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A Tip of the Iceberg on the Mechanism of SARS-CoV-2–Induced Liver Injury

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(CSPH) in a multicenter cohort of com-
pensated advanced chronic liver disease
(cACLD) of dierent etiologies (1). The
authors developed simple classication
rules to detect CSPH, validated ANTCI-
PATE study models for predicting CSPH
in cohorts of hepatitis C virus (HCV) and
alcoholic liver disease. In addition, a nor-
mogram based on liver stiness measure-
ment (LSM), platelet counts, and body
mass index predicted CSPH in patients
with nonalcoholic steatohepatitis with
good accuracy. The results are important
as detection and treatment of CSPH with
beta-blockers improve survival. We would
like to highlight a few important points
pertaining to the ndings of this study.
With most patients recruited retro-
spectively, there is a possibility of selection
bias. As such, prevalence of portal hyper-
tension and CSPH may have been over-
estimated. Although CSPHusually exists in
patients above an LSM of 10 kPa, mild
portal hypertension can be present in
patients with lower LSM (which were ex-
cluded from the study). Hence, it is dicult
to give accurate estimatesof true prevalence
in view of nonconsecutive recruitment.
In the absence of validation cohorts,
the results of LSM indices derived to
diagnose/exclude CSPH are dicult to
generalize. The authors derived and then
tested the best discriminative values of
LSM to rule in/out CSPH in the etiological
subgroups of same cohort. Similarly, ac-
curacy of assessing CSPH at dierent
point of time is important in patients with
HCV with advent of direct acting anti-
virals (DAA). CSPH reverses in about 40%
of patients treated with DAA; hence, its
assessment is more relevant in patients
after treatment (2). The utility of ANTI-
CPATE model (derived in pre-DAA era)
needs conrmation in patients who have
received DAA.
An important issue detecting CSPH
with noninvasive models is the target
population on which they should be ap-
plied. Detecting CSPH in patients with
cACLD without varices on endoscopy
should be the focus as this is the subset for
modynamic studies. Such patients have
lower LSM and a lower prevalence of
CSPH than those with varices (3). Con-
structing models for detecting CSPH may
be more relevant in this subgroup of
cACLD than deriving them in entire co-
hort as prevalence of CSPH is an impor-
tant determinant of performance of
indices detecting it.
Guarantor of article: Sanchit Sharma, MD.
Specic author contributions: S.S.: writing
and critical revision of manuscript. S.A.:
writing of manuscript. A.A.: writing of
Financial support: None to report.
Potential competing interests: None to
1. Pons M, Augustin S, Scheiner B, et al.
Noninvasive diagnosis of portal hypertension
in patients with compensated advanced
chronic liver disease. Am J Gastroenterol 2020;
2. Lens S, Baiges A, Alvarado-Tapias E, et al.
Clinical outcome and hemodynamic changes
following HCV eradication with oral antiviral
therapy in patients with clinically signicant
portal hypertension. J Hepatol 2020. doi: 10.
3. Jindal A, Bhardwaj A, Kumar G, Sarin SK.
Clinical decompensation and outcomes in
patients with compensated cirrhosis and
hepatic venous pressure gradient $20 mm
Hg. Am J Gastroenterol 2020;115(10):
Department of Gastroenterology and Human
Nutrition, All India Institute of Medical Sciences,
New Delhi, India. Correspondence: Sanchit
Sharma, MD. E-mail:
A Tip of the
Iceberg on the
Mechanism of
Induced Liver
Runsheng Wang, MS
, Lijing Yang, MD, PhD
Chao Hu, MS
, Junhong Yan, MD
Peng Hu, MS
, Hongxia Li, MD
Guogang Xu, MD, PhD
, Lei Pan, MD, PhD
Lei Tu, MD, PhD
Am J Gastroenterol 2021;116:10971098. https://
We thank Gao et al. for their interest in our
research in The American Journal of Gas-
troenterology (1). Their correspondence
letter entitled ACE2: A Linkage for the
Interplay Between COVID-19 and
Decompensated Cirrhosisraised a good
idea toward the better understanding of
decompensated cirrhosis in COVID-19(2).
