Abstract

Immunosuppressive has been the main treatment for patients with moderate or severe autoimmune hepatitis (AIH) as the survival benefits have clearly been demonstrated in clinical trials. Seasonal variations in treatment have not been studied yet, hence, we aim to study the potential relationship between the Lunar month of diagnosis and treatment options in AIH. All cases of AIH who presented to our hospitals between Jan 2016 and Jan 2021 were reviewed. Data was analyzed using the binary logistic regression model and Chi-square test of association to establish any potential relationship between the Lunar month of diagnosis and treatment response in AIH. Total number of patients with clinically and histologically proven AIH was sixty. Forty-seven were females (78.33%) and 28.33% were males (n=17). Liver biopsies were recorded in twenty-six cases (43.3%) among whom, interface hepatitis was found in ten patients (16.7%).

Total of twelve patients were not on any treatment and five of them (41.6%) had been diagnosed during the Full Moon (FM) phase. Patients who have been diagnosed with AIH during the Third Quarter (TQ) Phase were only three (5.0%), however 66.6% of them were on combination therapy of Steroids and Azathioprine (AZA). Interestingly, fifth of the patients were diagnosed during the First Quarter phase and only one of them were on combined therapy.

Ten patients in total were on steroids only among whom 40% were diagnosed during the FM phase. The Chi-square test of association showed a non-significant association of the lunar month of diagnosis with the treatment they receive, X² (9, N= 31) = 7.99, p = .535.

Steroids and AZA treatment exhibited lower frequency on full moon and third quarter moon than new and first quarter moon. Our data show that patients diagnosed with AIH during the FM phase of the lunar cycle are less likely to require combination therapy of steroids and AZA. We could not establish any significant relation between the lunar month of diagnosis and treatment response in AIH.

Introduction

New moon (NM), first quarter (FQ), full moon (FM), and third quarter (TQ) of the lunar month have varying gravitational pulls on the earth ^[1,2]. The amplitude of ocean tidal currents varies as per the relative location of the moon in its orbit, demonstrating this fluctuation in lunar gravitational force ^[1,3,4]. The moon's gravitational pull could have an impact on the human body's fluid compartments ^[1]. The human body contains around 42 liters of water (60 percent of body weight) ^[5] and, like sea water, the body water may form some type of tidal wave, which has been dubbed "human tidal wave" or "biological tide" ^[1,6]. The idea of "biological tide" was utilised by these authors to describe the moon effect on human emotional disturbance. Though there is much debate concerning the impact of lunar rhythm on human behaviour and illness onset ^[7-10], the fundamental concerns about lunar rhythm's influence on physiological systems remain unsolved. The lunar cycle has been attributed with the power to influence a variety of human phenomena across history. Nonetheless, proof supporting the moon's alleged impact on human behaviour has proven difficult, and research has tended to suffer from methodological and data analysis flaws. We reviewed Medline, PubMed, and the bibliographies of similar papers and were unable to find any research that examined the lunar fluctuation and its impacts on areas of human life such as, relationship of lunar month of diagnosis with gender, month of birth, symptoms of presentations, ALP/AST ratio, treatment they receive, other autoimmune diseases, special moon events, relationship of lunar month of diagnosis with cirrhosis, and relationship of special moon events with cirrhosis.

Material and methods

Study design and setting

A prospective cohort study was used to assess the relation of Lunar Month of Diagnosis with clinical and sociodemographic characteristics including Month of Birth, Gender, Histological findings Symptoms of Presentation, nature of Treatment patient is on (AzA: azathioprine, steroids etc.), Development of ALF (Acute Liver failure), Association with other Autoimmune Disease.

Data analysis

Microsoft Excel was used for data management (Microsoft Office, Redmond, Washington, United States) and statistical analysis was performed by using statistical package for social sciences (SPSS v26) and Jamovi (v 2.2.3). The categorical data were presented as frequency and percentage while the continuous data were presented as a mean and standard deviation. The binary logistic regression model was implied to assess the association association of Special Moon event with Cirrhosis a Chi-square test of association was run. The P-value was stated significant if ≤ 0.5.

