
Citation: E.N. Baranova, R.M. Sarimov, A.A. Gulevich. Stress induced «railway for pre-ribosome export» structure as a new model for studying eukaryote ribosome biogenesis[J]. AIMS Biophysics, 2019, 6(2): 47-67. doi: 10.3934/biophy.2019.2.47
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Human norovirus is an RNA virus of the family Caliciviridae, and a leading cause of acute viral gastroenteritis, resulting in significant morbidity worldwide [1],[2]. In the United States, it has been estimated that there are 5.5 million cases of norovirus gastroenteritis per year, which represents 58% of cases of acute gastroenteritis [3]. Infection with norovirus typically causes nausea, vomiting, diarrhoea and abdominal pain. The symptoms usually develop 12 to 48 hours after infection, and on the average could last between 1 to 3 days. However, for some individuals, especially children, the elderly and individuals with underlying diseases, these symptoms can be severe and lead to dehydration, and in very rare cases even cause death [3],[4].
For decades, norovirus infection has not been associated with extra intestinal manifestation, particularly causing liver injury. Although, hepatotropic viruses, such as hepatitis A through to E, are the most common viral cause of acute hepatitis, other viruses such as rotavirus, Epstein-Barr virus (EBV), herpes simplex virus (HSV), cytomegalovirus (CMV), and varicella zoster virus (VZV) can also cause acute liver injury [5]. However, there has been recent reports of extra intestinal disease following norovirus infection [6]–[8], but little is known of norovirus association with acute hepatitis. We, therefore, review all published studies to evaluate the clinical presentation, management and outcomes of acute hepatitis following norovirus acute gastroenteritis. It is hoped that the findings of this review will provide clinicians with a robust evidence base to investigate and manage patients suspected with norovirus induced hepatitis.
A search strategy was designed to identify studies reporting elevated transaminitis (acute hepatitis) following norovirus acute gastroenteritis. We searched MEDLINE, EMBASE, and the Cochrane library from 01 January 1967 to 15 April 2019. The medical subject headings (MeSH) terms used included “hepatitis”, “transaminitis”, “liver function test”, “transaminases”, “liver”, “norovirus”, “norovirus-induced” and “Norwalk”. These MeSH terms were used in different combinations. The primary search strategy was “norovirus” AND (“hepatitis” OR “transaminitis” OR “transaminase” OR “liver”). We only included studies published in the English language in our review. In addition, we screened reference lists of selected papers to retrieve relevant studies. Appendix 1 shows the full search strategies used.
Inclusion criteria required the study to report norovirus induced hepatitis or transaminitis, which was defined as evidence by elevated transaminitis (Aspartate transaminase +/− Alanine aminotransferase). Studies were excluded if they were studies not written in the English language, laboratory, experimental, animal or not original studies. Two independent reviewers (C.H. and G.O.) screened the title and abstract of papers identified by the electronic searches, evaluating inclusion and exclusion criteria for all papers. We retrieved full articles of included publications and each publication was then independently reviewed for eligibility.
Two reviewers (C.H. and G.O.) independently reviewed the methodological quality of included studies, comparability of case and controls, and outcomes. Discrepancies were resolved by discussion with a third author (F.A.). The specific variables extracted from the publications included: study design, country, age of participants, year of study, method of data collection, method of diagnosis of norovirus, definition of hepatitis, whether other causes of hepatitis, such as EBV and CMV, were excluded, clinical presentation, liver function test (LFT) results, other abnormal test results, duration of illness, management, any previous medical issues and outcomes. The study quality assessment for reporting systematic reviews was done according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement [9].
All studies included in the review were summarised using descriptive analyses to provide an overview of the information on norovirus induced hepatitis, clinical presentations, management, complications and outcome.
We identified 126 potential studies during the initial search, of which 20 were duplicates. Of the remaining 106 studies, 98 studies were excluded on the basis of title and abstracts, and a further 3 articles did not meet the inclusion criteria (Figure 1). Kucuk et al. [10] investigated all cases of transaminitis following viral gastroenteritis but we were able to extract data on norovirus associated transaminitis. Of the included studies, all cases were identified using routine investigations. Five studies [6],[10]–[13] were eligible for inclusion in the final analysis. Most articles were published from Japan (60%, n = 3/5), and one study each from Turkey and USA respectively. Out of the five studies, 2 were case reports, 2 were case series and the remaining one was a retrospective hospital-based study. Three articles involved patients who were younger than 18 years old [10],[12],[13] and the remaining two articles described patients older than 18 years [6],[11]. Three articles had a detailed description of the patient's past medical history [6],[11],[13]. Two of the five articles [11],[13] mentioned using stool specimens for norovirus antigens and three articles used polymerase chain reaction (PCR) [6],[10],[12]. A third diagnostic method, used by two of the articles, were rapid antigen tests [6],[10]. All articles stated that they excluded other possible causes of hepatitis and all included the levels of aspartate transaminase (AST) and alanine aminotransferase (ALT) measured. A summary of the study design, data collection method, study subjects, definition of hepatitis, management and outcome is presented in Tables 1 and 2.