In general, we agree with the opinions;
however, there could be just a tip of the
iceberg unveiled so far on the full mecha-
nism of liver injury induced by severeacute
respiratory syndrome coronavirus 2
(SARS-CoV-2). Further research need to be
conducted with a focus on the mechanism
of angiotensin-converting enzyme 2
(ACE2) pathway between coronavirus
disease 2019 (COVID-19) and liver injury.
transmembrane zinc metalloenzyme. It has
an extracellar catalytic domain that is key in
metabolizing angiotensin (Ang)toAng-
(1-7), a heptapeptide interacting with the
Mas receptor for vasodilatory and anti-
proliferative functions (3). By such enzy-
matic capacities, ACE2 can balance the
ACE-related activity via reducing the
amount of Angwhile increasing the level
of Ang-(1-7). In addition to the high ex-
pression in the vascular endothelial cells, the
basal layer of the squamous epithelium in
nasopharynx and type 2 alveolar cells and
ACE2 receptor proteins also expressed
highly in the gastrointestinal tract (4). This
could contribute to the reason why many
COVID-19 patients exhibit notable di-
gestive symptoms, and the viral mRNA can
be detected in the patientsfeces via reverse
transcription polymerase chain reaction (5).
Up to now, the comprehensive patho-
logical reports of liver biopsy from patients
who died from COVID-19 are not
abundant. A report of a deceased COVID-
19 case with liver biopsy specimens by Xu
et al. showed that there was moderate
microvesicular steatosis in addition to mild
lobular and portal activity. However, these
pathological ndings cannot conrm
SARS-CoV-2 as the direct cause of liver
injury (6). Moreover, the authors did not
observe viral inclusions in the liver tissue
from the COVID-19 patient using a series of
pathological analytical methods (6). Beig-
mohammadi et al. analyzed lung, liver, and
heart tissues from 7 patients who died of
COVID-19 by postmortem core needle bi-
opsies. These patients were selected because
of the presence of elevated liver enzymes in
the serum before death. The liver biopsies in
most cases showed hepatic congestion,
macrovesicular and microvesicular stea-
tosis, and some portal inammation. In fact,
ischemia changes of the liver were not
commonly seen in these patients. Most l iver
tissue slides exhibited nonspecicndings
© 2021 by The American College of Gastroenterology The American Journal of GASTROENTEROLOGY
Correspondence 1097
Copyright © 2021 by The American College of Gastroenterology. Unauthorized reproduction of this article is prohibited.
(7). Because all these COVID-19 patients
showed pathological changes of hepatic
congestion ranging from mild-to-severe
degree, the authors predicted that SARS-
CoV-2induced severe respiratory infec-
tions might cause a right ventricular failure
of the patient, which therefore could lead to
a passive venous congestion of the liver (7).
Recently, Chai et al. have showed a sig-
nicantly higher enrichment of ACE2 ex-
pression in cholangiocytes than hepatocytes
(59.7% of cells vs 2.6%) via single-cell RNA
sequencing method. Furthermore, the av-
erage ACE2 mRNA expression level in
cholangiocytes is 20-folds higher than that
in hepatocytes. Based on these data, the
authors speculated that liver damage in
COVID-19 patients may not be caused di-
rectly by viral infection of hepatocytes (8).
Using the same method, Seow et al. reported
the expression of ACE2 and trans-
membrane serine protease 2 (TMRPSS2) in
a tumor-associated calcium signal trans-
ducer 2 positive (TROP21) liver progenitor
population. By contrast, no detectable
ACE2 expression in hepatocyte and other
hepatic immune and stromal cells was
reported. It was predicted that viral in-
fection of liver progenitors might handicap
the regeneration of liver cells, thus causing
relevant pathological changes (9).
