Pre-existing Liver Cirrhosis Research Articles

Severe Alcoholic Hepatitis-optimizing Medical Management: Whether we need a Liver Transplant

Severe alcoholic hepatitis is an ethical and clinical conundrum, wherein a liver transplant is often recommended. The adequacy of medical treatment versus the risk of recidivism after transplant is often debated. Complete recovery in 26 of 27 patients with severe alcoholic hepatitis was observed, and hence the data was retrospectively analysed. Methods: 27 patients, with severe alcoholic hepatitis, with Maddrey's discriminant function between 59.7 to 165.2 (mean 107.53), from June 2017 to May 2022, were followed up for between 11 months to 6 years. INR ranged from 1.99 to 3.7 (mean 2.709), and bilirubin was between 7.6 to 37.01, (mean 20.859). 8 patients had pre-existing liver cirrhosis. All patients received probiotics, nutritional support, physical rehabilitation, saturated fat (clarified butter/ desi ghee) supplementation, and anti-oxidant support. At 90 days, total bilirubin improved to between 1.0 to 6.8 (mean 2.625). ALT (Alanine Transaminase/ SGPT) ranged from 65 to 550 (mean ALT – 197); and AST (Aspartate Transaminase / SGOT) ranged from 58 to 810 (mean AST – 271.51). Both the AST and ALT were near normal after 90 days. One patient died due to bacterial pneumonia and sepsis; the remaining 26 patients made a complete recovery. All patients including those with diagnosed liver cirrhosis, had complete resolution of their ascites, and near-normal liver function. At the last outpatient visit, none had ascites, edema, or encephalopathy, and had normal albumin levels and INR values. Conclusion: Probiotics, nutrition, a saturated fat diet, and exercise; all have shown benefits in patients with severe alcoholic hepatitis when tested individually. Concomitant use of all the above has not been reported in the treatment of alcoholic hepatitis. The role of nutrition alone versus the contribution of nutritional deficiencies and the role of gut-derived endotoxemia need to be studied in detail. How to identify patients who need a transplant, if it is needed at all, remains a challenge.

Liver diseases in the intensive care unit

The frequency of liver diseases in the intensive care unit has increased significantly in recent years and is now observed in up to 20% of critically ill patients. The occurrence of liver disease is associated with significantly increased morbidity and mortality. Two groups of liver diseases in the intensive care unit can be distinguished. First, the group of "primary hepatic dysfunctions", which includes primary acute liver failure as well as acute-on-chronic liver failure in patients with pre-existing liver cirrhosis. The second group of "secondary or acquired liver diseases" includes cholestatic liver diseases, as well as hypoxic liver injury and mixed forms, as well as other rarer liver diseases. Due to the diversity of liver diseases and the very different triggers, sufficient knowledge of the underlying changes (including hemodynamic changes, inflammatory states or drug-related) is essential. Early recognition, diagnosis, and treatment of the underlying disease are essential for all liver dysfunction in critically ill patients in the intensive care unit. This review article aims to take acloser look at liver diseases in the intensive care unit and provides insight into diagnostics and treatment options.

Soluble Semaphorin 4D Serum Concentrations Are Elevated in Critically Ill Patients with Liver Cirrhosis and Correlate with Aminotransferases.

Semaphorin 4D (Sema4D), also known as CD100, is a multifunctional transmembrane protein with immunoregulatory functions. Upon the activation of immune cells, soluble Semaphorin 4D (sSema4D) is proteolytically cleaved from the membrane by metalloproteinases. sSema4D levels are elevated in various (auto-)inflammatory diseases. Our aim was to investigate sSema4D levels in association with sepsis and critical illnesses and to evaluate sSema4D's potential as a prognostic biomarker. We measured sSema4D levels in 192 patients upon admission to our medical intensive care unit. We found similar levels of sSema4D in 125 patients with sepsis compared to 67 non-septic patients. sSema4D levels correlated with leukocytes but not with other markers of systemic inflammation such as C-reactive protein or procalcitonin. Most interestingly, in a subgroup of patients suffering from pre-existing liver cirrhosis, we observed significantly higher levels of sSema4D. Consistently, sSema4D was also positively correlated with markers of hepatic and cholestatic injury. Our study suggests that sSema4D is not regulated in sepsis compared to other causes of critical illness. However, sSema4D seems to be associated with hepatic injury and inflammation.

