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Microcystins and Daily Sunlight: Predictors of Chronic Liver Disease and Cirrhosis Mortality

Article Information

Rajesh Melaram

School of Health Sciences, Walden University, Minnesota, USA

*Corresponding Author: Rajesh Melaram, School of Health Sciences, Walden University, Minneapolis, Minnesota, USA

Received: 15 May 2021; Accepted: 20 May 2021; Published: 11 June 2021

Citation: Rajesh Melaram. Microcystins and Daily Sunlight: Predictors of Chronic Liver Disease and Cirrhosis Mortality. Journal of Environmental Science and Public Health 3 (2019): 379-388.

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Abstract

Cyanobacteria (blue-green algae) may rapidly propagate under favorable conditions, forming dense blooms. As blooms deteriorate, blue-green algae can generate potent toxins, potentially harmful to companion animals, wildlife, and humans. Microcystin is a widely studied toxin, and ingestion of contaminated drinking water is a frequent route of human exposure. The algae toxin has been detected in global drinking water supplies, particularly in regions plagued by liver disease. Microcystin production is dependent on environmental factors driven by changes in weather, including nutrient levels, pH, and water temperature. No prior study examined the ecological association between microcystins and liver disease mortality, accounting for meteorological factors. The purpose of the ecological study was to determine if meteorological factors and microcystins predicted liver disease mortality rates in the United States. Environmental data (CDC WONDER) and toxin data (USEPA) were used in multiple linear regression analyses. Mean daily sunlight and mean total microcystins significantly predicted age-adjusted chronic liver disease and cirrhosis death rates (p < 0.05). Mean annual precipitation (p = 0.156) and mean daily maximum temperature (p = 0.149) non-significantly predicted age-adjusted chronic liver disease and cirrhosis death rates. The study demonstrated that meteorological factors and concurrent microcystin concentrations might contribute to an increase in liver disease mortality across the United States. The results can prompt others to study environmental exposures of chronic liver diseases, guiding environmental health and the water industry of human survival needs.

Keywords

Chronic liver disease and cirrhosis; Daily sunlight; Meteorologic factors; Microcystins

Chronic liver disease and cirrhosis articles; Daily sunlight articles; Meteorologic factors articles; Microcystins articles

Article Details

Abbreviations

CDC WONDER-Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research; ELISA-Enzyme-linked immunosorbent assay; ICD-10-International Classification of Disease, Tenth Revision; NLDAS-North America Land Data Assimilation System; SPSS-Statistical Package for the Social Sciences; USEPA-United States Environmental Protection Agency; WHO-World Health Organization

1. Introduction

In the United States (US), chronic liver disease (CLD) and cirrhosis represent a significant cause of mortality. CLD and cirrhosis was the 12th leading cause of death in 2013, resulting in more than 36,000 deaths [1]. The figure has been underestimated for over two decades as researchers have indicated an annual mortality near 66,000 deaths [2]. CLD is a debilitating condition in which the liver progressively worsens for six months or greater, terminating with cirrhosis. Major causes of CLD in the US include alcoholic liver disease and hepatitis C, though non-alcoholic fatty liver disease has become the most common etiology [3, 4]. Racial/ethnic differences in CLD and cirrhosis prevalence are evident in the US, despite limited and restricted data on few racial/ethnic groups [5]. In developing countries, varied etiologies for cirrhosis have been reported, such as malnutrition, tropical infections, and toxins [6]. While certain risk factors may be region-specific, identifying CLD and cirrhosis risk factors constitutes an essential step in exposure prevention.

Microcystins are cyclic heptapeptide structures produced by cyanobacteria in aquatic environments [7, 8]. They may be released into the water column via cell rupture or after bloom senescence [9-11]. Colonial Microcystis primarily manufactures microcystin, although other freshwater cyanobacterial genera can synthesize the biotoxin [12-15]. Microcystin is a contaminant of water sources used for agriculture, drinking water, and recreation [16, 17]. Additionally, microcystin fatalities are common in animals, livestock, and pets [18, 19].

