla, Nakajima, Atsushi, Nava, Edna, Nersesov, Alexander V., Nikolova, Dafina, Norris, Suzanne, Novak, Katja, Kautz, Achim, Oben, Jude, Ong, Janus P., Onyekwere, Charles, Papatheodoridis, George, Paruk, Imran, Patel, Keyur, Macedo, M. Paula, Penha-Gonçalves, Carlos, Figueroa, Marlene Pérez, Hofmann, Wolf Peter, Sarin, Shiv Kumar, Petta, Salvatore, de Oliveira, Claudia Pinto Marques Souza, Puri, Puneet, Pan, Calvin Q., Rac, Marek, Ralston, Johanna, Ramji, Alnoor, Razavi, Homie, Alvares-da-Silva, Mario Reis, Roberts, Stuart, Loomba, Rohit, Roden, Michael, Rose, Tamsin, Rouabhia, Samir, Rovere-Querini, Patrizia, Rowe, Ian A., Sadirova, Shakhlo, Salupere, Riina, Saparbu, Tobokalova, Sayegh, Raymond, Sebastiani, Giada, Miller, Veronica, Seki, Yosuke, Selmo, Josefina, Serme, Abdel Karim, Shaw, Jonathan E., Shenoy, Thrivikrama, Sheron, Nick, Shibolet, Oren, Silva, Marcelo, Skrypnyk, Igor, Socha, Piotr, Newsome, Philip N., Soriano, Joan, Spearman, C. Wendy, Sridharan, Kannan, Suárez, Juan José, Sheriff, Dhastagir Sultan, Sung, Ki-Chul, Swain, Mark, Tacke, Frank, Taheri, Shahrad, Tan, Soek-Siam, Ninburg, Michael, Tapper, Elliot B., Yki-Järvinen, Hannele, Thiele, Maja, Shawa, Isaac Thom, Tolmane, Ieva, Torres, Esther A., Trauner, Michael, Treeprasertsuk, Sombat, Turcanu, Adela, Valantinas, Jonas, Ocama, Ponsiano, Vesterhus, Mette, Waked, Imam, Wild, Sarah H., Willemse, Jose, Wong, Robert J., Xanthakos, Stavra, Young, Dan Yock, Yu, Ming-Lung, Zheng, Kenneth I., Zeybel, Mudjat, Ratziu, Vlad, Zheng, Ming-Hua, Rinella, Mary, Romero, Diana, Romero-Gómez, Manuel, Schattenberg, Jörn M., Tsochatzis, Emmanuel A., Valenti, Luca, Wong, Vincent Wai-Sun, Yilmaz, Yusuf, Younossi, Zobair M., Zelber-Sagi, Shira, Åberg, Fredrik, Adams, Leon, Khatry, Maryam Salem Al, Naamani, Khalid Al, Murillo, Omar Alfaro, Allen, Alina M., Alnaser, Faisal, Alqahtani, Saleh A., Alswat, Khalid, Alvaro, Domenico, Andrade, Raúl J., Arrese, Marco, Awuku, Yaw Asante, Ayesha, Motala, Baatarkhuu, Oidov, Bakieva, Shokhista, Basu, Rita, Bataller, Ramon, Bedri, Shahinaz, Bosi, Emanuele, Bourliere, Marc, Bruha, Radan, Bugianesi, Elisabetta, Burra, Patrizia, Buti, Maria, Byrne, Christopher D., Calleja, Jose Luis, Carrieri, Patrizia, Carter, Flloyd, Fernandez, Marlen Ivon Castellanos, Castillo-Lopez, Gabriela, Castro-Narro, Graciela E., Chan, Henry Lik Yuen, Chan, Wah-Kheong, Chang, Yoosoo, Colombo, Massimo, Coppell, Kirsten J., Corey, Kathleen, Craxi, Antonio, Cryer, Donna, Dassanayake, Anuradha, Martins, Antonieta de Ascenção Soares, de Ledinghen, Victor, DelPrato, Stefano, Demaio, Alessandro, Desalegn, Hailemichael, Dillon, John, Duseja, Ajay, Dorairaj, Prabhakaran, Ekstedt, Mattias, El Kassas, Mohamed, Elsanousi, Osama M., Esmat, Gamal, Fan, Jian-Gao, Farpour-Lambert, Nathalie, Flisiak, Robert, Fouad, Yasser, Fuchs, Michael, Gani, Rino A., Gerber, Lynn, Ghazinyan, Hasmik, Gheorghe, Liana, Goh, George Boon-Bee, Grønbæk, Henning, Gulnara, Aghayeva, Hamid, Saeed, Hebditch, Vanessa, Repositório da Universidade de Lisboa, Masira, Lazarus, Jeffrey, V, Mark, Henry E., Anstee, Quentin M., Arab, Juan Pablo, Batterham, Rachel