Clinical and Etiological Profile of Acute Undifferentiated Fever With Thrombocytopenia in an Emergency Department.

Acute undifferentiated fever with thrombocytopenia is a common and challenging clinical presentation encountered in the emergency departments of tertiary care centers, particularly in tropical regions, often requiring prompt evaluation and management. The study aimed to explore the clinical and etiological profile of acute undifferentiated fever with thrombocytopenia in the Emergency Department of Indira Gandhi Institute of Medical Sciences, Patna. It investigates factors associated with patient outcomes and compares platelet transfusion requirements among different etiological groups. In this cross-sectional observational study, 350 patients with acute undifferentiated fever with thrombocytopenia were analyzed for one year from October '21 to September '22. Pre-existing chronic infectious diseases, liver cirrhosis, and autoimmune conditions were excluded. Thrombocytopenia was observed in all patients, with 65% having platelet counts below 50,000/µL. Associations were found between the degree of thrombocytopenia and organ dysfunction, shock, and third space loss. Logistic regression analysis identified thrombocytopenia, organ dysfunction, and platelet transfusion requirement as significant predictors of the overall outcome. Etiological group comparisons revealed higher platelet transfusion requirements in the bacterial group. Prompt recognition and management of thrombocytopenia in acute undifferentiated fever are vital. Thrombocytopenia, along with organ dysfunction and shock, significantly influence patient outcomes. Tailored interventions based on etiological factors are crucial. Further research should focus on specific viral aetiologies in acute undifferentiated fever with thrombocytopenia.

Prevention, diagnostic evaluation, management and prognostic implications of liver disease in critically ill patients with COVID-19.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, broke out in December 2019 in Wuhan city of China and spread rapidly worldwide. Therefore, by March 2020, the World Health Organization declared the disease a global pandemic. Apart from the respiratory system, various other organs of the human body are also seriously affected by the virus. Liver injury in patients with a severe form of COVID-19 is estimated to be 14.8%-53.0%. Elevated levels of total bilirubin, aspartate aminotransferase and alanine aminotransferase and low levels of serum albumin and prealbumin are the main laboratory findings. Patients with pre-existing chronic liver disease and cirrhosis are much more prone to develop severe liver injury. This literature review presented the recent scientific findings regarding the pathophysiological mechanisms responsible for liver injury in critically ill patients with COVID-19, the various interactions between drugs used to treat the disease and the function of the liver and the specific tests providing the possibility of early diagnosis of severe liver injury in these patients. Moreover, it highlighted the burden that COVID-19 put on health systems worldwide and its effect on transplant programs and the care provided to critically ill patients in general and particularly to those with chronic liver disease.

Management of Multidrug-resistant Tuberculosis in a Ukrainian Refugee with HIV/HCV Coinfection: A Case Report

In this case study, we present a 53-year-old Ukrainian refugee with reactivation of multidrug-resistant tuberculosis, which was treated in Ukraine 4 years before he fled the country following the Russian invasion of Ukraine. The patient had a chronic HIV infection that had been treated with antiretroviral therapy and was newly diagnosed with severe acute respiratory syndrome coronavirus 2019 infection, hepatitis C infection and liver cirrhosis. Therefore, tuberculostatic therapy was individualized because of resistance against rifampicin, isoniazid, bedaquiline, and clofazimine and pre-existing liver cirrhosis and neuropathy. The latter was a sequela of a former tuberculosis treatment taken 4 years earlier. The treatment of the patient was complicated by superinfection of the lung cavity with carbapenemase-resistant Klebsiella pneumoniae and a life-threatening massive haemoptysis. He received a selective angiographic examination and bronchial artery embolization. This case report illustrates the complex management of several coinfections in the context of a humanitarian crisis following the on-going military conflict in Ukraine.

Hormone replacement therapy is associated with reduced hepatocellular carcinoma risk and improved survival in postmenopausal women with hepatitis B: A nationwide long-term population-based cohort study.

