MRE in NAFLD: Promising but Further Validation is Required
John D. Ryan, Emmanuel A. Tsochatzis
Corresponding author
UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital and UCL, London, UK
Read
1864
Timeswas read the article
344
Total PDF
1520
Total HTML
Share statistics
array:24 [ "pii" => "S1665268119304041" "issn" => "16652681" "doi" => "10.5604/16652681.1235474" "estado" => "S300" "fechaPublicacion" => "2017-05-01" "aid" => "70226" "copyright" => "Fundación Clínica Médica Sur, A.C." "copyrightAnyo" => "2017" "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2017;16:331-2" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 124 "formatos" => array:3 [ "EPUB" => 13 "HTML" => 67 "PDF" => 44 ] ] "itemSiguiente" => array:19 [ "pii" => "S1665268119304053" "issn" => "16652681" "doi" => "10.5604/16652681.1235475" "estado" => "S300" "fechaPublicacion" => "2017-05-01" "aid" => "70227" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "rev" "cita" => "Ann Hepatol. 2017;16:333-41" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 150 "formatos" => array:3 [ "EPUB" => 10 "HTML" => 62 "PDF" => 78 ] ] "en" => array:10 [ "idiomaDefecto" => true "titulo" => "What is Changing in Indications and Treatment of Focal Nodular Hyperplasia of the Liver. Is There any Place for Surgery?" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "333" "paginaFinal" => "341" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Aristotelis Perrakis, Nikolaos Vassos, Robert Grützmann, Roland S. Croner" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Aristotelis" "apellidos" => "Perrakis" ] 1 => array:2 [ "nombre" => "Nikolaos" "apellidos" => "Vassos" ] 2 => array:2 [ "nombre" => "Robert" "apellidos" => "Grützmann" ] 3 => array:2 [ "nombre" => "Roland S." "apellidos" => "Croner" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119304053?idApp=UINPBA00004N" "url" => "/16652681/0000001600000003/v1_201905301200/S1665268119304053/v1_201905301200/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S166526811930403X" "issn" => "16652681" "doi" => "10.5604/01.3001.0009.8585" "estado" => "S300" "fechaPublicacion" => "2017-05-01" "aid" => "70225" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 0 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2017;16:328-30" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 102 "formatos" => array:3 [ "EPUB" => 15 "HTML" => 43 "PDF" => 44 ] ] "en" => array:10 [ "idiomaDefecto" => true "titulo" => "The Direct-Acting Antivirals for Hepatitis C Virus and the Risk for Hepatocellular Carcinoma" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "328" "paginaFinal" => "330" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Paulina Chinchilla-López, Xingshun Qi, Eric M. Yoshida, Nahum Méndez-Sánchez" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Paulina" "apellidos" => "Chinchilla-López" ] 1 => array:2 [ "nombre" => "Xingshun" "apellidos" => "Qi" ] 2 => array:2 [ "nombre" => "Eric M." "apellidos" => "Yoshida" ] 3 => array:2 [ "nombre" => "Nahum" "apellidos" => "Méndez-Sánchez" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S166526811930403X?idApp=UINPBA00004N" "url" => "/16652681/0000001600000003/v1_201905301200/S166526811930403X/v1_201905301200/en/main.assets" ] "en" => array:14 [ "idiomaDefecto" => true "titulo" => "MRE in NAFLD: Promising but Further Validation is Required" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "331" "paginaFinal" => "332" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "John D. Ryan, Emmanuel A. Tsochatzis" "autores" => array:2 [ 0 => array:2 [ "nombre" => "John D." "apellidos" => "Ryan" ] 1 => array:4 [ "nombre" => "Emmanuel A." "apellidos" => "Tsochatzis" "email" => array:1 [ 0 => "e.tsochatzis@ucl.ac.uk" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor1" ] ] ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "UCL Institute for Liver and Digestive Health and Sheila Sherlock Liver Unit, Royal Free Hospital and UCL, London, UK" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor1" "etiqueta" => "*" "correspondencia" => "Correspondence and reprint request:" ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="p0010" class="elsevierStylePara elsevierViewall">Non-alcoholic fatty liver disease (NAFLD) is a hugely prevalent condition affecting up to 30% of adults in the developed world. The diagnosis is associated with an increased risk of liver-related morbidity and mortality. The best determinant of major outcomes (liver-related events, need for liver transplant or death) is the presence of fibro-sis on a liver biopsy. In a recent retrospective study of 619 NAFLD patients followed for a median of 12.6 years, An-gulo, <span class="elsevierStyleItalic">et al.