L., Castera, Laurent, Cortez-Pinto, Helena, Crespo, Javier, Cusi, Kenneth, Dirac, M. Ashworth, Francque, Sven, George, Jacob, Hagstrom, Hannes, Huang, Terry T-K, Ismail, Mona H., Kautz, Achim, Sarin, Shiv Kumar, Loomba, Rohit, Miller, Veronica, Newsome, Philip N., Ninburg, Michael, Ocama, Ponsiano, Ratziu, Vlad, Rinella, Mary, Romero, Diana, Romero-Gomez, Manuel, Schattenberg, Jorn M., Tsochatzis, Emmanuel A., Valenti, Luca, Wong, Vincent Wai-Sun, Yilmaz, Yusuf, Younossi, Zobair M., Zelber-Sagi, Shira, Lazarus, J. V., Mark, H. E., Anstee, Q. M., Arab, J. P., Batterham, R. L., Castera, L., Cortez-Pinto, H., Crespo, J., Cusi, K., Dirac, M. A., Francque, S., George, J., Hagstrom, H., Huang, T. T. -K., Ismail, M. H., Kautz, A., Sarin, S. K., Loomba, R., Miller, V., Newsome, P. N., Ninburg, M., Ocama, P., Ratziu, V., Rinella, M., Romero, D., Romero-Gomez, M., Schattenberg, J. M., Tsochatzis, E. A., Valenti, L., Wong, V. W. -S., Yilmaz, Y., Younossi, Z. M., Zelber-Sagi, S., Aberg, F., Adams, L., Khatry, M. S. A., Naamani, K. A., Murillo, O. A., Allen, A. M., Alnaser, F., Alqahtani, S. A., Alswat, K., Alvaro, D., Andrade, R. J., Arrese, M., Awuku, Y. A., Ayesha, M., Baatarkhuu, O., Bakieva, S., Basu, R., Bataller, R., Bedri, S., Bosi, E., Bourliere, M., Bruha, R., Bugianesi, E., Burra, P., Buti, M., Byrne, C. D., Calleja, J. L., Carrieri, P., Carter, F., Fernandez, M. I. C., Castillo-Lopez, G., Castro-Narro, G. E., Chan, H. L. Y., Chan, W. -K., Chang, Y., Colombo, M., Coppell, K. J., Corey, K., Craxi, A., Cryer, D., Dassanayake, A., Martins, A. A. S., de Ledinghen, V., Delprato, S., Demaio, A., Desalegn, H., Dillon, J., Duseja, A., Dorairaj, P., Ekstedt, M., El Kassas, M., Elsanousi, O. M., Esmat, G., Fan, J. -G., Farpour-Lambert, N., Flisiak, R., Fouad, Y., Fuchs, M., Gani, R. A., Gerber, L., Ghazinyan, H., Gheorghe, L., Goh, G. B. -B., Gronbaek, H., Gulnara, A., Hamid, S., Hebditch, V., Hickman, I. J., Hocking, S. L., Hunyady, B., Idilman, R., Isakov, V. A., Jamal, M. H., Jepsen, P., Iskandar, N. J., Song, M. J., Sudhamshu, K. C., Kakizaki, S., Kalamitsis, G., Kanwal, F., Kao, J. -H., Kaplan, L., Kawaguchi, T., Khader, Y., Kim, S. U., Kodjoh, N., Koek, G., Koike, K., Komas, N. P., Korenjak, M., Kugelmas, M., Labidi, A., Lange, N. F., Lavine, J. E., Lazo, M., Lee, N., Lesmana, C. R. A., Liu, C. -J., Long, M. T., Lopez-Jaramillo, P., Malekzadeh, R., Mahtab, M. A., Marchesini, G., Marinho, R., Vazquez, S. E. M., Mateva, L., Nlombi, C. M., Melin, P., Mikolasevic, I., Milovanovic, T., Musso, C., Nakajima, A., Nava, E., Nersesov, A. V., Nikolova, D., Norris, S., Novak, K., Oben, J., Ong, J. P., Onyekwere, C., Papatheodoridis, G., Paruk, I., Patel, K., Macedo, M. P., Penha-Goncalves, C., Figueroa, M. P., Hofmann, W. P., Petta, S., de Oliveira, C. P. M. S., Puri, P., Pan, C. Q., Rac, M., Ralston, J., Ramji, A., Razavi, H., Alvares-da-Silva, M. R., Roberts, S., Roden, M., Rose, T., Rouabhia, S., Rovere-Querini, P., Rowe, I. A., Sadirova, S., Salupere, R., Saparbu, T., Sayegh, R., Sebastiani, G., Seki, Y., Selmo, J., Serme, A. K., Shaw, J. E., Shenoy, T., Sheron, N., Shibolet, O., Silva, M., Skrypnyk, I., Socha, P., Soriano, J., Spearman, C. W., Sridharan, K., Suarez, J. J., Sheriff, D. S., Sung, K. -C., Swain, M., Tacke, F., Taheri, S., Tan, S. -S., Tapper, E. B., Yki-Jarvinen, H., Thiele, M., Shawa, I. T., Tolmane, I., Torres, E. A., Trauner, M., Treeprasertsuk, S., Turcanu, A., Valantinas, J., Vesterhus, M., Waked, I., Wild, S. H., Willemse, J., Wong, R. J., Xanthakos, S., Young, D. Y., Yu, M. -L., Zheng, K. I., Zeybel, M., Zheng, M. -H., NAFLD