3/6/2019

1. 3/6/2019 To Keep our liver healthy, beyond prevention of ViralHepatitis Dr TAI Ling-fung Specialist in Gastroenterology and Hepatology Associate Consultant, Pamela Youde Nethersole EasternHospital 4 JUNE 2019 Liverhealth Common Causes of liverdisease Spectrum of liverdisease • Viralhepatitis • Non-alcoholic liver disease (NAFLD) • Alcoholic liver disease(ALD) • Autoimmune liverdiseases • Copper/ Ironoverload • Simple Hepatic steatosis (“Fatty liver”) • Hepatitis (acute/chronic) • Liver fibrosis • Liver cirrhosis • Hepatocellular carcinoma (HCC) Fattyliver NAFLD:complications Non-alcoholic fattyliver (NAFL) Non-alcoholic Steatohepatitis (NASH) ClinMed2006;6:19–25 TreatmentofNAFLD:Dietandphysicalexercise Journal of Hepatology 2017 vol. 67,829–846 • Slide on diet infographic:JHEPAT Treatment received and patient survival:similar

2. 3/6/2019 AnimalmodelforNAFLD:foiegras Force-feedwithwhat?Notwithfat “Apicius made the discovery, that we may employ the same artificial method of increasing the size of the liver of the sow, as of that of thegoose; .... ....it consists in cramming them with dried figs, and when they are fat enough, they are drenched with wine mixed with honey, and immediatelykilled.” — Pliny the Elder, Natural History, BookVIII. (~1st centuryAD) NAFLDvs. ALD NAFLD ALD AlcoholicliverdiseaseALD 酒精性肝病 • NAFL • NASH • NASHcirrhosis • HCC • AFL (Alcoholic fattyliver) • AH/ ASH (Alcoholichepatitis) • Alcoholiccirrhosis • HCC • Male≈female • Overwhelminglymale • Asymptomatic elevation of liver enzymes • Tends to present late withcomplications; • canpresentacutelywithAH • ALD is 2 diseases: “AUD + liverdisease” • “Cirrhosis”carriesthestigmaofan alcoholic in theWest DiseasespectrumofALD Am J Gastroenterol2018 Themostimportanttreatment forallformsofALD: Abstinence

3. 3/6/2019 • It’s not easy to convince patients to quit drinking….untiltheyexperiencedhematemesis! • Varicealbleeding • Mallory-WeissTear • Very often patients do not appreciate the severity of their disease, until it’s toolate Whydopeopledrink? 1. Theydon’tappreciatetheharmofalcoholuse 2. Theyerroneouslythinkalcoholisbeneficialtohealth 3. Psychological/ socio-culturalreasons • Caloric density of: • Fats 8.8kcal/g • Ethanol 7kcal/g • Proteins 4kcal/g • Carbohydrate 4kcal/g • Remember alcohol is simply fermented sugar/starch • Pure Alcohol is nearly equivalent to pure fat in caloricdensity • Food conversion: 1 glass of wine = 1ice-cream! • Fatty liver can develop within 2-3 weeks of excessivedrinking! • Alcohol-derivedcalories areproducedattheexpenseofthemetabolismof normal nutrients since alcohol will be oxidized preferentially over other nutrients Alcohol isextra-fattening! • Liver: ALD,HCC • Brain: cerebellar degeneration, dementia, stroke, Wernicke- Korsakoff syndrome (via thiaminedeficiency) • Heart: Hypertension, Atrial fibrillation,Cardiomyopathy • Nerves: toxic neuropathy,falls • Pancreas (Acute and Chronic) • Fertility: Subfertility, erectiledysfunction • Psychiatric: depression,anxiety • Aldehyde, a metabolite of ethanol, is a group 1 carcinogen(IARC) • The carcinogenic effect is dose- dependent • There is no “safe-limit” for alcohol consumption Alcoholistoxictomultipleorgans, notjusttheliver! Alcohol is agroup 1 carcinogen!

