The sagittal abdominal diameter : Role in predicting severe liver disease in the general population

The role of the sagittal abdominal diameter (SAD) as a predictor of incident liver disease is unknown. 6626 individuals from the Finnish population-based Health 2000 Study were linked with national registers for liver-related admissions, mortality and cancer. SAD predicted incident liver disease (HR 1.32, 95% CI 1.06-1.65) when adjusted for age and sex, but the association was weaker than for waist-hip ratio (HR 1.86, 95% CI 1.35-2.55), waist circumference (HR 1.42, 95% CI 1.12-1.81), and waist-height ratio (HR 1.44, 95% CI 1.12-1.87); BMI was non-significant. In conclusion, SAD provided no additional benefit to other obesity measures in predicting incident severe liver disease. (C) 2018 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.Peer reviewe

Oral Health and Liver Disease: Bidirectional Associations—A Narrative Review

Several links between chronic liver disease and oral health have been described and are discussed in this narrative review. Oral manifestations such as lichen planus, ulcers, xerostomia, erosion and tongue abnormalities seem to be particularly prevalent among patients with chronic liver disease. These may be causal, coincidental, secondary to therapeutic interventions, or attributable to other factors commonly observed in liver disease patients. In addition, findings from both experimental and epidemiological studies suggest that periodontitis can induce liver injury and contribute to the progression of chronic liver disease through periodontitis-induced systemic inflammation, endotoxemia, and gut dysbiosis with increased intestinal translocation. This has brought forward the hypothesis of an oral-gut-liver axis. Preliminary clinical intervention studies indicate that local periodontal treatments may lead to beneficial liver effects, but more human studies are needed to clarify if treatment of periodontitis truly can halt or reverse progression of liver disease and improve liver-related outcomes

Oral Health and Liver Disease: Bidirectional Associations—A Narrative Review

Several links between chronic liver disease and oral health have been described and are discussed in this narrative review. Oral manifestations such as lichen planus, ulcers, xerostomia, erosion and tongue abnormalities seem to be particularly prevalent among patients with chronic liver disease. These may be causal, coincidental, secondary to therapeutic interventions, or attributable to other factors commonly observed in liver disease patients. In addition, findings from both experimental and epidemiological studies suggest that periodontitis can induce liver injury and contribute to the progression of chronic liver disease through periodontitis-induced systemic inflammation, endotoxemia, and gut dysbiosis with increased intestinal translocation. This has brought forward the hypothesis of an oral-gut-liver axis. Preliminary clinical intervention studies indicate that local periodontal treatments may lead to beneficial liver effects, but more human studies are needed to clarify if treatment of periodontitis truly can halt or reverse progression of liver disease and improve liver-related outcomes

From prolonging life to prolonging working life : Tackling unemployment among liver-transplant recipients

Return to active and productive life is a key goal of modern liver transplantation (LT). Despite marked improvements in quality of life and functional status, a substantial proportion of LT recipients are unable to resume gainful employment. Unemployment forms a threat to physical and psychosocial health, and impairs LT cost-utility through lost productivity. In studies published after year 2000, the average post-LT employment rate is 37%, ranging from 22% to 55% by study. Significant heterogeneity exists among studies. Nonetheless, these employment rates are lower than in the general population and kidney-transplant population. Most consistent employment predictors include pre-LT employment status, male gender, functional/health status, and subjective work ability. Work ability is impaired by physical fatigue and depression, but affected also by working conditions and society. Promotion of post-LT employment is hampered by a lack of interventional studies. Prevention of pre-LT disability by effective treatment of (minimal) hepatic encephalopathy, maintaining mobility, and planning work adjustments early in the course of chronic liver disease, as well as timely post-LT physical rehabilitation, continuous encouragement, self-efficacy improvements, and depression management are key elements of successful employment-promoting strategies. Prolonging LT recipients' working life would further strengthen the success of transplantation, and this is likely best achieved through multidisciplinary efforts ideally starting even before LT candidacy.Peer reviewe

