The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, has led to a major public health challenge.[1]Zhou P. Yang X.-L. Wang X.-G. Hu B. Zhang L. Zhang W. et al.A pneumonia outbreak associated with a new coronavirus of probable bat origin.Nature. 2020; 579: 270-273Crossref PubMed Scopus (13523) Google Scholar The high virulence and transmissibility of SARS-CoV-2 requires strong health-care policy actions to reduce its spread. Since February 21st, the SARS-CoV-2 outbreak smashed Northern and Central Italy and on March 9th the Italian government introduced a lockdown which lasted until May 3rd. Meanwhile non-urgent clinical care activity was deferred, potentially negatively impacting on patients with chronic diseases, including patients with cirrhosis.[2]Tapper E.B. Asrani S.K. The COVID-19 pandemic will have a long-lasting impact on the quality of cirrhosis care.J Hepatol. 2020; 73: 441-445Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar Whether the lockdown determined clinical consequences in patients with cirrhosis is unknown. Herein we evaluated the characteristics, clinical course, in-hospital and 90-day mortality as well as the 30-day readmission rate in patients hospitalized for an acute decompensation of cirrhosis from March 2020 to April 2020 in 2 centers in Northern/Center Italy. Their characteristics and outcomes were compared with those of patients admitted in March-April 2019. Patients were retrospectively identified and demographic, clinical and laboratory data were collected reviewing electronic and paper charts. Data on readmissions and mortality at 90 days were collected as well. During the lockdown non-urgent visits were deferred and telemedicine/phone contacts were implemented. Day hospital activity for planned procedures (e.g. large volume paracentesis) and outpatient visits for patients at high risk of readmissions (readmitted in the prior 30 days, with acute-on-chronic liver failure during hospitalization or Child-Pugh class C) were maintained.[3]Morando F. Maresio G. Piano S. Fasolato S. Cavallin M. Romano A. et al.How to improve care in outpatients with cirrhosis and ascites: a new model of care coordination by consultant hepatologists.J Hepatol. 2013; 59https://doi.org/10.1016/j.jhep.2013.03.010Abstract Full Text Full Text PDF Scopus (124) Google Scholar,[4]Piano S. Morando F. Carretta G. Tonon M. Vettore E. Rosi S. et al.Predictors of early readmission in patients with cirrhosis after the resolution of bacterial infections.Am J Gastroenterol. 2017; 112https://doi.org/10.1038/ajg.2017.253Crossref PubMed Scopus (27) Google Scholar Overall, we observed a 65% reduction in outpatients visits. We identified 100 patients admitted for acute decompensation of cirrhosis, 55 were admitted in 2019 and 45 in 2020. Demographic characteristics and reasons for hospitalization were similar between the 2 groups (Table 1). Bilirubin was significantly higher in patients admitted during the lockdown (116 vs. 65 μmol/L; p = 0.032). There was a trend toward a higher model for end-stage liver disease-sodium (MELD-Na) score in patients admitted during the lockdown (22 vs. 19; p = 0.071). In spite of a similar rate of bacterial infections at admission, the level of C-reactive protein tended to be higher in patients admitted during the lockdown (45 vs. 29 mg/L; p = 0.057). Finally, patients admitted during the lockdown more frequently had acute kidney injury (AKI) at admission (42 vs. 22%; p = 0.028). In-hospital mortality and probability of 90-day survival were not significantly different between the 2 groups (7% vs. 7%; p = 1.00; and 23% vs. 25%; p = 0.951; Fig. 1). The proportion of patients transplanted within 90 days was not significantly different between patients admitted during the lockdown and those admitted in 2019 (7% vs. 13%; p = 0.505). After discharge, 21 out of 40 patients discharged alive during the lockdown were referred to the outpatient clinic for early post discharge management (53% vs. 81% in 2019; p = 0.004),[3]Morando F. Maresio G. Piano S. Fasolato S. Cavallin M. Romano A. et al.How to improve care in outpatients with cirrhosis and ascites: a new model of care coordination by consultant hepatologists.J Hepatol. 