4. 3/6/2019 https://www.cancerresearchuk.org/ https://www.cancerresearchuk.org/ A bottleofwinehasthecancer-causingpotentialof 5to10Cigarettes Hydes et al. BMC Public Health (2019)19:316 Summary:theharmofdrinkingjustonedrinkperdayonhealth From: “Drink or not Drink? Be Informed If You Drink”booklet Data Source: Adopted from Communicating Alcohol-Related Health Risks: Canada’s Low Risk Alcohol DrinkingGuidelines Alcohol-attributable fractions(AAFs) for selected causes of death, disease and injury,2012 WHO Global status report on alcohol and health –2014 Alcoholkillnotjustbycausingdisease (list notexhaustive)

5. 3/6/2019 • Harmful use of alcohol is responsible for: • 3.3 million deaths every year Worldwide (= 6 deaths everyminute) • alcohol isacausalfactorinmorethan200 disease and injuryconditions • Alcohol consumption causes death and disability relatively early inlife • In the age group 20 – 39 years, ~25 % of the total deaths arealcohol-attributable • WHO Global status report on alcohol and health –2014 • Standardized mortality per 100 000 person-years.Men. • Three Scandinavian countries whereAUD is prevalent • Lifeexpectancywas24–28yearsshorterinpeoplewithalcoholusedisorder thaninthegeneralpopulation • Peoplewithalcoholusedisorderhadhighermortalityfrom • allcausesofdeath(mortalityrateratio,3.0–5.2) • alldiseasesandmedicalconditions(2.3–4.8) • suicide(9.3–35.9) Women are more susceptible to the toxic effects of alcohol compared with men after ingestion of the same amount ofalcohol ……because of humanphysiology Heavy alcohol consumption reduceslifeexpectancyby24–28years! Womenareharmedmorebyalcoholthanmen, gram forgram • Female breast cancer • More easily drunk; more vulnerable to sexcrimes • Subfertility • Fetal alcohol spectrum disorder (FASD)/ Fetal alcohol Syndrome(FAS) Womenfacegender-specificrisks posedbyharmfulalcoholuse • Gastric "first-pass metabolism" ofethanol • Asubstantialfractionoforallyadministeredethanoldidnotentertheportalorsystemic circulationbutwasoxidizedmainlybygastricmucosalalcoholdehydrogenase(ADH) • First-pass in men >women • First-passdecreasewithlong-termethanolconsumption • Volumeofdistributionofethanol • alcoholdisperses inbodywater • poundforpound,womenhavelesswaterintheirbodiesthanmendo • onaverage,womenweighlessthanmen • Thus Vd Women < VdMen FREZZA et al. NEJM 1990

6. 3/6/2019 https://www.cancerresearchuk.org/ • FetalAlcoholSyndrome(FAS) • Facialdysmorphism • short palpebralfissures • thin vermillionborder • smoothphiltrum • Growthretardation • Microcephaly • Structural brainanomaly • Recurrent nonfebrileseizures • Developmental, learning,and • cognitive problems, including schoolfailure • Behavioral problems(e.g., • hyperactivity, impaired executive functioningskills) • Social-emotionalproblems • Summary:Theharmofalcohol • Alcohol isextra-fattening • Alcohol is toxic to multipleorgans • Alcohol iscarcinogenic • Alcohol decreases yourlife-expectancy • Alcohol is a cause of accident/ violence/ mortality, especially in theyoung • Femalesaremoresusceptibletotheharmofalcoholthan males Whydopeopledrink? 1. Theydon’tappreciatetheharmofalcoholuse 2. Theyerroneouslythinkalcoholisbeneficialtohealth 3. Psychological/ socio-culturalreasons “Medicinalalcohol”? • TopicalDisinfectant • Kills germs • Percutaneous Ethanol Injection (100% alcohol) forHCC • Kills cancercells • Antidote for Ethylene Glycol (anti-freeze) poisoning when Fomepizole is notavailable • “以毒攻毒” Legitimatemedicinalusesofethanolareconcerned withthecontrolleddestructionoflife.