Results

To explore the association of Lunar Month of Diagnosis with clinical and sociodemographic characteristics including Month of Birth, Gender, Histological findings Symptoms of Presentation, nature of Treatment patient is on (AzA: azathioprine, steroids etc.), Development of ALF (Acute Liver failure), Association with other Autoimmune Disease, Special Moon event, and Cirrhosis a series of Chi-square test of Association were run using Jamovi. Further to examine the association of Special Moon event with Cirrhosis a Chi-square test of association was run. Table 1 to 9 shows the detail results of Chi-square test of association.

Furthermore, to explore the clinical characteristics including Liver Biopsy, DEXA Scan, Histological findings, Treatment they on, level of serum globulin and the history of ANA positive of the patients with Autoimmune Hepatitis reviewed in the hospital over the last 5 years, descriptive statistics were run using Jamovi. Table 10 and Figure 1-8 shows the details.

A Chi-square test of Association was performed to examine the relationship of Lunar Month of Diagnosis with Gender. The Chi-square test of association showed a non-significant association of Lunar Month of Diagnosis with Gender, X² (3, N= 31) = 3.50, p = .321. Further, the findings showed that despite the non-significant Chi-square test of association, the male exhibited higher frequency on new moon than female. However, male exhibited lower frequency on full moon than female.

A Chi-square test of Association was performed to examine the relationship of Lunar Month of Diagnosis with Month of Birth. The Chi-square test of association showed a non-significant association of Lunar Month of Diagnosis with Month of Birth, X² (30, N= 31) = 36.30, p = .200.

A Chi-square test of Association was performed to examine the relationship of Lunar Month of Diagnosis with Symptoms of presentations. The Chi-square test of association showed a non-significant association of Lunar Month of Diagnosis with Symptoms of presentations, X² (18, N= 31) = 18.50, p = .420. Further, the findings showed that despite the non-significant Chi-square test of association, the No symptoms exhibited higher frequency on full moon than new, first quarter and third quarter moon.

A Chi-square test of Association was performed to examine the relationship of Lunar Month of Diagnosis with ALPAST or ALT Ratio. The Chi-square test of association showed a non-significant association of Lunar Month of Diagnosis with ALPAST or ALT Ratio, X² (6, N= 31) = 3.74, p = .711. Further, the findings showed that despite the non-significant Chi-square test of association, the 1.5-3.0 range of ALPAST or ALT Ratio exhibited lower frequency on new moon than full, first quarter and third quarter moon.

A Chi-square test of Association was performed to examine the relationship of Lunar Month of Diagnosis with Treatment they receive. The Chi-square test of association showed a non-significant association of Lunar Month of Diagnosis with Treatment they Receive, X² (9, N= 31) = 7.99, p = .535. Further, the findings showed that despite the non-significant Chi-square test of association, the Steroids and AZA treatment exhibited lower frequency on full moon and third quarter moon than new and first quarter moon.

A Chi-square test of Association was performed to examine the relationship of Lunar Month of Diagnosis with Other Autoimmune Diseases. The Chi-square test of association showed a non-significant association of Lunar Month of Diagnosis with Other Autoimmune Diseases, X² (3, N= 31) = 0.79, p = .851.

A Chi-square test of Association was performed to examine the relationship of Lunar Month of Diagnosis with Special Moon Events. The Chi-square test of association showed a non-significant association of Lunar Month of Diagnosis with Special Moon Events, X² (18, N= 22) = 25.20, p = .120. Further, the findings showed that despite the non-significant Chi-square test of association, the super new moon exhibited higher frequency on new moon than new, first quarter and third quarter moon.

