Browsing by Subject "LIVER-DISEASE"

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  • Lovric, Alen; Graner, Marit; Bjornson, Elias; Arif, Muhammad; Benfeitas, Rui; Nyman, Kristofer; Ståhlman, Marcus; Pentikäinen, Markku O.; Lundbom, Jesper; Hakkarainen, Antti; Siren, Reijo; Nieminen, Markku S.; Lundbom, Nina; Lauerma, Kirsi; Taskinen, Marja-Riitta; Mardinoglu, Adil; Boren, Jan (2018)
    Non-alcoholic fatty liver disease (NAFLD) is recognized as a liver manifestation of metabolic syndrome, accompanied with excessive fat accumulation in the liver and other vital organs. Ectopic fat accumulation was previously associated with negative effects at the systemic and local level in the human body. Thus, we aimed to identify and assess the predictive capability of novel potential metabolic biomarkers for ectopic fat depots in non-diabetic men with NAFLD, using the inflammation-associated proteome, lipidome and metabolome. Myocardial and hepatic triglycerides were measured with magnetic spectroscopy while function of left ventricle, pericardial and epicardial fat, subcutaneous and visceral adipose tissue were measured with magnetic resonance imaging. Measured ectopic fat depots were profiled and predicted using a Random Forest algorithm, and by estimating the Area Under the Receiver Operating Characteristic curves. We have identified distinct metabolic signatures of fat depots in the liver (TAG50:1, glutamate, diSM18:0 and CE20:3), pericardium (N-palmitoyl-sphinganine, HGF, diSM18:0, glutamate, and TNFSF14), epicardium (sphingomyelin, CE20:3, PC38:3 and TNFSF14), and myocardium (CE20:3, LAPTGF-beta 1, glutamate and glucose). Our analyses highlighted non-invasive biomarkers that accurately predict ectopic fat depots, and reflect their distinct metabolic signatures in subjects with NAFLD.
  • Lahelma, Mari; Sädevirta, Sanja; Lallukka-Brück, Susanna; Sevastianova, Ksenia; Mustelin, Linda; Gylling, Helena; Rockette-Wagner, Bonny; Kriska, Andrea M.; Yki-Järvinen, Hannele (2019)
    Background: Weighted hula-hoops have gained popularity, but whether they indeed reshape the trunk or have beneficial metabolic effects in overweight subjects is unknown. Objectives: To determine effects of hula-hooping and walking matched for energy expenditure on android fat %, trunk muscle mass, and metabolic parameters in a randomized cross-over study. Design: We recruited 55 overweight nondiabetic subjects, who were randomized to hula-hooping (HULA) for 6 weeks using a 1.5-kg weighted hula-hoop followed by walking (WALK) for another 6 weeks or vice versa. The increments in energy expenditure were similar by HULA and WALK. Body composition (dual-energy X-ray absorptiometry) and metabolic parameters were measured at baseline and after HULA and WALK. The primary endpoint was the change in fat % in the android region. Results: A total of 53subjects (waist 92 +/- 1 cm, body mass index 28 +/- 1 kg/m(2)) completed the study. Body weight changed similarly (-0.6 +/- 0.2 vs. -0.5 +/- 0.2 kg, nonsignificant; HULA vs. WALK). During the intervention the subjects hula-hooped on average 12.8 +/- 0.5 min/day and walked 9,986 +/- 376 steps/day. The % fat in the android region decreased significantly by HULA but not by WALK (between-group change p <0.001). Trunk muscle mass increased more by HULA than by WALK (p <0.05). Waist circumference decreased more by HULA than by WALK (-3.1 +/- 0.3 cm vs. -0.7 +/- 0.4 cm, p <0.001; HULA vs. WALK). WALK but not HULA significantly lowered systolic blood pressure and increased HDL cholesterol while HULA significantly decreased LDL cholesterol. Conclusions: Hula-hooping with a weighted hula-hoop can be used to decrease abdominal fat % and increase trunk muscle mass in overweight subjects. Its LDL lowering effect resembles that described for resistance training. (c) 2019 The Author(s) Published by S. Karger AG, Basel
  • Hukkinen, Maria; Merras-Salmio, Laura; Pakarinen, Mikko P. (2018)
    Treatment results of pediatric intestinal failure have improved markedly during the last decades. With improved survival the attention is turning to other essential outcomes including quality of life and neurodevelopment. So far, relatively few studies with limited number of patients and variable methodology have addressed these issues. Based on these studies using generic health related quality of life tools, children with intestinal failure demonstrate decreased physical health, while PN-dependence is also associated with compromised emotional functioning. Impairments of social functioning are frequently observed among older children and parents. Few recent studies on neurodevelopment imply significant impairments in motor and mental skills among children with intestinal failure despite small sample sizes and limited follow-up times. Development of a disease-specific survey designed for the pediatric intestinal failure population could better reveal the health issues with greatest impact on quality of life. Robust studies with appropriate methodology on neurodevelopment in pediatric intestinal failure with extended follow-up times are urgently needed. Quality of life and neurodevelopment requires greater attention from medical professionals managing children with intestinal failure. (C) 2018 Elsevier Inc. All rights reserved.
