Non-alcoholic fatty liver disease: Definition and subtypes

Non-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide, with a global prevalence of approximately 30%. However, the prevalence of NAFLD has been variously reported depending on the comorbidities. The rising prevalence of obesity in both the adult and pediatric populations is projected to consequently continue increasing NAFLD prevalence. It is a major cause of chronic liver disease worldwide, including cirrhosis and hepatocellular carcinoma (HCC). NAFLD has a variety of clinical phenotypes and heterogeneity due to the complexity of pathogenesis and clinical conditions of its occurrence, resulting in various clinical prognoses. In this article, we briefly described the basic definition of NAFLD and classified the subtypes based on current knowledge in this field.

Pulmonary Complications in Patients with Liver Cirrhosis / 대한소화기학회지

Portal hypertension is a clinical syndrome defined by an increased portal venous pressure. The most frequent cause of portal hypertension is liver cirrhosis, and many of the complications of cirrhosis, such as ascites and gastroesophageal variceal bleeding, are related to portal hypertension. Portal hypertension is a pathological condition caused by the accumulation of blood flow in the portal system. This blood flow retention reduces the effective circulation volume. To compensate for these changes, neurotransmitter hormone changes and metabolic abnormalities occur, which cause complications in organs other than the liver. A hepatic hydrothorax is fluid accumulation in the pleural space resulting from increased portal pressure. Hepatopulmonary syndrome and portopulmonary hypertension are the pulmonary complications in cirrhosis by deforming the vascular structure. Symptoms, such as dyspnea and hypoxia, affect the survival and the quality of life of patients. These lung complications are usually underestimated in the management of cirrhosis. This review briefly introduces the type of lung complications of cirrhosis.

Associations of Serum Uric Acid Level With Liver Enzymes, Nonalcoholic Fatty Liver Disease, and Liver Fibrosis in Korean Men and Women: A CrossSectional Study Using Nationally Representative Data

Background@#This study aimed to determine whether serum uric acid (SUA) levels are associated with various indices of liver damage in the adult Korean population. @*Methods@#We used the Seventh (VII) Korean National Health and Nutritional Examination Surveys. Our study population comprised 6,007 men and 8,488 women. Levels of SUA were divided into four groups (≤ 5.3, 5.3–6.0, 6.0–7.0, and > 7.0 mg/dL for men and ≤ 4.0, 4.0–4.8, 4.8–6.0, and > 6.0 mg/dL for women). Elevated liver enzyme levels were defined as > 35 (men) and > 31 (women) IU/L for aspartate aminotransferase (AST), > 45 (men) and > 34 (women) IU/L for alanine aminotransferase (ALT). Hepatic steatosis index and fibrosis (FIB)-4 index was used to determine nonalcoholic fatty liver disease (NAFLD) and liver FIB, respectively. Adjusted odds ratios (aORs) were calculated by logistic regression analysis for liver enzymes, NAFLD, and liver FIB, according to the SUA level. @*Results@#Among women, the 4.8–6.0 and > 6.0 mg/dL SUA groups showed higher ORs of elevated AST (aOR, 1.78 and 2.03; 95% confidence interval [CI], 1.37–2.32 and 1.40–2.96, respectively; P 6.0 mg/dL SUA groups showed a higher ORs of ALT elevation (aOR, 1.35, 2.26, and 2.37; 95% CI, 1.02–1.79, 1.72–2.97, and 1.60–3.50, respectively; P 6.0 mg/dL SUA group showed higher OR of NAFLD status (aOR, 1.52; 95% CI, 1.06–2.19). Among men and women with NAFLD, hyperuricemia showed higher ORs of liver FIB (aOR, 2.25 and 1.89; 95% CI, 1.21–4.19 and 1.09–3.27, respectively) than the lowest level SUA group. @*Conclusion@#High SUA levels may be associated with elevated liver enzymes and NAFLD, mainly in women. Even in women with normal ALT levels, SUA levels may predict the NAFLD status. Hyperuricemia may predict advanced liver FIB in both men and women with NAFLD. Further studies investigating the causal effects of SUA on liver damage are required.