2013; 59https://doi.org/10.1016/j.jhep.2013.03.010Abstract Full Text Full Text PDF Scopus (124) Google Scholar 4 were lost to follow-up while the remaining were followed up by telemedicine/phone contact. The proportion of patients readmitted within 30 days was not significantly different in lockdown and control groups (23 vs. 21%; p = 0.920).Table 1Clinical characteristics of patients admitted in the 2 cohorts.Variable2019 (n = 55)2020 (n = 45)p valueAge (years), m ± SD64±1161±140.228Gender (Male), n (%)35 (64)35 (78)0.125Etiology of cirrhosis, n (%) Alcohol24 (44)26 (58)0.159 HCV13 (24)8 (18)0.474 HBV8 (15)8 (18)0.661 NASH7 (13)6 (13)0.929 Other10 (18)5 (11)0.325Main cause of admission, n (%) Ascites11 (20)6 (13)0.674 Gastrointestinal bleeding11 (20)13 (29) Hepatic encephalopathy14 (26)8 (18) Infections7 (13)7 (16) Others12 (22)11 (24)Ascites at admission, n (%)32 (58)32 (71)0.180HE at admission, n (%)18 (33)13 (29)0.680Bacterial infections at admission, n (%)14 (26)10 (22)0.887AKI at admission, n (%)12 (22)19 (42)0.028Leukocytes (x109/L), median (IQR)6.7±3.66.9±4.00.783C-reactive protein, median (IQR)29±3045 ± 510.057Bilirubin (mmol/l) , median (IQR)65 ± 67116 ± 1580.032Albumin (g/l) , median (IQR)29 ± 530 ± 50.551INR, median (IQR)1.6 ± 0.81.6 ± 0.50.693Creatinine (μmol/l), median (IQR)100 ± 57119 ± 660.128Serum sodium (mmol/L), mean ± SD136 ± 6135 ± 80.129MELD-Na, mean ± SD19 ± 722 ± 100.071Continuous variables were compared with Student's t test or Mann-Whitney U test. Categorical variables were compared with Chi-squareor Fisher's exact test. AKI, acute kidney injury; HE, hepatic encephalopathy; INR, international normalized ratio; MELD-Na, model of end stage liver disease sodium; NASH, non-alcoholic steatohepatitis. Open table in a new tab Continuous variables were compared with Student's t test or Mann-Whitney U test. Categorical variables were compared with Chi-squareor Fisher's exact test. AKI, acute kidney injury; HE, hepatic encephalopathy; INR, international normalized ratio; MELD-Na, model of end stage liver disease sodium; NASH, non-alcoholic steatohepatitis. This study showed 2 main findings. The first is that during the lockdown patients admitted to the hospital for an acute decompensation of cirrhosis had a more advanced liver disease, a higher proportion of AKI and higher inflammatory biomarkers. One may hypothesize that during the lockdown patients with cirrhosis delayed their access to medical care because of concerns over contracting COVID-19 in hospital. This is relevant for patients with cirrhosis that are at risk of severe COVID-19[5]Iavarone M. D'Ambrosio R. Soria A. Triolo M. Pugliese N. Del Poggio P. et al.High rates of 30-day mortality in patients with cirrhosis and COVID-19.J Hepatol. 2020; https://doi.org/10.1016/j.jhep.2020.06.001Abstract Full Text Full Text PDF PubMed Scopus (224) Google Scholar,[6]Bajaj J.S. Garcia-Tsao G. Biggins S.W. Kamath P.S. Wong F. McGeorge S. et al.Comparison of mortality risk in patients with cirrhosis and COVID-19 compared with patients with cirrhosis alone and COVID-19 alone: multicentre matched cohort.Gut. 2020; https://doi.org/10.1136/gutjnl-2020-322118Crossref PubMed Scopus (148) Google Scholar and is in keeping with the delayed access to care observed for patients with stroke and myocardial infarction during the peak of the COVID-19 outbreak in Spain and England.