  • Roumans, Kay H. M.; Lindeboom, Lucas; Veeraiah, Pandichelvam; Remie, Carlijn M. E.; Phielix, Esther; Havekes, Bas; Bruls, Yvonne M. H.; Brouwers, Martijn C. G. J.; Stahlman, Marcus; Alssema, Marjan; Peters, Harry P. F.; de Mutsert, Renee; Staels, Bart; Taskinen, Marja-Riitta; Boren, Jan; Schrauwen, Patrick; Schrauwen-Hinderling, Vera B. (2020)
    Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Hepatic saturated fatty acids (SFA) may be a marker of DNL and are suggested to be most detrimental in contributing to insulin resistance. Here, we show in a cross-sectional study design ( ID: NCT03211299) that we are able to distinguish the fractions of hepatic SFA, mono- and polyunsaturated fatty acids in healthy and metabolically compromised volunteers using proton magnetic resonance spectroscopy (H-1-MRS). DNL is positively associated with SFA fraction and is elevated in patients with non-alcoholic fatty liver and type 2 diabetes. Intriguingly, SFA fraction shows a strong, negative correlation with hepatic insulin sensitivity. Our results show that the hepatic lipid composition, as determined by our H-1-MRS methodology, is a measure of DNL and suggest that specifically the SFA fraction may hamper hepatic insulin sensitivity. Hepatic steatosis is associated with poor cardiometabolic health, with de novo lipogenesis (DNL) contributing to hepatic steatosis and subsequent insulin resistance. Here, the authors use H-1-MRS methodology to show hepatic SFA fraction is a measure of DNL and specifically may hamper hepatic insulin sensitivity.
  • Luukkonen, Panu K.; Zhou, You; Haridas, Nidhina P. A.; Dwivedi, Om P.; Hyotylainen, Tuulia; Ali, Ashfaq; Juuti, Anne; Leivonen, Marja; Tukiainen, Taru; Ahonen, Linda; Scott, Emma; Palmer, Jeremy M.; Arola, Johanna; Orho-Melander, Marju; Vikman, Petter; Anstee, Quentin M.; Olkkonen, Vesa M.; Oresic, Matej; Groop, Leif; Yki-Jarvinen, Hannele (2017)
    Background: Carriers of the transmembrane 6 superfamily member 2 E167K gene variant (TM6SF2(EK/KK)) have decreased expression of the TM6SF2 gene and increased risk of NAFLD and NASH. Unlike common 'obese/metabolic' NAFLD, these subjects lack hypertriglyceridemia and have lower risk of cardiovascular disease. In animals, phosphatidylcholine (PC) deficiency results in a similar phenotype. PCs surround the core of VLDL consisting of triglycerides (TGs) and cholesteryl-esters (CEs). We determined the effect of the TM6SF2 E167K on these lipids in the human liver and serum and on hepatic gene expression and studied the effect of TM6SF2 knockdown on hepatocyte handling of these lipids. Methods: Liver biopsies were taken from subjects characterized with respect to the TM6SF2 genotype, serum and liver lipidome, gene expression and histology. In vitro, after TM6SF2 knockdown in HuH-7 cells, we compared incorporation of different fatty acids into TGs, CEs, and PCs. Results: The TM6SF2(EK/KK) and TM6SF2EE groups had similar age, gender, BMI and HOMA-IR. Liver TGs and CEs were higher and liver PCs lower in the TM6SF2(EK/KK) than the TM6SF2EE group (p Conclusions: Hepatic lipid synthesis from PUFAs is impaired and could contribute to deficiency in PCs and increased intrahepatic TG in TM6SF2 E167K variant carriers. (C) 2017 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
  • Karila, Kristiina; Anttila, Annaleena; Iber, Tarja; Pakarinen, Mikko; Koivusalo, Antti (2019)
