Systematic Review With Meta-analysis

Coffee Consumption and the Risk of Cirrhosis

O. J. Kennedy; P. Roderick; R. Buchanan; J. A. Fallowfield; P. C. Hayes; J. Parkes

Disclosures

Aliment Pharmacol Ther. 2016;43(5):562-574. 

In This Article

Results

Details of the study selection process and the included studies

Figure 1 illustrates the process for selecting the studies for inclusion in this meta-analysis. The searches returned 2023 studies. After OJK first excluded 1290 duplicates, OJK and RB separately reviewed titles and abstracts and excluded 646 irrelevant studies. OJK and RB then examined the full text of the remaining studies and excluded a further 78 studies for not meeting the eligibility criteria described above. Nine studies remained and we included all in this meta-analysis.[7–9,12–14,27–29]

Figure 1.

A schematic showing the selection of relevant studies for inclusion in the meta-analysis.

Table 1 summarises the characteristics of the nine included studies, which included eight journal articles and one conference abstract.[27] The studies were published between 1994 and 2015 and involved 1990 cases and 432 133 participants. Five were cohort studies, involving 1364 cases and 429 202 participants, and four were case–control studies, involving 626 cases and 2305 controls (2931 participants in total). Two of the studies were in the USA, six in Europe and one in Singapore. Seven studies included men and women. One case–control study included males only.[27] One cohort study included only male smokers without a history of malignancy, alcoholism or major health problems.[13] The other cohort studies all involved men and women recruited as summarised in Table 1. The cohort studies measured outcomes using death and/or hospitalisation records and, thus, lost few participants to follow-up. Participants in the case–control studies were recruited from hospital records (i.e. both cases and controls). The studies adjusted for a variable mix of relevant confounders, but all adjusted for alcohol (the exact adjustments used in the conference abstract were unclear[27]). All the studies measured coffee consumption by means of a self-completion questionnaire or interview, in which participants selected a pre-defined category of consumption. All measurements were in cups. One study asked about the type of coffee preparation (e.g. boiled, filtered, etc.) and cup size.[13] Another study asked whether the coffee was caffeinated or decaffeinated.[8] For that study, we used the RRs for caffeinated coffee consumption in our analysis, whereas for the other studies we used the RRs for total coffee consumption.

Figure S1 https://onlinelibrary.wiley.com/store/10.1111/apt.13523/asset/supinfo/apt13523-sup-0001-SupInfo.docx?v=1&s=9520c67a54f85b05865c25d7a4d69bd0eeea2e38 illustrates the results of the risk of bias assessment for the individual studies. In summary, we found a high risk of bias for the following domains: confounding, selection and outcome measurement. We performed an assessment of the overall quality of evidence for the effect of coffee on cirrhosis using the GRADE system. We rated the quality of evidence based on risk of bias, inconsistency, indirectness, imprecision, publication bias and factors that increase the quality of evidence. We rated the quality of evidence as low, as indicated in the Table S2 https://onlinelibrary.wiley.com/store/10.1111/apt.13523/asset/supinfo/apt13523-sup-0001-SupInfo.docx?v=1&s=9520c67a54f85b05865c25d7a4d69bd0eeea2e38.

To understand better the magnitude and direction of overall confounding across all studies, we compared the pooled adjusted and unadjusted RRs of cirrhosis for an increase in coffee consumption of two cups per day. After adjustment, the pooled RR decreased from 0.66 (95% CI 0.47–0.85) to 0.56 (95% CI 0.44–0.68), indicating the overall effect of adjusting for confounding increase the effect size away from null.

In determining the overall risk of bias in the individual studies, we found a high risk in all the case–control studies because of the potential for selection bias in choosing cases and controls and for recall bias in determining exposure to confounders. We found an unclear overall risk of bias in the cohort studies. We did not assign a 'low' risk of overall bias to any study even if there was no obvious source of bias that would have affected the results. This was in accordance with the ACROBAT-NRSI, which indicates that only randomised trials should be considered 'low' overall risk of bias.

Coffee Consumption and Cirrhosis

Table 2 summarises the results as reported by the studies. Figure 2 is a forest plot of the calculated RRs of cirrhosis for an increase in coffee consumption of two cups per day for each study and overall. In eight studies, increasing coffee consumption by two cups per day was associated with a statistically significant reduction in the risk of cirrhosis. In the other study, Goh et al., the corresponding RR was 0.75 (95% CI 0.55–1.02). The pooled RR across all studies was 0.56 (95% CI 0.44–0.68). In all but one study, Goh et al., there was evidence of a dose-dependent relationship, with generally lower RRs for higher consumption categories. The data as reported by the studies are illustrated as a semi-log plot in Figure 3. We calculated that compared to no consumption the pooled RRs of cirrhosis were 0.78 (95% CI 0.68–0.90), 0.57 (95% CI 0.50–0.65), 0.43 (95% CI 0.37–0.50) and 0.35 (95% CI 0.30–0.41) for one to four cups of coffee per day respectively.

Figure 2.

Forest plot showing the associations of cirrhosis with drinking an additional two cups of coffee per day as reported by the included studies individually and pooled overall. The pooled RRs were calculated by random effects meta-analyses. The sizes of the squares represent the weighting of each study in the calculation and the pooled RRs are represented by diamonds.

Figure 3.

A semi-log plot of the adjusted study-specific and overall RRs of cirrhosis vs. cups of coffee per day. The study-specific RRs are plotted against the estimated median coffee consumption in each reported category.

Egger's regression test gave no indication of statistically significant publication bias (P > 0.05). Cochran's Q and I2 were 48 (P = 0.0) and 83.3%, respectively, and showed statistically significant heterogeneity between the studies. We further investigated this heterogeneity by means of a sensitivity analysis, in which we calculated pooled RRs while excluding the studies one at a time. The pooled RRs in the sensitivity analysis and the Q and I2 varied most substantially when Lai et al. was excluded. Without Lai et al., the pooled RR for an increase in coffee consumption of two cups per day was 0.61 (95% CI 0.53–0.68). The corresponding Q and I2 values were 11 (P = 0.14) and 36.1%, showing markedly reduced heterogeneity compared to when Lai et al. was included. The pooled RR of cirrhosis for an increase of two cups per day in cohort studies was 0.58 (95% CI 0.41–0.76; I2 91.1%) and in case–control studies it was 0.52 (95% CI 0.40–0.63; I2 0.0%). The RRs of alcoholic cirrhosis, calculated from two studies,[9,12] and death from liver disease, calculated from four studies,[8,12–14] for an increase in coffee consumption of two cups per day were 0.62 (95% CI 0.51–0.73; I 2 0.0%) and 0.55 (95% CI 0.35–0.74; I 2 90.3%) respectively.

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