When some patients with liver cirrho-
sis were unfortunately infected with
SARS-CoV-2, the situation might be
worse and the mechanism under the liver
injury may be more complex. As showed
by Paizis et al., ACE2 could be observed in
the hepatocytes surrounding occasionally
larger central veins in a normal human
liver. However, in the cirrhotic liver, the
ACE2 expression was widespread
throughout cirrhotic nodules and endo-
thelial cells lining small blood vessels and
bile duct cells (10). Theoretically, upre-
gulation of ACE2 on the cell surface will
predispose the cell to SARS-CoV-2 in-
fection, but as cirrhotic nodules expressing
ACE2 perhaps have lost the normal liver
function, it may be dicult to evaluate the
eect of infected cirrhotic nodules on the
whole function of the liver. Although
compared with the normal liver, the
compensation potential of cirrhotic is de-
creased, which may make the liver more
vulnerable to internal environmental fac-
tors in the body, such as inammatory
cytokines storm, drug toxicity, and in-
testinal dysbiosis in addition to the direct
eect of viral infection. As severe liver
injury has correlation with worse clinical
outcome, it is not sucient to explain this
correlation just by the direct eect of
SARS-CoV-2 on the liver. Cytokines
storm might also contribute to the liver
injury and multiorgan dysfunctions. Un-
der normal conditions, cytokines main-
tain dynamic homeostasis as a part of the
human immune response to microbial
infections. However, when the release of
cytokines is a large quantity in a short
time, for instance, high loads of SARS-
CoV-2 infection, cytokines storm could
cause multiple organ failure, including
liver damage, and high mortality in some
severe cases.
In general, the precise mechanisms of
liver injury by SARS-CoV-2 infection remain
to be elucidated. It is recognized that the level
of liver injury is associated with the severity
of COVID-19 in many patients. Therefore,
all the possible factors that might aect the
liver functions need to be considered when
treating COVID-19 patients. Full consid-
erations of the patientsconditions will not
only facilitate the therapeutic eects on liver
injury but also avail the general rehabilitation
of severe COVID-19 patients (11). In the
near future, we advocate further biopsies
from post-mortem assessments of patients
who died from COVID-19 for more detailed
research to conrm the pathophysiology
of SARS-CoV-2induced liver injury as
commonly reported by clinicians.
Guarantor of the article: Hongxia Li, MD,
Guogang Xu, MD, PhD, Lei Pan, MD, PhD,
and Lei Tu, MD, PhD.
Specic author contributions: Runsheng
Wang, MS, Lijing Yang, MD, PhD, Chao Hu,
MS, Hongxia Li, MD, Guogang Xu, MD,
PhD, Lei Pan, MD, PhD and Lei Tu, MD,
PhD, contributed equally to this work. Study
concept and design: H.L., G.X., L.P., L.T.
Analysis and interpretation of data: R.W.,
L.Y., C.H. and J.Y. Drafting of the
manuscript: R.W., L.Y. and C.H. Critical
revision of the manuscript: H.L., G.X., L.P.,
P.H., L.T. Study supervision: H.L., G.X., L.P.,
L.T. All authors contributed to the
manuscript for important intellectual
contents and approved the submission.
Financial support: National Key Research
Program(2018YFC2002400), National
Natural Science Foundation of China (CN,
81700490), Health and Family Planning
Commission of Shandong Province (CN,
2017WS366), Traditional Chinese Medicine
Administration Plan Project of Shandong
Province (CN, 2019-0503), and Technology
Plan Project of Binzhou Medical University
(CN, BY2017KJ30).
Potential competing interests: None to
1. Pan L, Mu M, Yang P, et al. Clinical
characteristics of COVID-19 patients with
digestive symptoms in Hubei, China: A
descriptive, cross-sectional, multicenter
study. Am J Gastroenterol 2020;115:76673.
2. Gao F, Zheng KI, Fan YC, et al. ACE2: A
linkage for the Interplay between COVID-19
and decompensated cirrhosis. Am J
Gastroenterol 2020;115(9):1544.