Långtidsresultat efter levertransplantationer

With transplant rejection rendered a minor concern and survival rates after liver transplantation (LT) steadily improving, long-term complications are attracting more attention. Current immunosuppressive therapies, together with other factors, are accompanied by considerable long-term toxicity, which clinically manifests as renal dysfunction, high risk for cardiovascular disease, and cancer. This thesis investigates the incidence, causes, and risk factors for such renal dysfunction, cardiovascular risk, and cancer after LT. Long-term effects of LT are further addressed by surveying the quality of life and employment status of LT recipients. The consecutive patients included had undergone LT at Helsinki University Hospital from 1982 onwards. Data regarding renal function – creatinine and estimated glomerular filtration rate (GFR) – were recorded before and repeatedly after LT in 396 patients. The presence of hypertension, dyslipidemia, diabetes, impaired fasting glucose, and overweight/obesity before and 5 years after LT was determined among 77 patients transplanted for acute liver failure. The entire cohort of LT patients (540 patients), including both children and adults, was linked with the Finnish Cancer Registry, and numbers of cancers observed were compared to site-specific expected numbers based on national cancer incidence rates stratified by age, gender, and calendar time. Health-related quality of life (HRQoL), measured by the 15D instrument, and employment status were surveyed among all adult patients alive in 2007 (401 patients). The response rate was 89%. Posttransplant cardiovascular risk factor prevalence and HRQoL were compared with that in the age- and gender-matched Finnish general population. The cumulative risk for chronic kidney disease increased from 10% at 5 years to 16% at 10 years following LT. GFR up to 10 years after LT could be predicted by the GFR at 1 year. In patients transplanted for chronic liver disease, a moderate correlation of pretransplant GFR with later GFR was also evident, whereas in acute liver failure patients after LT, even severe pretransplant renal dysfunction often recovered. By 5 years after LT, 71% of acute liver failure patients were receiving antihypertensive medications, 61% were exhibiting dyslipidemia, 10% were diabetic, 32% were overweight, and 13% obese. Compared with the general population, only hypertension displayed a significantly elevated prevalence among patients – 2.7-fold – whereas patients exhibited 30% less dyslipidemia and 71% less impaired fasting glucose. The cumulative incidence of cancer was 5% at 5 years and 13% at 10. Compared with the general population, patients were subject to a 2.6-fold cancer risk, with non-melanoma skin cancer (standardized incidence ratio, SIR, 38.5) and non-Hodgkin lymphoma (SIR 13.9) being the predominant malignancies. Non-Hodgkin lymphoma was associated with male gender, young age, and the immediate posttransplant period, whereas old age and antibody induction therapy raised skin-cancer risk. HRQoL deviated clinically unimportantly from the values in the general population, but significant deficits among patients were evident in some physical domains. HRQoL did not seem to decrease with longer follow-up. Although 87% of patients reported improved working capacity, data on return to working life showed marked age-dependency: Among patients aged less than 40 at LT, 70 to 80% returned to work, among those aged 40 to 50, 55%, and among those above 50, 15% to 28%. The most common cause for unemployment was early retirement before LT. Those patients employed exhibited better HRQoL than those unemployed. In conclusion, although renal impairment, hypertension, and cancer are evidently common after LT and increase with time, patients’ quality of life remains comparable with that of the general population.Levertransplantationer inleddes i Finland år 1982, som första land i Norden. Idag har det gjorts 800 levertransplantationer i Finland, och 10-års levnadsprognosen ligger nu vid 80%. I takt med att resultaten hela tiden förbättrats och då akut rejektion pga effektiv medicinering inte längre är ett så stort problem, så har långtidsbieffekterna vuxit till en allt större utmaning. Dessa bieffekter anses delvis bero på den rejektionsförhindrande medicineringen som behövs livet ut. Denna avhandling utreder förekomsten av njursvikt, riskfaktorer för hjärt- och kärlsjukdomar, samt cancer efter levertransplantation. Dessutom utforskas patienternas livskvalitet och arbetsförmåga efter transplantation. Forskningen bestod av alla vuxna – i cancerprojektet även barn – som genomgått levertransplantation i Finland. Man fann att den kumulativa frekvensen av kronisk njursvikt steg från 10% vid 5 år till 16% vid 10 år efter transplantation. Njurfunktionen vid 1 år förutspådde funktionen vid 10 år. Njursvikt var frekvent redan innan transplantationen; svikten fortsatte ofta hos patienter med kronisk leversjukdom, emedan njurfunktionen återhämtade sig efter transplantationen hos många av de med akut leversjukdom. Frekvensen av riskfaktorer för hjärt- och kärlsjukdomar undersöktes hos de patienter som genomgått levertransplantation pga akut leversjukdom. Dessa patienter är