Reappraisal of sepsis-3 and CLIF-SOFA as predictors of mortality in patients with cirrhosis and infection presenting to the emergency department: A multicenter study

Background/Aims@#Sepsis-3 criteria and quick Sequential Organ Failure Assessment (qSOFA) have been advocated to be used in defining sepsis in the general population. We aimed to compare the Sepsis-3 criteria and Chronic Liver Failure-SOFA (CLIF-SOFA) scores as predictors of in-hospital mortality in cirrhotic patients admitted to the emergency department (ED) for infections. @*Methods@#A total of 1,622 cirrhosis patients admitted at the ED for infections were assessed retrospectively. We analyzed their demographic, laboratory, and microbiological data upon diagnosis of the infection. The primary endpoint was inhospital mortality rate. The predictive performances of baseline CLIF-SOFA, Sepsis-3, and qSOFA scores for in-hospital mortality were evaluated. @*Results@#The CLIF-SOFA score proved to be significantly better in predicting in-hospital mortality (area under the receiver operating characteristic curve [AUROC], 0.80; 95% confidence interval [CI], 0.78–0.82) than the Sepsis-3 (AUROC, 0.75; 95% CI, 0.72–0.77, P10%; this is the cutoff point for the definition of sepsis. @*Conclusions@#Among cirrhosis patients presenting with infections at the ED, CLIF-SOFA scores showed a better predictive performance for mortality than both Sepsis-3 criteria and qSOFA scores, and can be a useful tool of risk stratification in cirrhotic patients requiring timely intervention for infection.

Autoimmune Hepatitis Following Vaccination for SARS-CoV-2 in Korea:Coincidence or Autoimmunity?

Autoimmune hepatitis (AIH) is a chronic, autoimmune disease of the liver that occurs when the body’s immune system attacks liver cells, causing the liver to be inflamed. AIH is one of the manifestations of a coronavirus disease 2019 (COVID-19), as well as an adverse event occurring after vaccination against severe acute respiratory syndrome coronavirus 2 (SARSCoV-2). Few cases of AIH have been described after vaccination with two messenger RNA (mRNA)-based vaccines—BTN162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)—against SARS-CoV-2. Herein, we report a case of AIH occurring after Pfizer-BioNTech COVID-19 vaccine. A 27-year-old female presented with jaundice and hepatomegaly, appearing 14 days after receiving the second dose of Pfizer-BioNTech vaccine. Her laboratory results showed abnormal liver function with high total immunoglobulin G level. She was diagnosed with AIH with histologic finding and successfully treated with oral prednisolone. We report an AIH case after COVID-19 vaccination in Korea.

Multidimensional Biomarker Analysis Including Mitochondrial Stress Indicators for Nonalcoholic Fatty Liver Disease

Nonalcoholic fatty liver disease (NAFLD) is accompanied by a complex and multifactorial pathogenesis with sequential progressions from inflammation to fibrosis and then to cancer. This heterogeneity interferes with the development of precise diagnostic and prognostic strategies for NAFLD. The current approach for the diagnosis of simple steatosis, steatohepatitis, and cirrhosis mainly consists of ultrasonography, magnetic resonance imaging, elastography, and various serological analyses. However, individual dry and wet biomarkers have limitations demanding an integrative approach for the assessment of disease progression. Here, we review diagnostic strategies for simple steatosis, steatohepatitis and hepatic fibrosis, followed by potential biomarkers associated with fat accumulation and mitochondrial stress. For mitochondrial stress indicators, we focused on fibroblast growth factor 21 (FGF21), growth differentiation factor 15 (GDF15), angiopoietin-related growth factor and mitochondrial-derived peptides. Each biomarker may not strongly indicate the severity of steatosis or steatohepatitis. Instead, multidimensional analysis of different groups of biomarkers based on pathogenic mechanisms may provide decisive diagnostic/prognostic information to develop a therapeutic plan for patients with NAFLD. For this purpose, mitochondrial stress indicators, such as FGF21 or GDF15, could be an important component in the multiplexed and contextual interpretation of NAFLD. Further validation of the integrative evaluation of mitochondrial stress indicators combined with other biomarkers is needed in the diagnosis/prognosis of NAFLD.

