Sex Differences in Treatment Response to Nucleos(t)ide Therapy in Chronic Hepatitis B: A Multicenter Longitudinal Study.

BACKGROUND & AIMS: It is unclear if there may be sex differences in response to nucleos(t)ide analogs including virologic response (VR), biochemical response (BR), complete response (CR), and hepatocellular carcinoma (HCC) incidence among hepatitis B patients. We compared nucleos(t)ide analog treatment outcomes by sex. METHODS: We performed a retrospective cohort study of 3388 treatment-naïve adult hepatitis B patients (1250 female, 2138 male) from the Real-World Evidence from the Global Alliance for the Study of Hepatitis B Virus consortium who initiated therapy with either entecavir or tenofovir from 22 sites (Argentina, Korea, Japan, Taiwan, and the United States). We used propensity-score matching to balance background characteristics of the male and female groups and competing-risks analysis to estimate the incidence and subdistribution hazard ratios (SHRs) of VR, BR, CR, and HCC. RESULTS: Females (vs males) were older (52.0 vs 48.6 y); less likely to be overweight/obese (49.3% vs 65.7%), diabetic (9.9% vs 13.1%), or cirrhotic (27.9% vs 33.0%); and had a lower HBV DNA level (5.9 vs 6.0 log10 IU/mL) and alanine aminotransferase level (91 vs 102 IU/L) (all P < .01). However, after propensity-score matching, relevant background characteristics were balanced between the 2 groups. Females (vs males) had similar 5-year cumulative VR (91.3% vs 90.3%; P = .40) and HCC incidence rates (5.1% vs 4.4%; P = .64), but lower BR (84.0% vs 90.9%; P < .001) and CR (78.8% vs 83.4%; P = .016). Males were more likely to achieve BR (SHR, 1.31; 95% CI, 1.17-1.46; P < .001) and CR (SHR, 1.16; 95% CI, 1.03-1.31; P = .016), but VR and HCC risks were similar. CONCLUSIONS: Sex differences exist for treatment outcomes among hepatitis B patients. Male sex was associated with a 16% higher likelihood of clinical remission and a 31% higher likelihood of biochemical response than females, while virologic response and HCC incidence were similar between the 2 groups.

Effect of sarcopenia on survival in patients with cirrhosis: A meta-analysis.

BACKGROUND & AIMS: The association between sarcopenia and prognosis in patients with cirrhosis remains to be determined. In this study, we aimed to quantify the association between sarcopenia and the risk of mortality in patients with cirrhosis, stratified by sex, underlying liver disease etiology, and severity of hepatic dysfunction. METHODS: PubMed, Web of Science, EMBASE, and major scientific conference sessions were searched without language restriction through 13 January 2021 with an additional manual search of bibliographies of relevant articles. Cohort studies of ≥100 patients with cirrhosis and ≥12 months of follow-up that evaluated the association between sarcopenia, muscle mass and the risk of mortality were included. RESULTS: Twenty-two studies involving 6,965 patients with cirrhosis were included. The pooled prevalence of sarcopenia in patients with cirrhosis was 37.5% overall (95% CI 32.4%-42.8%), and was higher in male patients, those with alcohol-associated liver disease, those with Child-Pugh grade C cirrhosis, and when sarcopenia was defined by L3-SMI (third lumbar-skeletal muscle index). Sarcopenia was associated with an increased risk of mortality in patients with cirrhosis (adjusted hazard ratio [aHR] 2.30, 95% CI 2.01-2.63), with similar findings in a sensitivity analysis of patients with cirrhosis without hepatocellular carcinoma (aHR 2.35, 95% CI 1.95-2.83) and in subgroups stratified by sex, liver disease etiology, and severity of hepatic dysfunction. The association between quantitative muscle mass index and mortality further supports the association between sarcopenia and poor prognosis (aHR 0.95, 95% CI 0.93-0.98). There was no significant heterogeneity in any of our analyses. CONCLUSIONS: Sarcopenia was highly and independently associated with higher risk of mortality in patients with cirrhosis. LAY SUMMARY: The prevalence of sarcopenia and its association with death in patients with cirrhosis remain unclear. This meta-analysis indicated that sarcopenia affected about one-third of patients with cirrhosis and up to 50% of patients with alcohol-related liver disease or Child-Pugh class C cirrhosis. Sarcopenia was independently associated with an ∼2-fold higher risk of mortality in patients with cirrhosis. The mortality rate increased with greater severity or longer durations of sarcopenia. Increasing awareness about the importance of sarcopenia in patients with cirrhosis among stakeholders must be prioritized.