7. 3/6/2019 • J. Stud. Alcohol Drugs, 77, 185–198,2016 • FundedbyU.S.NationalInstitutesofHealth (NIH) • Meta-analysisofstudiesonall-causemortalityinmoderatedrinkersupto2/2015 • 87studiesanalyzed,involvingapopulationof3,998,626individuals • Definition:Low-volumedrinkers (1.3–24.9g ethanolperday);occasionaldrinkers(<1.3 gperday) • Commonmethodologicalflawsaddressed: • Drinker misclassification error (“Abstainerbias”) • Former drinkers grouped with life-time abstainers under“abstainers” • Studylevelvariables/confoundingfactors • E.g. Length of follow-up, median age, smoking status, ethnicityetc. Thecontroversialviewofhealthbenefitsfromalcohol waspromulgatedbytheinconvenient“truth”of theJ-Curveofmoderatealcoholdrinking inoldstudies • Previous meta-analysesof many large- • scaleprospectivecohortstudies • indicated a J-shaped relationship betweenalcoholconsumptionandall- • causemortality,withreducedriskfor low-volumedrinkers. • Similarfindingswereevidentfrom • studiesonrelationshipbetween alcohol consumption and cardiovascularrisks. Itappearedthatdrinkingalittle protectedyourheartandletyoulive longer(?) All-cause mortality relative-risk estimates for low-volumealcoholconsumersvslifetimeabstainers J. Stud. Alcohol Drugs, 77, 185–198,2016 All-causemortalityrelativeriskforlow-volumedrinkersvs lifetimeabstainersaftercontrollingfordesigncharacteristics bystudyselectioninadjustedmodels J. Stud. Alcohol Drugs, 77, 185–198,2016 • Results: • J-shaped curve replicated when only limited controls forstudy • characteristics were used (i.e., showing low-volume drinkers with reduced mortality risk and high-volume drinkers with increased mortalityrisk) • Evidence for reduced mortality risk among low-volume drinkerslargely • disappeared once design and methodological issues were controlled for directly in the analysis or by studyselection • Low-volume alcohol consumption has no netmortality benefit compared with lifetime abstention or occasionaldrinking • In summary: • our study suggests that a skeptical position is warranted in relation tothe • evidence that low-volume consumption is associated with net health benefits • J. Stud. Alcohol Drugs, 77, 185–198,2016 “Drinkingalittle”: beneficialornot? Verdict:Controversial! Highqualityevidencewithconfoundingaddressedsays: NObenefitofmoderatedrinkingonall-causemortalityandCV risks Doesitevenmakesensetodrinkacarcinogeneven ifithasdubiousbenefits?

8. 3/6/2019 • J.Stud. Alcohol Drugs, 73, 80–88,2012 • Whetherwineconsumptionmayprovidebenefitstolongevitybeyondthoseattributable toethanolperseremainsanopenquestion • Preference forwineconsumption,comparedwithpreferenceforotheralcoholic • beverages, is strongly associated with higher socioeconomic status, a healthier lifestyle, andbetterhealthstatusindicators,whichcouldallconfoundestimatesonmortality • 802adults,aged55–65atbaseline • Low-wine-consumption group: < 1/3Ethanol from wine • High-wine-consumption group: ≥ 2/3 Ethanolfrom wine • Alcoholconsumptionwasassessedatbaseline,totalmortalityassessedover20years Alcohol isalcohol. Thealcoholinwineisnolessharmthanthatin beer, viceversa. • Results: • failure to control for confounding factors produced a spurious effect of a mortality advantage for older moderate drinkerswho • preferredwinecomparedwiththosewho preferred other alcoholicbeverages • Controlling for these confounding factors eliminated the apparent beneficialmortality effect associated with wineconsumption Cumulativehazardofmortalityacross20yearsamongmoderate drinkersbyproportionofethanolfromwineconsumption initial model controlling only for overalldaily full model controlling for sociodemographic, behavioral, and health status factors, as well as for overall daily ethanol consumption ethanolconsumption • Insummary: • Those who preferred wine lived longer not because of the wine, but because of other (confounding) factors: they are wealthier, healthier to begin with, smoked less and were more physicallyactive Howaboutgrapeextracts? A human needs to drink >100 bottles of wine a day to receive the amount of resveratrol shown to be beneficial tomice