3. Imai Y, Kuba K, Ohto-Nakanishi T, et al.
Angiotensin-converting enzyme 2 (ACE2) in
disease pathogenesis. Circ J 2010;74:40510.
4. Jothimani D, Venugopal R, Abedin MF, et al.
COVID-19 and the liver. J Hepatol 2020;73:
5. Yang L, Tu L. Implications of gastrointestinal
manifestations of COVID-19. Lancet
Gastroenterol Hepatol 2020;5:62930.
6. Xu Z, Shi L, Wang Y, et al. Pathological
ndings of COVID-19 associated with acute
respiratory distress syndrome. Lancet Respir
Med 2020;8:4202.
7. Beigmohammadi MT, Jahanbin B, Safaei
M, et al. Pathological ndings of
postmortem biopsies from lung, heart, and
liver of 7 deceased COVID-19 patients. Int
J Surg Pathol 2020. [Epub ahead of print
June 19, 2020.] doi: 10.1177/
8. Allam Z, Jones DS. On the coronavirus
(COVID-19) outbreak and the smart city
network: Universal data sharing standards
coupled with articial intelligence (AI) to
benet urban Health monitoring and
management. Healthcare (Basel) 2020;8:46.
9. Arashiro T, Furukawa K, Nakamura A.
COVID-19 in 2 persons with mild upper
respiratory symptoms on a cruise ship, Japan.
Emerg Infect Dis 2020;26(6):13458.
10. Paizis G, Tikellis C, Cooper ME, et al. Chronic
liver injury in rats and humans upregulates the
novel enzyme angiotensin converting enzyme
2. Gut 2005;54:17906.
11. Peng F, Tu L, Yang Y, et al. Management and
treatment of COVID-19: The Chinese
experience. Can J Cardiol 2020;36(6):91530.
Department of Respiratory Medicine, The Second
Medical Center & National ClinicalResearch Center
for Geriatric Diseases, Medical College of PLA,
Chinese PLA General Hospital, Beijing, China;
Department of Radiation and Medical Oncology,
Zhongnan Hospital of Wuhan University, Wuhan,
Department of Ultrasound, Binzhou Medical
University Hospital, Binzhou, China;
The Second
Medical Center & National ClinicalResearch Center
for Geriatric Diseases, Chinese PLA General
Hospital, Beijing, China;
Department of Respiratory
and Critical Care Medicine, Binzhou Medical
University Hospital, Binzhou, China;
Division of
Gastroenterology, Union Hospital, Tongji Medical
College, Huazhong University of Science and
Technology, Wuhan, China. Correspondence: Lei
Tu, MD, PhD. E-mail: Lei
Pan, MD, PhD. E-mail:
Guogang Xu, MD, PhD. E-mail: Hongxia Li, MD.
Wang et al.1098
The American Journal of GASTROENTEROLOGY VOLUME 116 | MAY 2021
Copyright © 2021 by The American College of Gastroenterology. Unauthorized reproduction of this article is prohibited.
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Full-text available
Background. A novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been affecting almost all nations around the world. Most infected patients who have been admitted to intensive care units show SARS signs. In this study, we aimed to achieve a better understanding of pathological alterations that take place during the novel coronavirus infection in most presumed affected organs. Methods. We performed postmortem core needle biopsies from lung, heart, and liver on 7 deceased patients who had died of coronavirus disease 2019. Prepared tissue sections were observed by 2 expert pathologists. Results. Diffuse alveolar damage was the main pathologic finding in the lung tissue samples. Patients with hospitalization durations of more than 10 days showed evidence of organization. Multinucleated cells in alveolar spaces and alveolar walls, atypical enlarged cells, accumulation of macrophages in alveolar spaces, and congestion of vascular channels were the other histopathologic alteration of the lung. None of our heart biopsy samples met the criteria for myocarditis. Liver biopsies showed congestion, micro- and macro-vesicular changes, and minimal to mild portal inflammation, in the majority of cases. Conclusions. Similar to the previous coronavirus infection in 2003, the main pathologic finding in the lung was diffuse alveolar damage with a pattern of organization in prolonged cases. The SARS-CoV-2 infection does not cause myocarditis, and the ischemia of myocardium is the most probable justification of the observed pathologic changes in the heart. Liver tissue sections mostly showed nonspecific findings; however, ischemia of the liver can be identified in some cases.