Progression Rates by Age, Sex, Treatment, and Disease Activity by AASLD and EASL Criteria: Data for Precision Medicine.

BACKGROUND & AIMS: Antiviral treatment criteria are based on disease progression risk, and hepatocellular carcinoma (HCC) surveillance recommendations for patients with chronic hepatitis B (CHB) without cirrhosis is based on an annual incidence threshold of 0.2%. However, accurate and precise disease progression estimate data are limited. Thus, we aimed to determine rates of cirrhosis and HCC development stratified by age, sex, treatment status, and disease activity based on the 2018 American Association for the Study of Liver Diseases and 2017 European Association for the Study of the Liver guidelines. METHODS: We analyzed 18,338 patients (8914 treated, 9424 untreated) from 6 centers from the United States and 27 centers from Asia-Pacific countries. The Kaplan-Meier method was used to estimate annual progression rates to cirrhosis or HCC in person-years. RESULTS: The cohort was 63% male, with a mean age of 46.19 years, with baseline cirrhosis of 14.3% and median follow up of 9.60 years. By American Association for the Study of Liver Diseases criteria, depending on age, sex, and disease activity, annual incidence rates ranged from 0.07% to 3.94% for cirrhosis, from 0.04% to 2.19% for HCC in patients without cirrhosis, and from 0.40% to 8.83% for HCC in patients with cirrhosis. Several subgroups of patients without cirrhosis including males younger than 40 years of age and females younger than 50 years of age had annual HCC risk near or exceeding 0.2%. Similar results were found using European Association for the Study of the Liver criteria. CONCLUSION: There is great variability in CHB disease progression rates even among "lower-risk" populations. Future CHB modeling studies, public health planning, and HCC surveillance recommendation should be based on more precise disease progression rates based on sex, age, and disease activity, plus treatment status.

On-treatment gamma-glutamyl transferase predicts the development of hepatocellular carcinoma in chronic hepatitis B patients.

BACKGROUND & AIMS: Gamma-glutamyl transferase (GGT) has been predictive of chronic hepatitis C-related hepatocellular carcinoma (HCC) development. Its role in the risk of HCC in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues (NAs) is elusive. METHODS: A total of 2172 CHB patients from East Asia were randomized into development and validation groups in a 1:2 ratio. Serum GGT levels before and 6 months (M6) after initiating NAs and the potential risk factors were measured. The primary endpoint was HCC development 12 months after NA initiation. RESULTS: The annual incidence of HCC was 1.4/100 person-years in a follow-up period of 11 370.7 person-years. The strongest factor associated with HCC development was high M6-GGT levels (>25 U/L; hazard ratio [HR]/95% confidence interval [CI]: 3.31/2.02-5.42, P < .001), followed by cirrhosis (HR/CI: 2.06/1.39-3.06, P < .001), male sex (HR/CI: 2.01/1.29-3.13, P = .002) and age (HR/CI: 1.05/1.03-1.17, P < .001). Among cirrhotic patients, the incidence of HCC did not differ between those with high or low M6-GGT levels (P = .09). In contrast, among non-cirrhotic patients, the incidence of HCC was significantly higher for those with M6-GGT level >25 U/L than for their counterparts (P < .001). Cox regression analysis revealed that the strongest factor associated with HCC development in non-cirrhotic patients was high M6-GGT levels (HR/CI: 5.05/2.52-10.16, P < .001), followed by age (HR/CI: 1.07/1.04-1.09, P < .001). Non-cirrhotic elderly patients with high M6-GGT levels had a similarly high HCC risk as cirrhotic patients did (P = .29). CONCLUSIONS: On-treatment serum GGT levels strongly predicted HCC development in CHB patients, particularly non-cirrhotic patients, treated with NAs.