There was a total of 17 cases of norovirus induced hepatitis, and all had elevated ALT (146–458IU/l) and AST levels (700–1150IU/l). The exact peak AST and ALT values were not provided by Kucuk et al. Majority of the cases were below the age of 18 (88%, n = 15) and almost two-third (64.7%, n = 11) had supportive treatment with intravenous fluid administration. In cases reporting sex, there were more females than males (62.5%, 5/8 vs. 37.5%, 3/8). The timing between norovirus infection, as shown by the presence of symptoms, and the detection of elevated LFTs was not specified by Kucuk et al., however amongst the 4 patients in the study from Tsuge et al., on average, this was 6 days. For the 3 remaining studies, norovirus infection and detection of transaminitis was on the same day. The duration from onset of illness to recovery of symptoms was on average 10 days, but this value excludes the patients from Kucuk et al. [10] and Khayat et al. [13] because Kucuk et al. did not provide this information and Khayat et al. had a patient requiring 5 months to recover. This patient reported by Khayat et al., however, had an underlying disease. The duration from onset to recovery of the elevated LFT was available for 6 cases (excluding children with underlying conditions) at 22.5 days.
All cases recovered fully with no reported chronic liver disease or ongoing morbidity. There was no fatality reported.
Of all the cases with transaminitis, 17.6% (n = 3) had underlying medical conditions (comorbidities); one case previously had cholelithiasis and had undergone cholecystectomy, however the duration for recovery from norovirus induced acute hepatitis was not much longer than other cases. Two other cases previously had liver transplants; therefore, they were immunocompromised. Their duration for recovery of symptoms (14 days and 150 days respectively) and LFT results were significantly longer than other cases with an average of 375 days (Table 2).
Study reference | Year of Publication | Country | Study design | Age group studied (years) | Data collection methods | Diagnostic method for norovirus | Timing between norovirus infection and hepatitis/transaminitis | Definition of hepatitis | Excluded other hepatotrophic causes (Y/N) |
Nakajima H et al. [6] | 2012 | Japan (Tokyo) | Case Report | 48 | Retrospective routine laboratory investigations. | Detected by viral antigen check and confirmed by reverse transcription PCR. | Same day | Elevated LFTs | Y |
Zenda T et al. [11] | 2011 | Japan (Ishikawa) | Case Report | 56 | Retrospective routine laboratory investigations. | Positive test for norovirus antigens in stool using immunochromatographic assay kits. | Same day | Elevated LFTs | Y |
Kucuk O et al. [10] | 2016 | Turkey (Istanbul) | Retrospective hospital-based | 0 to 17 | Retrospective study from 2010 and 2013 of acute viral gastroenteritis. | Rapid antigen tests and PCR. | N/A | Elevated LFTs | Y |
Tsuge et al. [12] | 2010 | Japan (Okayama) | Case series | 1 to 7 | Prospective study measuring LFTs and bloods in children presenting with gastroenteritis. | RT-PCR assay | Case 1: 5 days Case 2: 1 day Case 3: 6 days Case 4: 11 days |
Elevated LFTs | Y |
Khayat AA et al. [13] | 2019 | USA (Wisconsin) | Case series | 3 and 8 | Retrospective routine laboratory investigations. | Stool specimens for norovirus antigens. | Case 1 and 2: Same day | Elevated LFTs | Y |
Notes: Abbreviations: FBC, full blood count; LFT, liver function test; USA, United States of America; PCR, polymerase chain reaction; RT-PCR, reverse transcription-polymerase chain reaction.
Characteristics | Studies | ||||
Study reference | Nakajima H et al. [6] | Zenda T et al. [11] | Kucuk O et al. [10] | Tsuge et al. [12] | Khayat AA et al. [13] |
No. of patients | 1 | 1 | 74 | 4 | 2 |
No. of cases | 1 | 1 | 9 | 4 | 2 |
Sex (M/F) | F | F | N/A | Case 1: F; Case 2: F Case 3: M; Case 4: M |
Case 1: F Case 2: M |
Patient Age (yrs) | 48 | 56 | 0–17 | 1–7 | Case 1: 3 Case 2: 8 |
Symptoms | Abdominal pain and diarrhoea. Tenderness in epigastrium and right hypochondrium. | Abdominal cramps, vomiting, diarrhoea. Tenderness in left lower abdomen. |
Vomiting, diarrhoea, and dehydration. | Vomiting, diarrhoea, dehydration, and fever with reduced bowel sounds. Case 2 had convulsions. |
Anaemia, haematemesis, diarrhoea. |
Peak AST (IU/l) | 892 | 1150 | 45.6 | 794 | 700 |
Peak ALT (IU/l) | 146 | 458 | 31.7 | 423 | 400 |
Peak GGT (IU/l) | N/A | 73 | N/A | N/A | N/A |
Peak ALP (IU/l) | No rise | 318 | N/A | N/A | N/A |
Other abnormal results | None | None | Hct 36.9, WCC 13510, CRP 9.7 | Case 2: leucocytosis (WBC 13670IU/l) Case 3: hyponatraemia |
Case 1 had normal liver biopsy. |
Onset to recovery of symptoms (days) | 7 | 4 | N/A | Day 8, day 13, day 8 and day 18 in cases 1, 2, 3 and 4 respectively. | Case 1: 150; Case 2: 14. |
Onset of illness to LFT recovery (days) | 14 | 14 | N/A | Case 1: 26; Case 2: 26;Case 3: 27; Case4: 28 . | Case 1: 480; Case 2: 270 |
Requiring hospitalisation/IV support | Hospitalisation | Hospitalisation | 40 (54%) were hospitalized and 34 (46%) had an observed follow-up. | Cases 1–3 were hospitalized. | Hospitalised |
Management | Supportive therapy | Bowel rest and intravenous rehydration. | IV rehydration | Intravenous fluids for cases 1-3 and oral/IV glycyrrhizin for all. | Case 1 had IV IVIG during their recovery from norovirus infection. |
PMH | Cholelithiasis and cholecystectomy 4 years ago. Drinks alcohol. | Surgery for appendicitis, myoma uteri, gallstones (cholecystectomy) | N/A | N/A | Case 1 had a liver transplant due to hepatoblastoma. Case 2 had liver transplant due to congenital hepatic fibrosis and Caroli's disease. |
Outcome of cases | Alive without chronic liver disease. | Alive without chronic liver disease. | N/A | Alive without chronic liver disease. | Alive without chronic liver disease. |
Notes: Abbreviations: PMH, past medical history; IV, intravenous; Hct, haematocrit; WCC, white cell count; CRP, c-reactive protein; IVIG, immunoglobulins; M, male; F, female; N/A, not available.
