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  • 1. Baumeister, Sebastian E.
    et al.
    Schlesinger, Sabrina
    Aleksandrova, Krasimira
    Jochem, Carmen
    Jenab, Mazda
    Gunter, Marc J.
    Overvad, Kim
    Tjonneland, Anne
    Boutron-Ruault, Marie-Christine
    Carbonnel, Franck
    Fournier, Agnes
    Kuehn, Tilman
    Kaaks, Rudolf
    Pischon, Tobias
    Boeing, Heiner
    Trichopoulou, Antonia
    Bamia, Christina
    La Vecchia, Carlo
    Masala, Giovanna
    Panico, Salvatore
    Fasanelli, Francesca
    Tumino, Rosario
    Grioni, Sara
    de Mesquita, Bas Bueno
    Vermeulen, Roel
    May, Anne M.
    Borch, Kristin B.
    Oyeyemi, Sunday O.
    Ardanaz, Eva
    Rodriguez-Barranco, Miguel
    Chirlaque Lopez, Maria Dolores
    Felez-Nobrega, Mireia
    Sonestedt, Emily
    Ohlsson, Bodil
    Hemmingsson, Oskar
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Kirurgi.
    Werner, Mårten
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Perez-Cornago, Aurora
    Ferrari, Pietro
    Stepien, Magdalena
    Freisling, Heinz
    Tsilidis, Konstantinos K.
    Ward, Heather
    Riboli, Elio
    Weiderpass, Elisabete
    Leitzmann, Michael F.
    Association between physical activity and risk of hepatobiliary cancers: A multinational cohort study2019Ingår i: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 70, nr 5, s. 885-892Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background & Aims: To date, evidence on the association between physical activity and risk of hepatobiliary cancers has been inconclusive. We examined this association in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC).

    Methods: We identified 275 hepatocellular carcinoma (HCC) cases, 93 intrahepatic bile duct cancers (IHBCs), and 164 non-gallbladder extrahepatic bile duct cancers (NGBCs) among 467,336 EPIC participants (median follow-up 14.9 years). We estimated cause-specific hazard ratios (HRs) for total physical activity and vigorous physical activity and performed mediation analysis and secondary analyses to assess robustness to confounding (e.g. due to hepatitis virus infection).

    Results: In the EPIC cohort, the multivariable-adjusted HR of HCC was 0.55 (95% CI 0.38–0.80) comparing active and inactive individuals. Regarding vigorous physical activity, for those reporting >2 hours/week compared to those with no vigorous activity, the HR for HCC was 0.50 (95% CI 0.33–0.76). Estimates were similar in sensitivity analyses for confounding. Total and vigorous physical activity were unrelated to IHBC and NGBC. In mediation analysis, waist circumference explained about 40% and body mass index 30% of the overall association of total physical activity and HCC.

    Conclusions: These findings suggest an inverse association between physical activity and risk of HCC, which is potentially mediated by obesity.

    Lay summary: In a pan-European study of 467,336 men and women, we found that physical activity is associated with a reduced risk of developing liver cancers over the next decade. This risk was independent of other liver cancer risk factors, and did not vary by age, gender, smoking status, body weight, and alcohol consumption.

  • 2. Bureau, Christophe
    et al.
    Adebayo, Danielle
    Chalret de Rieu, Mael
    Elkrief, Laure
    Valla, Dominique
    Peck-Radosavljevic, Markus
    McCune, Anne
    Vargas, Victor
    Simon-Talero, Macarena
    Cordoba, Juan
    Angeli, Paolo
    Rosi, Silvia
    MacDonald, Stewart
    Malago, Massimo
    Stepanova, Maria
    Younossi, Zobair M
    Trepte, Claudia
    Watson, Randall
    Borisenko, Oleg
    Sun, Sun
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa. Synergus AB, Danderyd, Sweden; Health Outcomes and Economic Evaluation Research Group, Department of Learning, Information, Management and Ethics, Karolinska Institutet, Stockholm, Sweden.
    Inhaber, Neil
    Jalan, Rajiv
    Alfapump® system vs. large volume paracentesis for refractory ascites: a multicenter randomized controlled study2017Ingår i: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 67, nr 5, s. 940-949Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and aims: Patients with refractory ascites (RA) require repeated large volume paracenteses (LVP), which involves frequent hospital visits and is associated with a poor quality-of-life. This study assessed safety and efficacy of an automated, low-flow pump (alfapump® [AP]) compared with LVP standard of care [SoC].

