Dynamic analysis of acute deterioration in chronic liver disease patients using modified quick sequential organ failure assessment

Background/Aims@#Quick sequential organ failure assessment (qSOFA) is believed to identify patients at risk of poor outcomes in those with suspected infection. We aimed to evaluate the ability of modified qSOFA (m-qSOFA) to identify high-risk patients among those with acutely deteriorated chronic liver disease (CLD), especially those with acute-onchronic liver failure (ACLF). @*Methods@#We used data from both the Korean Acute-on-Chronic Liver Failure (KACLiF) and the Asian Pacific Association for the Study of the Liver ACLF Research Consortium (AARC) cohorts. qSOFA was modified by replacing the Glasgow Coma Scale with hepatic encephalopathy, and an m-qSOFA ≥2 was considered high. @*Results@#Patients with high m-qSOFA had a significantly lower 1-month transplant-free survival (TFS) in both cohorts and higher organ failure development in KACLiF than those with low m-qSOFA (Ps<0.05). Subgroup analysis by ACLF showed that patients with high m-qSOFA had lower TFS than those with low m-qSOFA. m-qSOFA was an independent prognostic factor (hazard ratios, HR=2.604, 95% confidence interval, CI 1.353–5.013, P=0.004 in KACLiF and HR=1.904, 95% CI 1.484– 2.442, P<0.001 in AARC). The patients with low m-qSOFA at baseline but high m-qSOFA on day 7 had a significantly lower 1-month TFS than those with high m-qSOFA at baseline but low m-qSOFA on day 7 (52.6% vs. 89.4%, P<0.001 in KACLiF and 26.9% vs. 61.5%, P<0.001 in AARC). @*Conclusions@#Baseline and dynamic changes in m-qSOFA may identify patients with a high risk of developing organ failure and short-term mortality among CLD patients with acute deterioration.

Performance of Simple Fibrosis Score in Non-Alcoholic Fatty Liver Disease with and without Type 2 Diabetes

This cross-sectional study enrolled 267 patients with metabolic risk factors and established non-alcoholic fatty liver disease in the prospective cohort. The performance of fibrosis-4 (FIB-4) score (≥1.3) to diagnose advanced fibrosis using transient elastography (liver stiffness measurement [LSM] ≥8 kPa) was analyzed. Comparing patients with type 2 diabetes (T2D, n=87) and without (n=180), not FIB-4, but LSM was significantly higher in T2D (P=0.026). The prevalence of advanced fibrosis was 17.2% in T2D and 12.8% in non-T2D. FIB-4 exhibited higher proportion of false negatives in T2D patients (10.9%) than those without (5.2%). The diagnostic performance of FIB-4 was suboptimal in T2D (area under curve [AUC], 0.653; 95% confidence interval [CI], 0.462 to 0.844) compared to that in non-T2D (AUC, 0.826; 95% CI, 0.724 to 0.927). In conclusion, patients with T2D might be beneficial to conduct transient elastography without screening to avoid missing advanced fibrosis.

Diagnostic Approach to Autoimmune Hepatitis / 대한내과학회지

Autoimmune hepatitis (AIH) is a chronic liver disease caused by unknown etiology, characterized by elevated liver enzyme, hypergammaglobulinemia, circulating autoantibodies, and histological interface hepatitis. As untreated AIH often leads to decompensated cirrhosis and even death, prompt and timely diagnosis is essential. However, about 1/3 of patients with AIH have cirrhosis at diagnosis. On the other hand, new onset acute or acute exacerbation of previous undiagnosed AIH can be presented as acute hepatitis. Thus, any patients with acute or chronic liver disease with hypergammagloblinemia without other cause should be considered to evaluate circulating non-organ specific autoantibodies for diagnosis of AIH. In case of suspected AIH, liver biopsy should be considered to evaluate its histological characteristics including interface hepatitis, plasma cell infiltration, emperipolesis, and rosettes. When the diagnosis is made, prompt treatment with prednisolone followed by combined azathioprine should be considered to improve its prognosis.

Multicenter Analysis of Clinical Features and Prognosis of COVID-19 Patients with Hepatic Impairment

Background/Aims@#Recent data indicate the presence of liver enzyme abnormalities in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical features and treatment outcomes of COVID-19 patients with abnormal liver enzymes. @*Methods@#We performed a retrospective, multicenter study of 874 COVID-19 patients admitted to five tertiary hospitals from February 20 to April 14, 2020. Data on clinical features, laboratory parameters, medications, and treatment outcomes were collected until April 30, 2020, and compared between patients with normal and abnormal aminotransferases. @*Results@#Abnormal aminotransferase levels were observed in 362 patients (41.1%), of which 94 out of 130 (72.3%) and 268 out of 744 (36.0%) belonged to the severe and non-severe COVID-19 categories, respectively. The odds ratios (95% confidence interval) for male patients, patients with a higher body mass index, patients with severe COVID-19 status, and patients with lower platelet counts were 1.500 (1.029 to 2.184, p=0.035), 1.097 (1.012 to 1.189, p=0.024), 2.377 (1.458 to 3.875, p=0.001), and 0.995 (0.993 to 0.998, p>0.001), respectively, indicating an independent association of these variables with elevated aminotransferase levels. Lopinavir/ ritonavir and antibiotic use increased the odds ratio of abnormal aminotransferase levels after admission (1.832 and 2.646, respectively, both p<0.05). The median time to release from quarantine was longer (22 days vs 26 days, p=0.001) and the mortality rate was higher (13.0% vs 2.9%, p<0.001) in patients with abnormal aminotransferase levels. @*Conclusions@#Abnormal aminotransferase levels are common in COVID-19 patients and are associated with poor clinical outcomes. Multivariate analysis of patients with normal aminotransferase levels on admission showed that the use of lopinavir/ritonavir and antibiotics was associated with abnormal aminotransferase levels; thus, careful monitoring is needed.