    Background: Surgery for necrotizing enterocolitis (NEC) and spontaneous intestinal perforation (SIP) is often complicated by intestinal failure (IF) and intestinal failure associated cholestasis (IFAC). Objective: Assessment of incidence, predictors, and mortality associated with IFAC in surgically treated NEC and SIP. Methods: A retrospective observational study based on hospital records during 1986-2014 in the two largest Finnish neonatal intensive care units was performed. IFAC was defined as conjugated bilirubin >34 mu mo1/1 (2.0 mg/dl) for >= two postoperative weeks while receiving parenteral nutrition (PN). Results: In total 225 patients underwent surgery for NEC (n 142; 63%) or SIP (n = 83; 37%). Included were 57 survivors with >= two weeks PN. Sixty-five (42%) patients developed IFAC. Two-year survival with IFAC was 80% and without IFAC 89% (p = 0.13). Of the 65 patients with IFAC, all eight with unresolved IFAC died in comparison to six of 57 (11%) whose IFAC resolved (p <0.0001), while IFAC resolved in all survivors. Survival among patients with resolved IFAC was 89% and with unresolved IFAC (n = 8) 0%, (p <0.0001).IFAC lasted for median 83 (IQR 45-120) days and correlated with the duration of PN (R2 = 0.16, p = 0.03), delay of starting enteral feeds (R2 = 0.12, p = 0.05) and PN lipid emulsion (RR = 1.0 (95% CI = 1.0-1.1) (p = 0.02). In multivariate logistic regression analysis, IFAC development associated with septicemias and reoperations. Conclusions: 42% of pre matures who underwent surgery for NEC or SIP developed IFAC. Reoperations and septicemias increased the risk of IFAC. None of the patients with unresolved IFAC survived, but IFAC did not increase overall mortality. Type of study: Retrospective prognosis study. (C) 2018 Elsevier Inc. All rights reserved.
  • Luoto, Topi T.; Koivusalo, Antti; Pakarinen, Mikko P. (2020)
    Objectives: Outcomes of pediatric-onset portal hypertension are poorly defined. We aimed to assess population-based long-term outcomes of pediatric-onset portal hypertension complicated by varices. Methods: All children with esophageal varices (n = 126) were identified from 14,144 single nationwide referral center endoscopy reports during 1987 to 2013, and followed up through national health care and death registers. A questionnaire was sent to survivors (n = 94) of whom 65 (69%) responded. Results: Nineteen underlying disorders included biliary atresia (35%), extrahepatic portal vein obstruction (35%), autosomal recessive polycystic kidney disease (7%), and other disorders (23%). During median follow-up of 15.2 (range 0.5-43.1) years patients underwent median 9 (1-74) upper gastrointestinal endoscopies. Esophageal varices were first observed at a median age of 4.0 (0.3-18.2) years, 112 (89%) patients underwent median 6 (1-56) sclerotherapy/banding sessions, and 61 (48%) experienced median 2 (range 1-20) variceal bleeding episodes. Forty-eight surgical shunt procedures were performed to 41 (36%) patients and 38% underwent liver transplantation. Portal hypertensive biliopathy was diagnosed in 4 patients. Hepatopulmonary syndrome necessitated liver transplantation in 2 patients, hepatic encephalopathy in 2, and hepatorenal syndrome in 1. No patient died of variceal bleeding. Patient-reported perception of health on a scale of 1 to 10 was 9 (range 4-10), and 86% reported no current symptoms attributable to esophageal varices. Conclusions: Pediatric-onset portal hypertension is a heterogeneous disease with significant long-term morbidity, requiring multimodal approach with considerable resources and continuation of follow-up in adulthood. Although mortality to variceal bleeding was avoided, bleeding episodes recurred also in adulthood, while patient-reported health of long-term survivors was encouraging.