Consensus Consortium, Lazarus J.V., Mark H.E., Anstee Q.M., Arab J.P., Batterham R.L., Castera L., Cortez-Pinto H., Crespo J., Cusi K., Dirac M.A., Francque S., George J., Hagstrom H., Huang T.T.-K., Ismail M.H., Kautz A., Sarin S.K., Loomba R., Miller V., Newsome P.N., Ninburg M., Ocama P., Ratziu V., Rinella M., Romero D., Romero-Gomez M., Schattenberg J.M., Tsochatzis E.A., Valenti L., Wong V.W.-S., Yilmaz Y., Younossi Z.M., Zelber-Sagi S., Aberg F., Adams L., Khatry M.S.A., Naamani K.A., Murillo O.A., Allen A.M., Alnaser F., Alqahtani S.A., Alswat K., Alvaro D., Andrade R.J., Arrese M., Awuku Y.A., Ayesha M., Baatarkhuu O., Bakieva S., Basu R., Bataller R., Bedri S., Bosi E., Bourliere M., Bruha R., Bugianesi E., Burra P., Buti M., Byrne C.D., Calleja J.L., Carrieri P., Carter F., Fernandez M.I.C., Castillo-Lopez G., Castro-Narro G.E., Chan H.L.Y., Chan W.-K., Chang Y., Colombo M., Coppell K.J., Corey K., Craxi A., Cryer D., Dassanayake A., Martins A.A.S., de Ledinghen V., DelPrato S., Demaio A., Desalegn H., Dillon J., Duseja A., Dorairaj P., Ekstedt M., El Kassas M., Elsanousi O.M., Esmat G., Fan J.-G., Farpour-Lambert N., Flisiak R., Fouad Y., Fuchs M., Gani R.A., Gerber L., Ghazinyan H., Gheorghe L., Goh G.B.-B., Gronbaek H., Gulnara A., Hamid S., Hebditch V., Hickman I.J., Hocking S.L., Hunyady B., Idilman R., Isakov V.A., Jamal M.H., Jepsen P., Iskandar N.J., Song M.J., Sudhamshu K.C., Kakizaki S., Kalamitsis G., Kanwal F., Kao J.-H., Kaplan L., Kawaguchi T., Khader Y., Kim S.U., Kodjoh N., Koek G., Koike K., Komas N.P., Korenjak M., Kugelmas M., Labidi A., Lange N.F., Lavine J.E., Lazo M., Lee N., Lesmana C.R.A., Liu C.-J., Long M.T., Lopez-Jaramillo P., Malekzadeh R., Mahtab M.A., Marchesini G., Marinho R., Vazquez S.E.M., Mateva L., Nlombi C.M., Melin P., Mikolasevic I., Milovanovic T., Musso C., Nakajima A., Nava E., Nersesov A.V., Nikolova D., Norris S., Novak K., Oben J., Ong J.P., Onyekwere C., Papatheodoridis G., Paruk I., Patel K., Macedo M.P., Penha-Goncalves C., Figueroa M.P., Hofmann W.P., Petta S., de Oliveira C.P.M.S., Puri P., Pan C.Q., Rac M., Ralston J., Ramji A., Razavi H., Alvares-da-Silva M.R., Roberts S., Roden M., Rose T., Rouabhia S., Rovere-Querini P., Rowe I.A., Sadirova S., Salupere R., Saparbu T., Sayegh R., Sebastiani G., Seki Y., Selmo J., Serme A.K., Shaw J.E., Shenoy T., Sheron N., Shibolet O., Silva M., Skrypnyk I., Socha P., Soriano J., Spearman C.W., Sridharan K., Suarez J.J., Sheriff D.S., Sung K.-C., Swain M., Tacke F., Taheri S., Tan S.-S., Tapper E.B., Yki-Jarvinen H., Thiele M., Shawa I.T., Tolmane I., Torres E.A., Trauner M., Treeprasertsuk S., Turcanu A., Valantinas J., Vesterhus M., Waked I., Wild S.H., Willemse J., Wong R.J., Xanthakos S., Young D.Y., Yu M.-L., Zheng K.I., Zeybel M., and Zheng M.-H.