ofta för övrigt friska från tidigare. Vid 5 år efter transplantation hade 71% medicineringskrävande blodtryckssjukdom, 61% dyslipidemi, 10% diabetes, 32% övervikt, och 13% obesitet. Endast blodtrycksjukdom förekom oftare hos patienter jämfört med den övriga Finska befolkningen: 2.7-gånger så ofta. Å andra sidan förekom dyslipidemi 30% mer sällan hos patienterna. Förekomsten av cancer klargjordes med hjälp av Finlands Cancerregister. Vid uppföljning upptäcktes 39 fall av cancer, vilket motsvarar en 2.6-gånger så stor cancer risk jämfört med den övriga befolkningen. På basis av studien uppskattas det att 1 av 6 patienter ligger i risk att insjukna i någon form av cancer inom 20 år från levertransplantationen. Riskförhållandena var högre hos barnpatienter. Tidpunkten då cancern upptäcktes varierade från 4 månader upp till 14 år efter transplantationen. De vanligaste cancertyperna var hudcancer av typ icke-melanom (riskfaktorer hög ålder och antikroppar som används mot rejektion) samt non-Hodgkins lymfom (riskfaktorer manligt kön, ung ålder, och tidsperioden nära transplantationen). Levertransplantations patienters livskvalitet skiljde sig inte från den övriga befolkningens på ett kliniskt betydelsefullt sätt. Tidpunkten efter transplantationen påverkade heller ej livskvaliteten. Patienterna rapporterade aningen lägre resultat i vissa fysiska dimensioner. 87% av patienterna ansåg att deras arbetsförmåga hade förbättrats i.o.m. transplantationen, men åldern påverkade märkbart förmågan att återvända till arbete: 70-80% av under 40-åringar återvände till arbete, 55% av 40-50-åringar, och under en tredjedel av över 50-åringar. Den vanligaste orsaken var förtidspensionering. Studien markerar betydelsen av uppföljning efter levertransplantation. Även om njursvikt, riskfaktorer för hjärt- och kärlsjukdomar, samt cancer förefaller relativt vanliga efter levertransplantation, så förblir patienternas livskvalitet på en nivå jämförbar med den övriga befolkningens.Maksansiirrot aloitettiin Suomessa vuonna 1982, ensimmäisenä maana Pohjoismaissa. 2009 loppuun mennessä on Suomessa tehty 800 maksansiirtoa. Tällä hetkellä kymmenen vuoden eloonjäämisennuste on lähes 80%. Kun tulokset ovat parantuneet ja kun äkillinen hylkiminen tehokkaan lääkityksen ansiosta ei ole enää ongelma on haasteeksi noussut altistuminen erilaisille pitkäaikaishaittavaikutuksille, osin pysyvän hyljinnänestolääkityksen vuoksi. Tässä väitöskirjassa selvitettiin munuaisten vajaatoiminnan, sydän- ja verisuonisairauksien riskitekijöiden, sekä syövän esiintymistä maksansiirron jälkeen. Lisäksi tutkittiin potilaiden elämänlaatua ja työkykyä maksansiirron jälkeen. Tutkimuksessa oli mukana Suomen aikuismaksansiirtopotilaat ja syöpätutkimuksessa myös lapsena siirretyt. Tutkimuksessa havaittiin että kroonisen munuaisten vajaatoiminnan kumulatiivinen esiintyvyys oli 10% 5 vuotta siirron jälkeen, ja nousi 16%:iin 10 vuoden kohdalla. Munuaistoiminta 1 vuoden kohdalla ennakoi toiminnan 10 vuoden kohdalla. Munuaisten vajaatoiminta oli tavallista myös jo ennen maksansiirtoa; kroonisen maksasairauden takia siirron saaneilla potilailla tämä vajaatoiminta usein jatkui siirron jälkeenkin, kun taas akuuttipotilailla vajaatoiminta korjaantui monella. Sydän- ja verisuonisairauksien riskitekijöiden esiintyvyys tutkittiin 5 vuotta siirron jälkeen äkillisen maksasairauden vuoksi maksansiirron saaneilla, jotka yleensä muuten ovat olleet terveitä aiemmin. Viisi vuotta maksansiirron jälkeen 71%:lla esiintyi lääkitystä vaativaa verenpainetautia, 61%:lla oli dyslipidemia, 10%:lla diabetestä, 32%:lla ylipainoa, ja 13%:lla obesiteettia. Verrattuna Suomen muuhun väestöön, vain verenpainetauti esiintyi merkitsevästi enemmän potilailla: 2.7-kertaisesti. Toisaalta potilailla oli muuhun väestöön nähden 30% vähemmän dyslipidemiaa. Suomen Syöpärekisterin avulla selvitettiin syöpien esiintyvyys. Seurannan aikana löytyi 39 syöpätapausta mikä tarkoittaa 2.6-kertaista suhteellista riskiä muuhun väestöön nähden. Tutkimuksemme tulosten perusteella arvioidaan yhden kuudesta potilaasta sairastuvan johonkin syöpään 20 vuoden kuluessa maksansiirrosta. Riskisuhteet olivat suuremmat lapsena maksansiirron saaneilla potilailla. Syöpien ilmaantumisajankohta siirron jälkeen vaihteli neljästä kuukaudesta 14 vuoteen. Tavallisimmat syövät olivat non-melanooma ihosyövät (riskitekijöitä korkea ikä ja hyljinnän estoon käytetyt vasta-aineet) sekä non-Hodgkin lymfoomat (riskitekijöitä miessukupuoli, nuori ikä sekä ajanjakso pian maksansiirron jälkeen). Maksansiirtopotilaiden elämänlaatu seuranta-ajasta riippumatta ei eronnut kliinisesti merkittävästi Suomen muuhun väestöön nähden. Potilaat raportoivat hiukan huonompaa elämänlaatua lähinnä joissakin fyysisissä dimensioissa. 87% potilaista raportoi työkyvyn parantuneen maksansiirron myötä mutta ikä vaikutti huomattavasti siihen palasiko potilas töihin: alle 40-vuotiaista 70-80% palasi töihin, 40-50 vuotiaista 55%, ja yli 50-vuotiaista alle kolmasosa. Tärkein työttömyyden syy oli varhaiseläke. Tutkimus osoittaa maksansiirron jälkeisen seurannan tärkeyden. Vaikka munuaisten vajaatoiminta, syöpä, sekä sydän- ja verisuoniriskitekijät ovat suhteellisen tavallisia maksansiirron jälkeen, niin potilaiden elämänlaatu säilyy vastaavanlaisena kuin muussa väestössä