The cut-off value of transient elastography to the value of hepatic venous pressure gradient in alcoholic cirrhosis

Background/Aims@#The hepatic venous pressure gradient (HVPG) reflects portal hypertension, but its measurement is invasive. Transient elastography (TE) is a noninvasive method for evaluating liver stiffness (LS). We investigated the correlation between the value of LS, LS to platelet ratio (LPR), LS-spleen diameter-to-platelet ratio score (LSPS) and HVPG according to the etiology of cirrhosis, especially focused on alcoholic cirrhosis. @*Methods@#Between January 2008 and March 2017, 556 patients who underwent HVPG and TE were consecutively enrolled. We evaluated LS, LPR, and LSPS according to the etiology of cirrhosis and analyzed their correlations with HVPG. @*Results@#The LS value was higher in patients with alcoholic cirrhosis than viral cirrhosis based on the HVPG (43.5 vs. 32.0 kPa, P<0.001). There were no significant differences in the LPR or LSPS between alcoholic and viral cirrhosis groups, and the areas under the curves for the LPR and LSPS in subgroups according to HVPG levels were not superior to that for LS. In alcoholic cirrhosis, the LS cutoff value for predicting an HVPG ≥10 mmHg was 32.2 kPa with positive predictive value (PPV) of 94.5% and 36.6 kPa for HVPG ≥12 mmHg with PPV of 91.0%. @*Conclusions@#The LS cutoff value should be determined separately for patients with alcoholic and viral cirrhosis. In alcoholic cirrhosis, the LS cutoff values were 32.2 and 36.6 kPa for predicting an HVPG ≥10 and ≥12 mmHg, respectively. However, there were no significant differences in the LPR or LSPS between alcoholic and viral cirrhosis groups.

Mesenchymal Stem Cells for the Treatment of Liver Disease: Present and Perspectives

Mesenchymal stem cell transplantation is an emerging therapy for treating chronic liver diseases. The potential of this treatment has been evaluated in preclinical and clinical studies. Although the mechanisms of mesenchymal stem cell transplantation are still not completely understood, accumulating evidence has revealed that their immunomodulation, differentiation, and antifibrotic properties play a crucial role in liver regeneration. The safety and therapeutic effects of mesenchymal stem cells in patients with chronic liver disease have been observed in many clinical studies. However, only modest improvements have been seen, partly because of the limited feasibility of transplanted cells at present. Here, we discuss several strategies targeted at improving viable cell engraftment and the potential challenges in the use of extracellular vesicle-based therapies for liver disease in the future.

Application of Baveno Criteria and Modified Baveno Criteria with Shear-wave Elastography in Compensated Advanced Chronic Liver Disease

Background@#We aimed to validate Baveno VI and expanded Baveno VI criteria using two dimensional shear-wave elastography (2D-SWE) in compensated advanced chronic liver disease (cACLD) patients with alcohol as the main etiology. @*Methods@#Clinical data from 305 patients with cACLD who underwent a liver stiffness measurement (LSM) with 2D-SWE and endoscopy were consecutively collected. @*Results@#Among 305 patients, high-risk varix (HRV) was identified in 21.3% (n = 65). The main etiology was alcoholic liver disease (51.8%), followed by hepatitis B virus (29.8%) and hepatitis C virus (9.1%). Baveno VI criteria spared endoscopy in 118 of the 305 (38.7%) patients, and 7 (5.9%) were missed with HRV. Expanded Baveno VI criteria spared more endoscopies (60.0%), but missed more HRV (9.8%) compared with Baveno VI criteria. The other classification described as the modified Baveno VI criteria were LSM < 25 kPa and PLT ≥ 150 × 103/mm3. In total, 131 of the 305 (43.0%) patients were within the modified Baveno VI criteria, of whom seven (5.3%) had missed HRV. After adding spleen diameter < 12 cm to the modified Baveno VI criteria, the number of spared endoscopies increased by 106/305 (34.8%), with three (2.8%) presenting with HRV, indicating a risk of missing HRV. @*Conclusion@#Baveno VI and expanded Baveno VI criteria with 2D-SWE were insufficient with an HRV miss rate of over 5%. The modified Baveno VI criteria with spleen diameters < 12 cm with 2D-SWE spared more endoscopies with a minimal risk of missing HRV in cACLD patients with alcohol as the main etiology.

Bone Marrow-Derived Mesenchymal Stem Cells Isolated from Patients with Cirrhosis and Healthy Volunteers Show Comparable Characteristics