[7]Montaner J. Barragán-Prieto A. Pérez-Sánchez S. Escudero-Martínez I. Moniche F. Sánchez-Miura J.A. et al.Break in the stroke chain of survival due to COVID-19.Stroke. 2020; 51: 2307-2314Crossref PubMed Scopus (111) Google Scholar,[8]Kwok C.S. Gale C.P. Kinnaird T. Curzen N. Ludman P. Kontopantelis E. et al.Impact of COVID-19 on percutaneous coronary intervention for ST-elevation myocardial infarction.Heart. 2020; https://doi.org/10.1136/heartjnl-2020-317650Crossref Scopus (68) Google Scholar Anyway, this is a speculation that has to be proven in well-designed studies. Despite a more severe disease at admission, we did not find an increase in mortality rate in patients admitted during the lockdown, however the sample size was underpowered to identify such a difference. In preparing to face the new COVID-19 outbreaks worldwide, patients with cirrhosis should be advised to seek care without delay when signs of decompensation/infection occur. In keeping with data of other Italian Hepatology units, outpatient activity was significantly reduced in our center during the lockdown.[9]Aghemo A. Masarone M. Montagnese S. Petta S. Ponziani F.R. Russo F.P. Assessing the impact of COVID-19 on the management of patients with liver diseases: a national survey by the Italian association for the study of the Liver.Dig Liver Dis. 2020; 52: 937-941Abstract Full Text Full Text PDF PubMed Scopus (43) Google Scholar One potential drawback of this reduction could be the increase of early readmissions for patients discharged. The second main finding of this study is that the reorganization of outpatient management (prioritizing urgent visits and those for patients at risk of readmissions) could have mitigated the risk of early readmissions. This was obtained with no undermining of patient and staff safety. All physicians and nurses at our institutions wore personal protective equipment during visits and a negative nasopharyngeal swab was required within a week for patients before their planned day admission. None of the medical staff contracted SARS-CoV-2 infection during the study period. In conclusion, a reorganization of outpatient management, prioritizing visits for high-risk patients and maintaining day hospital activity, mitigated the risk of 30-day readmissions and 90-day mortality for patients admitted for decompensated cirrhosis during lockdown. Such a policy was effective for a short-term lockdown period. Whether that policy is safe for longer periods of lockdown is yet to be explored; similarly, unintended long-term consequences for less sick patients should be better explored in the future. The authors received no financial support to produce this manuscript. SP: Study concept and design, collection of data, analysis and interpretation of data, drafting of the manuscript. MM: Study concept and design, collection of data, study supervision, interpretation of data, drafting of the manuscript, critical revision for important intellectual content. PA: Study concept and design, study supervision, interpretation of data, drafting of the manuscript, critical revision for important intellectual content. The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details. Marta Tonon, Department of Medicine – DIMED, University and Hospital of Padova, Padova, ItalyMarta Mazzetti, Clinic of Gastroenterology and Hepatology, Università Politecnica delle Marche – "Ospedali Riuniti" University Hospital, Ancona, ItalyValeria Calvino, Department of Medicine – DIMED, University and Hospital of Padova, Padova, ItalyLuca Maroni, Clinic of Gastroenterology and Hepatology, Università Politecnica delle Marche – "Ospedali Riuniti" University Hospital, Ancona, ItalyPatrizia Pontisso, Department of Medicine – DIMED, University and Hospital of Padova, Padova, Italy Download .pdf (.24 MB) Help with pdf files disclosures.pdf