Acute hepatitis due to non-hepatotropic viruses such as EBV and HSV have been well described in the literature, but extra intestinal presentations of norovirus, such as disseminated coagulopathy and febrile convulsions, have been considered until recently, a rare phenomenon [7],[8]. A thorough review of the literature identified a very low reported rate of norovirus induced hepatitis, most likely because norovirus gastroenteritis is usually self-limiting and there has been no indication for invasive investigations, such as LFTs, in patients presenting with norovirus. There was a good clinical history of transaminitis, and acutely elevated liver enzymes as described by Zenda T and colleagues [11].
Interestingly, all published articles of norovirus induced acute hepatitis are less than a decade, which also support our findings. This review, in addition to other previously reported cases, would suggest that norovirus induced transaminitis is more common than previously reported in the literature. However, the mechanism of liver injury caused by norovirus remains unclear. One of the factors postulated is the release of pro-inflammatory cytokines induced by the viruses, which affects the inherent hepatic function, while other authors propose a host immune response with activated cytotoxic T cells affecting the hepatocytes [14],[15]. These presumptions are yet to be established by further studies.
Clinical presentations were similar in all cases, mainly vomiting and diarrhoea except one case that was complicated with convulsions [12], and another case with anaemia and haematemesis [13]. However, there seems to be an increase in abdominal tenderness in those with elevated transaminitis. Majority of the cases reported occurred in children and over two-thirds were treated in hospital with intravenous fluid administration. This was not surprising as children are likely to deteriorate faster with norovirus gastroenteritis compared to adults, but whether the liver of a child is more prone to extra intestinal manifestations of norovirus with acute hepatitis will require further investigations. Similar to the management of non-hepatotropic viruses, the treatment of acute hepatitis following norovirus gastroenteritis is mainly supportive, involving primarily rehydration and correction of electrolyte abnormalities. These patients are expected to recover, on average, between 1 to 3 days. However, for some individuals, particularly children, the elderly and individuals with underlying diseases, these symptoms can be severe and lead to dehydration, and in very rare cases even cause death [3],[4]. It is also important to note that many of these patients would have severe dehydration from vomiting and diarrhoea, which are both common symptoms of norovirus infection. As a result, elevated LFTs may result, however, this would not explain the lymphocytic infiltration seen using pathological investigations in the study from Khayat et al.
A longer recovery period in cases with norovirus induced hepatitis was observed. In another retrospective study in Japan, including 71 children with norovirus acute gastroenteritis, the mean duration of illness was twice as long in infants and these infants have a greater severity of illness [16]. However, concomitant extra intestinal manifestations were not explored, possibly because this is such a rare event and there was no robust evidence base to investigate children with suspected norovirus induced acute hepatitis, it is therefore prudent that children with protracted course of illness following norovirus gastroenteritis should be evaluated for possible extra intestinal manifestation, including acute hepatitis.
This study is not without limitations. Most of the included studies were either case reports or case series, which are generally of low evidence. In addition, 17.6% cases had an underlying liver disease, which will predispose them to liver diseases, and these were adjusted for in this review. In particular, Khayat et al. [13] describes two patients with liver transplants and who experienced norovirus induced hepatitis. Nevertheless, all cases were thoroughly investigated for other possible causes of liver dysfunction, and one of the articles completely excluded patients who were positive for other viruses [10]. All papers defined hepatitis as having elevated LFT results. Reassuringly, the elevated LFTs settled within three weeks and all cases recovered with no evidence of chronicity including fatality, but we observed a much longer recovery period in cases with underlying medical conditions.
Norovirus gastroenteritis is usually a self-limiting illness, requiring mainly supportive therapy. This review therefore highlights the need for clinicians to consider norovirus induced acute hepatitis, especially in children with protracted illness, and as a potential cause of elevated transaminases.