Postmenopausal women with hepatitis B virus (HBV) infection are more likely to have accelerated liver fibrosis, eventually advancing to liver cirrhosis or hepatocellular carcinoma (HCC). The association between sex hormones and HBV-related HCC risk is unclear. We investigated whether hormone replacement therapy (HRT) is beneficial to postmenopausal women with HBV infection. This retrospective study selected the data of 44,465patients with HBV infection between January 2000 and December 2018 from Taiwan’s National Health Insurance Research Database. After excluding patients with preexisting liver diseases, liver cirrhosis, or liver malignancies, we grouped the remaining 10,474 patients by whether they had undergone HRT for at least 3 months (n = 5,638) and whether they had not received HRT (n = 4,836). After propensity score matching, we assigned 3080 patients to an HRT cohort and matched them (1:1) with those in a non-HRT cohort. The incidence of HCC (P < 0.022) and all-cause mortality rate (P < 0.001) were lower in the HRT cohort than in the non-HRT cohort. The liver cirrhosis risk was not significantly higher in the HRT cohort (P = 0.355). HRT is associated with reduced HCC risk and improved survival outcomes but is unrelated to liver cirrhosis development in postmenopausal women.

Suppressed serological vitamin A in patients with liver cirrhosis is associated with impaired liver function and clinical detoriation.

BackgroundThe liver is of critical importance for the homeostasis of metabolic and immunomodulatory properties as well as the storage of vitamins, especially vitamin A. In this prospective analysis, the incidence of serological vitamin A deficiency and the association with disease severity as well as clinical complications in patients with liver cirrhosis were investigated.MethodFrom May 2017 to May 2018, 159 patients with primarily alcohol-associated and non-alcoholic steatohepatitis (NASH)-associated preexisting liver cirrhosis were prospectively enrolled and vitamin A status was collected. Clinical complications and infections were followed and recorded over a period of 1-year follow-up. Selected findings were validated in an independent cohort of 44 patients.ResultsAt study inclusion, 77% of patients showed decreased serological vitamin A. Suppressed vitamin A was more common in alcoholic (52 vs. 8%) and NASH-associated liver cirrhosis (16 vs. 9%) than in viral-associated liver cirrhosis. MELD score as well as Child-Pugh score were significantly associated with suppressed vitamin A (P < 0.001). The association between the degree of vitamin A suppression and liver function was confirmed in univariate and multivariate regression analysis. After 1 year of follow-up, 57 patients died and 21 patients received a liver transplant. In addition, low vitamin A levels were more commonly observed in patients with severe ascites (P = 0.001), hepatic encephalopathy (P = 0.002) and hepatorenal syndromes (P = 0.008). In addition, patients with reduced vitamin A showed an increased incidence of infections (P = 0.02), especially respiratory infections (P = 0.04).Conclusion:Suppressed serological Vitamin A is common in patients with liver cirrhosis and is associated with liver function. Clinical complications and infections are more frequent in patients with liver cirrhosis and vitamin A suppression.

The Importance of Metabolic Syndrome Status for the Risk of Non-Viral Hepatocellular Carcinoma: A Nationwide Population-Based Study.

The positive association between metabolic syndrome (MetS) and hepatocellular carcinoma (HCC) has been suggested. However, no studies have yet looked at how the risk of developing HCC varies with changes in MetS status. Therefore, we aimed to investigate the association between changes in MetS and subsequent HCC development. Data were obtained from the Korean National Health Insurance Service. In this study, 5,975,308 individuals who participated in health screenings both in 2009–2010 and 2011–2012 were included. Individuals with preexisting viral hepatitis, liver cirrhosis, or cancer diagnoses were excluded. Subjects were divided into four groups according to change in MetS status during the 2-year interval screening (from 2009 to 2011): sustained non-MetS, transition to MetS, transition to non-MetS, and sustained MetS. Cox regression analysis was used to examine the hazard ratios of HCC. The subjects were followed through December 31, 2018. During a median of 7.3 years of follow-up, 25,880 incident HCCs were identified. Compared to the sustained non-MetS group, age, sex, smoking, alcohol, regular exercise, and body mass index-adjusted hazard ratios (95% confidence interval) for HCC development were 1.01 (0.97–1.05) for the transition to MetS group, 1.05 (1.003–1.09) for the transition to non-MetS group, and 1.07 (1.03–1.10) for the sustained MetS group. Stratified analyses according to age, sex, smoking, alcohol intake, exercise, diabetes mellitus, hypertension, dyslipidemia, and chronic kidney disease showed similar results. A significantly increased HCC risk was observed in the sustained MetS and transition to non-MetS groups. The baseline status of MetS was associated with the risk of HCC development. Strategies to improve MetS, especially targeting insulin resistance, might prevent HCC development.