Though rare, the largest microcystin episode in humans occurred in Caruaru, Brazil, killing 52 hemodialysis patients. Cylindrospermopsins were also considered a contributing factor in hemodialysis deaths [20-24].  However, the most common exposure route for microcystin is the consumption of contaminated drinking water [25, 26]. Following oral ingestion, microcystin is transported by a bile acid transport system into the liver. Organic anion transporting polypeptides (OATP) 1A2, 1B1, and 1B3 transport microcystin into hepatocytes [27]. Herein, microcystin covalently binds protein phosphatases PP1 and PP2A, inactivating dephosphorylation capabilities. High microcystin concentrations, therefore, causes hyperphosphorylation among cytoskeletal proteins, subsequently disrupting hepatocyte structure and function [28, 29]. For example, microcystin-leucine arginine was found to stimulate hyperphosphorylation of cytokeratin 8 and 18 in primary cultured rat hepatocytes, a process associated with liver tumor promotion [30].

Furthermore, several epidemiologic investigations linked microcystin exposure to increased liver disease. Two surveys in China identified hepatotoxic blue-green algae toxins in drinking water sources as one potential risk factor for primary liver cancer [31]. In Florida, an increased risk for primary hepatocellular carcinoma occurred among persons within a serviced area of a surface water treatment plant [32]. Chronic exposure to freshwater microcystin in Three Gorges Region, China, may have induced liver damage in children [33]. On the contrary, one study determined that liver cancer was not associated with toxic cyanobacterial exposure [34]. These studies support a probable association between microcystin and liver disease, but none considered meteorological factors in their assessment.

Apart from anthropogenic eutrophication, global climate change is a key driver of cyanobacterial expansion worldwide [35]. Combustion of fossil fuels and concomitant air temperatures may enhance algae productivity. Similarly, variations in weather patterns, resulting in severe droughts and rainfall, can leach nitrates and phosphate into eutrophic waters [36]. Research has indicated a synergistic interaction between climate-related changes and increased nutrients [37]. Thus, climatic factors and nutrient levels may enhance the frequency and severity of potentially toxic blooms in freshwater ecosystems. Since climate is long-term and can trigger bloom formation and ensuing health risks, little is known about short-term meteorologic factors on liver disease. Furthermore, the influence of meteorological patterns on liver diseases has not been extensively studied in the field [38]. A population-based study determined that acute-on-chronic liver disease prevalence was influenced by lower temperatures [39]. Therefore, we conducted an ecological study to examine whether meteorological factors, including daily sunlight, daily maximum temperature, and daily precipitation, in conjunction with microcystin, associated with liver disease mortality. Understanding if meteorological factors increase a secondary factor of liver disease mortality, such as microcystin, further warranted examination.

2. Materials and Methods

Secondary data on total microcystins were collected from the 2007 United States Environmental Protection Agency (USEPA) National Lakes Assessment. An enzyme-linked immunosorbent assay (ELISA) (Abraxis, LLC, Warminster, PA) analyzed total microcystins in lake samples (limit of detection < 0.10 μg/L). A composite average of total microcystins was computed for each state by averaging two or more repeated measurements from the same county with individual measurements from different counties. Non-detectable levels of total microcystins or lack of toxin data in the dataset resulted in the exclusion of seven states (Alaska, Hawaii, New Hampshire, New Mexico, South Carolina, Vermont, Wyoming). Mean total microcystins in each state were compared against the WHO relative probable health risk due to microcystins (low, moderate, high).

Environmental data on annual precipitation, average daily max temperature, daily precipitation, and daily sunlight, derived from the North America Land Data Assimilation System (NLDAS) (1979-2011), were gathered from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research (CDC WONDER). Data from 2007 were used to coincide with concentrations of total microcystins. The Underlying Cause of Death database was used to retrieve age-adjusted CLD and cirrhosis death rates of the United States between 2003 and 2007. The International Classification of Disease, Tenth Revision (ICD-10) 113 Cause List was utilized to examine records of age-adjusted CLD and cirrhosis death rates (K70, K73-K74). All ages, genders, origins, and races were selected in the demographics of age-adjusted CLD and cirrhosis death rates (Table A1). Multiple linear regressions were performed in Statistical Package for the Social Sciences (SPSS) version 25. Normality was achieved by log-transforming (base 10) all variables in the analysis.