[1] | Tarduno JA, Cottrell RD, Davis WJ, et al. (2015) A Hadean to Paleoarchean geodynamo recorded by single zircon crystals. Science 349: 521‒524. |
[2] | Martin A, McMinn A (2018) Sea ice, extremophiles and life on extra-terrestrial ocean worlds. Int J Astrobiol 17: 1‒16. |
[3] | Stevenson DJ (2003) Planetary magnetic fields. Earth Planet Sci Lett 208: 1‒11. |
[4] | Purucker ME, Clark DA (2011) Mapping and interpretation of the lithospheric magnetic field. In: Mandea M, Korte M, Geomagnetic Observations and Models. Dordrecht: Springer, 311‒337. |
[5] | Da Silva JAT, Dobránszki J (2016) Magnetic fields: how is plant growth and development impacted? Protoplasma 253: 231‒248. |
[6] |
Cucinotta FA, Cacao E (2017) Non-targeted effects models predict significantly higher mars mission cancer risk than targeted effects models. Sci Rep 7: 1832. doi: 10.1038/s41598-017-02087-3
![]() |
[7] | Agliassa C, Maffei ME (2019) Reduction of geomagnetic field (GMF) to near null magnetic field (NNMF) affects some Arabidopsis thaliana clock genes amplitude in a light independent manner. J Plant Physiol 232: 23‒26. |
[8] | Novitskii YI, Novitskaya GV (2016) Action of Permanent Magnetic Field on Plants, Moscow: Nauka. |
[9] | Maffei ME (2014) Magnetic field effects on plant growth, development, and evolution. Front Plant Sci 5: 445. |
[10] |
Binhi VN, Prato FS (2017) Biological effects of the hypomagnetic field: an analytical review of experiments and theories. Plos One 12: e0179340. doi: 10.1371/journal.pone.0179340
![]() |
[11] | Galland P, Pazur A (2005) Magnetoreception in plants. J Plant Res 118: 371‒389. |
[12] |
Belyavskaya NA (2001) Ultrastructure and calcium balance in meristem cells of pea roots exposed to extremely low magnetic fields. Adv Space Res 28: 645-650. doi: 10.1016/S0273-1177(01)00373-8
![]() |
[13] |
Belyavskaya NA (2004) Biological effects due to weak magnetic field on plants. Adv Space Res 34: 1566-1574. doi: 10.1016/j.asr.2004.01.021
![]() |
[14] | Belyavskaya NA, Fomicheva VM, Govorun RD, et al. (1992) Structure-functional organization of meristem cells of pea, flax and lentil roots under conditions of the geomagnetic field screening. Biofizika 37: 759-768. |
[15] | Baranova EN, Baranova GB, Kharchenko PN (2011) Effect of weak magnetic field and low positive temperature on chromatin and nucleolus ultrastructure of rye and barley. Russ Agric Sci 37: 453‒461. |
[16] |
Mo WC, Zhang ZJ, Liu Y, et al. (2013) Magnetic shielding accelerates the proliferation of human neuroblastoma cell by promoting G1-phase progression. Plos One 8: e54775. doi: 10.1371/journal.pone.0054775
![]() |
[17] |
Mo WC, Zhang ZJ, Wang DL, et al. (2016) Shielding of the geomagnetic field alters actin assembly and inhibits cell motility in human neuroblastoma cells. Sci Rep 6:1-15. doi: 10.1038/s41598-016-0001-8
![]() |
[18] |
Belyaev IY, Alipov YD, Harms-Ringdahl M (1997) Effects of zero magnetic field on the conformation of chromatin in human cells. Biochim Biophys Acta Gen Sub 1336:465-473. doi: 10.1016/S0304-4165(97)00059-7
![]() |
[19] | Lee SK, Park S, Kim YW (2016) The effects of extremely low-frequency magnetic fields on reproductive function in rodents. In: Insights from Animal Reproduction. |
[20] | Sarimov R, Malmgren LOG, Markova E, et al. (2004) Nonthermal GSM microwaves affect chromatin conformation in human lymphocytes similar to heat shock. IEEE Trans Plasma Sci 32: 1600‒1608. |
[21] | Sarimov R, Alipov ED, Belyaev IY (2011) Fifty hertz magnetic fields individually affect chromatin conformation in human lymphocytes: dependence on amplitude, temperature, and initial chromatin state. Bioelectromagnetics 32: 570‒579. |
[22] | Maffei ME (2019) Plant Responses to Electromagnetic Fields, In: Greenebaum B, Barnes F, Biological and Medical Aspects of Electromagnetic Fields, 4 Eds., CRC Press, 89‒110. |
[23] | Binhi VN (2016) Primary physical mechanism of the biological effects of weak magnetic fields. Biophysics 61: 170‒176. |
[24] | Shatalov VM (2009) Degasation of bioliquids as the target of weak electromagnetic field biological effects. Biophys Bull 23: 92‒99. |
[25] |
Silletta EV, Tuckerman ME, Jerschow A (2018) Unusual proton transfer kinetics in water at the temperature of maximum density. Phys Rev Lett 121: 076001. doi: 10.1103/PhysRevLett.121.076001
![]() |
[26] |
Kalinina NO, Makarova S, Makhotenko A, et al. (2018) The multiple functions of the nucleolus in plant development, disease and stress responses. Front Plant Sci 9: 132. doi: 10.3389/fpls.2018.00132
![]() |
[27] | Sirri V, Jourdan N, Hernandez-Verdun D, et al. (2016) Sharing of mitotic pre-ribosomal particles between daughter cells. J Cell Sci 129: 1592‒1604. |
[28] | Sato S, Myoraku A (1994) Three-dimensional organization of nuclear DNA in the higher plant nucleolonema studied by immunoelectron microscopy. Micron 25: 431‒437. |
[29] | Henras AK, Plisson‐Chastang C, O'Donohue MF, et al. (2015) An overview of pre‐ribosomal RNA processing in eukaryotes. Wiley Interdiscip Rev: RNA 6: 225‒242. |