Clinical characteristics and outcomes of drug-induced liver injury in Taiwan: With emphasis on the impact of chronic hepatitis B infection.

Whether hepatitis B virus (HBV) infection can affect the outcomes of drug-induced liver injury (DILI) is controversial. This study aimed to evaluate the characteristics and outcomes of DILI in Taiwan, with an emphasis on the impact of HBV infection. We prospectively recruited patients with DILI from multiple centers in Taiwan from 2010 to 2018. A total of 1,014 patients were enrolled. The leading culprit drug category was antimicrobials (481, 47.4%), followed by nonsteroidal anti-inflammatory drugs, anticonvulsants, and statins. Among the antimicrobials, antituberculosis agents were most likely to induce liver injury (257, 25.3%), followed by antibacterial, antifungal, and antiviral agents. The liver-related mortality rate was 8.2% (83/1,014). The patients who died had higher rates of hepatocellular-type liver injury, elevated liver biochemical tests, preexisting liver cirrhosis, jaundice, chronic HBV infection, and antituberculosis drug-induced liver injury (ATDILI) than the survivors. A total of 131 patients (12.9%) with DILI were HBV carriers, of whom 23 (17.6%) died of hepatic failure. The rate of HBV-DNA > 2000 IU/mL was higher in the patients who died (47.8% vs. 26.9%, p = 0.047) than in the survivors. After adjusting for possible risk factors, active HBV infection with HBV-DNA > 2000 IU/mL was the most significant risk factor for liver-related mortality (adjusted HR, 4.40, 95% CI, 2.31%-8.38%, p < 0.001). The other independent risk factors for mortality were ATDILI and albumin-bilirubin (ALBI) score (adjusted HR, 1.25 and 4.09, respectively, p < 0.003). Antituberculosis agents were the leading cause of DILI in Taiwanese, and they were associated with poorer outcomes than other drug categories. Active HBV infection, ATDILI and ALBI score were independent risk factors for fatal DILI. Close monitoring of liver tests and timely antiviral therapy should be implemented in HBV carriers during the administration of high-risk drugs, such as antituberculosis agents.

Association between direct-acting antiviral agents in hepatitis C virus treatment and hepatocellular carcinoma occurrence and recurrence: The endless debate.

Since direct-acting antiviral agents (DAAs) have been introduced into hepatitis C virus treatment, the sustained viral response (SVR) rate has significantly increased to more than 95%. Scientific evidence supports the idea that SVR after interferon therapy has beneficial effects related to cirrhosis progression, resulting in a reduction in the incidence of hepatocellular carcinoma (HCC). However, a significant debate exists related to DAA impact on HCC development. We reviewed the current literature highlighting the controversial data related to DAA association with de novo HCC occurrence or recurrence and possible pathophysiology of HCC related to DAAs. After a review of the published literature, we believe that the current evidence does not confirm or repudiate a higher rate of de novo HCC occurrence or recurrence related to DAA therapy. More trials are needed to determine if there is an association between HCC occurrence or recurrence and DAA or if it is related to preexisting liver cirrhosis.

Hip Fractures in Patients With Liver Cirrhosis: Worsening Liver Function Is Associated with Increased Mortality.