Background and Objectives@#Autologous or allogeneic bone marrow-derived mesenchymal stem cells (BMSCs) have been applied in clinical trials to treat liver disease. However, only a few studies are comparing the characteristics of autologous MSCs from patients and allogeneic MSCs from normal subjects. @*Methods@#and Results: We compared the characteristics of BMSCs (BCs and BPs, respectively) isolated from six healthy volunteers and six patients with cirrhosis. In passage 3 (P3), senescent population and expression of p53 and p21 were slightly higher in BPs, but the average population doubling time for P3–P5 in BPs was approximately 65.3±11.1 h, which is 18.4 h shorter than that in BCs (83.7±9.2 h). No difference was observed in the expression of CD73, CD90, or CD105 between BCs and BPs. Adipogenic differentiation slightly increased in BCs, but the expression levels of leptin, peroxisome proliferator-activated receptor γ, and CCAAT-enhancer-binding protein α did not vary between differentiated BCs and BPs. While ATP and reactive oxygen species levels were slightly lower in BPs, mitochondrial membrane potential, oxygen consumption rate, and expression of mitochondria-related genes such as cytochrome c oxidase 1 were not significantly different between BCs and BPs. @*Conclusions@#Taken together, there are marginal differences in the proliferation, differentiation, and mitochondrial activities of BCs and BPs, but both BMSCs from patients with cirrhosis and healthy volunteers show comparable characteristics.

Hepatocellular carcinoma in old age: are there any benefits of liver resection in old age?

Purpose@#Elderly individuals have comorbidities that can adversely affect surgical outcomes. Some studies reported that elderly patients with hepatocellular carcinoma (HCC) have higher liver- and non-liver–related deaths. Therefore, palliative treatments are preferred in these patients. We compared surgical treatment outcomes between young and old age groups. @*Methods@#In total, 233 liver resections were performed in patients with HCC from March 2012 to December 2018. We retrospectively reviewed medical records. The old age group was defined as patients aged more than 70 years. We compared perioperative characteristics and surgical outcomes and analyzed the prognostic factors for disease-free survival (DFS) and overall survival (OS) rates. @*Results@#The young and old age group included 184 and 49 patients, respectively. Preoperative characteristics were similar. Major liver resection rate was similar (young age group, 26.1% vs. old age group, 20.4%), but the operation time was a little bit shorter in old age group. Major postoperative complications were 23 (12.5%) and 9 (18.4%) in the young and old age group (P = 0.351). Median non-liver–related overall survival were 80 and 76 months (P = 0.889) and liver-related OS were 76 and 76 months (P = 0.514) in the young and old age groups, respectively. Age was not an independent risk factor for DFS and OS. @*Conclusion@#Elderly patients showed similar non-liver- and liver-related OS rates as young patients after liver resection. Postoperative complications were also similar. If elderly patients are well selected, they can receive curative treatment and show good surgical outcomes.

Hepatocellular carcinoma in old age: are there any benefits of liver resection in old age?

Purpose@#Elderly individuals have comorbidities that can adversely affect surgical outcomes. Some studies reported that elderly patients with hepatocellular carcinoma (HCC) have higher liver- and non-liver–related deaths. Therefore, palliative treatments are preferred in these patients. We compared surgical treatment outcomes between young and old age groups. @*Methods@#In total, 233 liver resections were performed in patients with HCC from March 2012 to December 2018. We retrospectively reviewed medical records. The old age group was defined as patients aged more than 70 years. We compared perioperative characteristics and surgical outcomes and analyzed the prognostic factors for disease-free survival (DFS) and overall survival (OS) rates. @*Results@#The young and old age group included 184 and 49 patients, respectively. Preoperative characteristics were similar. Major liver resection rate was similar (young age group, 26.1% vs. old age group, 20.4%), but the operation time was a little bit shorter in old age group. Major postoperative complications were 23 (12.5%) and 9 (18.4%) in the young and old age group (P = 0.351). Median non-liver–related overall survival were 80 and 76 months (P = 0.889) and liver-related OS were 76 and 76 months (P = 0.514) in the young and old age groups, respectively. Age was not an independent risk factor for DFS and OS. @*Conclusion@#Elderly patients showed similar non-liver- and liver-related OS rates as young patients after liver resection. Postoperative complications were also similar. If elderly patients are well selected, they can receive curative treatment and show good surgical outcomes.

Biomarker microfibril-associated glycoprotein 4 for non-invasive diagnosis and therapeutic evaluation of hepatic fibrosis in patients with hepatitis C

No abstract available.

Contrast-enhanced Ultrasonography: The Third Modality for Differentiation of Liver Mass

Contrast-enhanced ultrasonography (CEUS) using microbubble ultrasonography contrast agent can show the vascular structure and unique contrast enhancement patterns of focal liver lesions, including hepatocellular carcinoma (HCC). CEUS shows three phases, similar to a vascular pattern on computer tomography (CT), and typical arterial enhancement and portal or late phase washout in HCC. CEUS can show real-time images without nephrotoxicity or radiation hazard and can be used as guidance for loco-regional treatment and estimation of treatment response of HCC. In addition, some data recently revealed the usefulness of CEUS in the early estimation of response to anti-cancer pharmacological (i.e., sorafenib) therapy in advanced HCC. Although CEUS has limitations in clinical practice and more investigation is needed for its validation, it is recommended as a main diagnostic modality in a few major clinical practice guidelines for HCC. Thus, greater understanding of CEUS is necessary to extend its application in real practice for diagnosis and management of diseases.