Further examination identified extraneous variables within the dataset. The removal of outliers resulted in 35 states in the final analysis (Table A2). Statistical significance was based on p < 0.05. Descriptive statistics on mean total microcystins and mean meteorological factors were grouped by census region and state. Inferential statistics were applied to aggregate national data to assess the ecological association between total microcystins, meteorological factors, and age-adjusted CLD and cirrhosis death rates.

3. Results

3.1 Mean total microcystins and meteorological factors by census region

Table 1 displays a summary of mean total microcystins and meteorological factors by census region in 2007. Mean total microcystins was highest in the Midwest, with a concentration of 3.90 μg/L. The South and West had mean total microcystins of 0.858 μg/L and 1.99 μg/L, respectively. Mean total microcystins was lowest in the Northeast, at 0.688 μg/L. Mean daily maximum temperature ranged between 15.44 C in the Midwest to 22.10 C in the South. The West received the least mean daily precipitation at 1.28 mm, while the Northeast received the most at 3.06 mm. Mean daily sunlight ranged from 15064.91 KJ/m2 in the Northeast to 17635.69 KJ/m2 in the West.

Census region

Mean total microcystins (μg/L)

WHO relative probable health risk

Mean daily maximum temperature (C)

Mean daily precipitation (mm)

Mean daily sunlight (KJ/m2)

South

n =15

0.851 σ = 0.60

Low

22.10

2.71

17171.66

Northeast

n = 7

0.688 σ = 0.29

Low

15.98

3.06

15064.91

Midwest

n = 12

3.90 σ = 5.60

Low

15.44

2.33

15409.55

West

n = 9

2.00 σ = 1.95

Low

15.52

1.28

17635.69

Table 1: Summary of mean total microcystins and mean meteorological factors by census region in 2007. n = number of states, σ = standard deviation, WHO = World Health Organization, Low = 0.10 µg/L ≤ 10 μg/L. C = Celsius, mm = millimeters, KJ/m2 = Kilojoule per square meter.

State

Mean total microcystins (μg/L)

WHO relative probable health risk

Mean daily maximum temperature (C)

Mean daily precipitation (mm)

Mean daily sunlight (KJ/m2)