[30] | Schellhaus AK, De Magistris P, Antonin W (2016) Nuclear reformation at the end of mitosis. JMol Biol 428: 1962‒1985. |
[31] | Petrovská B, Šebela M, Doležel J (2015) Inside a plant nucleus: discovering the proteins. J Exp Bot 66: 1627‒1640. |
[32] | Sato S (1992) Three‐dimensional architecture of the higher plant nucleolonema disclosed on serial ultrathin sections. Biol Cell 75: 225‒233. |
[33] | Bernhard W (1969) A new staining procedure for electron microscopical cytology. J Ultrastruct Res 27: 250‒265. |
[34] | Lafontaine JG, Lord AA (1974) Correlated light and electron microscope investigation of the structural evolution of the nucleolus during the cell cycle in plant meristematic cells (Allium porrum). J Cell Sci 16: 63‒93. |
[35] | Baranova EN, Gulevich AA (2009) Structural organization of nuclei and nucleoli of wheat shoot and root meristem during germination under alkaline pH conditions. Russ Agri Sci 35: 11‒14. |
[36] | Baranova EN, Gulevich AA, Lavrova NV (2010) Vliyanie kisloj rN sredy na strukturnuyu organizaciyu yader i yadryshek kletok pobegovoj i kornevoj meristem pshenicy pri prorastanii (in Russian) Influence of acid pH of the environment on the structural organization of nuclei and nucleoli of cells of shoot and root meristems of wheat during germination. Izv Timiryazevsk S Kh Akad 2: 44-51. |
[37] | Wang J, Zhang F (2015) Nucleolus disassembly and distribution of segregated nucleolar material in prophase of root-tip meristematic cells in Triticum aestivum L. Arch Biol Sci 67: 405‒410. |
[38] | Zharskaya OO, Zatsepina OV (2007) The dynamics and mechanisms of nucleolar reorganization during mitosis. Cell Tiss Biol 1: 277‒292. |
[39] | Avetisova LV, Kadykov VA (1985) Ul'trastruktura kletok apikal'noj meristemy pobega pshenicy, razvivayushchegosya pri nizkih temperaturah (in Russian) Ultrastructure of wheat apical meristem cells at low positive temperatures, 1: Nuclear structure. Tsitologiya 27: 28-32. |
[40] | Avetisova LV, Shaposhnikov JD, Kadykov VA (1988) Izmeneniya ul'trastruktury yader kletok apeksa pobega pshenicy v processe prorastaniya (in Russian) Changes in the ultrastructure of nuclei in cells of the apical meristem during germination of wheat. Ontogenez 19: 181-190. |
[41] | Kinoshita T, Seki M (2014) Epigenetic memory for stress response and adaptation in plants. Plant Cell Phys 55: 1859‒1863. |
[42] | Baranova EN, Chaban IA, Kononenko NV, et al. (2017) Ultrastructural organization of the domains in the cell nucleus of dicotyledonous and monocotyledonous plants under abiotic stress. Russ Agri Sci 43: 199‒206. |
[43] | Yang X, Timofejeva L, Ma H, et al. (2006) The Arabidopsis SKP1 homolog ASK1 controls meiotic chromosome remodeling and release of chromatin from the nuclear membrane and nucleolus. J Cell Sci 119: 3754‒3763. |
[44] |
West G, Inzé D, Beemster GT (2004) Cell cycle modulation in the response of the primary root of Arabidopsis to salt stress. Plant Phys 135: 1050-1058. doi: 10.1104/pp.104.040022
![]() |
[45] |
Skirycz A, Claeys H, De Bodt S, et al. (2011) Pause-and-stop: the effects of osmotic stress on cell proliferation during early leaf development in Arabidopsis and a role for ethylene signaling in cell cycle arrest. Plant Cell 23: 1876-1888. doi: 10.1105/tpc.111.084160
![]() |
[46] | Lord A, Lafontaine JG (1969) The organization of the nucleolus in meristematic plant cells: a cytochemical study. J Cell Biol 40: 633‒647. |
[47] | Hozak P, Zatsepina O, Vasilyeva I, et al. (1986) An electron microscopic study of nucleolus‐organizing regions at some stages of the cell cycle (G0 period, G2 period, mitosis). Biol Cell 57: 197‒205. |
[48] | Cuylen S, Blaukopf C, Politi AZ, et al. (2016) Ki-67 acts as a biological surfactant to disperse mitotic chromosomes. Nature 535: 308‒312. |
[49] | Hayashi Y, Kato K, Kimura K (2017) The hierarchical structure of the perichromosomal layer comprises Ki67, ribosomal RNAs, and nucleolar proteins. Biochem Biophys Res Commun 493: 1043‒1049. |
[50] |
Sarkar A, Thoms M, Barrio-Garcia C, et al. (2017) Preribosomes escaping from the nucleus are caught during translation by cytoplasmic quality control. Nat Struct Mol Biol 24: 1107. doi: 10.1038/nsmb.3495
![]() |
[51] | Azum-Gélade MC, Noaillac-Depeyre J, Caizergues-Ferrer M, et al. (1994) Cell cycle redistribution of U3 snRNA and fibrillarin. Presence in the cytoplasmic nucleolus remnant and in the prenucleolar bodies at telophase. J Cell Sci 107: 463‒475. |
[52] | Boulon S, Westman BJ, Hutten S, et al. (2010) The nucleolus under stress. Mol Cell 40: 216‒227. |
[53] | Couté Y, Burgess JA, Diaz JJ, et al. (2006) Deciphering the human nucleolar proteome. Mass Spectrom Rev 25: 215‒234. |
[54] | Moisa SS, Tsetlin VV, Levinskich MA, et al. (2016) Low doses of ionized radiation and hypomagnetic field alter redox properties of water and physiological characteristics of seeds of the highest plants. J Biomed Sci Engin 9: 410‒418. |
