Table 3.
Effect estimate of areca nut chewing with reference to the type, duration and amount of areca nut chewed
| Study ID | Effect Estimate | Conclusion of study |
|---|---|---|
| Tsai et al. (2001)[13] | Independent risk of BQ chewing in HCC (OR=4.05, 95% CI, 2.35–7.00) | Risk of HCC increased as duration and amount of BQ chewing increased |
| Estimated population attributable risk BQ chewing 20.19% (95% CI, 9.81–23.78) | ||
| Risk of HCC based on type of BQ ingredients | ||
| Maximum risk: Areca-nut with betel fruit OR=5.02 (95% CI, 2.25–11.50) | ||
| Risk of HCC based on duration of BQ consumed | ||
| Maximum risk: >30 times OR=15.06 (95% CI, 4.36–39.09) | ||
| Risk of HCC based on total amount of BQ consumed (quids×1000) | ||
| High risk: >299 OR=8.78 (95% CI, 1.87–34.01) | ||
| Lin et al. (2002)[18] | CLD risk due to Habitual BQ chewing | Increasing linear trend in CLD risk is noted |
| Never chewer OR=1.0 (95% CI) | ||
| Ex-chewer-OR=2.0 (95% CI, 0.7–5.7) | ||
| Current chewer OR=3.9 (95% CI, 1.6–10.1) | ||
| Multivariate-adjusted ORs were 4.7 (95% CI, 1.3–16.8) and 7.9 (95% CI, 2.1–30.4) for subjects with 1–2 and 3 habits, respectively, compared to subjects with no habit | ||
| Wang et al. (2003)[19] | BQ chewers RR=1.59 (95% CI: 0.89–2.85) among three habits of substance use | Habitual BQ chewing is associated with an increased risk of HCC |
| RR based on Quantity of BQ chewed per day | ||
| Nonchewers RR=1.00 | ||
| 1–10 RR=1.44 (95% CI, 0.66–3.14) | ||
| >10 RR=1.92 (95% CI, 0.87–4.22) | ||
| Tsai et al. (2003)[16] | Risk for Cirrhosis in BN chewing OR 5.94 (95% CI, 3.01–11.79) | BQ chewing appears to be an independent risk factor for cirrhosis |
| The estimated population-attributable risks for BQ chewers was 11.60% | ||
| Type of BQ ingredients–Maximum risk in AN with betel leaf OR=5.93 (95% CI, 1.87–16.65) | ||
| Duration of chewing-maximum risk if duration >30 years OR=9.04 (95% CI, 1.13–67.21) | ||
| Total amount consumed (quids×1000) >200 OR=6.40 (95% CI, 1.73–20.82) | ||
| Sun et al. (2003)[25] | Risk for HCC in BQ chewing RR=0.7 (95% CI, 0.4–1.3) | There is an additive interaction between BQ chewing and chronic hepatitis B and/or hepatitis C virus infection |
| Joint effect of HCV infection and lifestyle habits on the risk of HCC is reported | There is an additive interactive effect in causation of HCC | |
| Tsai et al. (2004)[14] | Population-attributable risk was 20.10% for BQchewers | |
| BQ OR=5.94 (95% CI, 3.01–11.79) | ||
| Type of BQ ingredients maximum risk: ANwith betel leaf OR=7.55 (95% CI, 2.42–20.18) | ||
| Duration of chewing maximum risk: >30 years OR=18.89 (95% CI, 2.58–92.44) | ||
| Total amount consumed (quids×1,000) maximum risk 100–200 quids OR=12.59 (95% CI, 2.78–49.11) | ||
| Hsiao et al. (2007)[12] | Combined effect of other risk factors with BQ on the development of LC | BQ chewing in combination with other risk factors is more harmful |
| HBsAg positive+>55 quids/year OR=4.8 (95% CI, 1.2–19.3) | ||
| Cigarette smoking >5 pack-year s+>55 quids/year OR=5.2 (95% CI, 1.8–14.8) | ||
| Alcohol drinking + >55 quids/year OR=7.7 (95% CI, 2.3–25.8) | ||
| Lan et al. (2007)[23] | HR by liver cirrhosis and BQ chewing status | The effects of BQ chewing on mortality from all causes may be cumulative |
