COVID-19 Sequelae and Their Implications on Social Services.

BACKGROUND: The impact of persistent coronavirus disease 2019 (COVID-19) symptoms on quality of life remains unclear. This study aimed to describe such persistent symptoms and their relationships with quality of life, including clinical frailty and subjective health status. METHODS: A prospective longitudinal 3-month follow-up survey monitored symptoms, health quality, support needs, frailty, and employment. RESULTS: A total of 82 patients with a mean age of 52 years (ranging from 23-84 years) were enrolled, including 48 (58.6%) men, and 34 (41.5%) women. The fully active status decreased from 87.8% before admission to 78.1% post discharge. Two patients (2.4%) were ambulatory and capable of all self-care but unable to carry out any work-related activities 12 weeks after discharge. Clinical frailty scale (CFS) levels 1, 2, 3 and 4 changed drastically between admission and 12 weeks later after discharge. Just after admission, the median EuroQol visual analogue scales (EQ-VAS) was 82.23 (± 14.38), and it decreased to 78.10 (± 16.02) 12 weeks after discharge; 62 (75.6%) of patients reported at least one symptom 12 weeks after discharge. The most frequent symptom was fatigue followed by smell disorder, anxiety, sleep disorder, headache, depressive mood, dyspnea, and taste disorder. CFS was definitively associated with fatigue. Decreased EQ-VAS was associated with fatigue and palpitation, cough, taste disorder, and chest pain. EQ-VAS was worse in women (28%) than in men. Compared with regular outpatient clinic visits before admission, 21 patients (25.6%) reported increased outpatient clinic visits, one (1.4%) reported readmission, and one (1.4%) reported emergency room visits. Six of the 54 (77.1%) patients who were employed before admission lost their jobs. And most vulnerable type was self-employed, because three self-employed job workers were not working at 12 weeks after discharge. CONCLUSION: COVID-19 sequelae should not be underestimated. We find a decrease in health quality and increase in psychological problems in discharged COVID-19 patients, and some patients experience unemployment. The number of patients suffering from COVID-19 sequelae would not be negligible considering there are more than one million COVID-19 infection cases in Korea. Hence, the government should start a systematic monitoring system for discharged patients and prepare timely medical and social interventions accordingly.

Changing Features of Liver Injury in COVID-19 Patients: Impact of Infection with the SARS-CoV-2 Delta (B.1.617.2) Variants.

BACKGROUND: There is growing evidence that abnormal liver function tests (LFTs) are common in patients with coronavirus disease 2019 (COVID-19). However, it is not known whether viral involvement in the liver differs according to the strain. We investigated the impact on liver injury in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta (B.1.617.2) variants. MATERIALS AND METHODS: We conducted a single-center, retrospective cohort study, including 372 patients admitted during the pre-Delta period (PDP: between February 1 and November 30, 2020) and 137 patients admitted during the Delta period (DP: between August 1 and August 31, 2021). Initial liver injury was defined as alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels ≥3 × the upper limit of normal (ULN) or alkaline phosphatase (ALP) or total bilirubin ≥2 × the ULN within 3 days from admission. RESULTS: Of 509 patients with COVID-19 included in our study, 38 (7.5%) patients had initial liver injury. The DP group had a significantly higher rate of initial liver injury than the PDP group (PDP: 5.9% vs. DP: 11.7%, P = 0.028). The DP group (adjusted odds ratio [aOR]: 2.737, 95% confidence interval [CI]: 1.322 - 5.666) was independently associated with initial liver injury. During hospitalization, 160 (31.4%) patients had severe COVID-19. The DP group and initial liver injury had higher odds of progressing to severe COVID-19 (aOR: 2.664, 95% CI: 1.526 - 4.648, and aOR: 4.409, 95% CI: 1.816 - 10.707, respectively). The mediation analysis suggested that initial liver injury mediates the relationship between SARS-CoV-2 Delta variant infection and severe COVID-19 (unstandardized beta coefficient = 0.980, Standard error = 0.284, P = 0.001). CONCLUSION: Initial liver injury is more common in COVID-19 patients with Delta variants. Also, Delta variants and initial liver injury are associated with poor clinical outcomes.

Clinical Characteristics and Treatment Outcomes of Patients with Hepatitis C Virus and Human Immunodeficiency Virus Coinfection: Experience at a Single Center in Korea.