</span> highlighted the independent association of any stage of liver fibrosis on biopsy (present in > 50% of the study patients) and these outcomes. For instance, hazard ratios for factors associated with death or liver transplant included fibrosis stage 1 (HR, 1.88; 95% confidence interval [CI], 1.28-2.77), stage 2 (HR, 2.89; 95% CI, 1.93-4.33), stage 3 (HR, 3.76; 95% CI, 2.40-5.89), and stage 4 (HR, 10.9; 95% CI, 6.06-19.62) compared with stage 0. Conversely, the presence or severity of steatosis or steatohepa-titis, a diagnostic feature of NAFLD and NASH, was not associated with outcomes.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">1</span></a> This valuable study underlined the importance of liver fibrosis detection in NAFLD patients to guide management and monitoring, but also the urgent need to identify robust non-invasive fibrosis markers in order to avert the need for an invasive liver biopsy with the associated risks, cost, and impracticalities when considering such a significant patient population.</p><p id="p0015" class="elsevierStylePara elsevierViewall">Thankfully, a burgeoning market of non-invasive tests for liver fibrosis has developed over the past decade. These tests are either blood or imaging-based, with the former often utilized as cheaper screening tools with high negative predictive values allowing the reliable exclusion of advanced fibrosis (F3-F4); while the latter techniques are performed in specialist centres, and offer the advantage of a targeted assessment for liver fibrosis along with simultaneous detection of steatosis in NAFLD. Despite very good diagnostic performance for advanced fibrosis detection in NAFLD, both non-invasive techniques tend to lack diagnostic accuracy for delineating earlier fibrosis stages, an important factor when deciding on the need for aggressive therapy and follow up. Moreover, knowing that the presence of any fibrosis on biopsy has implications for disease outcomes means that a diagnostic test with high diagnostic accuracy across all fibrosis stages would be of significant value.</p><p id="p0020" class="elsevierStylePara elsevierViewall">In a recent prospective cross-sectional study by Park, <span class="elsevierStyleItalic">et al.</span> from California, USA, two of the most studied imag-ing-based techniques for the non-invasive assessment of liver fibrosis, ultrasound transient elastography (TE) or Fibroscan®, and magnetic resonance elastography (MRE) were compared.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">3</span></a> Elastography measures liver stiffness, a surrogate of liver fibrosis, by analyzing the speed at which mechanical waves can propagate through the liver. Both TE and MRE can also estimate liver steatosis simultaneously, using the controlled attenuation parameter (CAP) or MRI-based proton density fat fraction (MRI-PDFF) methods, respectively. One short-coming of TE is high failure rates in obese patients, which has been reduced by the advent of an XL-probe. Indeed, another recent Japanese study by Imajo, <span class="elsevierStyleItalic">et al.</span> also compared MRE with TE in NAFLD patients, but reported a 10% failure rate for TE in part due to a lack of the XL-probe.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">4</span></a> In the Park study both the standard ‘M’ and XL probes were available for use, potentially allowing a more meaningful assessment of the performance of MRE <span class="elsevierStyleItalic">vs.</span> TE in fibrosis detection in NAFLD. The authors also felt that the US-based cohort would yield more generalizable results to Western NAFLD populations than that described in the Imajo paper. The Park study involved 104 consecutive NAFLD patients who had undergone a liver biopsy, MRE and TE assessment. The patient cohort was 56.7% female, with a mean (± SD) age of 50.8 (± 14.6) years, BMI of 30.4 (± 5.2) kg/m<span class="elsevierStyleSup">2</span> and diabetes prevalence of 27.9%. The XL probe was used in approximately 50% of cases, although a failure rate of 6.7% was reported. At first glance, the study results were impressive; MRE significantly outperformed TE in the detection of any stage of fibrosis (stage 1 and above), with an area under the receiver operating characteristic curve (AUROC) of 0.82 (95% confidence interval [CI], 0.74-0.91), for MRE compared with an AUROC of 0.67 (95% CI, 0.56-0.78) for TE (p = 0.0116). MRI-PDFF detected any steatosis with an AUROC of 0.99 (95% CI, 0.98-1.00), significantly higher than that of CAP (AUROC, 0.85; 95% CI, 0.75-0.96), p = 0.0091, and MRE was also significantly better at distinguishing grades of steatosis than CAP.