| Never chewer HR=1.00 | ||
| Ever chewer HR=1.62 (95% CI, 0.79–3.31) | ||
| Wu et al. (2009)[15] | Adjusted HR for associations between exposure to betel chewing and LC/HCC: Current chewer HR=3.87 (95% CI, 2.62–5.73) | Increased risks of LC and HCC were found in betel chewers |
| Quantity of betel chewed (portions/d), Nil if >20 portions/dHR=4.83 (2.54–9.18) | ||
| Duration of betel chewing (years) | ||
| 10–19 HR=5.69 (95% CI, 3.21–10.08) | ||
| Cumulative exposure to betel chewing (portion-days) | ||
| If >8.8×104 HR=3.94 (95% CI, 2.35–6.62) | ||
| Age betel first chewed (years) | ||
| If 20–29 years HR=3.71 (95% CI, 2.24–6.14) | ||
| Lin et al. (2008)[20] | ALT-OR=1.5 (95% CI, 1.1–1.8) | BQ chewers were associated with biochemical dysfunction and LC |
| AST OR=1.3 (95% CI, 1.1–1.7) | ||
| GGT OR=0.7 (95% CI 0.5–1.1) | ||
| BQ chewing was independently associated with risk of LC diagnosed by USG with an adjusted OR of 1.7 (95% CI, 1.2–2.3) | ||
| Jeng et al. (2014)[17] | Habitual BQ chewing OR=4.95 (95% CI, 2.54–9.65) was associated with HCC | Adverse hepatic fibrosis play important role in the pathogenesis of BQ related HCC |
| Significant hepatic fibrosis was noted between 45.8% and 91.7% of patients with BQ chewing | ||
| Saawarn et al. (2016)[11] | 19% of total study subjects and none in control showed fibrotic changes in liver on USG | Ill effects of AN chewing may be evident in liver even before it involves the oral mucosa |
| Out of which 75% were OSMF patients and 25% were AN chewers without OSMF | ||
| Fatima and Sultana (2016)[24] | SGOT level was significantly high in non-BN chewers groups (24.7±6.40) as Compared to chewers group (17.5±5.72) | Controversial observations are reported |
| Bilirubin (total and direct) and alkaline phosphate was within normal range | ||
| Singroha and Kamath (2016)[21] | Statistically significant association (P=0.031) was observed between the control (mean=24.20) and cases (mean=33.80) for AST | Long-term chewing of AN is not hepatotoxic |
| Statistically significant association (P=0.02, P<0.05) was observed for ALP between control (mean=108) and cases (mean=155.38). The levels of ALT remained unaltered | ||
| Chu et al. (2018)[22] | There were significant relationships between cirrhosis and BN in both males and females (P<0.0001) | Significant relationships between BN chewing and cirrhosis in both male and female nonalcohol drinkers is reported |
| The risk of cirrhosis was greater in females than males | ||
| Females with LC-OR in occasional chewer OR=2.91 (95% CI: 1.75–4.83) and frequent chewers OR=3.06 (95% CI: 1.69-5.57) | ||
| LC in males-OR in occasional chewers OR=1.76 (95% CI: 1.47–2.10) and frequent chewers OR=2.32 (95% CI: 1.90-2.85) |
USG: Ultrasonography, AST: Aspartate aminotransferase, ALT: Alanine aminotransferase, ALP: Alkaline phosphatase, BQ: Betel quid, BN: Betel nut, SGOT: Serum lutamic-oxaloacetic transaminase, HBsAg: Hepatitis B surface antigen, HCV: Hepatitis C virus, HBV: Hepatitis B virus, CLD: Chronic liver disease, OR: Odds ratio, CI: Confidence interval, RR: Relative risk, HR: Hazard ratio, AN: Areca nut, HCC: Hepatocellular carcinoma, LC: Liver cirrhosis, OSMF: Oral submucous fibrosis, GGT: Gamma- glutamyl transferase