Perspectives on Acute Hepatitis A Control in Korea

Until 1995, the incidence of symptomatic acute hepatitis A was minimal and there were no cases of national outbreak in Korea. However, there was a nationwide outbreak of hepatitis A that peaked in 2009. In 2019, a total of 10,083 cases of acute hepatitis A were reported for seven months of the year according to the Korea Center for Disease Control and Prevention. This may be attributed to the proportion of susceptible subjects in the Korean population, as about 10 years have passed since herd immunity was induced by the epidemic occurring during the late 2000s. Recent studies have shown that the rate of seropositivity for anti-hepatitis A virus antibodies (anti-HAV) is the lowest in adults in their 20s and has not changed much over the past 10 years, and seropositivity of anti-HAV in adults in their 30s has continued to decline from 69.6% in 2005 to 32.4% in 2014. Most young adults who have not yet experienced hepatitis A and are not vaccinated are vulnerable to hepatitis A infection. This year's epidemic of hepatitis A is a predictable outcome for vulnerable populations. Therefore, effective acute hepatitis A control and prevention strategies are needed, particularly for those in their 20s and 30s.

The New Cutoff Value of the Hepatic Venous Pressure Gradient on Predicting Long-Term Survival in Cirrhotic Patients

BACKGROUND: This study aimed to determine the prognostic role of the categorized hemodynamic stage (HS) based on the hepatic venous pressure gradient (HVPG) in patients with portal hypertension. METHODS: Of 1,025 cirrhotic patients who underwent HVPG measurement, data on 572 non-critically-ill patients were collected retrospectively between 2008 and 2013. The following two HS categorizations were used: HS-1 (6–9, 10–12, 13–16, 17–20, and > 20 mmHg; designated as groups 1–5, respectively) and HS-2 (6–12, 13–20, and > 20 mmHg). Clinical characteristics, mortality rates, and prognostic predictors were analyzed according to the categorized HS. RESULTS: During the mean follow-up period of 25 months, 86 (15.0%) patients died. The numbers of deaths in HS-1 groups were 7 (6.3%), 7 (6.9%), 30 (18.0%), 20 (15.6%), and 22 (34.4%), respectively (P 20 mmHg; HR, 5.45) and intermediate model for end-stage liver disease (MELD) score (HVPG, 13–20 mmHg; HR, 3.86 and HVPG > 20 mmHg; HR, 8.77; P < 0.05). CONCLUSION: Categorizing HVPG values according to HS-2 is a useful prognostic modality in patients with portal hypertension and can play an independent role in predicting the prognosis in patients with hypoalbuminemia and an intermediate MELD score.

Efficacy of Pegylated Interferon Monotherapy versus Sequential Therapy of Entecavir and Pegylated Interferon in Hepatitis B e Antigen-Positive Hepatitis B Patients: A Randomized, Multicenter, Phase IIIb Open-Label Study (POTENT Study) / 中华医学杂志(英文版)