9. 3/6/2019 • Sources of resveratrol in food include the skin of grapes, blueberries, raspberries, mulberries, andpeanuts. • Although it is used as a dietary supplement, there is no evidence that consuming resveratrol positively affects life expectancy or humanhealth. • For the same amount of alcohol that is claimed to protect your heart, it increases your risk of other chronic diseases e.g. liver cirrhosis and certain cancers. Many other options such as healthy eating, active living and not smoking can benefit your heart directly and protect you from many otherdiseases; • Of note, the protective effects of alcohol on the heart observed in individual studies in the West do not extend to all populations. Research on Hong Kong older Chinese adults has not shown any benefit of drinking to heart health. On the contrary, local evidence shows that drinking can increase the risk of death from ischaemic heart disease among the elderly. • From: ” Drink or not Drink? Be Informed If You Drink”booklet • Data Source: Adopted from Communicating Alcohol-Related Health Risks: Canada’s Low Risk Alcohol DrinkingGuidelines ItisNOTworthriskingyourhealthtodrink,for certainharmbutuncertainbenefits Thereisnoscientificevidencefortheclaimthat consumingresveratrolaffectslifeexpectancyor humanhealth. Evenifgrapeextractisbeneficial,doesitmakeany sensetodrinkitwithaknowncarcinogen? “This recommendation is largely driven by the fact that the estimated protective effects for ischaemic heart disease and diabetes in women are offsetby monotonic associations withcancer.” LANCET2018 http://dx.doi.org/10.1016/S0140- 6736(18)31571-X Thelevelofconsumptionthatminimizesan individual’sriskis0gofethanolperweek. • GlobalBurdenofDiseases,Injuries, andRiskFactorsStudy(GBD)2016 • GBD 2016 is the most comprehensive estimate of the global burden of alcohol use todate: • 1990-2016 • 195countries • Alcohol use, as in2016: • 7th leading risk factor for both deaths and disability-adjustedlife-years • (DALYs失能調整生命年*) • accounting for 2·2% of female deaths; 6·8% of maledeaths • among those aged 15–49 years, alcohol ranks as the leading cause ofDALYs *DALYs失能調整生命年=因為健康狀況不佳或失能而損失的『健康』年歲 Lancet 2018; 392:1015–35 Whydopeopledrink? Theydon’tappreciatetheharmofalcoholuse Theyerroneouslythinkalcoholisbeneficialtohealth Socio-culturalreasons todrink (ortomakeothersdrink) 3. Psychological/ socio-culturalreasons

10. 3/6/2019 Commerciallymediateddiseasearethedominant healthissueofthe21stcentury. “Cui bono?” • Examples: • Alcohol-related harms (selling alcoholic drinks) • Tobacco-related harms (selling cigarettes) • Obesity (sellingsugar) (誰人因此得益?) • Latin: • "to whom itbenefits?“ • "for whosegood?" “These diseases of unhealthy behaviours, facilitatedby unhealthy environmentsandfuelledby commercialinterestsputtingshareholder valueaheadofthetragichumanconsequences,arethedominanthealth issueofthe21stcentury.” “Thesolutionsarestraightforward:increasingtaxationcreatesincomefor hard-pressed healthministries, andreducingthe exposureofchildrenand adolescentstoalcoholmarketinghasnodownsides.” LANCET2018 http://dx.doi.org/10.1016/S0140- 6736(18)31571-X • “……the success of aggressive industry lobbying coupled with the absence of robust public health advocacy was the main driving force behind theunparalleled abolition of wine and beer duties in Hong Kong. Strong public health alliance and advocacy movement are needed to counteract the industry’s continuing aggressive lobby and promotion of alcoholicbeverages.” • ―Professor TH Lam(HKU) • SituationinHongKong,2016 • 葡萄酒和酒精濃度不多於30%的飲品酒稅自二零零八年二月起獲豁免 • 本港的人均飲酒量在二零零八年基於啤酒和葡萄酒的淨進口量顯著增加，以 致出現明顯升幅。 • 二零零四年至二零一六年期間，本港的人均飲酒量*介乎2.53至2.87升，呈上 升趨勢。 • http://www.change4health.gov.hk 資料來源：政府統計處、香港海關及本港啤酒生產商的相關公司年報 • DH/medicalcommunity’sresponseto“BeerRunning” • 「全城街馬」11月舉行「BeerRun2017」活動，香港醫學會今日再「發炮」，以新聞稿大 為反對參加者可一邊喝啤酒，一邊跑步的安排。醫學會質疑，衞生署去年已推出一系列有 關飲酒與健康的活動，當中特別針對青少年飲酒問題，不過發展局仍支持舉辦「BeerRun • 2017」活動，似乎與政府整體的控酒政策互相矛盾。 • 醫學會又質疑，「全城街馬」作為社會企業，舉辦運動比賽責任相當大，活動加入飲酒環 節定必令增加參加者受傷風險，若遇任何受傷索償，活動主辦方可能須於賠償和法律上負 上龐大責任。 • 醫學會又指，「全城街馬」旗下「街跑少年」以青少年為服務對象，不應連繋運動與酒精， 會令青少年誤以為飲酒不會對身體構成影響。 • 對於外地亦有類似以飲酒作推廣的馬拉松活動，醫學會認為，本港不應跟從並以運動作推 廣，若要認真舉辦運動項目，絕對不應邊飲啤酒邊跑步。醫學會又提醒，酒精利尿會脫水， 心臟病、肝病及腎病患者需特別小心，並提醒酒會令精神鬆散，減低跑手集中力，引致腳 步不穩，增加跌倒受傷甚至骨折的風險。 • 醫學會稍後將聯同衞生署推出有關呼籲不飲酒的運動，並重申醫學會多次建議應於酒類包 裝上加上警告標籤，提醒公眾飲酒對健康的影響。 • https://topick.hket.com/article/1871576 MeasurestocurtailharmfulalcoholuseinHK ―alas口ngba口le 10