Subjects
medicine.medical_specialty, Civil society, Delphi method, MEDLINE, Nash, MULTIDISCIPLINARY APPROACH, Disease, LATIN-AMERICAN ASSOCIATION, Multidisciplinary approach, QUALITY-OF-LIFE, Non-alcoholic Fatty Liver Disease, Epidemiology, Medicine, Humans, POSITION STATEMENT, BIOMEDICINE AND HEALTHCARE. Clinical Medical Sciences. Internal Medicine, FATTY LIVER-DISEASE, BIOMEDICINA I ZDRAVSTVO. Kliničke medicinske znanosti. Interna medicina, Hepatology, business.industry, Public health, Gastroenterology, ALCOHOLIC STEATOHEPATITIS, NONINVASIVE DIAGNOSIS, medicine.disease, Obesity, CARDIOVASCULAR-DISEASE, PRACTICE GUIDELINES, Family medicine, PRACTICAL APPROACH, Human medicine, business
Abstract

Digital, Non-alcoholic fatty liver disease (NAFLD) is a potentially serious liver disease that affects approximately one-quarter of the global adult population, causing a substantial burden of ill health with wide-ranging social and economic implications. It is a multisystem disease and is considered the hepatic component of metabolic syndrome. Unlike other highly prevalent conditions, NAFLD has received little attention from the global public health community. Health system and public health responses to NAFLD have been weak and fragmented, and, despite its pervasiveness, NAFLD is largely unknown outside hepatology and gastroenterology. There is only a nascent global public health movement addressing NAFLD, and the disease is absent from nearly all national and international strategies and policies for non-communicable diseases, including obesity. In this global Delphi study, a multidisciplinary group of experts developed consensus statements and recommendations, which a larger group of collaborators reviewed over three rounds until consensus was achieved. The resulting consensus statements and recommendations address a broad range of topics — from epidemiology, awareness, care and treatment to public health policies and leadership — that have general relevance for policy-makers, health-care practitioners, civil society groups, research institutions and affected populations. These recommendations should provide a strong foundation for a comprehensive public health response to NAFLD., Ciencias Médicas y de la Salud