  • Imbery, Carolin A.; Dieterle, Frank; Ottka, Claudia; Weber, Corinna; Schlotterbeck, Goetz; Mueller, Elisabeth; Lohi, Hannes; Giger, Urs (2022)
    Hepatopathies can cause major metabolic abnormalities in humans and animals. This study examined differences in serum metabolomic parameters and patterns in left-over serum samples from dogs with either congenital portosystemic shunts (cPSS, n = 24) or high serum liver enzyme activities (HLEA, n = 25) compared to control dogs (n = 64). A validated targeted proton nuclear magnetic resonance spectroscopy platform was used to assess 123 parameters. Principal component analysis of the serum metabolome demonstrated distinct clustering among individuals in each group, with the cluster of HLEA being broader compared to the other groups, presumably due to the wider spectrum of hepatic diseases represented in these samples. While younger and older adult control dogs had very similar metabolomic patterns and clusters, there were changes in many metabolites in the hepatopathy groups. Higher phenylalanine and tyrosine concentrations, lower branched-chained amino acids (BCAAs) concentrations, and altered fatty acid parameters were seen in cPSS dogs compared to controls. In contrast, dogs with HLEA had increased concentrations of BCAAs, phenylalanine, and various lipoproteins. Machine learning based solely on the metabolomics data showed excellent group classification, potentially identifying a novel tool to differentiate hepatopathies. The observed changes in metabolic parameters could provide invaluable insight into the pathophysiology, diagnosis, and prognosis of hepatopathies.
  • Mysore, Raghavendra; Zhou, You; Sädevirta, Sanja; Savolainen-Peltonen, Hanna; Haridas, P. A. Nidhina; Soronen, Jarkko; Leivonen , Marja; Sarin, Antti-Pekka; Fischer-Posovszky, Pamela; Wabitsch, Martin; Yki-Jarvinen, Hannele; Olkkonen, Vesa M. (2016)
    We investigated the expression of miR-192* (miR-192-3p) in the visceral adipose tissue (VAT) of obese subjects and its function in cultured human adipocytes. This miRNA is a 3' arm derived from the same pre-miRNA as miR-192 (miR-192-5p) implicated in type 2 diabetes, liver disease and cancers, and is predicted to target key genes in lipid metabolism. In morbidly obese subjects undergoing bariatric surgery preceded by a very low calorie diet, miR-192* in VAT correlated negatively (r = -0.387; p = 0.046) with serum triglyceride (TG) and positively with high-density lipoprotein (HDL) concentration (r = 0.396; p = 0.041). In a less obese patient cohort, the miRNA correlated negatively with the body mass index (r = -0.537; p = 0.026). To characterize the function of miR-192*, we overexpressed it in cultured adipocytes and analyzed the expression of adipogenic differentiation markers as well as cellular TG content. Reduced TG and expression of the adipocyte marker proteins aP2 (adipocyte protein 2) and perilipin 1 were observed. The function of miR-192* was further investigated by transcriptomic profiling of adipocytes expressing this miRNA, revealing impacts on key lipogenic genes. A number of the mRNA alterations were validated by qPCR. Western analysis confirmed a marked reduction of the lipogenic enzyme SCD (stearoyl coenzyme A desaturase-1), the fatty aldehyde dehydrogenase ALDH3A2 (aldehyde dehydrogenase 3 family member A2) and the high-density lipoprotein receptor SCARB1 (scavenger receptor B, type I). SCD and ALDH3A2 were demonstrated to be direct targets of miR-192*. To conclude, the present data identify miR-192* as a novel controller of adipocyte differentiation and lipid homeostasis. (C) 2016 Elsevier B.V. All rights reserved.