Alabama

0.33  n = 1

Low

24.83

2.43

17761.61

Arizona

1.0   n = 1

Low

22.62

0.85

19804.18

Arkansas

0.885  n = 2

Low

22.93

3.19

16681.82

California

0.22  n = 4

Low

21.0

0.99

19698.04

Colorado

2.73  n = 3

Low

13.66

1.36

17497.51

Connecticut

0.343  n = 6

Low

14.22

3.11

15452.60

Delaware

0.58  n = 6

Low

17.63

2.48

16249.63

Florida

1.62  n = 12

Low

27.28

3.09

18945.54

Georgia

0.31  n = 7

Low

24.80

2.47

18231.50

Idaho

3.04  n = 5

Low

12.30

1.35

16188.47

Illinois

1.47  n = 15

Low

17.77

2.56

15591.87

Indiana

0.55  n = 32

Low

17.36

2.93

15603.23

Iowa

0.69  n = 14

Low

15.06

2.82

15311.84

Kansas

0.98  n = 5

Low

19.16

2.57

16770.71

Kentucky

0.76  n = 2

Low

20.20

2.89

16220.59

Louisiana

0.631  n = 8

Low

25.37

3.71

17654.09

Maine

0.845  n = 5

Low

9.41

3.25

14242.49

Maryland

0.267  n = 3

Low

17.55

2.48

16034.71

Massachusetts

0.903  n = 2

Low

31.12

3.06

15315.42

Michigan

1.26  n = 23

Low

12.65

2.09

14985.34

Minnesota

1.79  n = 39

Low

11.77

1.83

14622.10

Mississippi

0.465  n = 2

Low

24.88

2.87

17554.24

Missouri

0.20  n = 11

Low

19.21

2.92

15957.14

Montana

1.27  n = 15

Low

12.22

1.30

15080.89

Nebraska

4.52  n = 28

Low

16.62

2.11

16054.05

Nevada

0.53  n = 1

Low

16.08

0.54

18346.94

New Jersey

0.703  n = 3

Low

16.28

3.25

15758.56

New York

0.593  n = 4

Low

11.92

3.06

14393.31

North Carolina

0.266  n = 12

Low

21.55

2.34

17402.86

North Dakota

18.18  n = 38

Moderate

12.02

1.40

14816.28

Ohio

13.91  n = 6

Moderate

16.41

2.75

15197.93

Oklahoma

1.03  n = 15

Low

21.59

3.09

16921.44

Oregon

1.18  n = 6

Low

13.71

1.84

16404.71

Pennsylvania

1.17  n = 7

Low

14.30

2.91

14594.54

Rhode Island

0.26  n = 4

Low

14.65

2.81

15697.50

South Dakota

2.53  n = 28

Low

14.88

1.61

15374.59

Tennessee

0.75  n = 4

Low

21.84

2.40

16648.09

Texas

2.48  n = 13

Low

24.95

2.52

17999.03

Utah

6.94  n = 4

Low

15.35

0.85

17701.46

Virginia

0.691  n = 6

Low

19.27

2.35

16634.94

Washington

1.14  n = 5

Low

12.76

2.52

17999.03

West Virginia

1.70  n = 1

Low

16.87

2.35

16634.94

Wisconsin

0.735  n = 16

Low

12.38

2.39

14629.55

Table 2: Summary of mean total microcystins above 0.10 μg/L and mean meteorological factors by state in 2007. n = number of measurements ≥ 0.10 µg/L, WHO = World Health Organization, Low = 0.10 µg/L ≤ 10 μg/L, Moderate = 10 ug/L ≤ 20 µg/L. C = Celsius, mm = millimeters, KJ/m2 = Kilojoule per square meter.

3.2 Mean total microcystins and meteorological factors by census region

Mean total microcystins and mean meteorological factors by state in 2007 are depicted in Table 2. The mean total microcystins for all 43 states was 1.91 μg/L. The lowest mean total microcystins occurred in Missouri (0.20 μg/L), and the highest mean total microcystins occurred in North Dakota (18.18 μg/L). 41 states (95.35%) had a low relative probable health risk, while 2 states (4.65%) had a moderate relative probable health risk. For meteorological factors, mean daily maximum temperature reached 17.87 C, mean daily precipitation 2.36 mm, and mean daily sunlight was 16434.07 KJ/m2.

State

Region

Age-adjusted chronic liver disease and cirrhosis death rates per 100,000

Alabama

South

9.6

Arizona

West

11.9

Arkansas

South

8.0

California

West

11.2

Colorado

West

9.9

Connecticut

Northeast

7.5

Delaware

South

8.6

Florida

South

10.5

Georgia

South

8.0

Idaho

West

9.1

Illinois

Midwest

8.2

Indiana

Midwest

7.6

Iowa

Midwest

6.2

Kansas

Midwest

7.4

Kentucky

South

8.3

Louisiana

South

7.9

Maine

Northeast

8.4

Maryland

South

7.5

Massachusetts

Northeast

7.8

Michigan

Midwest

9.4

Minnesota

Midwest

6.4

Mississippi

South

8.7

Missouri

Midwest

7.0

Montana

West

11.0

Nevada

West

11.1

New Jersey

Northeast

7.6

New York

Northeast

6.3

North Carolina

South

8.7

Oklahoma

South

11.2

Oregon

West

10.3

Pennsylvania

Northeast

7.6

Rhode Island

Northeast

9.4

South Dakota

Midwest

10.7

Tennessee

South

10.0

Texas

South

11.4

Virginia

South

7.4

Washington

West

9.0

Table 3: Age-adjusted chronic liver disease and cirrhosis death rates per 100,000 from 2003 to 2007 by state.