Liver cirrhosis is associated with osteoporosis, imbalance leading to falls, and subsequent fragility fractures. Knowing the prognosis of patients with liver cirrhosis of varying severity at the time of hip fracture would help physicians determine the course of treatment in this complex patient popultaion. (1) Is there an association between liver cirrhosis of varying severity and mortality in patients with hip fractures? (2) Is there an association between liver cirrhosis of varying severity and the in-hospital, 30-day, and 90-day postoperative complications of symptomatic thromboembolism and infections including wound complications, pneumonia, and urinary tract infections? Between 2015 and 2019, we identified 128 patients with liver cirrhosis who were treated for hip fractures at one of two Level I trauma centers. Patients younger than 18 years, those with incomplete medical records, fractures other than hip fractures or periprosthetic hip fractures, noncirrhotic liver disease, status after liver transplantation, and metastatic cancer other than hepatocellular carcinoma were excluded. Based on these exclusions, 77% (99 of 128) of patients were eligible; loss to follow-up was 0% within 1 year and 4% (4 of 99) at 2 years. The median follow-up duration was 750 days (interquartile range 232 to 1000). Ninety-four patients were stratified based on Model for End-stage Liver Disease (MELD) score subgroup (MELD scores of 6-9 [MELD6-9], 10-19 [MELD10-19], and 20-40 [MELD20-40]), and 99 were stratified based on compensation or decompensation status, both measures for liver cirrhosis severity. MELD scores combine laboratory parameters related to liver disease and are used to predict cirrhosis-related mortality based on metabolic abnormalities. Decompensation, however, is the clinical finding of acute deterioration in liver function characterized by ascites, hepatic encephalopathy, and variceal hemorrhage, associated with increased mortality. MELD analyses excluded 5% (5 of 99) of patients due to missing laboratory values. Median age at the time of hip fracture was 69 years (IQR 62 to 78), and 55% (54 of 99) of patients were female. The primary outcome of mortality was determined at 90 days, 1 year, and 2 years after surgery. Secondary outcomes were symptomatic thromboembolism and infections, defined as any documented surgical wound complications, pneumonia, or urinary tract infections requiring treatment. These were determined by chart review at three timepoints: in-hospital and within 30 days or 90 days after discharge. The primary outcome was assessed using a Cox proportional hazard analysis for the MELD score and compensation or decompensation classifications; secondary outcomes were analyzed using the Fisher exact test. Patients in the MELD20-40 group had higher 90-day (hazard ratio 3.95 [95% CI 1.39 to 12.46]; p = 0.01), 1-year (HR 4.12 [95% CI 1.52 to 11.21]; p < 0.001), and 2-year (HR 3.65 [95% CI 1.68 to 7.93]; p < 0.001) mortality than those in the MELD6-9 group. Patients with decompensation had higher in-hospital (9% versus 0%; p = 0.04), 90-day (HR 3.35 [95% CI 1.10 to 10.25]; p = 0.03), 1-year (HR 4.39 [95% CI 2.02 to 9.54]; p < 0.001), and 2-year (HR 3.80 [95% CI 2.02 to 7.15]; p < 0.001) mortality than did patients with compensated disease. All in-hospital deaths were related to liver failure and within 30 days of surgery. The 1-year mortality was 55% for MELD20-40 and 53% for patients with decompensated disease, compared with 16% for patients with MELD6-9 and 15% for patients with compensated disease. In both the MELD and (de)compensation analyses, in-hospital and postdischarge 30-day symptomatic thromboembolic and infectious complications were not different among the groups (all p > 0.05). Ninety-day symptomatic thromboembolism was higher in the MELD20-40 group compared with the other two MELD classifications (13% for MELD20-40 and 0% for both MELD6-9 and MELD10-19; p = 0.02). The mortality of patients with preexisting liver cirrhosis who sustain a hip fracture is high, and it is associated with the degree of cirrhosis and decline in liver function, especially in those with signs of decompensation, defined as ascites, hepatic encephalopathy, and variceal hemmorrhage. Patients with mild-to-moderate cirrhosis (MELD score < 20) and those with compensated disease may undergo routine fracture treatment based on their prognosis. Those with severe (MELD score > 20) or decompensated liver cirrhosis should receive multidisciplinary, individualized treatment, with consideration given to palliative and nonsurgical treatment given their high risk of death within 1 year after surgery. Level III, therapeutic study.

