WHO/HIV/2014.36 © World Health Organization 2014
Global Hepatitis Programme Guideline development for Hepatitis C virus Screening, Care and Treatment in low- and middle-income countries PICO 3 Care (Behavioural Interventions and Alcohol Consumption) – Decision Making Table
Health system and public health evidence to recommendations framework
Are behavioural interventions targeting alcohol consumption effective among persons with chronic HCV infection? Population: Individuals with chronic HCV infection Intervention: Behavioural alcohol-reduction interventions Comparison: No behavioural alcohol-reduction intervention Outcomes: Reduction or cessation of alcohol intake, SVR, liver fibrosis, decompensated liver cirrhosis (DCC), hepatocellular carcinoma (HCC), quality of life, all-cause mortality Background: Alcohol consumption has been shown to accelerate the progression of liver disease among people with HCV1. The impact of behavioural interventions to reduce consumption of alcohol among people with HCV is uncertain. The purpose of the systematic review was to investigate the effectiveness of behavioural interventions to reduce alcohol consumption among people with HCV, in terms of HCV treatment outcomes, liver disease progression, and quality of life.
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Problem: [Problem]
Option: [Option]
Comparison: [Comparison]
Setting: [Setting]
CRITERIA Is the problem a priority?
JUDGEMENTS No Probably No Uncertain Probably Yes Yes X Varies
RESEARCH EVIDENCE
ADDITIONAL INFORMATION
Alcohol consumption accelerates the rate of liver disease progression and reduces sustained virological response rates to HCV antiviral therapy2. A heavy alcohol intake, of between 210 and 560 g/week, has been shown to double the risk of cirrhosis and even moderate alcohol consumption can be detrimental3. Alcohol use in patients with HCV varies considerably in different contextual settings. Some countries such as Egypt and Saudi Arabia report extremely low or negligible alcohol use in patients with HCV4,5. Considerably higher alcohol use is evident in other countries, especially in injecting drug users (IDUs) and in prisoners. In China, the majority of IDUs in one region were found to use alcohol regularly prior to starting injecting drug use6 and in India, 38% of HCV-infected IDUs in Chennai drank alcohol at least once per week7. 26-30% of IDUs in Russia drank moderate-heavy amounts of alcohol8. In Brazil, HCV-infected youth offenders had high rates of alcohol use9 and in a study of Nigerian prisoners, 59% with HCV also drank alcohol10. Alcohol intake has also been found to be high in other groups of HCV-infected individuals; 37% of male and 9% of female commercial plasma donors inadvertently infected with HCV in Guan were found to drink >40g of alcohol per day11. The Guidelines Committee considered that even in countries where alcohol intake is low among the general population, alcohol reduction advice should be given as required. Alcohol use varies considerably in different geographical regions and in different risk groups. Many countries have no published prevalence rates of alcohol use in HCV-infected individuals. Further information collected by WHO on alcohol use by country is however available online: http://www.who.int/substance_abuse/publications/global_alcohol_report/profiles/en/index.html
P RO B LE M
Are a large number of people affected?
No
Probably No
Uncertain
Probably Yes
Yes X
Varies
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Problem: [Problem]
Option: [Option]
Comparison: [Comparison]
Setting: [Setting]
CRITERIA
JUDGEMENTS
RESEARCH EVIDENCE
ADDITIONAL INFORMATION
Are the desirable anticipated effects large?