3.3 Regression models

Multiple linear regressions were run to assess the predictive function of meteorological factors and total microcystins on age-adjusted CLD and cirrhosis death rates. All predictors were initially merged into the model. A positive association was observed between mean total microcystins, meteorological factors, and liver disease mortality (R = 0.726). Approximately 46.4% (R2 = 0.464) of variance in age-adjusted CLD was explained by the predictors. The simultaneous model partially supported the hypothesis that meteorological factors in concurrence with total microcystins predict liver disease mortality (Table 4). The stepwise method was selected to determine which explanatory variables fitted the regression model. In Table 4, the final model revealed a positive association between mean daily sunlight, total microcystins, and age-adjusted CLD and cirrhosis death rates (R = 0.676 and R2 = 0.423). Mean daily maximum temperature and mean daily precipitation were not statistically significant predictors (p > 0.05) (Table 5).

Model

R

R2

F-change

Simultaneous

0.726

0.464

0.000117

Stepwise

0.676

0.423

0.009

Table 4: Multiple linear regressions of exposure correlates and liver disease mortality.

Variables

β

p

Total Microcystins

0.365

0.009

Daily Sunlight

0.621

0.000044

Daily Maximum Temperature

-0.290

0.149

Daily Annual Precipitation

-0.188

0.156

Table 5: Coefficients of predictors for liver disease mortality.

4. Discussion

Liver disease is a serious health problem in the United States. In 2013, CLD and cirrhosis claimed over 33,000 lives, making it the 12th leading cause of death [1]. Liver disease mortality estimates remain conservative, although research suggests that nearly 66,000 individuals die from CLD and cirrhosis each year [2]. The condition is largely preventable, with alcohol, obesity, and viral hepatitis being three major risk factors [40]. Other risk factors, such as toxins, tropical infections, and malnutrition occur in developing countries [6]. These environmental factors may increase in developed countries due to constant lifestyle and weather changes.

Microcystin is a blue-green algal hepatotoxin secreted by freshwater cyanobacteria. When favorable environmental conditions persist within stagnant waters, cyanobacteria multiply to create thick blooms. Bloom senescence can promote microcystin release as cells lyse in water. Microcystin is hepatotoxic since it targets protein phosphates in hepatocytes upon oral ingestion of contaminated drinking water. Inactivation of protein phosphatases PP1 and PP2A stimulates hyperphosphorylation, which can drastically affect liver function [28-30].

Moreover, epidemiological studies indicate microcystin exposure may associate with liver disease. Yet, limited knowledge exists on meteorological factors and chronic liver disease. For instance, average humidity and temperature were shown to correlate with acute-on-chronic liver failure positively and negatively, respectively [39]. The present study explored the ecological association between microcystins, meteorological factors, and liver disease mortality. Study results demonstrated a positive association between daily sunlight, total microcystins, and age-adjusted CLD and cirrhosis death rates. The observed association mirrored previous epidemiological investigations connecting freshwater microcystins with liver disease [31-33]. Daily sunlight exposure was a strong predictor of age-adjusted CLD and cirrhosis death rates. In a different study examining sunlight exposure and end stage renal disease, low amounts of daily sunlight increased the risk of all-cause mortality in dialysis patients, especially among diabetics and individuals age 75 and older [41].

There were a few limitations inherent within the study. First, the study was ecological in design, meaning interpreted results strictly concerned populations, not individuals. The ecological fallacy is a major limitation of an ecological study in which inferences from group data generalize among individuals. In the study context, people who consume drinking water contaminated with microcystin and receive sunlight exposure over their lifetime may die from liver disease. However, one should note that people drink treated water sourced from potable supplies, and CLD and cirrhosis may result from a combination of environmental and health risk factors. Another limitation involves confounding bias, which is not uncommon in ecological studies. The current study lacked known risk factors for CLD and cirrhosis, such as alcohol consumption and obesity. The variables were omitted due to incomplete data of risk factors in the collected secondary data sources. Missing pertinent variables in regression models can increase or decrease the predictivity of exposure variables on a health outcome. Hence, the effect of total microcystin and daily sunlight exposure is perhaps higher than expected if other risk factors were embedded in the model. A third limitation rests with ELISA for total microcystins quantitation. The method is subject to cross-reactivity, matrix interference, and low specificity despite screening multiple samples concurrently. Consequently, the identity of specific congeners and their associated concentrations in lake samples is unknown. Microcystin detection via liquid chromatography mass spectrometry can offer valuable information by distinguishing various congeners in the environment [42].  