A Chi-square test of Association was performed to examine the relationship of Lunar Month of Diagnosis with Cirrhosis. The Chi-square test of association showed a significant association of Lunar Month of Diagnosis with Cirrhosis, X² (3, N= 31) = 8.93, p = .030. Further, the findings showed that having cirrhosis exhibited higher frequency on the first quarter and third quarter moon than new moon and full moon.

A Chi-square test of Association was performed to examine the relationship of Special Moon Events with Cirrhosis. The Chi-square test of association showed a non-significant association of Special Moon Events with Cirrhosis, X² (6, N= 22) = 4.63, p = .593. Further, the findings showed that having cirrhosis exhibited higher frequency on the first quarter and third quarter moon than new moon and full moon.

Table 10 shows the descriptive statistics of clinical characteristics for the study population. The findings indicated that about 43% of the sample had liver biopsy. Further the findings indicated that only 17% had Interface Hepatitis while majority had no liver histology (57%) followed by those had no record (20%). Furthermore, the results indicated that majority (57%) had a history of alcohol intake less than 25g/day, followed by greater than 60g/day (5%). However, 22% had no history followed by patients had not taking alcohol (15%). In terms of Hepatitis viral marker, only 5% cases had a history of Positive while majority (77%) had negative history followed by 18% who had no record. Further the results indicated that only 3% had a AMA positive and majority (83%) had no AMA positive. Moreover, the findings showed that majority (80%) had no vaccination history. In terms of DEXA the results indicated that about 28% had DEXA, however, majority (51%) had no DEXA. Lastly, the findings indicated that serum globulin concentration <1 were found in 26% of the cases, followed by 1.5-2 (22%). However, 25% of the cases had not tested for serum globulin concentration.

Figure 1. Figure 1 : shows the graphical representation of Liver Biopsy

Figure 2. Figure 2 : shows the graphical representation of Liver Histology

Figure 3. Figure 3 : shows the graphical representation of Alcohol Intake

Figure 4. Figure 4 : shows the graphical representation of Hepatitis Viral Marker

Figure 5. Figure 5 : shows the graphical representation of AMA Positive

Figure 6. Figure 6 : shows the graphical representation of Vaccination History

Figure 7. Figure 7 : shows the graphical representation of DEXA

Figure 8. Figure 8 shows the graphical representation of Serum Globulin Concentration.

Discussion

In this cohort to test the association between the lunar month of diagnosis with clinical and sociodemographic characteristics, we found that the male exhibited higher frequency on new moon than female. However, male exhibited lower frequency on full moon than female. No symptoms exhibited higher frequency on full moon than new, first quarter and third quarter moon. Moreover, the 1.5-3.0 range of ALPAST or ALT Ratio exhibited lower frequency on new moon than full, first quarter and third quarter moon. It was also observed that the Steroids and AZA treatment exhibited lower frequency on full moon and third quarter moon than new and first quarter moon. The super new moon exhibited higher frequency on new moon than new, first quarter and third quarter moon. When seeing Lunar Month of Diagnosis with Cirrhosis, patients having cirrhosis exhibited higher frequency on the first quarter and third quarter moon than new moon and full moon. Similarly, when considering Special Moon Events with Cirrhosis, having cirrhosis exhibited higher frequency on the first quarter and third quarter moon than new moon and full moon.

Pliny the Elder stated that the moon's influence "pierces all things," including plants, fish, animals, and mankind ^[11]. He also made the connection between the Moon and tides, which Newton validated quantitatively. The lunar surroundings in the geomagnetic tail is an exciting field of research with extensive implications for surface-bounded exospheres across our planetary system and well beyond, along with our knowledge of the classical physics of plasma discharges in delicate settings. The existence of lunar-derived plasma in the geomagnetic tail may potentially have implications for the Moon-Earth interaction. Charged particles can move from the Moon to the near-Earth environment ^[12], impacting the environment not just near the Moon, but also where magnetic field lines connect the Moon to the Earth's ionosphere. Plasma detected near the Moon, on the other hand, may contain material produced not just from the Moon but also from the terrestrial ionosphere ^[13]. A survey of recent research on the ubiquitous nature of this lunar power is confirmed by biological responses, particularly from plants and animals. However, physics computations and other reasons reject the alleged gravitational processes and light. With evidence of electromagnetic fields related with recent space travel, a new method is possible, comparable, but more limited, effects from the Earth's magnetotail at full moon during the night, and similar, but more restricted, effects from the Earth's magnetotail at full moon during the day. At new moon during the day, the Moon's wake on the magnetosphere is visible ^[11].