Computed Tomography-Determined Body Composition Abnormalities Usefully Predict Long-term Mortality in Patients With Liver Cirrhosis.

OBJECTIVE: We evaluated the prognostic impacts of body composition components measured by computed tomography (CT) in patients with liver cirrhosis. METHODS: A total of 160 cirrhotic patients who underwent CT and hepatic venous pressure gradient measurements were retrospectively enrolled. Cross-sectional areas of skeletal muscle, visceral and subcutaneous fat, and mean CT attenuation of trabecular bone of the fourth lumbar vertebral level (L4HU) were measured. RESULTS: Multivariate analysis showed model for end-stage liver disease score [hazard ratio (HR), 1.086; 95% confidence interval (CI), 1.020-1.156; P = 0.010], hepatic venous pressure gradient (HR, 1.076; 95% CI, 1.021-1.135; P = 0.006), sarcopenia (HR, 1.890; 95% CI, 1.032-3.462; P = 0.039), and L4HU (HR, 1.960 for L4HU <145 Hounsfield units; 95% CI, 1.094-3.512; P = 0.024) were independently associated with long-term mortality. In patients with decompensated cirrhosis, subcutaneous adipose tissue index was the only independent predictor (HR, 0.984; 95% CI, 0.969-0.999; P = 0.039). CONCLUSION: Body composition abnormalities determined by CT are associated with long-term prognosis in cirrhotic patients.

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.

No Difference in Incidence of Hepatocellular Carcinoma in Patients With Chronic Hepatitis B Virus Infection Treated With Entecavir vs Tenofovir.

BACKGROUND & AIMS: Studies to evaluate risks of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B virus (HBV) infection treated with the nucelos(t)ide analogues entecavir or tenofovir have produced contradictory results. These differences are likely to be the result of censored data, insufficient observation periods, and different observation periods for patients treated with different drugs. We aimed to compare the incidence of HCC development between patients treated with oral entecavir or tenofovir and followed up for the same time periods. METHODS: We performed a retrospective study, collecting data from 1560 treatment-naive patients with chronic HBV infection who were first treated with entecavir (n = 753) or tenofovir (n = 807) from 2011 through 2015 at 9 academic hospitals in Korea. Clinical outcomes were recorded over a mean time period of 4.7 ± 1.0 years, from 92.4% of patients treated with tenofovir and 92.7% of patients treated with entecavir. RESULTS: Thirty-four patients in the entecavir group (4.5%) and 45 patients in the tenofovir group (5.6%) developed HCC during the follow-up period. The incidence of HCC did not differ significantly between groups, even in a 516-pair propensity score-matched population. CONCLUSIONS: In a retrospective study of 1560 treatment-naive patients with chronic HBV infection, the incidence of HCC did not differ significantly between patients treated with entecavir vs tenofovir over the same observation period. CLINICAL TRIAL: KCT0003487.

Spleen Stiffness Measurement Using 2-Dimensional Shear Wave Elastography: The Predictors of Measurability and the Normal Spleen Stiffness Value.