Liver disease is a major public health problem and continues to grow as population growth increases and people age. The study identified a positive association between mean total microcystins, daily sunlight exposure, and age-adjusted CLD and cirrhosis death rates. The association, however, does not imply causation. Future research should consider behavioral and environmental lifestyle factors when exploring associations between meteorological factors, hepatotoxins, and liver disease mortality. Findings may encourage routine biomonitoring practices in endemic areas of liver disease where lakes bloom. Health and medical professionals can use the results to aid in the prevention, diagnosis, and treatment of liver diseases.

Acknowledgments

This research received no external funding.

Conflict of Interest

The author declares no conflict of interest.

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  42. Massey IY, Wu P, Wei J, et al. A mini-review on detection methods of microcystins. Toxins 12 (2020).

Appendix

State

Race

Gender

Deaths

Population

Age-adjusted chronic liver disease and cirrhosis death rates rate per 100,000

Alabama

Black or African American

Female

136

3248829

4.4

Alabama

Black or African American

Male

282

2825850

12

Alabama

White

Female

721

8359324

7

Alabama

White

Male

1238

8072164

13.7

Arizona

American Indian or Alaska Native

Female

204

804525

33.7

Arizona

American Indian or Alaska Native

Male

303

780419

55

Arizona

Black or African American

Female

17

586581

4.0 (Unreliable)

Arizona

Black or African American

Male

33

638129

9.7

Arizona

White

Female

995

12817699

7

Arizona

White

Male

1957

12724498

15.1

Arkansas

Black or African American

Female

48

1167578

4.7

Arkansas

Black or African American

Male

69

1052648

7.9

Arkansas

White

Female

365

5782643

5.2

Arkansas

White

Male

717

5626527

11.6

California

American Indian or Alaska Native

Female

118

1450691

11.2

California

American Indian or Alaska Native

Male

205

1467249

19.9

California

Asian or Pacific Islander

Female

284

12721237

2.4

California

Asian or Pacific Islander

Male

525

11690059

5.3

California

Black or African American

Female

363

6642153

6

California

Black or African American

Male

701

6428279

13.4

California

White

Female

5512

69075470

7.8

California

White

Male

11555

69452053

17.7

Colorado

American Indian or Alaska Native

Female

20

178431

17.1

Colorado

American Indian or Alaska Native

Male

27

183167

17.9

Colorado

Black or African American

Female

12

511727

2.8 (Unreliable)

Colorado

Black or African American

Male

46

554676

11.5

Colorado

White

Female

773

10516402

7.1

Colorado

White

Male

1384

10603678

13.3

Connecticut

Black or African American

Female

41

999520

4.9

Connecticut

Black or African American

Male

53

911084

8

Connecticut

White

Female

478

7656792

4.9

Connecticut

White

Male

870

7261770

10.9

Delaware

Black or African American

Female

13

478336

3.2 (Unreliable)

Delaware

Black or African American

Male

36

429534

10.5

Delaware

White

Female

133

1619511

6.7

Delaware

White

Male

204

1546378

11.9

Florida

American Indian or Alaska Native

Male

16

222951

8.7 (Unreliable)

Florida

Asian or Pacific Islander

Female

10

1179080

1.3 (Unreliable)

Florida

Asian or Pacific Islander

Male

32

1037038

4.3

Florida

Black or African American

Female

275

7452040

4.4

Florida

Black or African American

Male

477

6914609

9.1

Florida

White

Female

3505

36539331

7.2

Florida

White

Male

6627

35245038

15.6

Georgia

Asian or Pacific Islander

Male

15

671654

4.0 (Unreliable)

Georgia

Black or African American

Female

273

7211431

4.6

Georgia

Black or African American

Male

386

6395644

8.4

Georgia

White

Female

977

14854398

6

Georgia

White

Male

1728

14791423

11.9

Idaho

American Indian or Alaska Native

Female

24

61511

54.7

Idaho

American Indian or Alaska Native

Male

20

61828

38.1

Idaho

White

Female

209

3424909

5.9

Idaho

White

Male

390

3447041

11.6

Illinois

American Indian or Alaska Native

Male

13

160226

11.8 (Unreliable)

