Table 2.

Disease conditions which are not wholly attributable to alcohol identified by various meta-analyses and reviews (at least one review has concluded that there is a relationship of the condition with alcohol)

GBD category	N GBD 2005 code	ICD-10#	Reference to meta-analyses/systematic reviews	Effect
Tuberculosis	IA	A15-A19, B90	[32;34;241] Technical meeting 2008 concluded sufficient evidence for a causal impact [32].	Detrimental
Human Immunodeficiency Virus / Acquired Immune Deficiency Syndrome (HIV/AIDS)	IB	B20-B24	[32;43;44;46;48] There is not sufficient evidence to conclude a causal impact on incidence, but there is sufficient evidence of causal impact on course of disease, which can in part be modelled.	Detrimental
Mouth, nasopharynx, other pharynx and oropharynx cancer	IIA1-IIA2b	C00-C13	[4;9;16-20;242;243] Enough data to calculate RR for subcategories of disease, e.g. [68;244]. IARC confirmed cancers of the oral cavity and pharynx to be causally related to alcohol drinking in monograph meeting of February 2007 [59].	Detrimental
Oesophagus cancehr	IIA3	C15	[4;9;16-20;68;242;245] IARC confirmed oesophagus cancer to be causally related to alcohol drinking in monograph meeting of February 2007 [59].	Detrimental
Stomach cancer	IIA4	C16	[246] IARC concluded inadequate evidence that alcohol causes stomach cancer because of the inconsistency of the research evidence. Last IARC meeting concluded a possible relationship but confounding of smoking and dietary habits could not be excluded [59].	Detrimental
Colon and rectum cancer	IIA5	C18-C21	[9;67-69;244;247] IARC newly included colorectal cancer as causally related to alcohol drinking in monograph meeting of February 2007 [59].	Detrimental
Liver cancer	IIA6	C22	[4;9;16-20;68;244] IARC confirmed primary liver cancer as causally related to alcohol drinking in monograph meeting of February 2007 [59].	Detrimental
Larynx cancer	IIA9	C32	[4;9;16-20;68;242-244;248;249] IARC confirmed larynx cancer to be causally related to alcohol drinking in monograph meeting of February 2007 [59].	Detrimental
Trachea, bronchus and lung cancer	IIA10	C33, C34	Was excluded from the list of outcomes causally related to alcohol by [4]. This decision has not been revised by any further meta-analysis. Recent meta-analyses on alcohol and lung cancer found mixed results [244;250-252], but even when RRs were elevated for heavy consumption, confounding by smoking could not be fully excluded [250]. The last substantive reviews found no sufficient support for a causal relation [253;254]. Last IARC meeting concluded a possible relationship but confounding of smoking and dietary habits could not be excluded [59].	Detrimental
Breast cancer (female)	IIA13	C50	[9;16-20;68;70-73;244;255-257] [4] concluded there was only limited evidence for causality, although they found a consistent relationship. Subsequent studies using the same criteria concluded that there was sufficient evidence of a relationship. IARC newly included breast cancer as causally related to alcohol drinking in monograph meeting of February 2007 [59].	Detrimental
Other neoplasms	IIB	D00-D48 (except D09.9, D37.9, D38.6, D39.9, D40.9, D41.9, D48.9)	[9] Mixed category, no assessment of causality possible.	Detrimental
Diabetes mellitus	IIC	E10-E13	[4;9;16;17;19;258-260] [4] found only inadequate evidence of causality. Subsequent studies using the same criteria for causality revised this decision (see also [261]).	Mainly beneficial
Alzheimer’s disease and other dementias	IIF1	F01-F03, G30, G31	[262-265] Overall, studies showed a beneficial effect with the beneficial effects on the ischaemic system being the main potential explanation [266]. However, studies show substantial heterogeneity and confounding and other explanations could not be ruled out [261;264;267].	Mainly beneficial
Unipolar depressive disorders	IIE1	F32, F33, F34.1	[9] Available data is not sufficient for meta-analyses, for estimating RRs or AAFs. While there is agreement that some of the unipolar depressive disorders are caused by alcohol consumption (for a examination of causal criteria see [1]), the determination of the AAF was not possible, as it could not be determined which portion of the association between alcohol consumption and depressive disorders was caused by alcohol consumption, which portion by depression, and which portion by a third cause impacting both alcohol consumption and depression.	Detrimental
Epilepsy	IIF3	G40, G41	[4;9;16-20;89] Meta-analyses did not distinguish between primary epilepsy/unprovoked seizures and provoked seizures such as alcohol withdrawal induced seizures. We will conduct a new systematic review and meta-analysis consistent with GBD definition of primary epilepsy/unprovoked seizures.	Detrimental
Hypertensive heart disease	IIH2	I11-I13	[4;9;10;16-20;68] Because of lack of data for I11-I13 only, we included essential hypertension in our analyses (I10).	Detrimental, may depend on patterns of drinking for low volume