The majority of chronobiology research has focused on solar cycles (daily and yearly); moonlight and the lunar cycle have gotten far less attention. The impacts of the moon cycle have been extensively researched in intertidal settings, with an emphasis on behaviour and reproductive synchronization ^[14]. The impacts of moonlight have long been recognised by terrestrial ecologists. Foraging behaviour has an impact on predation success and, as a result, predation danger and the usage of habitat ^[15].

The lunar cycle corresponds to the 29.5-days necessary for Moon to orbit the Earth, as well as the 24.8-hours required for the Moon to pass through the same position over the Earth ^[16]. These two cycles are responsible for a variety of environmental cycles, including lighting levels, tides, and geomagnetic fields. The Moon, the Earth, and the Sun are on about the same axis every 14.5 days as a result of the Moon's orbit around the Earth, and this causes spring tides. The 24.8-hour lunar day, on the other hand, results in a 12.4-hour tidal cycle, with high tides occurring when the Moon is immediately over the sea water or on the diametrically opposing point on the horizon. Finally, since the Moon's orbit deviates from the Earth's equatorial plane, the amplitude of the semidiurnal tides (with a period of 12.4 h) is asymmetrical, resulting in semidiurnal inequality in the tides, which in certain circumstances is so uneven that only one large ebb of water occurs every 24.8 h and not every 12.4 h ^[17]. All of these environmental changes may be recognised by animals and plants, affecting their behaviour, physiology, and the adaptive value of completing a certain activity at a specific moment, as well as their viability.

However, through research, the lunar orbit has been found to have no correlation with the induction of labor and delivery of newborns (specifically single births and first births) ^[18-20], menstrual cycles ^[21], ED and ambulance call volumes, general inpatient and critical care admission rates ^[22], postoperative nausea and complications ^[23], prison inmate outbursts and assaults ^[24], erratic or violent behaviors (‘lunacy’) ^[25,26], the occurrence of cardiac disease exacerbation (angina, myocardial infarction, and congestive heart failure) ^[27], the occurrence of trauma ^[28], its severity, mortality, or length of hospital stay ^[29], homicides ^[30]; and suicides ^[31] and even dog bites ^[32].

A full moon, on the other hand, has been linked to symptomatic atrial fibrillation episodes ^[33], paroxysmal supraventricular tachycardias ^[34], a slight reduction in absenteeism ^[35], inpatient admissions due to diarrheal illness complications ^[36], multiple births and births to mothers with multiple children ^[18], A small decrease in the number of trauma patients ^[37], the crime rate ^[38], poison centre calls and unintended ingestions ^[39], mental inpatient institution census ^[40,41], gout attacks and bronchial asthma exacerbations in children ^[34] have all been linked to the full moon. The new moon has been linked to a reduction in paroxysmal supraventricular tachycardias ^[34], as well as increases in bronchial asthma exacerbations in children ^[34], suicide attempts and drug usage ^[39], and symptomatic urine incontinence ^[42] retention ^[42], gout attacks ^[43].

Declarations

Ethics approval and consent to participate

Not Applicable

Data Availability

All data are available in the article and further details can be requested directly from the corresponding author.

Conflicts of Interest

“The author(s) declare(s) that there is no conflict of interest regarding the publication of this paper.”

Funding Statement

This article received no external funding.