OBJECTIVES: To investigate the success rate of spleen stiffness measurement and factors that affect measurement success and to determine the spleen stiffness value of normal individuals by 2-dimensional shear wave elastography. METHODS: The spleen and liver stiffnesses of 313 consecutive patients were measured with SWE. The body mass index, abdominal wall thickness, spleen size, and liver stiffness of the patients were evaluated to identify factors associated with successful measurement of spleen stiffness. Patients were grouped by body mass index, spleen size, and liver stiffness, and the success rates and mean spleen stiffness values of the groups were compared. Independent predictors for successful spleen stiffness measurement and their cutoff values were evaluated. The mean spleen stiffness values of patients considered to have normal spleen stiffness were investigated. RESULTS: The overall success rate of spleen stiffness measurement was 52.9%. It was significantly higher in nonobese than in obese patients and in patients with splenomegaly and liver cirrhosis. The spleen stiffness value was higher in the splenomegaly group than the nonsplenomegaly group (P < .001) and increased as liver stiffness increased (P < .001). There was no significant difference in spleen stiffness values between the obese and nonobese groups. Abdominal wall thickness and splenic longitudinal diameter were identified as independent predictors of successful spleen stiffness measurement, and their cutoff values were 17.2 mm or less and greater than 9.4 cm, respectively. The mean spleen stiffness value ± SD of the normal patient group was 20.5 ± 5.4 kPa. CONCLUSIONS: The success rate of spleen stiffness measurement is lower than that of liver stiffness measurement. Spleen stiffness measurement is affected by abdominal wall thickness and spleen size.

Effect of a synthetic osteoconductive bone graft substitute with zeta potential control (geneX®ds) in the treatment of intertrochanteric fracture: A single center experience of 115 consecutive proximal femoral nail antirotations.

INTRODUCTION: Although various clinical applications of geneX®ds have been reported, no study has reported the clinical application of geneX®ds in osteoporotic hip fracture. The present study aimed to identify the clinical effect of the application of geneX®ds in elderly patients with intertrochanteric fracture treated using proximal femoral nail antirotation (PFNA). MATERIALS AND METHODS: From March 2014 to October 2017, 233 patients with intertrochanteric fracture (65 men and 168 women) were enrolled in this study. All patients received surgical treatment using PFNA. Patients were classified into two groups: those in whom geneX®ds which is synthetic osteoconductive bone graft substitute with the unique property of Zeta Potential Control (ZPC®), was use, and those in whom it was not. We compared the preoperative details and surgical outcomes, including radiologic outcome (postoperative reduction, tip apex distance, sliding distance of the helical blade, union, and union time) and clinical outcomes (Harris Hip Score and the walking ability at the last follow-up) between the groups. RESULTS: In patients with unstable fracture who achieved anatomical or extramedullary type of reduction, the average sliding distance at 1, 3, and 12 months was 4.9 mm, 7.5 mmm and 8.1 mm in the geneX®ds group and 7.5 mm, 10.8 mm, and 12.1 mm in the no geneX®ds group, respectively. There were significant differences in the sliding distance at 1, 3, and 12 months between these two groups. CONCLUSION: The use of this synthetic osteoconductive bone graft substitute with zeta potential control may have positive effect on the controlled sliding of the helical blade and the healing of intertrochanteric fracture.

Presence of Sarcopenia and Its Rate of Change Are Independently Associated with Long-term Mortality in Patients with Liver Cirrhosis.

BACKGROUND: Sarcopenia is associated with a poor prognosis in patients with liver cirrhosis. However, it is not known whether the rate of skeletal muscle depletion is also associated with a poor prognosis. We investigated the prognostic impact of the rate of skeletal muscle depletion in patients with liver cirrhosis. METHODS: We included retrospectively all patients with liver cirrhosis who underwent both multiple computed tomography scans and hepatic venous pressure gradient (HVPG) measurements. RESULTS: A total of 131 patients with liver cirrhosis were enrolled. The mean age of the patients was 53.7 years and alcoholic liver disease was the most common cause (61.8%). Sixty-four patients (48.9%) were diagnosed with sarcopenia. The median changes in skeletal muscle area per year (ΔSMA/y) were -0.89%. During a median follow-up period of 46.2 months (range, 3.4-87.6), 45 patients (34.4%) died. In multivariate analyses, age, Child-Pugh score, HVPG, presence of sarcopenia and ΔSMA/y were independently associated with mortality. Cumulative mortality was significantly higher in patients with ΔSMA/y < -2.4% than those with ΔSMA/y ≥ -2.4% (log-rank test, P < 0.001). CONCLUSION: Both the presence and rate of change of sarcopenia are independently associated with long-term mortality in patients with liver cirrhosis.