Illinois

Asian or Pacific Islander

Female

26

1426761

2.9

Illinois

Asian or Pacific Islander

Male

33

1356464

3

Illinois

Black or African American

Female

269

5161785

5.7

Illinois

Black or African American

Male

472

4568874

12.6

Illinois

White

Female

1618

25402857

5.6

Illinois

White

Male

2768

24861441

11.1

Indiana

Black or African American

Female

64

1526741

5

Indiana

Black or African American

Male

129

1414048

12

Indiana

White

Female

814

14149157

5.1

Indiana

White

Male

1466

13743938

10.5

Iowa

American Indian or Alaska Native

Female

11

32209

55.4 (Unreliable)

Iowa

American Indian or Alaska Native

Male

12

31776

55.8 (Unreliable)

Iowa

Black or African American

Male

14

225798

9.5 (Unreliable)

Iowa

White

Female

365

7163517

4.2

Iowa

White

Male

599

6937325

8

Kansas

American Indian or Alaska Native

Male

14

87936

20.4 (Unreliable)

Kansas

Black or African American

Female

15

439847

4.1 (Unreliable)

Kansas

Black or African American

Male

29

449629

8.7

Kansas

White

Female

350

6250696

4.9

Kansas

White

Male

643

6103273

10.2

Kentucky

Black or African American

Female

28

849334

3.7

Kentucky

Black or African American

Male

67

822665

11

Kentucky

White

Female

596

9661234

5.3

Kentucky

White

Male

1142

9301818

11.8

Louisiana

Black or African American

Female

135

3843199

3.9

Louisiana

Black or African American

Male

303

3465126

10.6

Louisiana

White

Female

465

7362405

5.3

Louisiana

White

Male

880

7151226

11.5

Maine

White

Female

243

3275144

5.9

Maine

White

Male

412

3126808

11.4

Maryland

Asian or Pacific Islander

Female

14

769240

2.5 (Unreliable)

Maryland

Asian or Pacific Islander

Male

14

706625

2.9 (Unreliable)

Maryland

Black or African American

Female

162

4476007

3.9

Maryland

Black or African American

Male

353

3908074

10.4

Maryland

White

Female

586

9119527

5.4

Maryland

White

Male

1032

8797543

10.9

Massachusetts

Black or African American

Female

35

1251232

3.4

Massachusetts

Black or African American

Male

76

1163882

9.4

Massachusetts

White

Female

905

14423604

5.1

Massachusetts

White

Male

1692

13483281

11.7

Michigan

American Indian or Alaska Native

Female

34

200968

21.8

Michigan

American Indian or Alaska Native

Male

35

195793

21.1

Michigan

Asian or Pacific Islander

Male

19

604778

5.2 (Unreliable)

Michigan

Black or African American

Female

226

3916102

6.2

Michigan

Black or African American

Male

441

3546973

14.8

Michigan

White

Female

1442

20806241

6

Michigan

White

Male

2776

20296999

12.8

Minnesota

American Indian or Alaska Native

Female

47

175152

36.5

Minnesota

American Indian or Alaska Native

Male

48

175077

36.4

Minnesota

Asian or Pacific Islander

Male

12

476958

5.8 (Unreliable)

Minnesota

Black or African American

Female

20

622804

5.7

Minnesota

Black or African American

Male

22

656943

6.1

Minnesota

White

Female

567

11618936

4.3

Minnesota

White

Male

974

11408579

8.2

Mississippi

American Indian or Alaska Native

Male

14

37529

43.6 (Unreliable)

Mississippi

Black or African American

Female

89

2838543

3.7

Mississippi

Black or African American

Male

192

2521161

9.8

Mississippi

White

Female

356

4527502

6.5

Mississippi

White

Male

625

4405730

13

Missouri

Black or African American

Female

71

1830161

4.4

Missouri

Black or African American

Male

113

1643300

9.2

Missouri

White

Female

678

12661755

4.5

Missouri

White

Male

1296

12190948

10

Montana

American Indian or Alaska Native

Female

78

161583

60.1

Montana

American Indian or Alaska Native

Male

56

159717

45

Montana

White

Female

152

2157596

5.9

Montana

White

Male

290

2163816

11.5

Nevada

American Indian or Alaska Native

Female

17

103775

22.1 (Unreliable)