    Methods: A randomized controlled trial, in seven centers, with six month patient observation was conducted. Primary outcome was time to first LVP. Secondary outcomes included paracentesis requirement, safety, health-related quality-of-life (HRQoL), and survival. Nutrition, hemodynamics, and renal injury biomarkers were assessed in a sub-study at three months.

    Results: Sixty patients were randomized and 58 were analyzed (27 AP, 31 SoC, mean age 61.9years, mean MELD 11.7). Eighteen patients were included in the sub-study. Compared with SoC, median time to first LVP was not reached after six months in the AP group, meaning a significant reduction in LVP requirement for the AP patients (AP, median not reached; SoC, 15.0days (HR 0.13; 95%CI 13.0-22.0; p<0.001), and AP patients also showed significantly improved Chronic Liver Disease Questionnaire (CLDQ) scores compared with SoC patients (p<0.05 between treatment arms). Improvements in nutritional parameters were observed for hand-grip strength (p=0.044) and body mass index (p<0.001) in the sub-study. Compared with SoC, more AP patients reported adverse events (AEs; 96.3% vs. 77.4%, p=0.057) and serious AEs (85.2 vs. 45.2%, p=0.002). AEs consisted predominantly of acute kidney injury in the immediate post-operative period, and re-intervention for pump related issues, and were treatable in most cases. Survival was similar in AP and SoC.

    Conclusions: The AP system is effective for reducing the need for paracentesis and improving quality of life in cirrhotic patients with RA. Although the frequency of SAEs (and by inference hospitalizations) was significantly higher in the AP group, they were generally limited and did not impact survival.

    Lay summary: The alfapump® moves abdominal fluid into the bladder from where it is then removed by urination. Compared with standard treatment, the alfapump reduces the need for large volume paracentesis (manual fluid removal by needle) in patients with medically untreatable ascites. This can improve life quality for these patients.

  • 3. Coelho, T
    et al.
    Maia, L
    Martins da Silva, A
    Waddington Cruz, M
    Plante-Bordeneuve, V
    Suhr, Ole B
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Conceicao, I
    Schmidt, H
    Trigo, P
    Packman, J
    Harnett, M
    Grogan, DR
    Long-term effects of tafamidis: a new therapeutic option for patients with transthyretin familial amyloid polyneuropathy (ttr-fap)2012Ingår i: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 56, nr Suppl 2, s. S543-S543Artikel i tidskrift (Övrigt vetenskapligt)
  • 4.
    Danielsson Borssen, Åsa
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Lindgren, S
    Bergquist, A
    Almer, S
    Sangfelt, P
    Werner, Mårten
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Risk for hepatocellular carcinoma in autoimmune hepatitis: is there an indication for surveillance?2013Ingår i: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 58, nr Suppl. 1, s. S382-S383Artikel i tidskrift (Refereegranskat)
  • 5. Hindorf, Ulf
    et al.
    Jahed, Khatoon
    Bergquist, Annika
    Verbaan, Hans
    Prytz, Hanne
    Wallerstedt, Sven
    Werner, Mårten
    Umeå universitet, Medicinsk fakultet, Folkhälsa och klinisk medicin, Medicin.
    Olsson, Rolf
    Björnsson, Einar
    Peterson, Curt
    Almer, Sven H C
    Characterisation and utility of thiopurine methyltransferase and thiopurine metabolite measurements in autoimmune hepatitis.2010Ingår i: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 52, nr 1, s. 106-111Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND & AIMS: Corticosteroids alone or in conjunction with azathioprine (AZA) is the standard treatment in autoimmune hepatitis (AiH). Individual variations in thiopurine (TP) metabolism may affect both drug efficacy and toxicity. Our aim was to investigate the utility of thiopurine methyltransferase (TPMT) as well as thioguanine nucleotide (TGN) and methylthioinosine monophosphate (meTIMP) metabolite measurements with regard to clinical outcome. METHODS: Two hundred thirty-eight patients with AiH were included in this cross-sectional study. TPMT status was assessed in all patients, while TGN and meTIMP were measured in patients with ongoing TP medication. Clinical outcome was evaluated by liver tests and the ability to withdraw steroids. RESULTS: TPMT genotyping (n=229) revealed 207 (90.4%) wild-type and 22 heterozygous patients. One hundred forty-three patients had ongoing TP therapy with AZA (n=134) or mercaptopurine (MP; n=9); response was judged as complete response (CR) in 113 patients and partial response (PR) in 30 patients. Both TP dose (1.64 vs 1.19mg/kg; p=0.012) and TPMT activity (14.3 vs 13.5; p=0.05) were higher in PR, resulting in similar TGN levels (PR: 121pmol/8x10(8) red blood cells [RBC]; CR: 113pmol/8x10(8) RBC; p=0.33) but higher meTIMP levels in PR (1350 vs 400pmol/8x10(8) RBC; p=0.004). Patients able to withdraw steroids or who were using 5mg prednisolone daily were treated with lower TP doses than patients on higher steroid doses (1.15 vs 1.18 vs 1.82mg/kg; p<0.001). CONCLUSIONS: TP metabolite measurements are of clinical value in AiH patients who do not respond to standard TP treatment and for the identification of a shifted metabolism, which may demand an alternative treatment strategy.