No
Probably No
Uncertain
Probably Yes X
Yes
Varies
Behavioural alcohol-reduction interventions in HCV-infected individuals A systematic review of studies examining an alcohol reduction intervention in HCV-infected individuals identified 5 trials that met the PICO criteria for assessment (data shown in Table 1, p7); two randomised control trials12,13 and three cohort studies14,15,16. Despite a limited number of relevant studies, there is moderate evidence that alcohol reduction interventions can reduce alcohol consumption among people living with chronic HCV. However, a significant limitation for data analysis was the heterogeneity of the interventions and comparison groups across the studies. Also, whilst alcohol-targeted interventions reduced consumption in each study, participants in the two RCT comparison groups also received varying broad support and reduced their drinking. The heterogeneity of the intervention and comparison groups makes it difficult to draw any firm conclusions about the effect of specific alcohol-focused interventions for this population. Behavioural alcohol-reduction interventions In addition to these studies, which involve interventions amongst people with HCV, two Cochrane reviews offer summaries of evidence for brief alcohol interventions for non-HCV populations. Kaner et al. (2009)17 found that amongst 5860 hazardous or dependent drinkers across 22 studies, HCV screening followed by brief intervention, compared with no intervention, significantly reduced mean weekly alcohol consumption from 313g per week by 38.42g per week. Klimas et al. (2012) investigated the efficacy of psychosocial interventions for drinkers with concurrent illicit drug use. Amongst 594 participants across 4 studies, alcohol-focused interventions resulted in significant reductions in alcohol consumption at 3 months (RR 0.32, 95%CI 0.19 to 0.54) and 9 months (RR 0.16, 95%CI 0.08 to 0.33) compared to treatment as usual. The quality of the evidence overall was considered to be moderate.
Are the undesirable anticipated effects small?
No
Probably No
Uncertain
Probably Yes
Yes X
Varies
B E NE F IT S & HA RM S O F T HE O P T IO NS
What is the overall certainty of this evidence?
No included studies
Very low
Low
Moderate X
High
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Problem: [Problem]
Option: [Option]
Comparison: [Comparison]
Setting: [Setting]
CRITERIA
JUDGEMENTS
RESEARCH EVIDENCE
ADDITIONAL INFORMATION
Implications for clinical practice Brief alcohol reduction interventions for chronic HCV patients could encourage abstinence or reduce the number of drinking days per month. However, there are no data on whether longer-term important outcomes including treatment response, morbidity, mortality and quality of life are affected by alcohol reduction interventions. PICO 3 Alcohol intervention systematic review
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Problem: [Problem]
Option: [Option]
Comparison: [Comparison]
Setting: [Setting]
CRITERIA
JUDGEMENTS
RESEARCH EVIDENCE
ADDITIONAL INFORMATION
The relative importance or values of the main outcomes of interest: Outcome Reduction or cessation of alcohol intake SVR Liver fibrosis Decompensated liver cirrhosis (DCC) Hepatocellular carcinoma (HCC) Quality of life All-cause mortality Relative importance Certainty of the evidence Moderate
How certain is the relative importance of the desirable and undesirable outcomes? V A LUE S
Possibly Important important uncertainty uncertainty or variability or variability
Probably no No important important No known uncertainty uncertainty undesirable or variability or variability outcomes X
No evidence No evidence No evidence No evidence No evidence No evidence
Are the desirable effects large relative to undesirable effects?
No
Probably No
Uncertain
Probably Yes X
Yes
Varies
The evidence in favour of a brief alcohol intervention was considered to be moderate and the evidence of undesirable effects minimal. However, the relevance of this advice is highly likely to be context-specific and those countries with low alcohol use may not wish to commit time and resources to this.
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Problem: [Problem]
Option: [Option]
Comparison: [Comparison]
Setting: [Setting]
CRITERIA
JUDGEMENTS
RESEARCH EVIDENCE
ADDITIONAL INFORMATION
Main resource requirements Resource Training Are the resources required small? No Probably No Uncertain Probably Yes X Yes Varies
Settings Practice-based training in behavioural intervention 1. 5-10 minute intervention 2. 4 sessions of Alcohol targeted Motivational Enhancement Therapy (MET) 3. 6 x 2hr professional led sessions stressing dangers of alcohol use and benefits held over 3 weeks Promotional materials for health care provider and patients
RE S O URCE US E
Supervision and monitoring
Supplies Is the incremental cost small relative to the net benefits? What would be the impact on health inequities?
No
Probably No
Uncertain
Probably Yes X
Yes
Varies
A 5-10 minute intervention was considered to be unlikely to substantially increase costs.