Multicenter Analysis of Clinical Features and Prognosis of COVID-19 Patients with Hepatic Impairment

Background/Aims@#Recent data indicate the presence of liver enzyme abnormalities in patients with coronavirus disease 2019 (COVID-19). We aimed to evaluate the clinical features and treatment outcomes of COVID-19 patients with abnormal liver enzymes. @*Methods@#We performed a retrospective, multicenter study of 874 COVID-19 patients admitted to five tertiary hospitals from February 20 to April 14, 2020. Data on clinical features, laboratory parameters, medications, and treatment outcomes were collected until April 30, 2020, and compared between patients with normal and abnormal aminotransferases. @*Results@#Abnormal aminotransferase levels were observed in 362 patients (41.1%), of which 94 out of 130 (72.3%) and 268 out of 744 (36.0%) belonged to the severe and non-severe COVID-19 categories, respectively. The odds ratios (95% confidence interval) for male patients, patients with a higher body mass index, patients with severe COVID-19 status, and patients with lower platelet counts were 1.500 (1.029 to 2.184, p=0.035), 1.097 (1.012 to 1.189, p=0.024), 2.377 (1.458 to 3.875, p=0.001), and 0.995 (0.993 to 0.998, p>0.001), respectively, indicating an independent association of these variables with elevated aminotransferase levels. Lopinavir/ ritonavir and antibiotic use increased the odds ratio of abnormal aminotransferase levels after admission (1.832 and 2.646, respectively, both p<0.05). The median time to release from quarantine was longer (22 days vs 26 days, p=0.001) and the mortality rate was higher (13.0% vs 2.9%, p<0.001) in patients with abnormal aminotransferase levels. @*Conclusions@#Abnormal aminotransferase levels are common in COVID-19 patients and are associated with poor clinical outcomes. Multivariate analysis of patients with normal aminotransferase levels on admission showed that the use of lopinavir/ritonavir and antibiotics was associated with abnormal aminotransferase levels; thus, careful monitoring is needed.

Prognostic Value of Alpha-Fetoprotein in Patients Who Achieve a Complete Response to Transarterial Chemoembolization for Hepatocellular Carcinoma

Purpose@#Alpha-fetoprotein (AFP) is a prognostic marker for hepatocellular carcinoma (HCC). We investigated the prognostic value of AFP levels in patients who achieved complete response (CR) to transarterial chemoembolization (TACE) for HCC. @*Materials and Methods@#Between 2005 and 2018, 890 patients with HCC who achieved a CR to TACE were recruited. An AFP responder was defined as a patient who showed elevated levels of AFP (>10 ng/mL) during TACE, but showed normalization or a >50% reduction in AFP levels after achieving a CR. @*Results@#Among the recruited patients, 569 (63.9%) with naïve HCC and 321 (36.1%) with recurrent HCC after complete resection were treated. Before TACE, 305 (34.3%) patients had multiple tumors, 219 (24.6%) had a maximal tumor size >3 cm, and 22 (2.5%) had portal vein tumor thrombosis. The median AFP level after achieving a CR was 6.36 ng/mL. After a CR, 473 (53.1%) patients experienced recurrence, and 417 (46.9%) died [median progression-free survival (PFS) and overall survival (OS) of 16.3 and 62.8 months, respectively]. High AFP levels at CR (>20 ng/mL) were independently associated with a shorter PFS [hazard ratio (HR)=1.403] and OS (HR=1.284), together with tumor multiplicity at TACE (HR=1.518 and 1.666, respectively). AFP non-responders at CR (76.2%, n=359 of 471) showed a shorter PFS (median 10.5 months vs. 15.5 months, HR=1.375) and OS (median 41.4 months vs. 61.8 months, HR=1.424) than AFP responders (all p=0.001). @*Conclusion@#High AFP levels and AFP non-responders were independently associated with poor outcomes after TACE. AFP holds clinical implications for detailed risk stratification upon achieving a CR after TACE.

