The most severe manifestations of alcoholic liver disease (ALD) are alcoholic liver cirrhosis and alcoholic hepatitis (AH). The purpose of this study was to examine incidence, risk factors, prognosis and malignant comorbidities of ALD in a cohort of patients with alcoholic liver cirrhosis (n=7746) and AH (n=4127) as an inpatient diagnosis during years 1996-2012 identified from the national Hospital Discharge Registry and followed until death or incidence of cancer (41209 person-years). There was increase in incidence of alcoholic liver cirrhosis (by 66% among men and 75% among women) and AH (by 76% among men and 108% among women) during the study period. Survival of the patients was poor, 5-year relative survival rates for male and female alcoholic liver cirrhosis patients being 0.28 (95%CI 0.27-0.30) and 0.39 (95%CI 0.36-0.41), and for all patients with AH 0.46 (95%CI: 0.44-0.48) without difference between sexes. Majority of the patients died from alcohol-related causes. Risk for mortality from several other causes was increased: cancers (standardised mortality ratio [SMR] 6.82; 95%CI 6.35-7.29), digestive diseases (SMR 27.95; 95%CI 24.78–31.31), respiratory diseases (SMR 7.86; 95%CI 6.70–9.10) and circulatory diseases (SMR 6.13; 95%CI 5.74–6.52). The risk of accidental or violent death was increased (11.12; 95%CI 10.13-12.15), as well. Standardised cancer incidence among patients with advanced ALD was 2.86 (95%CI 2.69-3.03) There was increased risk for cancer of liver (SIR 59.20; 95%CI 53.11–65.61) pancreas (SIR 3.71; 95%CI 2.72-24.94), pharynx (SIR 9.25; 95%CI 6.05–13.56), mouth (SIR 8.31; 95%CI 4.84–13,29), tongue (SIR 7,21; 95%CI 3.60–12.89), oesophagus (SIR 7.92; 95%CI 5.49–11.07), larynx (SIR 5.20; 95%CI 2.77–8.89), lung (SIR 2.77; 95%CI 2.27– 3.32), stomach (SIR 2.76; 95%CI 1.79–4.07), kidney (SIR 2.69; 95 CI 1.84–3.79), colon (SIR 2.33; 95%CI 1.70–3.11), cervix uteri (SIR 4.93; 95%CI 1.34–12.63) and non-melanoma skin cancer (SIR 1.89; 95%CI 1.18–2.86) . Alterations in cholesterol metabolism in severe AH were studied among 24 hospitalised patients with severe AH treated with prednisolone and randomised to get either prednisolone alone or in combination with ciprofloxacin to identify potential prognostic factors to predict response to corticosteroid therapy at baseline. AH patients had a distinct profile of sterol metabolism compared to patients with primary sclerosing cholangitis and healthy individuals. Certain non-cholesterol sterols (i.e. plant sterols) putatively reflecting the nutritional status of the patients were related to response to corticosteroids. High serum level of ferritin at baseline predicted poor response to corticosteroid therapy. Potential risk factors besides alcohol for advanced liver disease were studied in a cohort of 41260 individuals comprised of persons participating Health2000 or FINRISK studies 1992-2012 without an underlying liver disease. Age, PNPLA3 haplotype and WHR increased the risk for advanced liver disease. There is synergism between alcohol intake and central obesity to the risk. Binge drinking poses an additional risk factor.
|Tila||Julkaistu - 2019|
|OKM-julkaisutyyppi||G5 Tohtorinväitöskirja (artikkeli)|
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