Full-text available
The current pandemic coronavirus labelled as Severe Acute Respiratory Distress Syndrome Coronavirus -2 (SARS -CoV-2) is a significant public health threat over for past few weeks. Overall case fatality rates range between 2-6%; however, the rates are higher in patients with severe disease, advanced age and underlying comorbidities like diabetes, hypertension and heart disease. Recent reports showed about 2-11% of patients with COVID-19 had underlying chronic liver disease. Experience from previous SARS epidemic suggest that 60% of patients developed various degrees of liver damage. In the current pandemic, hepatic dysfunction was seen in 14-53% of patients with COVID-19, particularly in those with severe disease. Cases of acute liver injury have been reported, associated with higher mortality. Hepatic involvement in COVID-19 could be multifactorial related to any of direct cytopathic effect of the virus, uncontrolled immune reaction, sepsis or drug induced liver injury. The postulated mechanism of viral entry is through the host ACE2 receptors that are abundantly present in type 2 alveolar cells. Interestingly, the expression of ACE2 receptors were identified in the gastrointestinal tract, vascular endothelium and cholangiocytes of the liver. Liver transplant recipients with COVID-19 have been reported recently. Effects of COVID-19 on underlying chronic liver disease requires a detailed evaluation and currently data is lacking and further research is warranted in this area. With lack of definitive therapy, patient education, hand hygiene and social distancing appears to be the cornerstone in minimising the disease spread.
Full-text available
Objective: Since the outbreak of Coronavirus Disease 2019 (COVID-19) in December 2019, various digestive symptoms have been frequently reported in patients infected with the virus. In this study, we aimed to further investigate the prevalence and outcomes of COVID-19 patients with digestive symptoms. Methods: In this descriptive, cross-sectional, multicenter study, we enrolled confirmed patients with COVID-19 who presented to 3 hospitals from January 18, 2020, to February 28, 2020. All patients were confirmed by real-time polymerase chain reaction and were analyzed for clinical characteristics, laboratory data, and treatment. Data were followed up until March 18, 2020. Results: In the present study, 204 patients with COVID-19 and full laboratory, imaging, and historical data were analyzed. The average age was 52.9 years (SD ± 16), including 107 men and 97 women. Although most patients presented to the hospital with fever or respiratory symptoms, we found that 103 patients (50.5%) reported a digestive symptom, including lack of appetite (81 [78.6%] cases), diarrhea (35 [34%] cases), vomiting (4 [3.9%] cases), and abdominal pain (2 [1.9%] cases). If lack of appetite is excluded from the analysis (because it is less specific for the gastrointestinal tract), there were 38 total cases (18.6%) where patients presented with a gastrointestinal-specific symptom, including diarrhea, vomiting, or abdominal pain. Patients with digestive symptoms had a significantly longer time from onset to admission than patients without digestive symptoms (9.0 days vs 7.3 days). In 6 cases, there were digestive symptoms, but no respiratory symptoms. As the severity of the disease increased, digestive symptoms became more pronounced. Patients with digestive symptoms had higher mean liver enzyme levels, lower monocyte count, longer prothrombin time, and received more antimicrobial treatment than those without digestive symptoms. Discussion: We found that digestive symptoms are common in patients with COVID-19. Moreover, these patients have a longer time from onset to admission, evidence of longer coagulation, and higher liver enzyme levels. Clinicians should recognize that digestive symptoms, such as diarrhea, are commonly among the presenting features of COVID-19 and that the index of suspicion may need to be raised earlier in at-risk patients presenting with digestive symptoms. However, further large sample studies are needed to confirm these findings.