[55] | Basto S, Thompson K, Rees M (2015) The effect of soil pH on persistence of seeds of grassland species in soil. Plant Ecol 216: 1163‒1175. |
[56] | Binhi VN, Prato FS (2017) A physical mechanism of magnetoreception: extension and analysis. Bioelectromagnetics 38: 41‒52. |
[57] |
Binhi VN, Prato FS (2018) Rotations of macromolecules affect nonspecific biological responses to magnetic fields. Sci Rep 8: 13495. doi: 10.1038/s41598-018-31847-y
![]() |
[58] | Belova NA, Ermakova ON, Ermakov AM, et al. (2007) The bioeffects of extremely weak power-frequency alternating magnetic fields. Environmentalist 27: 411‒416. |
[59] | Binhi VN (2011) Microwave absorption by magnetic nanoparticles in the organism. Biophysics 56: 1096‒1098. |
[60] |
Fu JP, Mo WC, Liu Y, et al. (2016) Elimination of the geomagnetic field stimulates the proliferation of mouse neural progenitor and stem cells. Protein Cell 7: 624-637. doi: 10.1007/s13238-016-0300-7
![]() |
[61] |
Mo WC, Liu Y, Bartlett PF, et al. (2014) Transcriptome profile of human neuroblastoma cells in the hypomagnetic field. Sci China: Life Sci 57: 448-461. doi: 10.1007/s11427-014-4644-z
![]() |
[62] | Wiltschko W, Wiltschko R (2005) Magnetic orientation and magnetoreception in birds and other animals. J Comp Physiol A 191: 675‒693. |
[63] | Dhiman SK, Galland P (2018) Effects of weak static magnetic fields on the gene expression of seedlings of Arabidopsis thaliana. J Plant Physiol 231: 9‒18. |
[64] | Lednev VV (1996) Bioeffects of weak static and alternating magnetic fields. Biofizika 41: 224-232. |
[65] |
Alipov YD, Belyaev IY (1996) Difference in frequency spectrum of extremely-low-frequency effects on the genome conformational state of AB 1157 and EMG2 E. coli cells. Bioelectromagnetics 17: 384-387. doi: 10.1002/(SICI)1521-186X(1996)17:5<384::AID-BEM5>3.0.CO;2-#
![]() |
[66] | Bunkin NF, Shkirin AV, Ignatiev PS, et al. (2012) Nanobubble clusters of dissolved gas in aqueous solutions of electrolyte. I. Experimental proof. J Chem Phys 137: 054706. |
[67] | Liu S, Kawagoe Y, Makino Y, et al. (2013) Effects of nanobubbles on the physicochemical properties of water: the basis for peculiar properties of water containing nanobubbles. Chem Engin Sci 93: 250‒256. |
[68] | Liu S, Oshita S, Makino Y, et al. (2016) Oxidative capacity of nanobubbles and its effect on seed germination. ACS Sustainable Chem Eng 4: 1347‒1353. |
[69] | Binhi VN (2002) Magnetobiology: underlying physical problems, San Diego: Academic Press. |
[70] |
Wan GJ, Wang WJ, Xu JJ, et al. (2015) Cryptochromes and hormone signal transduction under near-zero magnetic fields: New clues to magnetic field effects in a rice planthopper. Plos One 10: e0132966. doi: 10.1371/journal.pone.0132966
![]() |
[71] |
Xu C, Yu Y, Zhang Y, et al. (2017) Gibberellins are involved in effect of near-null magnetic field on Arabidopsis flowering. Bioelectromagnetics 38: 1-10. doi: 10.1002/bem.22004
![]() |
[72] | Krylov VV (2017) Biological effects related to geomagnetic activity and possible mechanisms. Bioelectromagnetics 38: 497‒510. |
[73] | Polyn S, Willems A, De Veylder L (2015) Cell cycle entry, maintenance, and exit during plant development. Curr Opin Plant Biol 23: 1‒7. |
[74] |
Shaw PJ, Brown JWS (2004) Plant Nuclear Bodies. Curr Opin Plant Biol 7: 614-620. doi: 10.1016/j.pbi.2004.09.011
![]() |
[75] | Raška I, Shaw PJ, Cmarko D (2006) New insights into nucleolar architecture and activity. Int Rev Cytol 255: 177‒235. |
[76] | Hernandez-Verdun D (2011) Assembly and disassembly of the nucleolus during the cell cycle. Nucleus 2: 189‒194. |
[77] | Kiryanov GI, Manamshjan TA, Polyakov VY, et al. (1976) Levels of granular organization of chromatin fibres. FEBS Lett 67: 323‒327. |
[78] | Paweletz N, Risueno MC (1982) Transmission electron microscopic studies on the mitotic cycle of nucleolar proteins impregnated with silver. Chromosoma 85: 261‒273. |
[79] | Van Hooser AA, Yuh P, Heald R (2005) The perichromosomal layer. Chromosoma 114: 377‒388. |
[80] | Hernandez‐Verdun D, Roussel P, Thiry M, et al. (2010) The nucleolus: structure/function relationship in RNA metabolism. Wiley Interdisciplinary Reviews: RNA 1: 415‒431. |
[81] | Shaw P, Brown J (2012) Nucleoli: composition, function, and dynamics. Plant Physiol 158:44‒51. |
[82] | Feric M, Vaidya N, Harmon TS, et al. (2016) Coexisting liquid phases underlie nucleolar subcompartments. Cell 165: 1686‒1697. |
[83] | Nerurkar P, Altvater M, Gerhardy S, et al. (2015) Eukaryotic ribosome assembly and nuclear export, In: Jeon KW, ed., International review of cell and molecular biology, Academic Press, 319: 107‒140. |
1. | He-Teng Zhang, Hao Wang, Hai-Sheng Wu, Jian Zeng, Yan Yang, Comparison of viromes in vaginal secretion from pregnant women with and without vaginitis, 2021, 18, 1743-422X, 10.1186/s12985-020-01482-z | |
2. | Yalda Lucero, David O. Matson, Shai Ashkenazi, Sergio George, Miguel O’Ryan, Norovirus: Facts and Reflections from Past, Present, and Future, 2021, 13, 1999-4915, 2399, 10.3390/v13122399 | |