Validation of a Paper and Pencil Test Battery for the Diagnosis of Minimal Hepatic Encephalopathy in Korea.

The aim of this study was to validate a new paper and pencil test battery to diagnose minimal hepatic encephalopathy (MHE) in Korea. A new paper and pencil test battery was composed of number connection test-A (NCT-A), number connection test-B (NCT-B), digit span test (DST), and symbol digit modality test (SDMT). The norm of the new test was based on 315 healthy individuals between the ages of 20 and 70 years old. Another 63 healthy subjects (n = 31) and cirrhosis patients (n = 32) were included as a validation cohort. All participants completed the new paper and pencil test, a critical flicker frequency (CFF) test and computerized cognitive function test (visual continuous performance test [CPT]). The scores on the NCT-A and NCT-B increased but those of DST and SDMT decreased according to age. Twelve of the cirrhotic patients (37.5%) were diagnosed with MHE based on the new paper and pencil test battery. The total score of the paper and pencil test battery showed good positive correlation with the CFF (r = 0.551, P < 0.001) and computerized cognitive function test. Also, this score was lower in patients with MHE compared to those without MHE (P < 0.001). Scores on the CFF (32.0 vs. 28.7 Hz, P = 0.028) and the computer base cognitive test decreased significantly in patients with MHE compared to those without MHE. Test-retest reliability was comparable. In conclusion, the new paper and pencil test battery including NCT-A, NCT-B, DST, and SDMT showed good correlation with neuropsychological tests. This new paper and pencil test battery could help to discriminate patients with impaired cognitive function in cirrhosis (registered at Clinical Research Information Service [CRIS], https://cris.nih.go.kr/cris, KCT0000955).

Outcomes of Propofol Sedation During Emergency Endoscopy Performed for Upper Gastrointestinal Bleeding.

BACKGROUND: Although propofol-based sedation can be used during emergency endoscopy for upper gastrointestinal bleeding (UGIB), there is a potential risk of sedation-related adverse events, especially in patients with variceal bleeding. AIM: We compared adverse events related to propofol-based sedation during emergency endoscopy between patients with non-variceal and variceal bleeding. METHODS: Clinical records of patients who underwent emergency endoscopy for UGIB under sedation were reviewed. Adverse events, including shock, hypoxia, and paradoxical reaction, were compared between the non-variceal and variceal bleeding groups. RESULTS: Of 703 endoscopies, 539 and 164 were performed for non-variceal and variceal bleeding, respectively. Shock was more common in patients with variceal bleeding compared to those with non-variceal bleeding (12.2 vs. 3.5%, P < 0.001). All patients except one recovered from shock after normal saline hydration, and emergency endoscopy could be finished without interruption in most cases. The incidence of hypoxia and paradoxical reaction did not differ based on the source of bleeding (non-variceal bleeding vs. variceal bleeding: hypoxia, 3.5 vs. 1.8%, P = 0.275; paradoxical reaction interfering with the procedure, 4.1 vs. 5.5%, P = 0.442). CONCLUSIONS: Although shock was more common in patients with variceal bleeding compared to those with non-variceal bleeding, most cases could be controlled without procedure interruption. Paradoxical reaction, rather than shock or hypoxia, was the most common cause of procedure interruption in patients with variceal bleeding, but the rate did not differ between patients with non-variceal and variceal bleeding.

Does submucosal fibrosis affect the results of endoscopic submucosal dissection of early gastric tumors?