BACKGROUND: Because of the very low incidence of human immunodeficiency virus (HIV) coinfection in Korea, data on hepatitis C virus (HCV)/HIV coinfection are limited. This study aimed to investigate the clinical characteristics and treatment outcomes of patients with HCV/HIV coinfection in Korea. METHODS: We performed a retrospective cohort study of all HCV-monoinfected and HCV/HIV-coinfected patients treated with antivirals at National Medical Center in Seoul, Korea, between January 2009 and March 2020. RESULTS: We enrolled 220 HCV-monoinfected and 23 HCV/HIV-coinfected patients treated with antivirals. The HCV/HIV-coinfected patients were younger (HCV vs. HCV/HIV: 57.3 ± 11.3 vs. 40.7 ± 10.1 years, P < 0.001) and had a higher proportion of men (HCV vs. HCV/HIV: 54.5% [n = 120] vs. 91.3% [n = 21], P < 0.001) than the HCV-monoinfected patients. Genotype 1b and 2 were most common in both HCV monoinfection and HCV/HIV coinfection groups. HCV-monoinfected patients had a higher incidence of genotype 1b and 2 than HCV/HIV-coinfected patients (HCV vs. HCV/HIV: 95.4% [n = 210] vs. 73.9% [n = 17], P < 0.001), while the HCV/HIV-coinfected patients had genotype 1a (HCV vs. HCV/HIV: 1.8% [n = 4] vs. 21.7% [n = 5], P < 0.001). The fibrosis-4 index was significantly lower in the HCV/HIV-coinfected patients than in the HCV-monoinfected patients (HCV vs. HCV/HIV: 3.81 ± 3.38 vs. 1.66 ± 1.10, P < 0.001). Among the direct-acting antivirals (DAA)-treated patients, the sustained viral response (SVR) rate did not differ significantly between both groups (HCV vs. HCV/HIV: 94.9% [93/99] vs. 90.9% [10/11], P = 0.480). CONCLUSION: In Korea, the HCV/HIV-coinfected patients who received antiviral treatment were younger, had higher proportion of men and incidence of genotype 1a, and had less advanced fibrosis than the HCV-monoinfected patients. In actual clinical settings, HCV/HIV-coinfected patients show excellent SVR to DAA treatment, similar to HCV-monoinfected patients.

Safety Monitoring after the BNT162b2 COVID-19 Vaccine among Adults Aged 75 Years or Older.

BACKGROUND: Older adults are given high priority for coronavirus disease 2019 (COVID-19) vaccination; however, little is known about the safety of vaccines. This study was conducted to examine the safety of the COVID-19 vaccine for people who were ≥ 75 years of age, specifically those who first took two doses of the vaccine at the COVID-19 central vaccination center in South Korea. METHODS: Safety monitoring after the BNT162b2 vaccine was conducted in three ways for older adults who received the first dose of the vaccine at our center between April 5 and April 23, 2021. For immediate adverse reactions, every person who was vaccinated was observed for 15-30 minutes after injection at the center. For active surveillance, a telephone interview was conducted for stratified randomly sampled people after 7 days of each vaccination to enquire regarding types of adverse reactions they experienced, and its severity and duration. For passive surveillance, reported adverse event data were collected from the COVID-19 vaccine adverse event following immunization (AEFI) surveillance system-run by the Korea Disease Control and Prevention Agency (KDCA). The data were then reviewed. RESULTS: In total, 2,123 older adults received at least one vaccine dose during the study period. The frequency of acute adverse reactions that developed during the observed 15-30 minutes after injection was 8.5 cases per 1,000 doses. None of the reactions was assessed as acute allergic reactions to the vaccine and no cases required special treatment or drug administration. Overall, 638 people were followed up at least once by telephone interview 7 days post vaccination. The overall response rate was 82.3%. The rates of local reactions were 50.3% after the first dose and 45.2% after the second dose, and the rates of systemic reactions were 15.2% and 26.0%, respectively. During the study period, 23 medically attended adverse events (5.4 cases per 1,000 administered doses) were reported to the KDCA AEFI surveillance system. The most common symptoms of medically attended cases were nonspecific general weakness (26%) and dizziness (26%), followed by muscle pain (22%), headache (13%), fever (13%), and skin rash or urticaria (13%). Among them, there were five serious adverse events reported, which required hospitalization, including one death. However, most of them were not related to the vaccines. CONCLUSION: BNT162b2 vaccination was tolerable among adults who were ≥ 75 years of age.

Nonalcoholic Steatohepatitis and HCC in a Hyperphagic Mouse Accelerated by Western Diet.