COVID-19: a fatal case of acute liver failure associated with SARS-CoV-2 infection in pre-existing liver cirrhosis

BackgroundThe detection of severe acute respiratory syndrome coronavirus (SARS-CoV-2) is challenging, particularly in post-mortem human tissues. However, there is increasing evidence for viral SARS-CoV-2 manifestation in non-respiratory tissues. In this context, it is a current matter of debate, whether SARS-CoV-2 shows hepatotropism.Case presentationHere, we report a case of an 88-year-old women with massive SARS-CoV-2 viremia, severe jaundice and clinical signs of an acute hepatitis, who died within a few days from an acute liver failure without showing any clinical signs of pneumonia. Autopsy revealed a severe chronic and acute liver damage with bile duct infestation by SARS-CoV-2 that was accompanied by higher expressions of angiotensin-converting enzyme-2 (ACE2), Cathepsin L and transmembrane serine protease 2 (TMPRSS2).ConclusionOur findings indicate an enhanced biliary susceptibility to viral infection with SARS-CoV-2, that might have resulted from pre-existing severe liver damage. Furthermore, our findings emphasize the differential diagnosis of coronavirus disease 2019 (COVID-19)-associated liver failure in the clinical setting of an inexplicable jaundice.

Autochthonous hepatitis E as a cause of acute-on-chronic liver failure and death: histopathology can be misleading but transaminases may provide a clue.

Acute decompensation and death have been observed in patients with acute hepatitis E virus (HEV) infection and preexisting liver cirrhosis. However, the clinical, laboratory and histological features need to be fully characterised. Some of us recently described the histological presentation of hepatitis E in a large panel of liver tissue specimens. Here, we conducted a case-control study to investigate the clinical and laboratory features of the subset of patients with HEV-related acute-on-chronic liver failure (ACLF) and death. Each patient was matched to three control patients with histologically confirmed severe alcoholic hepatitis based on sex, age, total bilirubin, INR, serum creatinine and MELD score on admission. Of 5 patients who died in a context of HEV-related ACLF, 3 (60%) were male and the median age was 66 years (range 51&ndash;76). Median alanine aminotransferase (ALT) at presentation was 2610 U/l (range 705&ndash;3134) and aspartate aminotransferase (AST) 2818 U/l (range 1176&ndash;8611). Liver function was heavily altered in all patients. Histological analyses revealed steatohepatitis on a background of cirrhosis, suggestive of an alcoholic or nonalcoholic origin. Based on histopathology, alcoholic hepatitis was initially suspected in two patients and corticosteroid treatment was initiated. Ribavirin was started in four patients. Median time from hospitalisation to death was 17 days (range 6&ndash;25 days). AST levels in patients with HEV-related ACLF were significantly higher as compared to the matched patients with severe alcoholic hepatitis. Typical histopathological features of viral hepatitis may be absent in ACLF caused by HEV infection. HEV infection should be sought in acute decompensation of cirrhosis and ACLF even in the absence of histological changes suggesting viral infection.

The Predictive Scoring Systems for Outcomes of Heart Transplantation in Patients with Pre-Existing Liver Cirrhosis

<h3>Purpose</h3> There are few data assessing factors and clinical outcomes in patients with liver cirrhosis for heart transplantation. The aim of this study was to compare the Model for End-Stage Liver Disease (MELD) score, the MELD-XI score and Child-Turcotte-Pugh (CTP) score risk prediction in cirrhotic patients undergoing heart transplantation. <h3>Methods</h3> Between 1994 and 2019, forty-nine consecutive patients (19 men and 30 women, median age 46 years, range 12-68 years) had liver cirrhosis, among 170 patients underwent heart transplantations in our institution. Potential preoperative predictors of outcomes, as well as preoperative MELD score, MELD-XI score and CTP classification were calculated. <h3>Results</h3> Causes of heart failure were dilated cardiomyopathy in 26, ischemic disease in 7, congenital heart disease in 6 and valvular heart disease 7 patients. Cause of liver cirrhosis was majority of cardiac origin, except hepatitis in two and alcoholism in one patient. The median follow-up duration was 45.2 months. The MELD score (p=0.010) and MELD-XI score (p=<0.001) were significantly differed between survivors and non-survivors. Cox regression analysis showed high MELD score (HR 1.211; 95% CI, 1.059-1.386; p=0.005), MELD-XI score (HR, 1.184; 95% CI, 1.042-1.345; p=0.010) and CTP score (HR, 1.694; 95% CI, 1.040-2.760; p=0.034) were associated with the risk of all-cause mortality. Receiver operating characteristic (ROC) curve analysis revealed the optimal cut-off value of MELD, MELD-XI and CTP score was 12.2, 12.0 and 7.5, respectively (sensitivity: 69.2 vs. 61.5 vs. 69.2%, specificity 68.6 vs. 60.0 vs. 62.9%) for all-cause mortality (AUC: 0.745 vs. 0.690, 0.729). <h3>Conclusion</h3> The patients with advanced heart failure and liver cirrhosis were high mortality and morbidity of heart transplantation. However, these scoring systems can be a tool to risk-stratification for liver cirrhotic patients undergoing heart transplantation.