Interaction Between Alcohol Use and Metabolic Risk Factors for Liver Disease : A Critical Review of Epidemiological Studies

Coexistence of alcohol use and metabolic risk-the 2 commonest population risk factors for nonviral chronic liver disease-is a growing concern. Clinical evidence and mechanistic evidence point to considerable supraadditive interaction effects for the development and progression of chronic liver disease between hazardous alcohol use and metabolic abnormalities including obesity, diabetes, and the metabolic syndrome (MetS). Intermittent binge drinking once monthly or more often seems to be associated with progression of liver disease even when average alcohol intake is within the currently allowed limits for a diagnosis of nonalcoholic fatty liver disease (NAFLD), and supraadditive interaction between binge drinking and the MetS has been reported. There are contradictory findings regarding the association between low alcohol use and liver steatosis, but, clearly, the mechanisms of alcoholic hepatotoxicity extend beyond simple fat accumulation. The presence of liver steatosis seems to amplify alcoholic hepatotoxicity. Recent longitudinal studies of NAFLD subjects report low alcohol use associated with both increased fibrosis progression and an elevated risk for liver cancer and severe liver disease. There is no clear safe limit of alcohol intake in the presence of NAFLD or metabolic risk. The interaction effects between alcohol and metabolic dysfunction merit increased attention in public health policy, individual counseling, and risk stratification. Based on current evidence, a strict dichotomization of liver disease into either pure alcoholic or nonalcoholic may be inappropriate.Peer reviewe