  • Matilainen, Johanna; Mustonen, Anne-Mari; Rilla, Kirsi; Kakela, Reijo; Sihvo, Sanna P.; Nieminen, Petteri (2020)
    Background Orotic acid (OA) has been intensively utilized to induce fatty liver in rats. Although the capacity of OA to cause steatosis is species-specific, previous in vitro studies indicate that humans could also be susceptible to OA-induced fatty liver. The aim of the present study was to re-elucidate the potential of OA exposure to modulate the cellular mechanisms involved in both non-alcoholic fatty liver disease pathogenesis and cellular protection from lipid accumulation. In addition, alterations in detailed fatty acid (FA) profiles of cells and culture media were analyzed to assess the significance of lipid metabolism in these phenomena. Methods In our experiments, human hepatocellular carcinoma HepG2 cells were exposed to OA. Bacterial endotoxin, lipopolysaccharide (LPS), was used to mimic hepatic inflammation. The lipogenic and inflammatory effects of OA and/or LPS on cells were assessed by labeling cellular lipids with Nile red stain and by performing image quantifications. The expression levels of key enzymes involved in de novo lipogenesis (DNL) and of inflammatory markers related to the disease development were studied by qRT-PCR. FA profiles of cells and culture media were determined from total lipids with gas chromatography-mass spectrometry. Results Our data indicate that although OA possibly promotes the first stage of DNL, it does not cause a definite lipogenic transformation in HepG2 cells. Reduced proportions of 16:0, increased stearoyl-Coenzyme A desaturase 1 mRNA expression and relatively high proportions of 16:1n-7 suggest that active delta9-desaturation may limit lipogenesis and the accumulation of toxic 16:0. Inflammatory signaling could be reduced by the increased production of long-chain n-3 polyunsaturated FA (PUFA) and the active incorporation of certain FA, including 18:1n-9, into cells. In addition, increased proportions of 20:4n-6 and 22:6n-3, total PUFA and dimethyl acetal 18:0 suggest that OA exposure may cause increased secretion of lipoproteins and extracellular vesicles. Conclusions The present data suggest that, apart from the transcription-level events reported by previous studies, modifications of FA metabolism may also be involved in the prevention of OA-mediated steatosis. Increased delta9-desaturation and secretion of lipoproteins and extracellular vesicles could offer potential mechanisms for further studies to unravel how OA-treated cells alleviate lipidosis.
  • Lensu, Sanna; Pariyani, Raghunath; Mäkinen, Elina; Yang, Baoru; Saleem, Wisam; Munukka, Eveliina; Lehti, Maarit; Driuchina, Anastasiia; Linden, Jere; Tiirola, Marja; Lahti, Leo; Pekkala, Satu (2020)
    Understanding the importance of the gut microbiota (GM) in non-alcoholic fatty liver disease (NAFLD) has raised the hope for therapeutic microbes. We have shown that high hepatic fat content associated with low abundance of Faecalibacterium prausnitzii in humans and, further, the administration of F. prausnitzii prevented NAFLD in mice. Here, we aimed at targeting F. prausnitzii by prebiotic xylo-oligosaccharides (XOS) to treat NAFLD. First, the effect of XOS on F. prausnitzii growth was assessed in vitro. Then, XOS was supplemented or not with high (HFD, 60% of energy from fat) or low (LFD) fat diet for 12 weeks in Wistar rats (n = 10/group). XOS increased F. prausnitzii growth, having only a minor impact on the GM composition. When supplemented with HFD, XOS ameliorated hepatic steatosis. The underlying mechanisms involved enhanced hepatic beta-oxidation and mitochondrial respiration. Nuclear magnetic resonance (H-1-NMR) analysis of cecal metabolites showed that, compared to the HFD, the LFD group had a healthier cecal short-chain fatty acid profile and on the HFD, XOS reduced cecal isovalerate and tyrosine, metabolites previously linked to NAFLD. Cecal branched-chain fatty acids associated positively and butyrate negatively with hepatic triglycerides. In conclusion, XOS supplementation can ameliorate NAFLD by improving hepatic oxidative metabolism and affecting GM.
  • Hukkinen, Maria; Mutanen, Annika; Pakarinen, Mikko P. (2017)
    Background. Liver disease occurs frequently in short bowel syndrome. Whether small bowel dilation in short bowel syndrome could influence the risk of liver injury through increased bacterial translocation remains unknown. Our aim was to analyze associations between small bowel dilation, mucosal damage, bloodstream infections, and liver injury in short bowel syndrome patients. Methods. Among short bowel syndrome children (n = 50), maximal small bowel diameter was measured in contrast series and expressed as the ratio to the height of the fifth lumbar vertebra (small bowel diameter ratio), and correlated retrospectively to fecal calprotectin and plasma citrulline respective markers of mucosal inflammation and mass bloodstream infections, liver biochemistry, and liver histology. Results. Patients with pathologic small bowel diameter ratio > 2.17 had increased fecal calprotectin and decreased citrulline (P <.04 each). Of 33 bloodstream infections observed during treatment with parenteral nutrition, 16 were caused by intestinal bacteria, cultured 15 times more frequently when small bowel diameter ratio was >2.17 (P <.001). Intestinal bloodstream infections were predicted by small bowel diameter ratio (odds ratio 1.88, P = .017), and their frequency decreased after operative tapering procedures (P = .041). Plasma bilirubin concentration, gamma-glutamyl transferase activity, and histologic grade of cholestasis correlated with small bowel diameter ratio (0.356-0.534, P <.014 each), and were greater in the presence of intestinal bloodstream infections (P <.001 for all). Bloodstream infections associated with portal inflammation, cholestasis, and fibrosis grades (P <.031 for each). In linear regression, histologic cholestasis was predicted by intestinal bloodstream infections, small bowel diameter ratio, and parenteral nutrition (beta = 0.36-1.29; P <.014 each), while portal inflammation by intestinal bloodstream infections only (beta = 0.62; P = .033). Conclusion. In children with short bowel syndrome, small bowel dilation correlates with mucosal damage, bloodstream infections of intestinal origin, and cholestatic liver injury. In addition to parenteral nutrition, small bowel dilation and intestinal bloodstream infections contribute to development of short bowel syndrome-associated liver disease.