E Q UIT Y
Increased Probably Uncertain Probably Reduced Varies increased reduced X
An intervention targeted at patients most at risk e.g. IDUs and prisoners is likely to improve health inequities.
A CCE P T A B ILIT Y
Is the option acceptable to key stakeholders?
No
Probably No
Uncertain
Probably Yes X
Yes
Varies
Alcohol reduction strategies may be more or less appropriate in settings with varying prevalence of alcohol use but the option was considered to be acceptable to key stakeholders.
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Problem: [Problem]
Option: [Option]
Comparison: [Comparison]
Setting: [Setting]
CRITERIA F E A S IB ILIT Y
JUDGEMENTS
RESEARCH EVIDENCE
ADDITIONAL INFORMATION
Is the option feasible to implement?
No
Probably No
Uncertain
Probably Yes X
Yes
Varies
This intervention is likely to be feasible to implement in most healthcare settings.
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Problem: [Problem]
Option: [Option]
Comparison: [Comparison]
Setting: [Setting]
Balance of consequences
Undesirable consequences clearly outweigh desirable consequences in most settings
Undesirable consequences probably outweigh desirable consequences in most settings
The balance between desirable and undesirable consequences is closely balanced or uncertain
Desirable consequences probably outweigh undesirable consequences in most settings X
Desirable consequences clearly outweigh undesirable consequences in most settings
Type of recommendation
We recommend against the option
We suggest considering the option Only in the context of rigorous research Only with targeted monitoring and evaluation Only in specific contexts
We recommend the option X
Recommendation
An alcohol intake assessment is recommended for all persons with HCV infection followed by the offer of a behavioural alcohol reduction intervention for persons with moderate to high alcohol intake. Strong recommendation, moderate quality of evidence. The quality of evidence was considered to be of moderate quality for the benefit of a brief alcohol reduction intervention and this was considered to outweigh any associated risk. Alcohol intake varies considerably in different cultural settings and time spent on alcohol reduction behavioural intervention is not of value in settings where alcohol intake is low. Alcohol reduction interventions should be voluntary.
Justification Implementation
considerations
Monitoring and evaluation Research priorities Additional research is required to fully assess the impact of behavioural interventions for HCV infected individuals, and also to determine whether alcohol reduction interventions have any impact on other important outcomes including morbidity, mortality and quality of life. Measuring alcohol consumption is complex and different instruments are used across studies making comparisons and synthesis of the evidence difficult. Future research should consider using validated and standardised tools for measuring alcohol consumption where possible.
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Problem: [Problem]
Option: [Option]
Comparison: [Comparison]
Setting: [Setting]
Evidence profile Authors: David Hunt, Esther Aspinall, and Hamish Innes Date: 2013-05-16 Question: Are behavioural interventions targeting alcohol consumption effective among persons with chronic HCV infection? Settings: Individuals with chronic HCV infection Bibliography: Table 1: GRADE Evidence Summary - Effect of alcohol reduction interventions among persons with chronic HCV Outcomes (Follow up) Alcohol consumption: Measure One: Mean Drinking Days in preceding month (at 6 months) Measure Two: Overall AUDIT score (at 6 months) Measure Three: AUDIT alcohol consumption score only (at 6 months) Measure Four: Achieved abstinence (at 6 months) Measure Five: Mean quantity of alcohol consumed on a drinking day during preceding month (at 1 month) No of participants (Studies) Quality of the Evidence (GRADE) Moderate1 Relative Effect (95% CI) Anticipated absolute effects Risk without intervention 20 mean drinking days per month Baseline data not available Baseline data not available 208 per 1000 abstinent Range from 20g to 133g EtOH/day 232 per 1000 increased abstinence Range from 3.1g less alcohol consumed on drinking day to 56g less alcohol consumed on drinking day Risk difference with alcohol reduction intervention A reduction of 4.2 mean drinking days per month