</p><p id="p0025" class="elsevierStylePara elsevierViewall">Despite these positive findings, several issues limit the interpretation and application of the study results. Although MRE performed well in the primary study objectives, TE seemed to grossly underperform compared to other published studies. Indeed, the study cohort suffered from a clear ‘spectrum bias’, where stages of fibrosis were unevenly distributed amongst the group making meaningful comparisons difficult. The vast majority of patients had no or mild fibrosis (45.6% F0; 23.3% F1; 10.7% F2; 12.6% F3; 7.8% F4). This meant that that cut-offs used to determine the diagnostic accuracy for TE were atypical; for instance a value of 6.9kPa was the threshold for distinguishing F4 from F0-3 stages, compared to a minimum of 11.7kPa in other, larger series. Unlike the Imajo study, no comparison was made with the efficacy of cheaper, more readily available, blood-based fibrosis scores such as the NAFLD fibrosis score (NFS) or the FIB-4 index. Indeed, the NFS performed as well as MRE in detecting any fibrosis, advanced fibrosis or cirrhosis in the larger group of 127 NAFLD patients from the Imajo study. Moreover, the MR facility used in the Park study was a 3.0T MR scanner, whose use would be typically confined to research facilities and associated with a significant cost. Finally, although the detection of steatosis is useful to aid the diagnosis of NAFLD due to false negatives with standard ultrasound, the grading of steatosis does not appear to have implications for disease severity and long-term out-comes.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">1</span></a> Nevertheless, hepatic steatosis seems to closely reflect adipose insulin resistance specifically, and highly sensitive techniques such as MRI-PDFF may yet prove useful in determining treatment choice and response for this multi-system disease in the future.</p><p id="p0030" class="elsevierStylePara elsevierViewall">In conclusion, although MRE is a useful addition to the available non-invasive fibrosis tests, it requires further validation in larger cohorts of patients with more even distribution of fibrosis. Ultimately, what is required is a non-invasive fibrosis test that can be used sequentially and accurately reflect the progression or regression of fibrosis, and therefore be used as a surrogate marker in clinical trials. It remains to be determined if MRE is such a test.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2017-04-02" "fechaAceptado" => "2017-04-02" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1116215" "palabras" => array:4 [ 0 => "Fibrosis" 1 => "Fibroscan" 2 => "Non-invasive" 3 => "Cirrhosis" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abs0010" class="elsevierStyleSection elsevierViewall"><p id="sp0010" class="elsevierStyleSimplePara elsevierViewall">MR elastography is a novel method for non-invasive fibrosis assessment, not yet sufficiently validated. In a recent study in 104 patients Park, <span class="elsevierStyleItalic">Gastroenterology</span> 2017; 152: 598-602), MRE was compared to transient elastography for the diagnosis of fibrosis is nonalcoholic fatty liver disease. The current viewpoint critically appraises this study.</p></span>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bs0010" "bibliografiaReferencia" => array:6 [ 0 => array:3 [ "identificador" => "bib0010" "etiqueta" => "1." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Liver Fibrosis but No Other Histologic Features, Is Associated With Long-term Outcomes of Patients With Nonalcoholic Fatty Liver Disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Angulo P." 1 => "Kleiner D.E." 2 => "Dam-Larsen S." 3 => "Adams L.A." 4 => "Bjornsson E.S." 5 => "Charatcharoenwitthaya P." 6 => "Mills P.R." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.gastro.2015.04.043" "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2015" "volumen" => "149" "paginaInicial" => "389" "paginaFinal" => "397" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25935633" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0015" "etiqueta" => "2." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Non-invasive markers of liver fibrosis: adjuncts or alternatives to liver biopsy?" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Chin J.L." 1 => "Pavlides M." 2 => "Moolla A." 3 => "Ryan J.D." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.3389/fphar.2016.00323" "Revista" => array:4 [ "tituloSerie" => "Frontiers in Pharmacology" "fecha" => "2016" "volumen" => "7" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27708582" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0020" "etiqueta" => "3." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Magnetic Resonance Elastogra-phy vs Transient Elastography in Detection of Fibrosis and Noninvasive Measurement of Steatosis in Patients With Biopsy-Proven Nonalcoholic Fatty Liver Disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Park C.C." 1 => "Nguyen P." 2 => "Hernandez C." 3 => "Bettencourt R." 4 => "Ramirez K." 5 => "Fortney L." 6 => "Hooker J." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.gastro.2016.10.026" "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2017" "volumen" => "152" "paginaInicial" => "598" "paginaFinal" => "607" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27911262" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0025" "etiqueta" => "4." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Magnetic Resonance Imaging More Accurately Classifies Steatosis and Fibrosis in Patients With Nonalcoholic Fatty Liver Disease Than Transient Elastogra-phy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:7 [ 0 => "Imajo K." 1 => "Kessoku T." 2 => "Honda Y." 3 => "Tomeno W." 4 => "Ogawa Y." 5 => "Mawa-tari H." 6 => "Fujita K." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1053/j.gastro.2015.11.048" "Revista" => array:6 [ "tituloSerie" => "Gastroenterology" "fecha" => "2016" "volumen" => "150" "paginaInicial" => "626" "paginaFinal" => "637" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26677985" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0030" "etiqueta" => "5." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Elastography for the diagnosis of severity of fibrosis in chronic liver disease: a meta-analy-sis of diagnostic accuracy" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "Tsochatzis E.A." 1 => "Gurusamy K.S." 2 => "Ntaoula S." 3 => "Cholongitas E." 4 => "Davidson B.R." 5 => "Burroughs A.K." ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Hepatology" "fecha" => "2011" "volumen" => "54" "paginaInicial" => "650" "paginaFinal" => "659" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0035" "etiqueta" => "6." "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Metabolic and histological implications of intrahepatic triglyceride content in nonalcoholic fatty liver disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "Bril F." 1 => "Barb D." 2 => "Portillo-Sanchez P." 3 => "Kusi K." ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/hep.28985" "Revista" => array:6 [ "tituloSerie" => "Hepatology" "fecha" => "2017" "volumen" => "65" "paginaInicial" => "1132" "paginaFinal" => "1144" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/27981615" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/16652681/0000001600000003/v1_201905301200/S1665268119304041/v1_201905301200/en/main.assets" "Apartado" => array:4 [ "identificador" => "77722" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Viewpoint" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/16652681/0000001600000003/v1_201905301200/S1665268119304041/v1_201905301200/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119304041?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 2 | 1 | 3 |
| 2024 October | 20 | 3 | 23 |
| 2024 September | 24 | 3 | 27 |
| 2024 August | 30 | 2 | 32 |
| 2024 July | 23 | 3 | 26 |
| 2024 June | 21 | 0 | 21 |
| 2024 May | 11 | 3 | 14 |
| 2024 April | 17 | 3 | 20 |
| 2024 March | 19 | 5 | 24 |
| 2024 February | 10 | 4 | 14 |
| 2024 January | 13 | 6 | 19 |
| 2023 December | 8 | 3 | 11 |
| 2023 November | 14 | 1 | 15 |
| 2023 October | 12 | 3 | 15 |
| 2023 September | 9 | 2 | 11 |
| 2023 August | 15 | 4 | 19 |
| 2023 July | 10 | 4 | 14 |
| 2023 June | 23 | 1 | 24 |
| 2023 May | 37 | 3 | 40 |
| 2023 April | 30 | 0 | 30 |
| 2023 March | 7 | 1 | 8 |
| 2023 February | 15 | 4 | 19 |
| 2023 January | 5 | 2 | 7 |
| 2022 December | 23 | 6 | 29 |
| 2022 November | 16 | 4 | 20 |
| 2022 October | 26 | 6 | 32 |
| 2022 September | 10 | 3 | 13 |
| 2022 August | 25 | 17 | 42 |
| 2022 July | 13 | 10 | 23 |
| 2022 June | 59 | 6 | 65 |
| 2022 May | 32 | 6 | 38 |
| 2022 April | 19 | 5 | 24 |
| 2022 March | 40 | 11 | 51 |
| 2022 February | 46 | 6 | 52 |
| 2022 January | 87 | 3 | 90 |
| 2021 December | 40 | 13 | 53 |
| 2021 November | 48 | 5 | 53 |
| 2021 October | 78 | 11 | 89 |
| 2021 September | 50 | 12 | 62 |
| 2021 August | 54 | 3 | 57 |
| 2021 July | 12 | 10 | 22 |
| 2021 June | 21 | 7 | 28 |
| 2021 May | 36 | 8 | 44 |
| 2021 April | 52 | 25 | 77 |
| 2021 March | 151 | 8 | 159 |
| 2021 February | 19 | 5 | 24 |
| 2021 January | 14 | 7 | 21 |
| 2020 December | 14 | 6 | 20 |
| 2020 November | 13 | 7 | 20 |
| 2020 October | 5 | 4 | 9 |
| 2020 September | 22 | 6 | 28 |
| 2020 August | 7 | 0 | 7 |
| 2020 July | 1 | 1 | 2 |
| 2020 June | 10 | 4 | 14 |
| 2020 May | 15 | 6 | 21 |
| 2020 April | 7 | 4 | 11 |
| 2020 March | 10 | 0 | 10 |
| 2020 February | 10 | 12 | 22 |
| 2020 January | 11 | 1 | 12 |
| 2019 December | 14 | 6 | 20 |
| 2019 November | 10 | 3 | 13 |
| 2019 October | 5 | 4 | 9 |
| 2019 September | 2 | 0 | 2 |
| 2019 August | 4 | 4 | 8 |
| 2019 July | 1 | 3 | 4 |
| 2019 June | 10 | 11 | 21 |
| 2019 May | 3 | 4 | 7 |
Show all