  • Sepanlou, Sadaf G.; Safiri, Saeid; Bisignano, Catherine; Ikuta, Kevin S.; Merat, Shahin; Saberifiroozi, Mehdi; Poustchi, Hossein; Tsoi, Derrick; Colombara, Danny V.; Abdoli, Amir; Adedoyin, Rufus Adesoji; Afarideh, Mohsen; Agrawal, Sutapa; Ahmad, Sohail; Ahmadian, Elham; Ahmadpour, Ehsan; Akinyemiju, Tomi; Akunna, Chisom Joyqueenet; Alipour, Vahid; Almasi-Hashiani, Amir; Almulhim, Abdulaziz M.; Al-Raddadi, Rajaa M.; Alvis-Guzman, Nelson; Anber, Nahla Hamed; Angus, Colin; Anoushiravani, Amir; Arabloo, Jalal; Araya, Ephrem Mebrahtu; Asmelash, Daniel; Ataeinia, Bahar; Ataro, Zerihun; Atout, Maha Moh'd Wahbi; Ausloos, Floriane; Awasthi, Ashish; Badawi, Alaa; Banach, Maciej; Bejarano Ramirez, Diana Fernanda; Bhagavathula, Akshaya Srikanth; Bhala, Neeraj; Bhattacharyya, Krittika; Biondi, Antonio; Bolla, Srinivasa Rao; Boloor, Archith; Borzi, Antonio M.; Butt, Zahid A.; Alberto Camera, Luis L. A.; Campos-Nonato, Ismael R.; Carvalho, Felix; Dinh-Toi Chu; Chung, Sheng-Chia; Cortesi, Paolo Angelo; Costa, Vera M.; Cowie, Benjamin C.; Daryani, Ahmad; de Courten, Barbora; Demoz, Gebre Teklemariam; Desai, Rupak; Dharmaratne, Samath Dhamminda; Djalalinia, Shirin; Hoa Thi Do; Dorostkar, Fariba; Drake, Thomas M.; Dubey, Manisha; Duncan, Bruce B.; Effiong, Andem; Eftekhari, Aziz; Elsharkawy, Aisha; Etemadi, Arash; Farahmand, Mohammad; Farzadfar, Farshad; Fernandes, Eduarda; Filip, Irina; Fischer, Florian; Gebremedhin, Ketema Bizuwork Bizuwork; Geta, Birhanu; Gilani, Syed Amir; Gill, Paramjit Singh; Alma Gutierrez, Reyna; Haile, Michael Tamene; Haj-Mirzaian, Arvin; Hamid, Saeed S.; Hasankhani, Milad; Hasanzadeh, Amir; Hashemian, Maryam; Hassen, Hamid Yimam; Hay, Simon I.; Hayat, Khezar; Heidari, Behnam; Henok, Andualem; Chi Linh Hoang; Hostiuc, Mihaela; Hostiuc, Sorin; Hsieh, Vivian Chia-rong; Igumbor, Ehimario U.; Ilesanmi, Olayinka Stephen; Irvani, Seyed Sina Naghibi; Balalami, Nader Jafari; James, Spencer L.; Jeemon, Panniyammakal; Jha, Ravi Prakash; Jonas, Jost B.; Jozwiak, Jacek Jerzy; Kabir, Ali; Kasaeian, Amir; Kassaye, Hagazi Gebremedhin; Kefale, Adane Teshome; Khan, Rovshan Khalilov Muhammad Ali; Khan, Ejaz Ahmad; Khater, Amir; Kim, Yun Jin; Koyanagi, Ai; La Vecchia, Carlo; Lim, Lee-Ling; Lopez, Alan D.; Lorkowski, Stefan; Lotufo, Paulo A.; Lozano, Rafael; Abd El Razek, Muhammed Magdy; Hue Thi Mai; Manafi, Navid; Manafi, Amir; Mansournia, Mohammad Ali; Mantovani, Lorenzo Giovanni; Mazzaglia, Giampiero; Mehta, Dhruv; Mendoza, Walter; Menezes, Ritesh G.; Mengesha, Melkamu Merid; Meretoja, Tuomo J.; Mestrovic, Tomislav; Miazgowski, Bartosz; Miller, Ted R.; Mirrakhimov, Erkin M.; Mithra, Prasanna; Moazen, Babak; Moghadaszadeh, Masoud; Mohammadian-Hafshejani, Abdollah; Mohammed, Shafiu; Mokdad, Ali H.; Montero-Zamora, Pablo A.; Moradi, Ghobad; Naimzada, Mukhammad David; Nayak, Vinod; Negoi, Ionut; Trang Huyen Nguyen; Ofori-Asenso, Richard; Oh, In-Hwan; Olagunju, Tinuke O.; Padubidri, Jagadish Rao; Pakshir, Keyvan; Pana, Adrian; Pathak, Mona; Pourshams, Akram; Rabiee, Navid; Radfar, Amir; Rafiei, Alireza; Ramezanzadeh, Kiana; Rana, Saleem Muhammad M.; Rawaf, Salman; Rawaf, David Laith; Reiner, Robert C.; Roever, Leonardo; Room, Robin; Roshandel, Gholamreza; Safari, Saeed; Samy, Abdallah M.; Sanabria, Juan; Sartorius, Benn; Schmidt, Maria Ines; Senthilkumaran, Subramanian; Shaikh, Masood