BACKGROUND: Endoscopic submucosal dissection (ESD) is an effective treatment of early gastric tumors, but submucosal fibrosis can be an obstacle to successful ESD. OBJECTIVE: To examine the association between endoscopic and pathologic factors and submucosal fibrosis in early gastric tumors, and to measure the association between degree of submucosal fibrosis and outcomes of ESD. DESIGN: A retrospective study. SETTING: An academic medical center. PATIENTS: From November 2006 to April 2011, 161 patients with 167 early gastric tumors treated by ESD. INTERVENTION: ESD. MAIN OUTCOME MEASUREMENTS: Endoscopic and pathologic factors related to submucosal fibrosis. Procedure time, en bloc resection rate, and complications according to degree of submucosal fibrosis. RESULTS: In univariate analysis, the presence of endoscopic submucosal fibrosis was significantly related to tumor size, location, ulceration, histologic findings, and submucosal invasion. Multivariate analysis for these factors showed that endoscopic submucosal fibrosis was independently associated with lesions in tumor size greater than 30 mm, in the proximal portion of the stomach, and more common in adenocarcinomas than in adenomas. After correction for multiple testing, only the middle of the stomach as a locational risk factor retains statistical significance. Also, the more advanced the endoscopic submucosal fibrosis, the longer the time required for ESD (P < .0001). The severity of endoscopic submucosal fibrosis was associated with a lower en bloc resection rate and with abundant immediate bleeding. LIMITATIONS: Retrospective, single-center study. CONCLUSION: Submucosal fibrosis of early gastric tumors is closely related to tumor size, location, ulceration, histologic findings, and submucosal invasion. Moreover, the greater the degree of submucosal fibrosis the longer the time taken for the ESD procedure and the higher the frequency of complications such as perforation and immediate bleeding.

Is use of PPIs related to increased intraepithelial lymphocytes in the colon?

BACKGROUND: The use of proton pump inhibitors (PPIs) is thought to increase the incidence of microscopic colitis (MC), although the exact mechanisms are not fully understood. Increased infiltration of intraepithelial lymphocytes (IELs) is a pathologic finding of MC (including collagenous or lymphocytic colitis). AIMS: We investigated whether PPI use is associated with increased IEL infiltration and inflammation in the lamina propria. METHODS: We retrospectively reviewed the medical records and histological reports of 78 patients receiving PPIs who had no symptoms of diarrhea, and their age- and gender- matched controls. The levels of IELs and inflammation in the lamina propria were assessed independently by two pathologists using H&E and immunohistochemical staining for CD3 and CD8. RESULTS: The IEL count was significantly higher in the PPI group than in controls (12.92 ± 6.27 vs. 8.10 ± 4.21 per 100 epithelial cells, p < 0.001), as was the extent of inflammation (1.74 ± 0.90 vs. 0.86 ± 0.78, p < 0.001). PPI use was associated with increased IEL infiltration in a multivariate analysis (OR, 3.232; 95 % CI, 1.631-6.404, p < 0.001). Within the PPI group, however, the IEL count was not significantly associated with gender, age, type of PPI, or duration of PPI use. CONCLUSIONS: The use of PPIs has a significant association with increased IEL infiltration for subjects without symptoms of diarrhea. This finding suggests that changes such histological alterations seen in the early phage seen in MC possibly represent the stage of the disease even before the onset of symptoms.

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.

The chronological changes in the seroprevalence of anti-hepatitis A virus IgG from 2005 to 2019: Experience at four centers in the capital area of South Korea.

Although universal vaccination has been administered to toddlers, South Korea has had periodic nationwide outbreaks of acute hepatitis A since the late 2000s. We examined the chronological changes in the seroprevalence of anti-hepatitis A virus (HAV) immunoglobulin G (IgG) over the past 15 years (2005-2019). We retrospectively collected data from 45,632 subjects who underwent anti-HAV IgG testing without evidence of acute HAV infection at four centers in the capital area of South Korea between January 2005 and December 2019. The seroprevalence of anti-HAV IgG was analyzed according to age and compared among seven age groups and five time periods. Additionally, age-period-cohort analyses were used to identify the age, period, and cohort effects of the seroprevalence of anti-HAV IgG. The mean age of the enrolled subjects was 39.2 ±â€…19.2 years, and the average anti-HAV IgG positivity rate was 66.4%. During the 15 years, the seroprevalence of anti-HAV IgG in people aged 0 to 19 years significantly increased over time (P < .001). In people aged 20 to 29 years, the seroprevalence slightly decreased to that of the early 2010s (31.3% in 2005-2007 to 19.7% in 2011-2013) but rebounded to 39.5% in 2017 to 2019. In contrast, the seroprevalence of anti-HAV IgG in those aged 30 to 49 years decreased over time (P < .001). The seroprevalence of anti-HAV IgG in those aged 20 to 39 years in 2017 to 2019 was still less than 40%. In addition, the seroprevalence of anti-HAV IgG in people aged 50 to 59 years has recently decreased. Since the introduction of the universal vaccination, the seroprevalence of anti-HAV IgG in children and young adults has gradually increased. However, the seroprevalence of anti-HAV IgG in people in their 20s remains low, and the seroprevalence of anti-HAV IgG in people in their 30s and 40s is gradually decreasing. Therefore, a new strategy for HAV vaccination is needed for those in their 20s to 40s.