3. | Syafruddin Ilyas, Salomo Hutahaean, Putri Cahaya Sit, Analysis of Cytochrome c Expression on Liver Histology of Hepatitis Rats after Administration of Tin and Olive Leaf Ethanol Extract, 2022, 25, 10288880, 835, 10.3923/pjbs.2022.835.842 | |
4. | Louisa F. Ludwig-Begall, Axel Mauroy, Etienne Thiry, Noroviruses—The State of the Art, Nearly Fifty Years after Their Initial Discovery, 2021, 13, 1999-4915, 1541, 10.3390/v13081541 | |
5. | Prashasti Sinha, Anil Kumar Yadav, Theoretical Study of Azetidine Derivative by Quantum Chemical Methods, Molecular Docking and Molecular Dynamic Simulations, 2023, 8, 2365-6549, 10.1002/slct.202300190 | |
6. | Rabab Taha, Noura Elazhary, Sarah Alqhtani, Walaa Almansouri, Fatal Acute Liver Failure Following Norovirus Gastroenteritis in a Child: A Case Report, 2025, 18760341, 102675, 10.1016/j.jiph.2025.102675 | |
7. | Yalda C. Lucero, Miguel L. O’Ryan, 2025, 9780323827638, 1643, 10.1016/B978-0-323-82763-8.00169-2 |
Study reference | Year of Publication | Country | Study design | Age group studied (years) | Data collection methods | Diagnostic method for norovirus | Timing between norovirus infection and hepatitis/transaminitis | Definition of hepatitis | Excluded other hepatotrophic causes (Y/N) |
Nakajima H et al. [6] | 2012 | Japan (Tokyo) | Case Report | 48 | Retrospective routine laboratory investigations. | Detected by viral antigen check and confirmed by reverse transcription PCR. | Same day | Elevated LFTs | Y |
Zenda T et al. [11] | 2011 | Japan (Ishikawa) | Case Report | 56 | Retrospective routine laboratory investigations. | Positive test for norovirus antigens in stool using immunochromatographic assay kits. | Same day | Elevated LFTs | Y |
Kucuk O et al. [10] | 2016 | Turkey (Istanbul) | Retrospective hospital-based | 0 to 17 | Retrospective study from 2010 and 2013 of acute viral gastroenteritis. | Rapid antigen tests and PCR. | N/A | Elevated LFTs | Y |
Tsuge et al. [12] | 2010 | Japan (Okayama) | Case series | 1 to 7 | Prospective study measuring LFTs and bloods in children presenting with gastroenteritis. | RT-PCR assay | Case 1: 5 days Case 2: 1 day Case 3: 6 days Case 4: 11 days |
Elevated LFTs | Y |
Khayat AA et al. [13] | 2019 | USA (Wisconsin) | Case series | 3 and 8 | Retrospective routine laboratory investigations. | Stool specimens for norovirus antigens. | Case 1 and 2: Same day | Elevated LFTs | Y |
Notes: Abbreviations: FBC, full blood count; LFT, liver function test; USA, United States of America; PCR, polymerase chain reaction; RT-PCR, reverse transcription-polymerase chain reaction.
Characteristics | Studies | ||||
Study reference | Nakajima H et al. [6] | Zenda T et al. [11] | Kucuk O et al. [10] | Tsuge et al. [12] | Khayat AA et al. [13] |
No. of patients | 1 | 1 | 74 | 4 | 2 |
No. of cases | 1 | 1 | 9 | 4 | 2 |
Sex (M/F) | F | F | N/A | Case 1: F; Case 2: F Case 3: M; Case 4: M |
Case 1: F Case 2: M |
Patient Age (yrs) | 48 | 56 | 0–17 | 1–7 | Case 1: 3 Case 2: 8 |
Symptoms | Abdominal pain and diarrhoea. Tenderness in epigastrium and right hypochondrium. | Abdominal cramps, vomiting, diarrhoea. Tenderness in left lower abdomen. |
Vomiting, diarrhoea, and dehydration. | Vomiting, diarrhoea, dehydration, and fever with reduced bowel sounds. Case 2 had convulsions. |
Anaemia, haematemesis, diarrhoea. |
Peak AST (IU/l) | 892 | 1150 | 45.6 | 794 | 700 |
Peak ALT (IU/l) | 146 | 458 | 31.7 | 423 | 400 |
Peak GGT (IU/l) | N/A | 73 | N/A | N/A | N/A |
Peak ALP (IU/l) | No rise | 318 | N/A | N/A | N/A |
Other abnormal results | None | None | Hct 36.9, WCC 13510, CRP 9.7 | Case 2: leucocytosis (WBC 13670IU/l) Case 3: hyponatraemia |
Case 1 had normal liver biopsy. |
Onset to recovery of symptoms (days) | 7 | 4 | N/A | Day 8, day 13, day 8 and day 18 in cases 1, 2, 3 and 4 respectively. | Case 1: 150; Case 2: 14. |
Onset of illness to LFT recovery (days) | 14 | 14 | N/A | Case 1: 26; Case 2: 26;Case 3: 27; Case4: 28 . | Case 1: 480; Case 2: 270 |
Requiring hospitalisation/IV support | Hospitalisation | Hospitalisation | 40 (54%) were hospitalized and 34 (46%) had an observed follow-up. | Cases 1–3 were hospitalized. | Hospitalised |
Management | Supportive therapy | Bowel rest and intravenous rehydration. | IV rehydration | Intravenous fluids for cases 1-3 and oral/IV glycyrrhizin for all. | Case 1 had IV IVIG during their recovery from norovirus infection. |
PMH | Cholelithiasis and cholecystectomy 4 years ago. Drinks alcohol. | Surgery for appendicitis, myoma uteri, gallstones (cholecystectomy) | N/A | N/A | Case 1 had a liver transplant due to hepatoblastoma. Case 2 had liver transplant due to congenital hepatic fibrosis and Caroli's disease. |
Outcome of cases | Alive without chronic liver disease. | Alive without chronic liver disease. | N/A | Alive without chronic liver disease. | Alive without chronic liver disease. |
Notes: Abbreviations: PMH, past medical history; IV, intravenous; Hct, haematocrit; WCC, white cell count; CRP, c-reactive protein; IVIG, immunoglobulins; M, male; F, female; N/A, not available.