Ali; Sharif, Mehdi; Sharifi, Amrollah; Shigematsu, Mika; Singh, Jasvinder A.; Soheili, Amin; Suleria, Hafiz Ansar Rasul; Teklehaimanot, Berhane Fseha; Tesfay, Berhe Etsay; Vacante, Marco; Vahedian-Azimi, Amir; Valdez, Pascual R.; Vasankari, Tommi Juhani; Giang Thu Vu; Waheed, Yasir; Weldegwergs, Kidu Gidey; Werdecker, Andrea; Westerman, Ronny; Wondafrash, Dawit Zewdu; Wondmieneh, Adam Belay; Yeshitila, Yordanos Gizachew; Yonemoto, Naohiro; Yu, Chuanhua; Zaidi, Zoubida; Zarghi, Afshin; Zelber-Sagi, Shira; Zewdie, Kaleab Alemayehu; Zhang, Zhi-Jiang; Zhao, Xiu-Ju; Naghavi, Mohsen; Malekzadeh, Reza (2020)
    Background Cirrhosis and other chronic liver diseases (collectively referred to as cirrhosis in this paper) are a major cause of morbidity and mortality globally, although the burden and underlying causes differ across locations and demographic groups. We report on results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 on the burden of cirrhosis and its trends since 1990, by cause, sex, and age, for 195 countries and territories. Methods We used data from vital registrations, vital registration samples, and verbal autopsies to estimate mortality. We modelled prevalence of total, compensated, and decompensated cirrhosis on the basis of hospital and claims data. Disability-adjusted life-years (DALYs) were calculated as the sum of years of life lost due to premature death and years lived with disability. Estimates are presented as numbers and age-standardised or age-specific rates per 100 000 population, with 95% uncertainty intervals (UIs). All estimates are presented for five causes of cirrhosis: hepatitis B, hepatitis C, alcohol-related liver disease, non-alcoholic steatohepatitis (NASH), and other causes. We compared mortality, prevalence, and DALY estimates with those expected according to the Socio-demographic Index (SDI) as a proxy for the development status of regions and countries. Findings In 2017, cirrhosis caused more than 1.32 million (95% UI 1.27-1.45) deaths (440000 [416 000-518 000; 33.3%] in females and 883 000 [838 000-967 000; 66.7%] in males) globally, compared with less than 899 000 (829 000-948 000) deaths in 1990. Deaths due to cirrhosis constituted 2.4% (2.3-2.6) of total deaths globally in 2017 compared with 1.9% (1.8-2.0) in 1990. Despite an increase in the number of deaths, the age-standardised death rate decreased from 21.0 (19.2-22.3) per 100 000 population in 1990 to 16.5 (15.8-18-1) per 100 000 population in 2017. Sub-Saharan Africa had the highest age-standardised death rate among GBD super-regions for all years of the study period (32.2 [25.8-38.6] deaths per 100 000 population in 2017), and the high-income super-region had the lowest (10.1 [9.8-10-5] deaths per 100 000 population in 2017). The age-standardised death rate decreased or remained constant from 1990 to 2017 in all GBD regions except eastern Europe and central Asia, where the age-standardised death rate increased, primarily due to increases in alcohol-related liver disease prevalence. At the national level, the age-standardised death rate of cirrhosis was lowest in Singapore in 2017 (3.7 [3.3-4.0] per 100 000 in 2017) and highest in Egypt in all years since 1990 (103.3 [64.4-133.4] per 100 000 in 2017). There were 10.6 million (10.3-10.9) prevalent cases of decompensated cirrhosis and 112 million (107-119) prevalent