Ischaemic heart disease	IIH3	I20-I25	[4;9;16-20;68;108;113;268] Most recent meta-analysis [108] found heterogeneity among studies. Pattern of drinking must be included in analysis [9;115;116;118] to reduce this heterogeneity.	Beneficial or detrimental, depending on patterns of drinking for low to medium volume; detrimental effect for high volume
Cardiomyopathy	IIH6	I42	Not clear if alcohol has a relationship to cardiomyopathy over and beyond the subcategory of alcoholic cardiomyopathy I42.6. Systematic review is ongoing.	Detrimental
Conduction disorders and other dysrhythmias	IIH7	I47-I48	[4;9;16-20] Not yet included into prior CRAs yet, but as GBD 2005 has established a new code for dysrhythmias, the epidemiological assessment of underlying causality applies.	Detrimental
Heart failure (no GBD category)		No GBD code; the respective ICD codes will be redistributed in GBD 2005	[4;9;16;17;19;20] This is an unspecific category with no identification of underlying pathology. Therefore, the relationship between average volume of consumption and outcome was usually not determined by meta-analyses, but indirectly from other circulatory diseases.	Detrimental
Ischaemic stroke	IIH4a	I63-I67, I69.3	[4;9;16-20;68;155;222;269;270]	Beneficial or detrimental dependent on patterns of drinking (similar to IHD)
Haemorrhagic and other non-ischaemic stroke	IIH4b	I60-I62, I69.0, I69.1, I69.2	[4;9;16-20;68;155;160;222;269-271]	Mainly detrimental, except for low doses
Oesophageal varices (no GBD category)		No GBD code; the respective ICD codes will be redistributed in GBD 2005	[4;9;16-20] Not based on meta-analyses. As most oesophageal varices are due to liver cirrhosis, the AAFs derived for unspecific liver cirrhosis are usually applied. No GBD category.	Detrimental
Lower respiratory infections: pneumonia	IK1	J09-J22, J85, P23	Influenza and pneumonia had not been included into GBD so far. However, the transfer to GBD is only possible for disease categories with J10-18 as definition, as the epidemiological studies are usually restricted to these codes. Also, the impact of alcohol use is restricted to community-acquired pneumonia.	Detrimental
Cirrhosis of the liver	IIJ6	K70, K73-K74	[4;9;16-20;68] and the other meta-analyses included studies on all kinds of liver cirrhosis, included the ones defined as caused by alcohol by definition (see Table 1 above).	Detrimental
Gall bladder and bile duct disease	IIJ7	K80-K83	[4;16-20] Beneficial effect only found for K80 (cholelithiasis); the above references are limited to this.	Beneficial
Pancreatitis	IIJ8	K85-K86	[4;9;16-20;68] Usually determined by clinical case studies (but see [222]. There are sub-categories of alcohol-induced acute (K85.2) and chronic pancreatitis (K86.0). We are currently conducting a new meta-analysis which will include all forms of pancreatitis.	Detrimental
Other digestive diseases	IIJ9	K20-K22, K28-K31, K38, K57-K63, K75.2, K75.3, K75.4, K76-K77, K90-K92 (except K92.0, K92.1, K92.2, K92.9)	[4;9;16-20] Detrimental effect of alcohol has only been found for K22.6 (gastro-oesophageal haemorrhage). AAFs for this category were not based on meta-analyses but clinically documented. The above references are limited to K22.6.	Detrimental
Psoriasis	IIL2	L40-L41	[4;9;16;17;19;20;184-186;189] Overall insufficient evidence on the causal impact of alcohol on the association with psoriasis. As this condition had been included in other analyses of alcohol on burden of disease, we included an overview on the evidence as part of the text.	Detrimental
Abortion	IIN1	O00-O08	[4;9;16;17;19;20] To be applied to the fraction of women with alcohol consumption during pregnancy.	Detrimental
Preterm birth complications	IM1	P05-P07, P22, P25-P28, P77	[4;9;16;17;19;20;272-276] To be applied to the fraction of women with alcohol consumption during pregnancy. [4] concluded that for all birth defects combined (ICD-10: Q00-Q99) there was inadequate evidence for a causation of alcohol during pregnancy. Other reviews, based on the same criteria for causality as [4] concluded sufficient evidence for a causal effect.	Detrimental

The shaded rows indicate conditions for which the current analyses concluded sufficient evidence for a causal relationship and sufficient data on outcomes and risk relations to be included into the CRA 2005.

^#The ICD-10 code refers to the respective categories as defined by GBD 2005. These may include fewer codes than elsewhere, as GBD separately identifies ill-specified codes [so called garbage code(s)], which are to be redistributed to more meaningful codes based on specified procedures.

AAF - alcohol-attributable fraction; CRA - Comparative Risk Assessment; GBD - Global Burden of Disease and Injury; IARC – International Agency for Research on Cancer; ICD - International Classification of Diseases; IHD - ischaemic heart disease; RR – relative risk