Study reference | Year of Publication | Country | Study design | Age group studied (years) | Data collection methods | Diagnostic method for norovirus | Timing between norovirus infection and hepatitis/transaminitis | Definition of hepatitis | Excluded other hepatotrophic causes (Y/N) |
Nakajima H et al. [6] | 2012 | Japan (Tokyo) | Case Report | 48 | Retrospective routine laboratory investigations. | Detected by viral antigen check and confirmed by reverse transcription PCR. | Same day | Elevated LFTs | Y |
Zenda T et al. [11] | 2011 | Japan (Ishikawa) | Case Report | 56 | Retrospective routine laboratory investigations. | Positive test for norovirus antigens in stool using immunochromatographic assay kits. | Same day | Elevated LFTs | Y |
Kucuk O et al. [10] | 2016 | Turkey (Istanbul) | Retrospective hospital-based | 0 to 17 | Retrospective study from 2010 and 2013 of acute viral gastroenteritis. | Rapid antigen tests and PCR. | N/A | Elevated LFTs | Y |
Tsuge et al. [12] | 2010 | Japan (Okayama) | Case series | 1 to 7 | Prospective study measuring LFTs and bloods in children presenting with gastroenteritis. | RT-PCR assay | Case 1: 5 days Case 2: 1 day Case 3: 6 days Case 4: 11 days |
Elevated LFTs | Y |
Khayat AA et al. [13] | 2019 | USA (Wisconsin) | Case series | 3 and 8 | Retrospective routine laboratory investigations. | Stool specimens for norovirus antigens. | Case 1 and 2: Same day | Elevated LFTs | Y |
Characteristics | Studies | ||||
Study reference | Nakajima H et al. [6] | Zenda T et al. [11] | Kucuk O et al. [10] | Tsuge et al. [12] | Khayat AA et al. [13] |
No. of patients | 1 | 1 | 74 | 4 | 2 |
No. of cases | 1 | 1 | 9 | 4 | 2 |
Sex (M/F) | F | F | N/A | Case 1: F; Case 2: F Case 3: M; Case 4: M |
Case 1: F Case 2: M |
Patient Age (yrs) | 48 | 56 | 0–17 | 1–7 | Case 1: 3 Case 2: 8 |
Symptoms | Abdominal pain and diarrhoea. Tenderness in epigastrium and right hypochondrium. | Abdominal cramps, vomiting, diarrhoea. Tenderness in left lower abdomen. |
Vomiting, diarrhoea, and dehydration. | Vomiting, diarrhoea, dehydration, and fever with reduced bowel sounds. Case 2 had convulsions. |
Anaemia, haematemesis, diarrhoea. |
Peak AST (IU/l) | 892 | 1150 | 45.6 | 794 | 700 |
Peak ALT (IU/l) | 146 | 458 | 31.7 | 423 | 400 |
Peak GGT (IU/l) | N/A | 73 | N/A | N/A | N/A |
Peak ALP (IU/l) | No rise | 318 | N/A | N/A | N/A |
Other abnormal results | None | None | Hct 36.9, WCC 13510, CRP 9.7 | Case 2: leucocytosis (WBC 13670IU/l) Case 3: hyponatraemia |
Case 1 had normal liver biopsy. |
Onset to recovery of symptoms (days) | 7 | 4 | N/A | Day 8, day 13, day 8 and day 18 in cases 1, 2, 3 and 4 respectively. | Case 1: 150; Case 2: 14. |
Onset of illness to LFT recovery (days) | 14 | 14 | N/A | Case 1: 26; Case 2: 26;Case 3: 27; Case4: 28 . | Case 1: 480; Case 2: 270 |
Requiring hospitalisation/IV support | Hospitalisation | Hospitalisation | 40 (54%) were hospitalized and 34 (46%) had an observed follow-up. | Cases 1–3 were hospitalized. | Hospitalised |
Management | Supportive therapy | Bowel rest and intravenous rehydration. | IV rehydration | Intravenous fluids for cases 1-3 and oral/IV glycyrrhizin for all. | Case 1 had IV IVIG during their recovery from norovirus infection. |
PMH | Cholelithiasis and cholecystectomy 4 years ago. Drinks alcohol. | Surgery for appendicitis, myoma uteri, gallstones (cholecystectomy) | N/A | N/A | Case 1 had a liver transplant due to hepatoblastoma. Case 2 had liver transplant due to congenital hepatic fibrosis and Caroli's disease. |
Outcome of cases | Alive without chronic liver disease. | Alive without chronic liver disease. | N/A | Alive without chronic liver disease. | Alive without chronic liver disease. |