Full-text available
We describe 2 cases of COVID-19 in patients with mild upper respiratory symptoms. Both patients worked on a cruise ship quarantined off the coast of Japan. One patient had persistent, low-grade upper respiratory tract symptoms without fever. The other patient had rapid symptom cessation but persistent viral RNA detection.
Introduction: We aimed to explore the prevalence of portal hypertension in the most common etiologies of patients with compensated advanced chronic liver disease (cACLD) and develop classification rules, based on liver stiffness measurement (LSM), that could be readily used to diagnose or exclude clinically significant portal hypertension (CSPH) in clinical practice. Methods: This is an international cohort study including patients with paired LSM/hepatic venous pressure gradient (HVPG), LSM ≥10 kPa, and no previous decompensation. Portal hypertension was defined by an HVPG >5 mm Hg. A positive predictive value ≥90% was considered to validate LSM cutoffs for CSPH (HVPG ≥10 mm Hg), whereas a negative predictive value ≥90% ruled out CSPH. Results: A total of 836 patients with hepatitis C (n = 358), nonalcoholic steatohepatitis (NASH, n = 248), alcohol use (n = 203), and hepatitis B (n = 27) were evaluated. Portal hypertension prevalence was >90% in all cACLD etiologies, except for patients with NASH (60.9%), being even lower in obese patients with NASH (53.3%); these lower prevalences of portal hypertension in patients with NASH were maintained across different strata of LSM values. LSM ≥25 kPa was the best cutoff to rule in CSPH in alcoholic liver disease, chronic hepatitis B, chronic hepatitis C, and nonobese patients with NASH, whereas in obese NASH patients, the positive predictive value was only 62.8%. A new model for patients with NASH (ANTICIPATE-NASH model) to predict CSPH considering body mass index, LSM, and platelet count was developed, and a nomogram was constructed. LSM ≤15 kPa plus platelets ≥150 × 10/L ruled out CSPH in most etiologies. Discussion: Patients with cACLD of NASH etiology, especially obese patients with NASH, present lower prevalences of portal hypertension compared with other cACLD etiologies. LSM ≥25 kPa is sufficient to rule in CSPH in most etiologies, including nonobese patients with NASH, but not in obese patients with NASH.
Background Clinically significant portal hypertension (CSPH, HVPG≥10mmHg) persists 24 weeks after sustained virological response (SVR) in up to 78% of patients with HCV-related cirrhosis treated with direct acting antivirals. These patients remain at risk of decompensation. However, long-term paired clinical and hemodynamic data are not available for this population. Methods Multicenter prospective study including 226 patients with HCV-related cirrhosis and CSPH achieving SVR after antiviral therapy. Patients with CSPH 24 weeks after therapy (SVR24) were offered another hemodynamic assessment 96 weeks after end of treatment (SVR96). Results All patients were clinically evaluated. One-hundred seventeen (66%) of the 176 patients with SVR24-CSPH underwent SVR96-HVPG (this was not done for several reasons in the remaining 59 patients). At SVR96, 55/117 (47%) patients had HVPG < 10mmHg and 53% had CSPH (65% if we assume persistence of CSPH in all 59 non-evaluated patients). The proportion of high-risk patients (HVPG ≥ 16mmHg) diminished from 41% to 15%. Liver stiffness decreased markedly after SVR (median decrease 10.5 ± 13kPa) but did not correlate with HVPG changes (30% of patients with LSM <13.6kPa still had CSPH). Seventeen (7%) patients presented de novo/additional clinical decompensation, which was independently associated with baseline HVPG ≥ 16mmHg and history of ascites. Conclusions Patients achieving SVR present a progressive reduction in portal pressure during follow-up. However, CSPH may persist in up to 53-65% of patients at SVR96, indicating persistent risk of decompensation. History of ascites and high-risk HVPG values identified patients at higher risk of de novo or further clinical decompensation.