A Danish population-based case series of patients with liver cirrhosis and coronavirus disease 2019

Objectives Coronavirus disease 2019 (COVID-19) is an ongoing major health emergency, but its occurrence and clinical impact on patients withliver cirrhosis is unknown. Therefore, we conducted a population-based study of 2.6 million Danish citizens investigating the occurrence and impact of COVID-19 in patients with liver cirrhosis. Materials and methods A prospective population-based cohort study was conducted in the Capital Region of Denmark and Region Zealand in the study period between 1 March 2020 up until 31 May 2020, with the only eligibility criteria being a reverse-transcriptase polymerase chain reaction for presence of viral genomic material confirming COVID-19. The patients were subsequently stratified according to presence of pre-existing liver cirrhosis. Results Among 575,935 individuals tested, 1713 patients had a diagnosis of cirrhosis. COVID-19 occurredsignificantly lessamongpatients with cirrhosis (n = 15; 0.9%, p < .01) compared with the population without cirrhosis (n = 10,593; 1.8%). However, a large proportion (n = 6;40.0%) required a COVID-19 related hospitalization which was correlated with higher values of alanine aminotransferase (p < .01) and lactate dehydrogenase (p = .04). In addition, one-in-three (n = 2; 13.3%) required intensive therapy. Four patients died (26.7%) and mortality was associated with higher MELD scores, co-existing type 2 diabetes, and bacterial superinfections. Conclusion In conclusion, patientswith cirrhosis may have a lower risk of COVID-19; but a higher risk of complications hereto and mortality.

The effect of vitamin K on prothrombin time in critically ill patients: an observational registry study

BackgroundPrevious studies have indicated that vitamin K deficiency is common in non-bleeding critically ill patients with slightly prolonged prothrombin time-international normalized ratio (PT-INR). It has never been investigated thoroughly whether the administration of vitamin K to these patients could affect their PT-INR. Therefore, the aim of this registry study was to evaluate changes in PT-INR in response to vitamin K in critically ill patients with PT-INR in the range of 1.3–1.9.MethodsPatients admitted to a mixed 9-bed general intensive care unit at a University Hospital, between 2013 and 2019 (n = 4541) with a PT-INR between 1.3 and 1.9 at any time during the stay were identified. Patients who received vitamin K with appropriate sampling times for PT-INR and without exclusion criteria were matched with propensity score to patients from the same cohort who did not receive vitamin K (controls). PT-INR was measured at admission, within 12 h before vitamin K administration and 12–36 h following vitamin K administration. Exclusion criteria included pre-existing liver cirrhosis, any plasma or platelet transfusion, or > 1 unit red blood cell transfusion between PT-INR samplings.ResultsPropensity score matching resulted in two groups of patients with 129 patients in each group. PT-INR decreased in both groups (1.4 [1.3–1.4] in the vitamin K group and 1.4 [1.3–1.6] in the controls, p < 0.001 and p = 0.004, respectively). The decrease in PT-INR was slightly more pronounced in patients who received vitamin K (delta PT-INR − 0.10 [− 0.30 to − 0.10] in the vitamin K group and − 0.10 [− 0.20 to 0.10] in the controls, p = 0.01).ConclusionIn critically ill patients with a PT-INR of 1.3–1.9, the administration of vitamin K resulted in a slightly larger decrease of PT-INR 12–36 h after administration compared to controls. Future studies should focus on identifying which patient populations may benefit most from vitamin K administration as well as whether vitamin K could be a better alternative than plasma or prothrombin complex concentrate to improve PT-INR before non-emergent invasive procedures.