Effect of L-carnitine on quality of life in covert hepatic encephalopathy: a randomized, double-blind, placebo-controlled study.

BACKGROUND/AIMS: L-carnitine is potentially beneficial in patients with hepatic encephalopathy (HE). We aimed to evaluate the impact of L-carnitine on the quality of life and liver function in patients with liver cirrhosis and covert HE. METHODS: We conducted an investigator-initiated, prospective, multi-center, double- blind, randomized phase III trial in patients with covert HE. A total of 150 patients were randomized 1:1 to L-carnitine (2 g/day) or placebo for 24 weeks. Changes in quality of life and liver function were assessed at 6 months. The model for end-stage liver disease (MELD), the 36-Item Short Form Survey (SF-36), the psychometric hepatic encephalopathy score (PHES), and the Stroop Test were evaluated in all patients. RESULTS: The total SF-36 score significantly improved in the L-carnitine group after 24 weeks (difference: median, 2; interquartile range, 0 to 11; p < 0.001); however, these values were comparable between the two groups. Furthermore, there was a significant ordinal improvement in PHES scores among patients with minimal HE who were in the L-carnitine group (p = 0.007). Changes in the total carnitine level also positively correlated with improvements in the Stroop test in the L-carnitine group (color test, r = 0.3; word test, r = 0.4; inhibition test, r = 0.5; inhibition/switching test, r = 0.3; all p < 0.05). Nevertheless, the MELD scores at week 24 did not differ between the groups. CONCLUSION: Twenty-four weeks of L-carnitine supplementation was safe but ineffective in improving quality of life and liver function.

Longitudinal renal changes in chronic hepatitis B patients treated with entecavir versus TDF: a REAL-B study.

BACKGROUND AND AIMS: We aimed to compare the longitudinal changes in estimated glomerular filtration rate (eGFR) in chronic hepatitis B (CHB) patients treated with entecavir (ETV) vs. tenofovir disoproxil fumarate (TDF). METHODS: This is a retrospective study of 6189 adult treatment-naïve CHB patients initiated therapy with TDF (n = 2482) or ETV (n = 3707) at 25 international centers using multivariable generalized linear modeling (GLM) to determine mean eGFR (mL/min/1.73 m2) and Kaplan-Meier method to estimate incidence of renal impairment (≥ 1 chronic kidney disease [CKD] stage worsening). We also examined above renal changes in matched ETV and TDF patients (via propensity score matching [PSM] on age, sex, diabetes mellitus [DM], hypertension [HTN], cirrhosis, baseline eGFR, and follow-up duration). RESULTS: In the overall cohort (mean age 49.7 years, 66.2% male), the baseline eGFR was higher for TDF vs. ETV group (75.9 vs. 74.0, p = 0.009). PSM yielded 1871 pairs of ETV or TDF patients with baseline eGFR ≥ 60 and 520 pairs for the eGFR < 60 group. GLM analysis of the overall (unmatched) cohort and PSM cohorts revealed lower adjusted mean eGFRs in TDF (vs. ETV) patients (all p < 0.01) during 10 years of follow-up. Among PSM eGFR ≥ 60 patients, the 5-year cumulative incidences of renal impairment were 42.64% for ETV and 48.03% for TDF (p = 0.0023). In multivariable Cox regression, TDF vs. ETV (adjusted HR 1.26, 95% CI 1.11-1.43) was associated with higher risk of worsening renal function. CONCLUSION: Over the 10-year study follow-up, compared to ETV, TDF was associated with a lower mean eGFR and higher incidence of renal impairment.