cases of compensated cirrhosis globally in 2017. There was a significant increase in age-standardised prevalence rate of decompensated cirrhosis between 1990 and 2017. Cirrhosis caused by NASH had a steady age-standardised death rate throughout the study period, whereas the other four causes showed declines in age-standardised death rate. The age-standardised prevalence of compensated and decompensated cirrhosis due to NASH increased more than for any other cause of cirrhosis (by 33.2% for compensated cirrhosis and 54.8% for decompensated cirrhosis) over the study period. From 1990 to 2017, the number of prevalent cases snore than doubled for compensated cirrhosis due to NASH and more than tripled for decompensated cirrhosis due to NASH. In 2017, age-standardised death and DALY rates were lower among countries and territories with higher SDI. Interpretation Cirrhosis imposes a substantial health burden on many countries and this burden has increased at the global level since 1990, partly due to population growth and ageing. Although the age-standardised death and DALY rates of cirrhosis decreased from 1990 to 2017, numbers of deaths and DALYs and the proportion of all global deaths due to cirrhosis increased. Despite the availability of effective interventions for the prevention and treatment of hepatitis B and C, they were still the main causes of cirrhosis burden worldwide, particularly in low-income countries. The impact of hepatitis B and C is expected to be attenuated and overtaken by that of NASH in the near future. Cost-effective interventions are required to continue the prevention and treatment of viral hepatitis, and to achieve early diagnosis and prevention of cirrhosis due to alcohol-related liver disease and NASH. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.
  • Hintikka, Jukka; Lensu, Sanna; Makinen, Elina; Karvinen, Sira; Honkanen, Marjaana; Linden, Jere; Garrels, Tim; Pekkala, Satu; Lahti, Leo (2021)
    We have shown that prebiotic xylo-oligosaccharides (XOS) increased beneficial gut microbiota (GM) and prevented high fat diet-induced hepatic steatosis, but the mechanisms associated with these effects are not clear. We studied whether XOS affects adipose tissue inflammation and insulin signaling, and whether the GM and fecal metabolome explain associated patterns. XOS was supplemented or not with high (HFD) or low (LFD) fat diet for 12 weeks in male Wistar rats (n = 10/group). Previously analyzed GM and fecal metabolites were biclustered to reduce data dimensionality and identify interpretable groups of co-occurring genera and metabolites. Based on our findings, biclustering provides a useful algorithmic method for capturing such joint signatures. On the HFD, XOS-supplemented rats showed lower number of adipose tissue crown-like structures, increased phosphorylation of AKT in liver and adipose tissue as well as lower expression of hepatic miRNAs. XOS-supplemented rats had more fecal glycine and less hypoxanthine, isovalerate, branched chain amino acids and aromatic amino acids. Several bacterial genera were associated with the metabolic signatures. In conclusion, the beneficial effects of XOS on hepatic steatosis involved decreased adipose tissue inflammation and likely improved insulin signaling, which were further associated with fecal metabolites and GM.