11. 3/6/2019 Howshouldhealthcareprofessionalsactinfaceof alcohol’sclearnetharmtosociety? Simple, don’tdrink! Educatethepublicabouttheharmofalcohol, andtellthemnottodrink! Alcohol was NOT served at the 130th Anniversary dinner of HKU Medical School,2017. “…….The Faculty will support the Change4Health Campaign of the Department of Health and will not be serving alcohol duringdinner. However we respect individual choice and have arranged for freecorkage. Friends attending the dinner may wish to bring their ownwine.” Billpassedon9/2/2018banningthesalesof alcoholicbeveragestominorsinretailshops Whosaysweneedwinetocelebrate?! 衞生署2016年展開名為「年少無酒」的新宣傳教育運動， 與青少年和家長團體、學界、醫護專業及相關政府決策局／部門攜手合作， 加強宣傳和教育未成年人士切勿飲酒。 http://www.info.gov.hk/gia/general/201612/15/P2016121500253.htm • 陳肇始今早在港台節目被問到，政府會舉辦推廣酒類的活動，或 與食衛局的控酒措施有衝突，長遠如何做控酒工作。 • 陳肇始回應，政府及食衛局有清晰立場，一定要加強非傳染病的防控工作，每個政策局 亦明白該防控計劃，讓政府內部知悉是第一步。她又指自己不飲酒，食 衛局的飲宴也不會供應酒，「相信 當我們以身作則，會有感染力，慢慢感染到其他人」。 明報2018年12月1日 10

12. 3/6/2019 http://www.change4health.gov.hk/tc/alcoholfails/index.html • 東華三院「遠酒高飛」 預防及治療酗酒服務 • 2005年成立，由資深社工、臨床心理學家及 醫護人員等專業人士合作，為受飲酒問題影響 的人士提供專業全面評估、治療、輔導及支援 服務。 • 『遠酒』去除與飲酒行為有關的非理性想法， 為家人提供支援，協助戒酒人士維持操守。 • 『高飛』提供健康生活活動，協助飲酒人士重 建自信，遠離酗酒行為。 • http://atp.tungwahcsd.org Thetwocampaignssnapshots • 酒精是致癌物，不應作為保健之用。 • 若無飲酒習慣，就不要開始飲酒。 • 若選擇飲酒，在理解風險後應節制以減低酒害： • 男士一天不應飲超過2個酒精單位*； • 女士一天不應飲超過1個酒精單位； • 請注意，這只是較低風險的飲酒行為，而飲酒並沒有安全水平。 • 為健康著想和減低患癌風險，遁序漸進地減少飲酒，直至完全不 飲酒是最佳選擇。 • 兒童、青少年及孕婦不應飲酒。 • *1個酒精單位=10 gm酒精 • Alcohol consumption causes alcoholic liver disease; the cornerstone of treatment isabstinence. • Alcohol causes harm to many other organsystems. • Alcohol is a type 1carcinogen. • Alcohol is responsible for excess mortality and morbidityworld-wide. • Womenaremorevulnerabletotheharmofalcoholthanmen. • There is no solid evidence for any human health benefit from moderate alcoholconsumption. • The level of consumption that minimizes an individual’s risk is 0 g of ethanol perweek. • Health-care professionals should be poised to educate the general public on theharm ofalcoholuse,andsetanexamplebyNOTdrinkingalcohol. Take homemessages Ourstanceonalcohol=Don’tdrinkanyALCOHOL. Thankyou ,Idon’tdrinkalcohol. 10