135 (1 RCT )
Cohen’s D = 0.40 (21% reduction in mean drinking days, no CI available) OR 0.99 (0.96-1.01) OR 1.03 (0.94-1.13) OR 3.36 (2.62-4.10) Pool RR cannot be calculated from data. Risk difference estimates: 3.1g EtOH/day (1 study, p<0.01); 56g EtOH/day (1 study, p<0.001)
334 (1 RCT) 334 (1 RCT) 53 (1 observational study) 64 (2 observational studies)
Moderate1 Moderate1 Low Very Low2
SVR Morbidity Mortality Quality of Life
No data No data No data No data
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Problem: [Problem] 1Assessed 2This
Option: [Option]
Comparison: [Comparison]
Setting: [Setting]
moderate GRADE evidence given some imprecision in measuring outcome outcome (drinking days/month) downgraded quality of evidence due to imprecision of outcome measurement, and inadequate level of detail in study data to estimate comparative effect sizes and pooling data across observational studies. (Return)
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Problem: [Problem]
Option: [Option]
Comparison: [Comparison]
Setting: [Setting]
References
1 Hutchinson SJ, Bird SM, Goldberg DJ. Influence of Alcohol on the Progression of Hepatitis C Virus Infection: A Meta-analysis. Clinical Gastroenterology and Hepatology, 2005; 3: 1150-1159 2 R. Bhattacharya, M.C. Shuhart Hepatitis C and alcohol: interactions, outcomes and implications J. Clin. Gastroenterol., 36 (2003), pp. 242–252 3 D.L. Thomas, J. Astemborski, R. Rai, F.A. Anania, M. Schaeffer, N. Galai, K. Nolt, K.E. Nelson, S.A. Strathdee, L. Hohnson, O. Laeyendecker, J. Boitnott, J.E. Wilson, D. Vlahov The natural history of hepatitis C virus infection; host, viral and environmental factors JAMA, 284 (2000), pp. 450–456 4 Mohamed MK, Bakr I, El-Hoseiny M, Arafa N, Hassan A, Ismail S, Anwar M, Attala M, Rekacewicz C, Zalata K, Abdel-Hamid M, Esmat G, Fontanet A. HCV-related morbidity in a rural community of Egypt. J Med Virol. 2006 Sep;78(9):1185-9. 5 Mughal TI, Patel SB. Hepatocellular carcinoma: A review of 140 cases. Ann Saudi Med. 1996;16(1):53-5. 6 Du WJ, Xiang YT, Wang ZM, Chi Y, Zheng Y, Luo XN, Cai ZJ, Ungvari GS, Gerevich J. Socio-demographic and clinical characteristics of 3129 heroin users in the first methadone maintenance treatment clinic in China. Drug Alcohol Depend. 2008 Apr 1;94(1-3):158-64. doi: 10.1016/j.drugalcdep.2007.11.009. 7 Mehta SH, Vogt SL, Srikrishnan AK, Vasudevan CK, Murugavel KG, Saravanan S, Anand S, Kumar MS, Ray SC, Celentano DD, Solomon S, Solomon SS. Epidemiology of hepatitis C virus infection & liver disease among injection drug users (IDUs) in Chennai, India. Indian J Med Res. 2010 Dec;132:706-14. 8 Cepeda JA, Niccolai LM, Eritsyan K, Heimer R, Levina O. Moderate/heavy alcohol use and HCV infection among injection drug users in two Russian cities. Drug Alcohol Depend. 2013 May 1. doi:pii: S0376-8716(13)00131-2. 10.1016/j.drugalcdep.2013.04.004. 9 Fialho M, Messias M, Page-Shafer K, Farre L, Schmalb M, Pedral-Sampaio D, Ramos M, Brites C. Prevalence and risk of blood-borne and sexually transmitted viral infections in incarcerated youth in Salvador, Brazil: opportunity and obligation for intervention. AIDS Behav. 2008 Jul;12(4 Suppl):S17-24. 10 Adoga MP, Banwat EB, Forbi JC, Nimzing L, Pam CR, Gyar SD, Agabi YA, Agwale SM. Human immunonodeficiency virus, hepatitis B virus and hepatitis C virus: sero-prevalence, co-infection and risk factors among prison inmates in Nasarawa State, Nigeria. J Infect Dev Ctries. 2009 Aug 30;3(7):539-47. 11 Rao HY, Sun DG, Yang RF, Liu F, Wang J, Feng B, Wu N, Fang JL, Song GJ, Ma H, Guo F, Wang JH, Li XB, Jin Q, Qin H, Zhuang H, Wei L. Outcome of hepatitis C virus infection in Chinese paid plasma donors: a 12-19year cohort study. J Gastroenterol Hepatol. 2012 Mar;27(3):526-32. HSPH EtR framework (Version 2): [Short title] 11