Nevada

American Indian or Alaska Native

Male

28

102707

32.8

Nevada

Asian or Pacific Islander

Female

12

489734

3.1 (Unreliable)

Nevada

Asian or Pacific Islander

Male

14

418091

4.6 (Unreliable)

Nevada

Black or African American

Female

19

513466

4.0 (Unreliable)

Nevada

Black or African American

Male

43

524606

10.9

Nevada

White

Female

389

4884637

7.5

Nevada

White

Male

870

5113929

16.1

New Jersey

Asian or Pacific Islander

Female

28

1682503

2.8

New Jersey

Asian or Pacific Islander

Male

45

1620193

3.7

New Jersey

Black or African American

Female

148

3415394

4.6

New Jersey

Black or African American

Male

244

3049039

10.2

New Jersey

White

Female

1090

17003539

5.2

New Jersey

White

Male

1968

16244174

11.2

New York

American Indian or Alaska Native

Female

17

418514

5.6 (Unreliable)

New York

American Indian or Alaska Native

Male

26

410289

9.5

New York

Asian or Pacific Islander

Female

34

3493849

1.3

New York

Asian or Pacific Islander

Male

109

3328806

4

New York

Black or African American

Female

274

9298457

3

New York

Black or African American

Male

581

8005171

8.9

New York

White

Female

1855

36260895

4.2

New York

White

Male

3529

34501101

9.6

Table A1: Demographics of age-adjusted chronic liver disease and cirrhosis death rates per 100,000 in the United States from 2003 to 2007. Death rates with a numerator of 20 or less are flagged as unreliable.

State

Mean Total Microcystins (μg/L)

Mean Daily Maximum Temperature (C)

Mean Daily Precipitation (mm)

Mean Daily Sunlight (KJ/m2)

Age-Adjusted Chronic Liver Disease and Cirrhosis Death Rates Per 100,000

Alabama

0.33

24.83

2.43

17761.61

9.6

Arizona

1.00

22.62

0.85

19804.18

11.9

Arkansas

0.885

22.93

3.19

16681.82

8.0

California

0.22

21.0

0.99

19698.04

11.2

Colorado

2.73

13.66

1.36

17497.51

9.9

Connecticut

0.343

14.22

3.11

15452.60

7.5

Delaware

0.58

17.63

2.48

16249.63

8.6

Florida

1.62

27.28

3.09

18945.54

10.5

Georgia

0.31

24.80

2.47

18231.50

8.0

Idaho

3.04

12.30

1.35

16188.47

9.1

Illinois

1.47

17.77

2.56

15591.87

8.2

Indiana

0.55

17.36

2.93

15603.23

7.6

Iowa

0.69

15.06

2.82

15311.84

6.2

Kansas

0.98

19.16

2.57

16770.71

7.4

Kentucky

0.76

20.20

2.89

16220.59

8.3

Louisiana

0.631

25.37

3.71

17654.09

7.9

Maine

0.845

9.41

3.25

14242.49

8.4

Maryland

0.267

17.55

2.48

16034.71

7.5

Massachusetts

0.903

31.12

3.06

15315.42

7.8

Michigan

1.26

12.65

2.09

14985.34

9.4

Minnesota

1.79

11.77

1.83

14622.10

6.4

Mississippi

0.465

24.88

2.87

17554.24

8.7

Missouri

0.20

19.21

2.92

15957.14

7.0

Montana

1.27

12.22

1.30

15080.89

11.0

Nevada

0.53

16.08

0.54

18346.94

11.1

New Jersey

0.703

16.28

3.25

15758.56

7.6

New York

0.593

11.92

3.06

14393.31

6.3

Table A2: Mean total microcystins and mean meteorological factors from 2007 and age-adjusted chronic liver disease and cirrhosis death rates from 2003 to 2007 in the United States.

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