BACKGROUND & AIMS: How benign liver steatosis progresses to nonalcoholic steatohepatitis (NASH), fibrosis, and hepatocellular carcinoma (HCC) remains elusive. NASH progression entails diverse pathogenic mechanisms and relies on complex cross-talk between multiple tissues such as the gut, adipose tissues, liver, and the brain. Using a hyperphagic mouse fed with a Western diet (WD), we aimed to elucidate the cross-talk and kinetics of hepatic and extrahepatic alterations during NASH-HCC progression, as well as regression. METHODS: Hyperphagic mice lacking a functional Alms1 gene (Foz/Foz) and wild-type littermates were fed WD or standard chow for 12 weeks for NASH/fibrosis and for 24 weeks for HCC development. NASH regression was modeled by switching back to normal chow after NASH development. RESULTS: Foz+WD mice were steatotic within 1 to 2 weeks, developed NASH by 4 weeks, and grade 3 fibrosis by 12 weeks, accompanied by chronic kidney injury. Foz+WD mice that continued on WD progressed to cirrhosis and HCC within 24 weeks and had reduced survival as a result of cardiac dysfunction. However, NASH mice that were switched to normal chow showed NASH regression, improved survival, and did not develop HCC. Transcriptomic and histologic analyses of Foz/Foz NASH liver showed strong concordance with human NASH. NASH was preceded by an early disruption of gut barrier, microbial dysbiosis, lipopolysaccharide leakage, and intestinal inflammation. This led to acute-phase liver inflammation in Foz+WD mice, characterized by neutrophil infiltration and increased levels of several chemokines/cytokines. The liver cytokine/chemokine profile evolved as NASH progressed, with subsequent predominance by monocyte recruitment. CONCLUSIONS: The Foz+WD model closely mimics the pathobiology and gene signature of human NASH with fibrosis and subsequent HCC. Foz+WD mice provide a robust and relevant preclinical model of NASH, NASH-associated HCC, chronic kidney injury, and heart failure.

Metastatic endophthalmitis and thyroid abscess complicating Klebsiella pneumoniae liver abscess.

The thyroid is resistant to infection due to its anatomical and physiological characteristics. We present a rare case of invasive liver abscess with metastatic thyroid abscess and endogenous endophthalmitis in a previously healthy 55-year-old female patient without diabetes or other medical illness. This report raises an important question of the virulence of Klebsiella pneumoniae as an increasingly common causative agent of liver abscess.

Characteristics and Discrepancies in Acute-on-Chronic Liver Failure: Need for a Unified Definition.

BACKGROUND & AIM: To investigate the prevalence, mortalities, and patient characteristics of Acute-on-chronic liver failure (ACLF) according to the AARC (Asian Pacific Association for the Study of the Liver ACLF Research Consortium) and European Association for the Study of the Liver CLIF-C (Chronic Liver Failure Consortium) definitions. METHODS: We collected retrospective data for 1470 hospitalized patients with chronic liver disease (CLD) and acute deterioration between January 2013 and December 2013 from 21 university hospitals in Korea. RESULTS: Of the patients assessed, the prevalence of ACLF based on the AARC and CLIF-C definitions was 9.5% and 18.6%, respectively. The 28-day and 90-day mortality rates were higher in patients with ACLF than in those without ACLF. Patients who only met the CLIF-C definition had significantly lower 28-day and 90-day survival rates than those who only met the AARC definition (68.0% vs. 93.9%, P<0.001; 55.1% vs. 92.4%, P<0.001). Among the patients who had non-cirrhotic CLD, the 90-day mortality of the patients with ACLF was higher than of those without ACLF, although not significant (33.3% vs. 6.0%, P = 0.192). Patients with previous acute decompensation (AD) within 1- year had a lower 90-day survival rate than those with AD more than 1 year prior or without previous AD (81.0% vs. 91.9% or 89.4%, respectively, all P<0.001). Patients who had extra-hepatic organ failure without liver failure had a similar 90-day survival rate to those who had liver failure as a prerequisite (57.0% vs. 60.6%, P = 0.391). CONCLUSIONS: The two ACLF definitions result in differences in mortality and patient characteristics among ACLF patients. We suggest that non-cirrhotic CLD, previous AD within 1 year, and extra-hepatic organ failure should be included in the ACLF diagnostic criteria. In addition, further studies are necessary to develop a universal definition of ACLF.

Emergence of adefovir-resistant mutants after reversion to YMDD wild-type in lamivudine-resistant patients receiving adefovir monotherapy.