<p><b>Background</b>Until now, various types of combined therapy with nucleotide analogs and pegylated interferon (Peg-INF) in patients with hepatitis B patients have been tried. However, studies regarding the benefits of de novo combination, late-add on, and sequential treatment are very limited. The objective of the current study was to identify the efficacy of sequential treatment of Peg-INF after short-term antiviral treatment.</p><p><b>Methods</b>Between June 2010 and June 2015, hepatitis B e antigen (HBeAg)-positive patients (n = 162) received Peg-IFN for 48 weeks (mono-treatment group, n = 81) and entecavir (ETV) for 12 weeks with a 48-week course of Peg-IFN starting at week 5 of ETV therapy (sequential treatment group, n = 81). The primary endpoint was HBeAg seroconversion at the end of follow-up period after the 24-week treatment. The primary endpoint was analyzed using Chi-square test, Fisher's exact test, and regression analysis.</p><p><b>Results</b>HBeAg seroconversion rate (18.2% vs. 18.2%, t = 0.03, P = 1.000) and seroclearance rate (19.7% vs. 19.7%, t = 0.03, P = 1.000) were same in both mono-treatment and sequential treatment groups. The rate of alanine aminotransferase (ALT) normalization (45.5% vs. 54.5%, t = 1.12, P = 0.296) and serum hepatitis B virus (HBV)-DNA <2000 U/L (28.8% vs. 28.8%, t = 0.10, P = 1.000) was not different in sequential and mono-treatment groups at 24 weeks of Peg-INF. Viral response rate (HBeAg seroconversion and serum HBV-DNA <2000 U/L) was not different in the two groups (12.1% vs. 16.7%, t = 1.83, P = 0.457). Baseline HBV-DNA level (7 logU/ml vs. 7.5 logU/ml, t = 1.70, P = 0.019) and hepatitis B surface antigen titer (3.6 logU/ml vs. 4.0 logU/ml, t = 2.19, P = 0.020) were lower and predictors of responder in mono-treatment and sequential treatment groups, respectively.</p><p><b>Conclusions</b>The current study shows no differences in HBeAg seroconversion rate, ALT normalization, and HBV-DNA levels between mono-therapy and sequential therapy regimens.</p><p><b>Trial Registration</b>ClinicalTrials.gov, NCT01220596; https://clinicaltrials.gov/ct2/show/NCT01220596?term=NCT01220596&rank=1.</p>

Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension

The renin-angiotensin system (RAS) is an important regulator of cirrhosis and portal hypertension. As hepatic fibrosis progresses, levels of the RAS components angiotensin (Ang) II, Ang-(1–7), angiotensin-converting enzyme (ACE), and Ang II type 1 receptor (AT1R) are increased. The primary effector Ang II regulates vasoconstriction, sodium homoeostasis, fibrosis, cell proliferation, and inflammation in various diseases, including liver cirrhosis, through the ACE/Ang II/AT1R axis in the classical RAS. The ACE2/Ang-(1–7)/Mas receptor and ACE2/Ang-(1–9)/AT2R axes make up the alternative RAS and promote vasodilation, antigrowth, proapoptotic, and anti-inflammatory effects; thus, countering the effects of the classical RAS axis to reduce hepatic fibrogenesis and portal hypertension. Patients with portal hypertension have been treated with RAS antagonists such as ACE inhibitors, Ang receptor blockers, and aldosterone antagonists, with very promising hemodynamic results. In this review, we examine the RAS, its roles in hepatic fibrosis and portal hypertension, and current therapeutic approaches based on the use of RAS antagonists in patients with portal hypertension.

The Impact of Sarcopenia and Its Rate of Change on Prognostic Value of Liver Cirrhosis

No abstract available.

Chronic Hepatitis B Infection Is Significantly Associated with Chronic Kidney Disease: a Population-based, Matched Case-control Study

BACKGROUND: Hepatitis B virus (HBV) infection leads to hepatic and extrahepatic manifestations including chronic kidney disease (CKD). However, the association between HBV and CKD is not clear. This study investigated the association between chronic HBV infection and CKD in a nationwide multicenter study. METHODS: A total of 265,086 subjects who underwent health-check examinations in 33 hospitals from January 2015 to December 2015 were enrolled. HBV surface antigen (HBsAg) positive cases (n = 10,048), and age- and gender-matched HBsAg negative controls (n = 40,192) were identified. CKD was defined as a glomerular filtration rate (GFR) < 60 mL/min/1.73 m² or proteinuria as at least grade 2+ of urine protein. RESULTS: HBsAg positive cases showed a significantly higher prevalence of GFR < 60 mL/min/1.73 m² (3.3%), and proteinuria (18.9%) than that of the controls (2.6%, P < 0.001, and 14.1%, P < 0.001, respectively). In the multivariate analysis, HBsAg positivity was an independent factor associated with GFR < 60 mL/min/1.73 m² along with age, blood levels of albumin, bilirubin, anemia, and hemoglobin A1c (HbA1c). Likewise, HBsAg positivity was an independent factor for proteinuria along with age, male, blood levels of bilirubin, protein, albumin, and HbA1c. A subgroup analysis showed that HBsAg positive men but not women had a significantly increased risk for GFR < 60 mL/min/1.73 m². CONCLUSION: Chronic HBV infection was significantly associated with a GFR < 60 mL/min/1.73 m² and proteinuria (≥ 2+). Therefore, clinical concern about CKD in chronic HBV infected patients, especially in male, is warranted.