Decompensation

Pandemic

10.1016/j.jhepr.2021.100229

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Comparison of Fondaparinux and Low-Molecular-Weight Heparin in the Treatment of Portal Vein Thrombosis in Cirrhosis

The American Journal of Medicine (2021)

Marco Senzolo Salvatore Piano Sarah Shalaby Marta Tonon S. Tonello

Portal vein thrombosis

Fondaparinux

10.1016/j.amjmed.2021.05.013

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Risk factors of early emergent hospital readmission and 6-month mortality in patients with cirrhosis after a recovery from bacterial or fungal infection

Digestive and Liver Disease (2017)

Filippo Morando Salvatore Piano S. Rosi M. Stanco Chiara Pilutti

Infection rate

10.1016/j.dld.2017.01.091

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Long-term albumin administration improves survival in outpatients with decompensated cirrhosis and diabetes: post-hoc analysis of the ANSWER Trial

Digestive and Liver Disease (2024)

Giacomo Zaccherini C. De Venuto Maurizio Baldassarre Enrico Pompili Giulia Iannone

Post-hoc analysis

Post hoc

10.1016/j.dld.2024.01.114

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Liver transplantation in the patient with physical frailty

Journal of Hepatology (2023)

Puneeta Tandon Alberto Zanetto Salvatore Piano Julie K. Heimbach Srinivasan Dasarathy

10.1016/j.jhep.2023.03.025

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Citations (19)

Brexit from current guideline recommendations?

Gut (2016)

Paolo Angeli Salvatore Piano Vicente Arroyo

Dear Editor, We appreciate the interest of O'Brien et al in our position paper recently published in Gut .1 O'Brien et al raised a very important question: is human serum albumin (HSA) the best resuscitation fluid in patients with cirrhosis and acute kidney injury (AKI)? In our minds, as in that of almost all experts in this field, the answer is absolutely yes. This certainty is based on several clinical and experimental evidences and cannot be challenged by studies performed in critically ill patients that are inconsistent for this purpose considering (a) the low percentage of patients with cirrhosis who were included and (b) the modest doses of …

Guideline

Brexit

10.1136/gutjnl-2016-312422

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Hyponatremia and other electrolyte/ion disorders

Salvatore Piano Filippo Morando Paolo Angeli

Hyponatremia is common in patients with cirrhosis and ascites. Patients with cirrhosis may develop two types of hyponatremia: (i) hypovolemic hyponatremia, and (ii) hypervolemic hyponatremia. Hypovolemic hyponatremia represents only 10% of all cases of hyponatremia in patients with cirrhosis. In hypervolemic hyponatremia, the extracellular fluid volume is increased, with ascites and edema in the absence of signs of dehydration. The pathogenesis of hypervolemic hyponatremia is complex and involves several factors that negatively affect the renal free water clearance. These factors include: (i) an increased plasma levels of vasopressin (AVP), (ii) a reduced renal synthesis of prostaglandins, and (iii) a reduced delivery of filtrate to the ascending limb of the loop of Henle, the diluting segment of the nephron. The first step in the management of hyponatremia in cirrhosis is to identify whether hyponatremia is hypovolemic or hypervolemic, because the management differs markedly according to the type. The management of hypovolemic hyponatremia is essentially based upon the administration of sodium with the aim of normalizing the depleted body sodium stores, while the key to management of hypervolemic hyponatremia is to increase renal solute-free water excretion. The other electrolyte disorders that can occur in patients with cirrhosis – hypokalemia, hyperkalemia, hypomagnesemia, and hypophosphatemia – are less common. Often, they represent only adverse effects of diuretics, as in the case of hyperkalemia and hypokalemia. Sometimes, their appearance seems to be more related to the etiology than to the severity of liver disease, as in the case of hypophosphatemia. Finally, their impact on the prognosis of cirrhotic patients is largely unknown or, at least, not comparable with that of hyponatremia. For all these reasons, the present chapter concentrates mainly on hypervolemic hyponatremia in cirrhosis.

Electrolyte Disorder

Hypochloremia

10.1002/9781118412640.ch18

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Comparison between conventional criterion and akin criteria in the definition of acute kidney injury in hospitalized patients with cirrhosis and ascites

Hepatology (2012)

Salvatore Piano S. Rosi Giulio Maresio Paolo Angeli E aal in L

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On-treatment serum albumin level can guide long-term treatment in patients with cirrhosis and uncomplicated ascites

Journal of Hepatology (2020)

Paolo Caraceni Manuel Tufoni Giacomo Zaccherini Oliviero Riggio Paolo Angeli

10.1016/j.jhep.2020.08.021

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Citations (55)