Published
2021
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5. Effects of hepatitis C virus on cardiovascular risk in infected patients: a comparative study.

Author

Oliveira CP, Kappel CR, Siqueira ER, Lima VM, Stefano JT, Michalczuk MT, Marini SS, Barbeiro HV, Soriano FG, Carrilho FJ, Pereira LM, and Alvares-da-Silva MR

Subjects
Adult, Biomarkers blood, Cardiovascular Diseases pathology, Female, Hepatitis C pathology, Hepatitis C virology, Humans, Inflammation epidemiology, Inflammation pathology, Inflammation virology, Male, Middle Aged, Risk Factors, Cardiovascular Diseases epidemiology, Cardiovascular Diseases virology, Hepacivirus pathogenicity, Hepatitis C epidemiology
Abstract

The role of hepatitis C virus (HCV) in the pathogenesis of atherosclerosis and cardiovascular events is unclear. The aim of this study was to evaluate the direct effect of HCV on cardiovascular risk and correlate it with pro and anti-inflammatory cytokines in patients with HCV. HCV monoinfected patients, genotype 1, naive, non-obese (BMI<30) and non-diabetics were included and compared to controls (blood donors). Patients with prior diagnosis of cardiovascular diseases, hypertension, chronic renal failure, cancer and chronic use of lipid-lowering drugs or immunosuppressants were excluded. Age, BMI, systolic blood pressure (SBP) and diastolic (DBP), fasting glucose and lipid levels were determined. Serum cytokines (IL-6, IL-10 and TNF-α) and Framingham score were also evaluated. 62 HCV patients, 34 (54.8%) were males and none of them was smoking. The Framingham scores (median and 25th and 75th percentiles) were 12% (6.5-14%), showing an intermediate cardiovascular risk in patients with HCV. There was significant direct correlation between Framingham and total cholesterol (p=0.043) and DBP (p=0.007). HDL-C (p=0.002) was inversely correlated with the Framingham score. HCV patients had higher levels of proinflammatory cytokines (IL-6 and TNF-α) compared to controls (p<0.0001) and the relation of proinflammatory/anti-inflammatory TNF-α/IL10 and IL-6/IL10 were higher in HCV patients (p<0.01). The Framingham score was directly correlated to IL-6 and TNF-α, but differences were not statistically significant. Patients with HCV monoinfected, nonobese, naïve and non diabetic have an intermediate cardiovascular risk, as measured by the Framingham score and high levels of proinflammatory cytokines (IL-6 and TNF)., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Published
2013
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6. S-Nitroso-N-acetylcysteine induces de-differentiation of activated hepatic stellate cells and promotes antifibrotic effects in vitro.

Author

Stefano JT, Cogliati B, Santos F, Lima VM, Mazo DC, Matte U, Alvares-da-Silva MR, Silveira TR, Carrilho FJ, and Oliveira CP

Subjects
Acetylcysteine chemical synthesis, Acetylcysteine chemistry, Acetylcysteine pharmacology, Animals, Cell Survival drug effects, Cells, Cultured, Dose-Response Relationship, Drug, Hepatic Stellate Cells metabolism, Liver Cirrhosis metabolism, Mice, Acetylcysteine analogs & derivatives, Cell Dedifferentiation drug effects, Hepatic Stellate Cells cytology, Hepatic Stellate Cells drug effects, Liver Cirrhosis drug therapy, Liver Cirrhosis pathology
Abstract

Nitric oxide (NO) has been shown to act as a potent antifibrogenic agent by decreasing myofibroblast differentiation. S-Nitroso-N-acetylcysteine (SNAC), a NO donor, attenuates liver fibrosis in rats, but the cellular and molecular mechanisms on liver myofibroblast-like phenotype still remain unknown. Here, we investigate the antifibrotic effects of SNAC on hepatic stellate cells, the major fibrogenic cell type in the liver. A murine GRX cell line was incubated with SNAC (100μM) or vehicle (control group) for 72h. Cell viability was measured by MTT colorimetric assay and the conversion of myofibroblast into quiescent fat-storing cell phenotype was evaluated by Oil-Red-O staining. TGFβ-1, TIMP-1, and MMP-13 levels were measure in the supernatant by ELISA. Profibrogenic- and fibrolytic-related gene expression was quantified using real-time qPCR. SNAC induced phenotype conversion of myofibroblast-like phenotype into quiescent cells. SNAC decreased gene and protein expression of TGFβ-1 and MMP-2 compared to control groups. Besides, SNAC down-regulated profibrogenic molecules and up-regulated MMP-13 gene expression, which plays a key role in the degradation of interstitial collagen in liver fibrosis. In conclusion, these findings demonstrate that SNAC efficiently can modulate the activation and functionality of murine hepatic stellate cells and could be considered as an antifibrotic treatment to human liver fibrosis., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Published
2011
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7. Does hepatocellular carcinoma in non-alcoholic steatohepatitis exist in cirrhotic and non-cirrhotic patients?