Changes over time in the Chronic Liver Disease risk score predict liver-related outcomes: longitudinal analysis of the Whitehall II study

BACKGROUND AND AIMS: The Chronic Liver Disease (CLivD) risk score was recently shown to predict future advanced liver disease in the general population. We here investigated the impact of individual CLivD-score changes over time. METHODS: Participants of both phase 3 (baseline, 1991-1994) and phase 5 (follow-up, 1997-1999) examinations of the Whitehall II study were followed for liver-related outcomes (hospitalization, cancer, death) until December 2019 through linkage with electronic healthcare registers. The CLivD score, its modifiable components (alcohol use, waist-hip ratio [WHR], diabetes, and smoking), and their individual changes were studied. RESULTS: Among 6590 adults (mean age 50 years, 30% women) with a median 21-year follow-up, there were 80 liver outcomes. A rise in the CLivD score between baseline and follow-up examinations significantly increased the risk for liver-related outcomes (adjusted hazard ratio [aHR] 1.62, 95% confidence interval [CI] 1.01-2.60), more so in subjects with baseline intermediate-high CLivD scores (HR 2.4 for a CLivD-change) compared to minimal-low CLivD scores. Adverse changes over time in alcohol use and WHR, and new-onset diabetes also predicted liver outcomes. In contrast to WHR, changes in body weight (kg) showed a U-shaped association with liver outcomes. CONCLUSIONS: A change in the CLivD score over time corresponds to a true change in the risk for liver-related outcomes, suggesting the usefulness of the CLivD score for assessing response to liver-directed lifestyle interventions. Changes in WHR predicted liver outcomes better than changes in body weight or waist circumference, independent of body mass index, supporting the WHR in assessing risk for future liver disease

Using visual lateralization to model learning and memory in zebrafish larvae.

Impaired learning and memory are common symptoms of neurodegenerative and neuropsychiatric diseases. Present, there are several behavioural test employed to assess cognitive functions in animal models, including the frequently used novel object recognition (NOR) test. However, although atypical functional brain lateralization has been associated with neuropsychiatric conditions, spanning from schizophrenia to autism, few animal models are available to study this phenomenon in learning and memory deficits. Here we present a visual lateralization NOR model (VLNOR) in zebrafish larvae as an assay that combines brain lateralization and NOR. In zebrafish larvae, learning and memory are generally assessed by habituation, sensitization, or conditioning paradigms, which are all representatives of nondeclarative memory. The VLNOR is the first model for zebrafish larvae that studies a memory similar to the declarative memory described for mammals. We demonstrate that VLNOR can be used to study memory formation, storage, and recall of novel objects, both short and long term, in 10-day-old zebrafish. Furthermore we show that the VLNOR model can be used to study chemical modulation of memory formation and maintenance using dizocilpine (MK-801), a frequently used non-competitive antagonist of the NMDA receptor, used to test putative antipsychotics in animal models

Letter to the Editor : Moderate Alcohol Use in Fatty Liver Disease: Don't Throw the Cabernet Out With the Bathwater REPLY

Non peer reviewe

Maksasairaan potilaan kipulääkitys

Vertaisarvioitu. English summaryKipulääkityksen valinta maksasairauden yhteydessä on vaativaa. Moni kipulääke metaboloituu maksan kautta ja saattaa aiheuttaa merkittäviä haittavaikutuksia. Jos potilaalla ei kuitenkaan ole akuuttia maksavauriota ja maksasairaus on kompensaatiossa, voidaan valtaosaa kipulääkkeistä käyttää ainakin lyhytaikaisesti. Parasetamolin käyttöä varotaan monesti turhaan, sillä sen käyttö pienennettyinä annoksina on yleensä turvallista, mikäli maksasairaus ei ole merkittävää eikä potilas käytä liikaa alkoholia tai kärsi aliravitsemuksesta. Sen sijaan tulehduskipulääkkeitä tulisi välttää muun muassa munuaisvaurion uhan ja verenvuotoriskin takia. Myös opioideja tulisi välttää tai käyttää pieninä annoksina harvoin annosvälein enkefalopatiariskin takia. Neuropaattisen kivun hyviä hoitovaihtoehtoja ovat trisykliset masennuslääkkeet, pregabaliini ja gabapentiini