Authors' contributions

Gadour E has contributed in studies selection, data analysis, study conception and drafting of the manuscript and writing the manuscript. NP, OA and HE have contributed to the data collection, case selection, and reviewing the final manuscript. All authors have approved the final manuscript. All authors read and approved the final manuscript."

References

1. Lieber AL, Sherin CR. Homicides and the lunar cycle: Toward a theory of lunar influence on human emotional disturbance. American Journal of Psychiatry. 1972;129(1):69-74.
2. Myers DE. Gravitational effects of the period of high tides and the new moon on lunacy. The Journal of emergency medicine. 1995;13(4):529-32.
3. Monkhouse FJ. Principles of physical geography: Rowman & Littlefield; 1964.
4. Morgan E. The moon and life on earth. Earth-Moon Relationships: Springer; 2001. p. 279-90.
5. Guyton A, Hall J. Textbook of medical physiology, 11th. Elsevier Inc.; 2006.
6. Thakur C, Sharma D. Full moon and crime. British medical journal (Clinical research ed). 1984;289(6460):1789-91.
7. Terra-Bustamante VC, Scorza CA, de Albuquerque M, Sakamoto AC, Machado HR, Arida RM, et al. Does the lunar phase have an effect on sudden unexpected death in epilepsy? Epilepsy & Behavior. 2009;14(2):404-6.
8. Polychronopoulos P, Argyriou A, Sirrou V, Huliara V, Aplada M, Gourzis P, et al. Lunar phases and seizure occurrence: just an ancient legend? Neurology. 2006;66(9):1442-3.
9. Kollerstrom N, Steffert B. Sex difference in response to stress by lunar month: a pilot study of four years' crisis-call frequency. BMC psychiatry. 2003;3(1):1-8.
10. Biermann T, Estel D, Sperling W, Bleich S, Kornhuber J, Reulbach U. Influence of lunar phases on suicide: the end of a myth? A population‐based study. Chronobiology international. 2005;22(6):1137-43.
11. Bevington M. Lunar biological effects and the magnetosphere. Pathophysiology. 2015;22(4):211-22.
12. Halekas JS, Benna M, Mahaffy PR, Elphic RC, Poppe AR, Delory GT. Detections of lunar exospheric ions by the LADEE neutral mass spectrometer. Geophysical Research Letters. 2015;42(13):5162-9.
13. Poppe AR, Fillingim MO, Halekas JS, Raeder J, Angelopoulos V. ARTEMIS observations of terrestrial ionospheric molecular ion outflow at the Moon. Geophysical Research Letters. 2016;43:6749-58.
14. Mead R. De imperio solis ac lunae in corpora humana, et morbis inde oriundis: Prostat apud Joannem Brindley, celsiss. Walliae Principis bibliopolam, in …; 1746.
15. Seifert S. Richard Mead: One for the ages. Clinical Toxicology. 2011;49(1):53-5.
16. Kronfeld-Schor N, Dominoni D, de la Iglesia H, Levy O, Herzog ED, Dayan T, et al. Chronobiology by moonlight. Proceedings Biological sciences. 2013;280(1765):20123088.
17. Barlow PW, Mikulecký M, Sr., Střeštík J. Tree-stem diameter fluctuates with the lunar tides and perhaps with geomagnetic activity. Protoplasma. 2010;247(1-2):25-43.
18. Ghiandoni G, Seclì R, Rocchi MB, Ugolini G. Does lunar position influence the time of delivery? A statistical analysis. European journal of obstetrics, gynecology, and reproductive biology. 1998;77(1):47-50.
19. Guillon P, Guillon D, Pierre F, Soutoul JH. [Seasonal, weekly and lunar cycles of birth. Statistical study of 12,035,680 births]. Revue francaise de gynecologie et d'obstetrique. 1988;83(11):703-8.
20. Joshi R, Bharadwaj A, Gallousis S, Matthews R. Labor ward workload waxes and wanes with the lunar cycle, myth or reality? Primary care update for Ob/Gyns. 1998;5(4):184.