Author

Chagas AL, Kikuchi LO, Oliveira CP, Vezozzo DC, Mello ES, Oliveira AC, Cella LC, Herman P, Bachella T, Caldwell SH, Alves VA, and Carrilho FJ

Subjects
Adult, Aged, Carcinoma, Hepatocellular pathology, Fatty Liver pathology, Female, Humans, Liver Cirrhosis pathology, Liver Neoplasms pathology, Male, Middle Aged, Neoplasm Staging, Carcinoma, Hepatocellular complications, Fatty Liver complications, Liver Cirrhosis complications, Liver Neoplasms complications
Abstract

Non-alcoholic steatohepatitis (NASH) has been associated with hepatocellular carcinoma (HCC) often arising in histologically advanced disease when steatohepatitis is not active (cryptogenic cirrhosis). Our objective was to characterize patients with HCC and active, histologically defined steatohepatitis. Among 394 patients with HCC detected by ultrasound imaging over 8 years and staged by the Barcelona Clinic Liver Cancer (BCLC) criteria, we identified 7 cases (1.7%) with HCC occurring in the setting of active biopsy-proven NASH. All were negative for other liver diseases such as hepatitis C, hepatitis B, autoimmune hepatitis, Wilson disease, and hemochromatosis. The patients (4 males and 3 females, age 63 +/- 13 years) were either overweight (4) or obese (3); 57% were diabetic and 28.5% had dyslipidemia. Cirrhosis was present in 6 of 7 patients, but 1 patient had well-differentiated HCC in the setting of NASH without cirrhosis (fibrosis stage 1) based on repeated liver biopsies, the absence of portal hypertension by clinical and radiographic evaluations and by direct surgical inspection. Among the cirrhotic patients, 71.4% were clinically staged as Child A and 14.2% as Child B. Tumor size ranged from 1.0 to 5.2 cm and 5 of 7 patients were classified as early stage; 46% of all nodules were hyper-echoic and 57% were <3 cm. HCC was well differentiated in 1/6 and moderately differentiated in 5/6. Alpha-fetoprotein was <100 ng/mL in all patients. HCC in patients with active steatohepatitis is often multifocal, may precede clinically advanced disease and occurs without diagnostic levels of alpha-fetoprotein. Importantly, HCC may occur in NASH in the absence of cirrhosis. More aggressive screening of NASH patients may be warranted.

Published
2009
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8. Liver mitochondrial dysfunction and oxidative stress in the pathogenesis of experimental nonalcoholic fatty liver disease.

Author

Oliveira CP, Coelho AM, Barbeiro HV, Lima VM, Soriano F, Ribeiro C, Molan NA, Alves VA, Souza HP, Machado MC, and Carrilho FJ

Subjects
Animals, Choline Deficiency complications, Disease Models, Animal, Fatty Acids, Omega-3 administration & dosage, Fatty Liver metabolism, Male, Mitochondria, Liver metabolism, Phosphorylation, Rats, Rats, Wistar, Reactive Oxygen Species, Severity of Illness Index, Fatty Liver etiology, Mitochondria, Liver physiology, Mitochondrial Diseases complications, Oxidative Stress physiology
Abstract

Oxidative stress and hepatic mitochondria play a role in the pathogenesis of nonalcoholic fatty liver disease. The aim of the present study was to evaluate the role of hepatic mitochondrial dysfunction and oxidative stress in the pathogenesis of the disease. Fatty liver was induced in Wistar rats with a choline-deficient diet (CD; N = 7) or a high-fat diet enriched with PUFAs-omega-3 (H; N = 7) for 4 weeks. The control group (N = 7) was fed a standard diet. Liver mitochondrial oxidation and phosphorylation were measured polarographically and oxidative stress was estimated on the basis of malondialdehyde and glutathione concentrations. Moderate macrovacuolar liver steatosis was observed in the CD group and mild liver steatosis was observed in the periportal area in the H group. There was an increase in the oxygen consumption rate by liver mitochondria in respiratory state 4 (S4) and a decrease in respiratory control rate (RCR) in the CD group (S4: 32.70 +/- 3.35; RCR: 2.55 +/- 0.15 ng atoms of O2 min-1 mg protein-1) when compared to the H and control groups (S4: 23.09 +/- 1.53, 17.04 +/- 2.03, RCR: 3.15 +/- 0.15, 3.68 +/- 0.15 ng atoms of O2 min-1 mg protein-1, respectively), P < 0.05. Hepatic lipoperoxide concentrations were significantly increased and the concentration of reduced glutathione was significantly reduced in the CD group. A choline-deficient diet causes moderate steatosis with disruption of liver mitochondrial function and increased oxidative stress. These data suggest that lipid peroxidation products can impair the flow of electrons along the respiratory chain, causing overreduction of respiratory chain components and enhanced mitochondrial reactive oxygen species. These findings are important in the pathogenesis of nonalcoholic fatty liver disease.

Published
2006
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