  • 6. Nystrom, K.
    et al.
    Pettersson, G.
    Wanrooij, Paulina
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Brunet, S.
    Said, J.
    Ortolani, G.
    Waldenstrom, J.
    Adamek, L.
    Tang, K. -W
    Norberg, P.
    Chabes, Andrei
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk kemi och biofysik.
    Hellstrand, K.
    Norder, H.
    Lagging, M.
    Inosine triphosphate pyrophosphatase enhances the effect of ribavirin on hepatitis C virus cell culture infection2017Ingår i: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 66, nr 1, s. S321-S321Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Genetic variants of the inosine triphosphate pyrophosphatase gene (ITPA), resulting in decreased enzymatic activity of the corresponding enzyme, ITPase, are known to correlate with a decreased risk of ribavirin-induced anemia, but are also associated with an increased SVR in patients treated with peginterferon-alpha and ribavirin. As both ITPase and ribavirin are involved in the nucleotide salvage pathway and reduced risk of relapse after treatment of hepatitis C, we have investigated the effect of ITPase activity and ribavirin treatment of HCVcc infection of hepatocytes

  • 7. Pourbasheer, E
    et al.
    Shahmohammadi, Mahdi Aghbolagh
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Aalizadeh, R
    Investigation of residuals responsible for binding of triazolo-pyrimidine inhibitors with HBsAg based on molecular docking and pharmacophore methods for designing potent HBsAg inhibitors2015Ingår i: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 62, s. S570-S570Artikel i tidskrift (Övrigt vetenskapligt)
  • 8.
    Shahmohammadi Aghbolagh, Mahdi
    et al.
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Kemiska institutionen.
    Pourbasheer, E
    Aalizadeh, R
    Interactions study of HCV NSB5 polymerase inhibitors with NSB5 non-structured proteins toward better design of new inhibitors based on molecular docking and pharmacophore methods2015Ingår i: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 62, s. S687-S687Artikel i tidskrift (Övrigt vetenskapligt)
  • 9.
    Werner, Mårten
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Almer, Sven
    Prytz, Hanne
    Lindgren, Stefan
    Wallerstedt, Sven
    Björnsson, Einar
    Bergquist, Annika
    Sandberg-Gertzén, Hanna
    Hultcrantz, Rolf
    Sangfelt, Per
    Weiland, Ola
    Danielsson, Åke
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Hepatic and extrahepatic malignancies in autoimmune hepatitis: A long-term follow-up in 473 Swedish patients2009Ingår i: Journal of Hepatology, ISSN 0168-8278, E-ISSN 1600-0641, Vol. 50, nr 2, s. 388-393Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND/AIMS: Autoimmune Hepatitis (AIH) is a liver disease which may lead to liver cirrhosis. Cirrhosis is a well-known risk factor for hepatocellular cancer. Lymphoma is a disease, where immune modulating drugs as well as the autoimmune disease itself may contribute to the elevated risk. The aim was to investigate the risks of malignancies in a large cohort of AIH patients. METHODS: Four hundred and seventy-three patients with AIH were matched to the Swedish national cancer register as well as to the death cause register. RESULTS: We found an overall higher risk of malignancies in the cohort of AIH patients from the date of diagnosis with a SIR of 1.51 (95% CI 1.10-2.03). SIR in the subpopulation of well defined catchment areas and complete case finding was 23.28 (95% CI 7.5-54.34) for HCC. Lymphomas were found a SIR of 13.09 (95% CI 4.22-30.56). CONCLUSIONS: There was an overall increased risk of malignancies in a cohort of AIH patients, which manly was caused by hepatobiliary cancers. However, the true risk of HCC in an AIH cirrhotic cohort has yet to be investigated. A significantly higher risk of lymphomas was also found, but no clear cut association to the use of immune modulators.

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