Objectives: Hepatic venous pressure gradient (HVPG) of ≥10 mm Hg predicts clinical decompensation (CD) in compensated cirrhosis. A proportion of cirrhotic patients at presentation have high HVPG (≥20 mm Hg) and are compensated. The natural history, spectrum of CD, and mortality in this group is largely unknown. Methods: Consecutive compensated cirrhotic patients with HVPG ≥6 mm Hg (n = 741) were followed up for 3-6 months for the development of any CD. Patients were classified based on the baseline HVPG (6 to <12 mm Hg [low HVPG, Gr.A, n = 163], 12 to <20 mm Hg [intermediate HVPG, Gr.B, n = 437] and ≥20 mm Hg [high HVPG, Gr.C, n = 141]). We analyzed the predictors of first CD, HVPG response to carvedilol, and mortality in these groups. Results: CD developed in 217 (29.3%) patients during a mean follow-up of 1.6 ± 0.4 years, and those who developed CD had higher baseline HVPG (17.02 ± 4.79 vs 14.28 ± 4.86; P < 0.001). First CD was seen earlier (1.3 ± 0.7 years vs 1.5 ± 0.6 years and 1.6 ± 0.5 years, P = 0.02) and more frequently (44.7% vs 11% and 31.1%, P < 0.01) in high HVPG groups compared with low and intermediate HVPG groups, with higher mortality rates. Patients in the high HVPG group compared with the low HVPG group more often had NASH-cirrhosis (35.5% vs 19.6%; P 0.001), higher liver stiffness values (45.06 ± 20.46 vs 20.09 ± 5.47 kPa, P < 0.001), and lower platelet counts (113.37 ± 72.57 vs 151.7 ± 87.30/cmm, P < 0.001). Patients with HVPG ≥12 mm Hg received carvedilol, and a repeat HVPG performed in a proportion after 9.3 ± 2.4 months showed response (≥20% reduction in HVPG or <12 mm Hg) in 31.6% patients (Gr. B, 44.9% > Gr. C, 22.2%, P < 0.05). Baseline HVPG (HVPG ≥12 to <20 mm Hg [Hazard ratio: 2.73] and HVPG ≥20 mm Hg [Hazard ratio: 4.48], P < 0.001) independently predicted CD. Discussion: HVPG ≥20 mm Hg in patients with compensated cirrhosis independently predicts early and more frequent CD and poor outcomes. These patients should be labeled as "high-risk compensated cirrhosis," and early and effective interventions to reduce portal pressure should be initiated to improve long-term outcomes.
With over 1,800,000 cases and 110,000 deaths globally, COVID-19 is one of worst infectious disease outbreaks in history. The objective of this paper is to critically review the available evidence regarding the lessons learned from the Chinese experience regarding COVID-19 prevention and management. The steps that have led to a near disappearance of new cases in China included rapid sequencing of the virus to establish testing kits which allowed tracking of infected persons in and out of Wuhan. In addition, aggressive quarantine measures included the complete isolation of Wuhan and then later Hebei and the rest of the country, as well as closure of all schools and non-essential businesses. Other measures included the rapid construction of two new hospitals and the establishment of Fangcang shelter hospitals. In the absence of a vaccine, the management of COVID-19 included antivirals, high flow oxygen, mechanical ventilation, corticosteroids, hydroxychloroquine, tocilizumab, interferons, intravenous immunoglobulin and convalescent plasma infusions. These measures appeared to provide only moderate success. While some measures have been supported by weak descriptive data, their effectiveness is still unclear pending well-controlled clinical trials. In the end, it was the enforcement of drastic quarantine measures that stopped SARS-CoV-2 from spreading. The earlier the implementation, the less likely resources will be depleted. The most critical factors in stopping a pandemic are early recognition of infected individuals, carriers and contacts, and early implementation of quarantine measures with an organized, proactive and unified strategy at a national level. Delays result in significantly higher death tolls.