Problem: [Problem]
Option: [Option]
Comparison: [Comparison]
Setting: [Setting]
12 Dieperink E, Fuller B, Thuras P, McMaken K, Lenox R, Isenhart C, et al. Randomized Controlled trial of Motivational Enhancement Therapy to Reduce Alcohol in Patients with Chronic Hepatitis C. Hepatology. 2012 October;56:579A. PubMed PMID: 70942384. 13 Drumright LN, Hagan H, Thomas DL, Latka MH, Golub ET, Garfein RS, et al. Predictors and effects of alcohol use on liver function among young HCV-infected injection drug users in a behavioural intervention. Journal of Hepatology. 2011 July;55(1):45-52. PubMed PMID: 2011327091. 14 Proeschold-Bell RJ, Patkar AA, Naggie S, Coward L, Mannelli P, Yao J, et al. An Integrated alcohol abuse and medical treatment model for patients with hepatitis c. Digestive Diseases and Sciences. 2012 April;57(4):108391. PubMed PMID: 2012426995. 15 Dieperink E, Ho SB, Heit S, Durfee JM, Thuras P, Willenbring ML. Significant reductions in drinking following brief alcohol treatment provided in a hepatitis C clinic. Psychosomatics. 2010 March-April;51(2):149-56. PubMed PMID: 2010186857. 16 Watson B, Conigrave KM, Wallace C, Whitfield JB, Wurst F, Haber PS. Hazardous alcohol consumption and other barriers to antiviral treatment among hepatitis C positive people receiving opioid maintenance treatment. Drug and Alcohol Review. 2007 May;26(3):231-9. PubMed PMID: 17454012 17 Kaner EF, Dickinson HO, Beyer F, Pienaar E, Schlesinger C, Campbell F, et al. The effectiveness of brief alcohol interventions in primary care settings: a systematic review. Drug Alcohol Rev 2009; 28:301-323.
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Explanations
Definitions for ratings of the certainty of the evidence (GRADE)** Ratings Definitions This research provides a very good indication of the likely effect. The likelihood that the effect will be substantially different* is low. This research provides a good indication of the likely effect. The likelihood that the effect will be substantially different4 is moderate. This research provides some indication of the likely effect. However, the likelihood that it will be substantially different4 is high. This research does not provide a reliable indication of the likely effect. The likelihood that the effect will be substantially different4 is very high. Implications This evidence provides a very good basis for making a decision about whether to implement the intervention. Impact evaluation and monitoring of the impact are unlikely to be needed if it is implemented. This evidence provides a good basis for making a decision about whether to implement the intervention. Monitoring of the impact is likely to be needed and impact evaluation may be warranted if it is implemented. This evidence provides some basis for making a decision about whether to implement the intervention. Impact evaluation is likely to be warranted if it is implemented. This evidence does not provide a good basis for making a decision about whether to implement the intervention. Impact evaluation is very likely to be warranted if it is implemented.
High
Moderate Low Very low
*Substantially different: large enough difference that it might have an effect on a decision **The Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group began in the year 2000 as an informal collaboration of people with an interest in addressing the shortcomings of present grading systems in health care. The working group has developed a common, sensible and transparent approach to grading quality of evidence and strength of recommendations. Many international organizations have provided input into the development of the approach and have started using it.
(Return)
For most recent version of this framework (and additional frameworks): www.decide-collaboration.eu/WP5/Strategies/Framework
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