Effectiveness of entecavir vs tenofovir disoproxil fumarate for functional cure of chronic hepatitis B in an international cohort.

INTRODUCTION: Both entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are first-line therapies for chronic hepatitis B (CHB), but their comparative effectiveness with regards to hepatitis B surface antigen (HBsAg) seroclearance remains unclear. METHODS: This international multicenter cohort study enrolled 7697 treatment-naïve CHB patients (median age 50 years; male 66.75%) initiated on either ETV (n = 5430) or TDF (n = 2267) without baseline malignancy or immunosuppression from 23 centers across 10 countries or regions. Patients were observed for HBsAg seroclearance until death, loss to follow-up, or treatment discontinuation or switching. The incidences of HBsAg seroclearance were adjusted for competing mortality and compared between ETV and TDF cohorts with inverse probability of treatment weighting (IPTW) and also by multivariable regression analysis. RESULTS: The study population was followed up for a median duration of 56.1 months with 36,929 11 person-years of observation. HBsAg seroclearance occurred in 70 ETV-treated and 21 TDF-treated patients, yielding 8-year cumulative incidence of 1.69% (95% confidence interval [CI] 1.32-2.17) for ETV and 1.34% (95% CI 0.85-2.10%), for TDF (p = 0.58). In the IPTW analysis with the two study cohorts more balanced in background covariates, the age-adjusted hazard ratio (HR) of TDF versus ETV for HBsAg seroclearance was 0.91 (95% CI 0.50-1.64; p = 0.75). Furthermore, there was no significant difference between the two medications in the multivariable competing risk regression model (adjusted sub-distributional HR 0.92 for TDF vs. ETV; 95% CI 0.56-1.53; p = 0.76). CONCLUSIONS: ETV and TDF did not differ significantly in the incidence of HBsAg seroclearance, which rarely occurred with either regimen.

Transition rates to cirrhosis and liver cancer by age, gender, disease and treatment status in Asian chronic hepatitis B patients.

BACKGROUND: Increasing hepatitis-related mortality has reignited interest to fulfill the World Health Organization's goal of viral hepatitis elimination by 2030. However, economic barriers have enabled only 28% of countries to implement countermeasures. Given the high disease burden among Asians, we aimed to present age, sex, disease activity and treatment-specific annual progression rates among Asian chronic hepatitis B (CHB) patients to inform health economic modeling efforts and cost-effective public health interventions. METHODS: We analyzed 18,056 CHB patients from 36 centers across the U.S. and seven countries/regions of Asia Pacific (9530 treated; 8526 untreated). We used Kaplan-Meier methods to estimate annual incidence of cirrhosis and hepatocellular carcinoma (HCC). Active disease was defined by meeting the APASL treatment guideline criteria. RESULTS: Over a median follow-up of 8.55 years, there were 1178 incidences of cirrhosis and 1212 incidences of HCC (297 without cirrhosis, 915 with cirrhosis). Among the 8526 untreated patients (7977 inactive, 549 active), the annual cirrhosis and HCC incidence ranged from 0.26% to 1.30% and 0.04% to 3.80% in inactive patients, and 0.55 to 4.05% and 0.19 to 6.03% in active patients, respectively. Of the 9530 treated patients, the annual HCC rates ranged 0.03-1.57% among noncirrhotic males and 2.57-6.93% among cirrhotic males, with lower rates for females. Generally, transition rates increased with age, male sex, the presence of fibrosis/cirrhosis, and active disease and/or antiviral treatment. CONCLUSION: Using data from a large and diverse real-world cohort of Asian CHB patients, the study provided detailed annual transition rates to inform practice, research and public health planning.