BACKGROUND: To evaluate the effect of reversion to YMDD wild-type on emergence of adefovir (ADV)-resistant mutation and antiviral activity of ADV in lamivudine (LAM)- resistant patients. METHODS: We determined YMDD mutations and ADV-resistant mutations before and every 3 months during ADV monotherapy in 33 LAM-resistant patients using the restriction fragment mass polymorphism (RFMP) method. RESULTS: Reversion to pure YMDD wild-type hepatitis B virus (HBV) occurred in 6% (2/33), 9% (3/33), 20% (4/20) and 35% (6/17) of patients after 12, 24, 36 and 48 weeks, respectively. Five (29%) patients were found to have pure YMDD mutants at 48 weeks of therapy. Among 33 patients, 4 (12%) patients developed ADV-resistant mutations at 48 weeks of therapy. Adefovir-resistant mutants emerged in all patients after reversion to YMDD wild-type HBV. The mean serum HBV reductions, evaluated at 24 weeks of therapy, were not different between patients with and without reversion to YMDD wild-type HBV (-3.1 log(10) copies/mL vs-3.4 log(10) copies/mL, P > 0.05). CONCLUSIONS: ADV-resistant mutations emerged after reversion to YMDD wild-type in LAM-resistant patients who received ADV monotherapy. Thus, ADV add-on therapy may be necessary to reduce the incidence of developing ADV resistance in patients with LAM resistance.

Association of lamivudine-resistant mutational patterns with the antiviral effect of adefovir in patients with chronic hepatitis B.

Adefovir has a potent antiviral activity as a rescue treatment against lamivudine-resistant strains. The aim of this study was to assess the patterns of lamivudine-resistant mutations and their influence on the virologic response to adefovir rescue therapy in patients with lamivudine-resistant chronic hepatitis B. Sixty-seven patients with lamivudine-resistant chronic hepatitis B were treated with adefovir monotherapy. Baseline blood samples were analyzed for lamivudine-resistant mutations via restriction fragment mass polymorphism. Virologic responses, ALT normalization and loss of HBeAg were assessed. Serum HBV DNA levels were measured using real-time PCR at baseline and 24 weeks of adefovir therapy. Of the 67 patients with chronic hepatitis B, 65 patients (97%) had lamivudine-resistant mutations in the YMDD motif [27 (41%) rtM204I, 22 (34%) rtM204V, and 16 (25%) rtM204I/V]. In addition to the YMDD mutations, the rtL180M, rtL80I, and rtV173L mutations were also present in 78%, 43%, and 11% of patients, respectively. The rtM204V mutation always accompanied rtL180M, and rtL80I was always observed in conjunction with rtM204I. Decrease in mean serum HBV did not differ between patients carrying the rtM204I versus rtM204V mutant at week 24 (-3.3 vs. -3.3 log(10) copies/ml, respectively; P = 0.303). The presence of the rtL180M, rtL80I, and rtV173L did not significantly affect viral load reduction during adefovir administration. These results demonstrate that the rtL80I mutant is co-selected with rtM204I as a compensatory mutation in the same manner as rtL180M with rtM204V, and that adefovir shows similar antiviral efficacy against all of the evaluated patterns of lamivudine-resistant HBV mutations.

[Effect of low dose 5-fluorouracil and cisplatin intra-arterial infusion chemotherapy in advanced hepatocellular carcinoma with decompensated cirrhosis].

BACKGROUND/AIMS: Advanced hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT) has a poor prognosis. The aim of this study was to evaluate the efficacy and safety of repeated arterial infusions of low dose cisplatin and 5-fluorouracil (FU) in patients with advanced HCC with decompensated cirrhosis. METHODS: Between January 1995 and December 2003, a total of 79 decompensated cirrhotic patients having HCC and PVT were enrolled and divided into 2 groups. Group 1 (n=40) received intra-arterial infusion chemotherapy with cisplatin (10 mg for 5 days) and 5-FU (250 mg for 5 days) via an implanted chemoport every 4 weeks' and group 2 (n=39) was managed with only conservative treatment. RESULTS: The two groups were well matched with respect to the features relating to the prognosis, including age, gender and the Child- Pugh class. Although diffuse tumor involvement, main portal vein tumor thrombosis and bi-lobar involvement were more frequent in group 1, the median survival period of group 1 was significantly longer than group 2 (5 months vs. 3 months, respectively, P=0.016). Also, the 1-year survival rate of group 1 (7.5%) was higher than that of group 2 (5.1%) (P=0.016). When we analyzed the patients with the Child class B, the survival benefits of intra-arterial chemotherapy were more significant (P=0.008). CONCLUSIONS: Intra-arterial chemotherapy consisting of low dose 5-FU and cisplatin achieved favorable results for advanced HCC patients who had decompensated cirrhosis, and it showed better survival in selected patients. This therapy may be useful as a palliative treatment for HCC patients with decompensated cirrhosis.