21. Tiagun NF. [Common periodicity of solar atmosphere rotation and function of the human body]. Biofizika. 1995;40(4):822-4.
22. Thompson DA, Adams SL. The full moon and ED patient volumes: unearthing a myth. The American journal of emergency medicine. 1996;14(2):161-4.
23. Smolle J, Prause G, Kerl H. A double-blind, controlled clinical trial of homeopathy and an analysis of lunar phases and postoperative outcome. Archives of dermatology. 1998;134(11):1368-70.
24. Simón A. Aggression in a prison setting as a function of lunar phases. Psychological reports. 1998;82(3 Pt 1):747-52.
25. Hicks-Caskey WE, Potter DR. Effect of the full moon on a sample of developmentally delayed, institutionalized women. Perceptual and motor skills. 1991;72(3 Pt 2):1375-80.
26. Byrnes G, Kelly IW. Crisis calls and lunar cycles: a twenty-year review. Psychological reports. 1992;71(3 Pt 1):779-85.
27. Segan L, Brennan A, Reid CM, Hiew C, Oqueli E, Ajani A, et al. Impact of lunar phase on outcomes following ST-elevation myocardial infarction. 2020;50(3):322-9.
28. Barr W. Lunacy revisited. The influence of the moon on mental health and quality of life. Journal of psychosocial nursing and mental health services. 2000;38(5):28-35.
29. Coates W, Jehle D, Cottington E. Trauma and the full moon: a waning theory. Annals of emergency medicine. 1989;18(7):763-5.
30. Maldonado G, Kraus JF. Variation in suicide occurrence by time of day, day of the week, month, and lunar phase. Suicide & life-threatening behavior. 1991;21(2):174-87.
31. Martin SJ, Kelly IW, Saklofske DH. Suicide and lunar cycles: a critical review over 28 years. Psychological reports. 1992;71(3 Pt 1):787-95.
32. Chapman S, Morrell S. Barking mad? another lunatic hypothesis bites the dust. BMJ (Clinical research ed). 2000;321(7276):1561-3.
33. Mikulecky M, Valachova A. Lunar influence on atrial fibrillation? Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas. 1996;29(8):1073-5.
34. Mikulecký M, Rovenský J. Gout attacks and lunar cycle. Medical hypotheses. 2000;55(1):24-5.
35. Sands JM, Miller LE. Effects of moon phase and other temporal variables on absenteeism. Psychological reports. 1991;69(3 Pt 1):959-62.
36. Mikulecký M, Schréter I. [Occurrence of acute infectious diarrhea during the lunar phases]. Casopis lekaru ceskych. 1993;132(16):498-501.
37. Nijsten MW, Willemsen SE. [Accidents a matter of chance? The significance of lunar phases and biorhythms in trauma patients]. Nederlands tijdschrift voor geneeskunde. 1991;135(51):2421-4.
38. Thakur CP, Sharma D. Full moon and crime. British medical journal (Clinical research ed). 1984;289(6460):1789-91.
39. Oderda GM, Klein-Schwartz W. Lunar cycle and poison center calls. Journal of toxicology Clinical toxicology. 1983;20(5):487-95.
40. Gorvin JJ, Roberts MS. Lunar phases and psychiatric hospital admissions. Psychological reports. 1994;75(3 Pt 2):1435-40.
41. Temte JL. Exploring environmental cycles in psychiatric patients. Wisconsin medical journal. 1989;88(1):17-20.
42. Payne SR, Deardon DJ, Abercrombie GF, Carlson GL. Urinary retention and the lunisolar cycle: is it a lunatic phenomenon? BMJ (Clinical research ed). 1989;299(6715):1560-2.
43. Rovenský J, Mikulecký M. Pseudogout: timing of attacks and the cosmo geophysical environment. Clinical and experimental rheumatology. 2000;18(4):507-9.