Clinical outcomes of coronavirus disease 2019 in patients with pre-existing liver diseases: A multicenter study in South Korea

Background/Aims@#Although coronavirus disease 2019 (COVID-19) has spread rapidly worldwide, the implication of pre-existing liver disease on the outcome of COVID-19 remains unresolved. @*Methods@#A total of 1,005 patients who were admitted to five tertiary hospitals in South Korea with laboratory-confirmed COVID-19 were included in this study. Clinical outcomes in COVID-19 patients with coexisting liver disease as well as the predictors of disease severity and mortality of COVID-19 were assessed. @*Results@#Of the 47 patients (4.7%) who had liver-related comorbidities, 14 patients (1.4%) had liver cirrhosis. Liver cirrhosis was more common in COVID-19 patients with severe pneumonia than in those with non-severe pneumonia (4.5% vs. 0.9%, P=0.006). Compared to patients without liver cirrhosis, a higher proportion of patients with liver cirrhosis required oxygen therapy; were admitted to the intensive care unit; had septic shock, acute respiratory distress syndrome, or acute kidney injury; and died (P @*Conclusions@#This study suggests liver cirrhosis is a significant risk factor for COVID-19. Stronger personal protection and more intensive treatment for COVID-19 are recommended in these patients.

Clinical characteristics of coronavirus disease 2019 patients with diarrhea in Daegu

Background/Aims@#Coronavirus disease 2019 (COVID-19) can reportedly cause gastrointestinal symptoms. Therefore, we investigated the clinical characteristics of COVID-19 patients with diarrhea. @*Methods@#We included 118 COVID-19 patients admitted to a single hospital from February 20 to March 31, 2020. Medical records with clinical characteristics, laboratory data, treatment course, and clinical outcomes were compared based on the presence or absence of diarrhea. Prognostic factors for disease severity and mortality in COVID-19 were also assessed. @*Results@#Among patients, 54 (45.8%) had diarrhea, whereas seven (5.9%) had only diarrhea. The median age of patients with diarrhea was 59 years (44 to 64), and 22 (40.7%) were male. Systemic steroid use, intensive care unit admission, septic shock, and acute respiratory distress syndrome were less frequent in the diarrhea group than in the non-diarrhea group. No significant differences were observed in total hospital stay and mortality between groups. On multivariate analysis, age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.01 to 1.12; p = 0.044), diabetes (OR, 3.00; 95% CI, 1.25 to 20.47; p = 0.042), and dyspnea (OR, 41.19; 95% CI, 6.60 to 823.16; p < 0.001) were independent risk factors for septic shock. On Cox regression analysis, diabetes (hazard ratio [HR], 4.82; 95% CI, 0.89 to 26.03; p = 0.043) and chronic obstructive pulmonary disease (HR, 16.58; 95% CI, 3.10 to 88.70; p = 0.044) were risk factors for mortality. @*Conclusions@#Diarrhea was present in 45.8% of patients and was a common symptom of COVID-19. Although patients with diarrhea showed less severe clinical features, diarrhea was not associated with disease severity or mortality.

Association between Atrial Fibrillation and Advanced Liver Fibrosis in Patients with Non-Alcoholic Fatty Liver Disease

Purpose@#Non-alcoholic fatty liver disease (NAFLD) is independently associated with the development of atrial fibrillation (AF). However, the association of AF with advanced liver fibrosis, which is related to all-cause, cardiovascular, and liver-related mortality, has not been established in NAFLD patients. We aimed to investigate the association between AF and advanced liver fibrosis in NAFLD patients. @*Materials and Methods@#Out of 53704 adults who participated in the health check-up program, 6293 subjects aged 35 years and older were diagnosed as NAFLD using ultrasound. The stage of liver fibrosis was assessed based on the newly adjusted NAFLD fibrosis score (NFS) and Fibrosis-4 (Fib-4) Index, which were used to determine the low and high cut-off values (COVs). @*Results@#Of 6293 patients with NAFLD, 59 (0.9%) were diagnosed with AF. Patients with AF were older (52.0 vs. 64.6 years, p< 0.001), had higher body mass index (25.2 vs. 26.6 kg/m2 , p<0.001), and had bigger waist circumference (84.0 vs. 89.9 cm, p<0.001) than those without AF. In NAFLD patients, AF was independently associated with advanced liver fibrosis, assessed using both COVs of NFS [low-COV group: final adjusted odds ratios (aORs)=2.85, p=0.004; high-COV group: ORs=12.29, p<0.001). AF was independently associated with advanced liver fibrosis, assessed using both COVs of Fib-4 (low-COV group: aORs=2.49, p<0.001; high-COV group: aORs=3.84, p=0.016). @*Conclusion@#AF is independently associated with advanced liver fibrosis in patients with NAFLD.

Anti-nuclear antibody-negative immunoglobulin G4-associated autoimmune hepatitis mimicking lymphoproliferative disorders / 영남의대학술지

Immunoglobulin G4 (IgG4)-associated autoimmune hepatitis (AIH) is a very rare subtype of autoimmune hepatitis and characterized by marked elevated serum IgG and hepatic infiltration of IgG4-expressing plasma cells. Pathologic confirmation of hepatic IgG4-expressing plasma cells is usually required for the final diagnosis of IgG4-associated AIH. Herein, we report the case of a 47-year-old female diagnosed with autoantibody-negative IgG4-associated AIH mimicking lymphoproliferative disorders.