A Review Article on Toxicity Induced Hepatocellular Carcinoma: Through Gara Visa perspective

Hepatocellular carcinoma is the most common primary malignancy of liver in adults and is the common cause of death in people with cirrhosis [1] . The majority of this disease occurs over pre-existing chronic liver cirrhosis but the increased changes in living conditions, food habits and sedentary life style has emerged the disease into a silent killer category independent of cirrhosis. The present modifications in food habits, drug induced toxicity and other environmental toxicity has led to a dramatic rise in HCC even in non-alcoholics. The symptoms and pathogenesis in HCC can be eventually be correlated with Garavisa Lakshana, Samprapthi and the judicious application of its treatment in Ayurveda can concrete a new path in its treatment aspect.

Impact of COVID-19 on the care of patients with liver disease: EASL-ESCMID position paper after 6 months of the pandemic.

SummaryDuring the early stages of the coronavirus disease 2019 (COVID-19) pandemic, EASL and ESCMID published a position paper to provide guidance for physicians involved in the care of patients with chronic liver disease. While some healthcare systems are returning to a more normal routine, many countries and healthcare systems have been, or still are, overwhelmed by the pandemic, which is significantly impacting on the care of these patients. In addition, many studies have been published focusing on how COVID-19 may affect the liver and how pre-existing liver diseases might influence the clinical course of COVID-19. While many aspects remain poorly understood, it has become increasingly evident that pre-existing liver diseases and liver injury during the disease course must be kept in mind when caring for patients with COVID-19. This review should serve as an update on the previous position paper, summarising the evidence for liver disease involvement during COVID-19 and providing recommendations on how to return to routine care wherever possible.

Predicting outcome in liver patients admitted to intensive care: A dual-centre non-specialist hospital external validation of the Liver injury and Failure evaluation score

Acute hepatic dysfunction in the critically ill population with pre-existing liver cirrhosis is associated with a high mortality. Several prediction models have been developed to risk stratify patients with liver disease. This UK dual-centre non-specialist hospital retrospective study (2015-2019) externally validated the Liver injury and Failure evaluation score (incorporating lactate, bilirubin and International Normalised Ratio), alongside two other general intensive care unit prediction models (Intensive Care National Audit and Research Centre and Acute Physiology and Chronic Health Evaluation II). Inclusion criteria matched a recent UK-wide study including at least one of biopsy proven cirrhosis, imaging suggestive of cirrhosis, hepatic encephalopathy or portal hypertension. One hundred and ninety-nine admissions met inclusion criteria over the study period (n = 169), mean age 57( ±13). In-hospital mortality was 40% in this cohort compared to 18% of all intensive care unit individuals during the same period. Variceal bleeding was associated with a lower short-term (18% versus 47%, P < 0.001, odds ratio 0.3 (95% confidence interval 0.1-0.5)) and longer-term mortality (log rank P = 0.015). In-patient mortality was higher in cases requiring renal replacement therapy (82% versus 29%, odds ratio 11.1 (95% confidence interval 4.6-26.9), P < 0.001) or ventilation (47% versus 32%, odds ratio 1.9 (1.1-3.4), P = 0.03). For in-patient mortality, area under the receiver operating characteristic curves were Liver injury and Failure evaluation 0.69 (95% confidence interval 0.62-0.77), Intensive Care National Audit and Research Centre 0.80 (0.74-0.86) and Acute Physiology and Chronic Health Evaluation II 0.73 (0.65-0.81). Forty-one per cent of cases were alive at one-year follow-up. Area under the receiver operating characteristic curves for one-year survival were Liver injury and Failure evaluation 0.69 (0.61-0.77), Intensive Care National Audit and Research Centre 0.75 (0.67-0.82) and Acute Physiology and Chronic Health Evaluation II 0.69 (0.61-0.77). This first Liver injury and Failure evaluation score validation in a UK non-specialist hospital setting suggests this parsimonious, easy to calculate model may have utility in prediction of short-term and one-year mortality. As with previous studies variceal haemorrhage was associated with lower mortality.