Metabolic self-feeding in HBV-associated hepatocarcinoma centered on feedback between circulation lipids and the cellular MAPK/mTOR axis.

INTRODUCTION: Hepatitis B Virus (HBV) is widely recognized as a "metabolic virus" that disrupts hepatic metabolic homeostasis, rendering it one of the foremost risk factors for hepatocellular carcinoma (HCC). Except for antiviral therapy, the fundamental principles underlying HBV- and HBV+ HCC have remained unchanged, limiting HCC treatment options. OBJECTIVES: In this study, we aim to identify the distinctive metabolic profile of HBV-associated HCC, with the promise of identifying novel metabolic targets that confer survival advantages and ultimately impede cancer progression. METHODS: We employed a comprehensive methodology to evaluate metabolic alterations systematically. Initially, we analyzed transcriptomic and proteomic data obtained from a public database, subsequently validating these findings within our test cohort at both the proteomic and transcriptomic levels. Additionally, we conducted a comprehensive analysis of tissue metabolomics profiles, lipidomics, and the activity of the MAPK and AKT signaling pathway to corroborate the abovementioned changes. RESULTS: Our multi-omics approach revealed distinct metabolic dysfunctions associated with HBV-associated HCC. Specifically, we observed upregulated steroid hormone biosynthesis, primary bile acid metabolism, and sphingolipid metabolism in HBV-associated HCC patients' serum. Notably, metabolites involved in primary bile acid and sphingolipids can activate the MAPK/mTOR pathway. Tissue metabolomics and lipidomics analyses further validated the serum metabolic alterations, particularly alterations in lipid composition and accumulation of unsaturated fatty acids. CONCLUSION: Our findings emphasize the pivotal role of HBV in HCC metabolism, elucidating the activation of a unique MAPK/mTOR signaling axis by primary bile acids and sphingolipids. Moreover, the hyperactive MAPK/mTOR signaling axis transduction leads to significant reprogramming in lipid metabolism within HCC cells, further triggering the activation of the MAPK/mTOR pathway in turn, thereby establishing a self-feeding circle driven by primary bile acids and sphingolipids.

The value of dynamic changes in FT3 level for predicting 90-day prognosis of HBV-ACLF patients.

OBJECTIVE: To explore the effect of dynamic changes in free triiodothyronine (FT3) level for predicting the 90 day prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). METHODS: The clinical data of 122 hospitalised patients with HBV-ACLF between September 2018 and January 2020 were collected and divided into a survival group (77 cases) and a death group (45 cases) according to the 90 day prognosis. We statistically analysed the characteristics of FT3 changes in the two groups of patients. Binary logistic regression one-way analysis was used to assess the degree of influence of each factor. The Kaplan-Meier survival curve and receiver operating characteristic curve were used to evaluate the effect of a single change in FT3 level difference (single △FT3) and the FT3 level change range (△FT3 range) in predicting the 90-day prognosis of patients. RESULTS: There were only three types of changes in FT3 levels, which included 19 (15.6%) cases of continuous normal type, 35 (28.7%) cases of continuous decrease type and 68 (55.7%) cases of U-shaped change type. The difference in survival curves between the three types of patients was statistically significant (P < 0.001). CONCLUSION: The dynamic change type of FT3 is related to the disease severity and 90-day prognosis of patients with HBV-ACLF. The single FT3 value and FT3 range could be used as a predictive factor for the 90-day prognosis of patients with HBV-ACLF. These results have a degree of research value and are worth further exploration in the future.

Analysis of hepatitis B virus infection in 1424 patients with different pathological types of lymphoma (2018-2022): A real-world, retrospective study.

OBJECTIVE: Recent studies have found a high prevalence of hepatitis B virus (HBV) infection in patients with non-Hodgkin's lymphoma (NHL), especially B-cell non-Hodgkin's lymphoma (B-NHL). However, most studies did not classify it and analyze the correlation between HBV and its various subtypes. METHODS: The authors retrospectively analyzed 1424 patients with lymphoma. Differences in the prevalence of HBV infection in patients with different pathological types of lymphoma were analyzed. The clinical characteristics, progression-free survival (PFS), and overall survival (OS) of HBV-positive and negative B-NHL subtypes were compared according to HBV infection. RESULTS: The HBV infection rate in NHL patients was 7.65%, which was higher than that in HL patients (2.59%, p < 0.05). The HBV infection rate in the B-NHL was higher than that in the T-cell non-Hodgkin's lymphoma (T-NHL) (8.14% vs. 4.95%). The HBV infection rate in the aggressive B-NHL was similar to that of the indolent B-NHL (8.30% vs. 7.88%), and the highest HBV infection rates were found in diffuse large B-cell lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, but no significant differences in clinical characteristics, PFS, and OS were seen between HBV-positive and negative patients in the two subtypes. CONCLUSIONS: There was an association between HBV infection and the development of NHL and HBV infection may play a role in the pathogenesis of B-NHL, but not T-NHL.

Hepatitis B and C viral coinfection and associated factors among HIV-positive patients attending ART clinics of Afar regional state, northeast Ethiopia.

BACKGROUND: Hepatitis B (HBV) and C virus (HCV) coinfection are the major causes of liver-related morbidity and mortality among people living with Human Immunodeficiency Virus (HIV). The burden of hepatitis among HIV-positive individuals has not been studied in the Afar region. Therefore, this study aimed to determine the prevalence of HBV and HCV coinfection and associated factors among HIV-positive patients in Afar Regional State, northeast Ethiopia. METHODS: A cross-sectional study was conducted on 477 HIV-positive patients between February 2019 and May 2019. A structured and pretested questionnaire was used to collect socio-demographic data and associated factors. Five milliliters of blood was collected, and Hepatitis B surface antigen (HBsAg) and HCV antibodies were detected using rapid test kits. Positive samples were confirmed using enzyme-linked immunosorbent assay (ELISA). Binary and multivariable logistic regression analyses were performed to identify associated factors. Statistical significance was set at P <0.05. RESULTS: Among the 477 study participants, 320/477(67.1%) of them were females and 157(32.9%) males. The overall prevalence of HIV-HBV and HIV-HCV coinfection was 25(5.2%) and 7(1.5%), respectively. Multi-sexual practice was significantly associated with HIV-HBV coinfection (AOR = 5.3; 95% CI: 1.2-24.4, P = 0.032). CONCLUSION: The prevalence of both HIV-HBV and HIV-HCV coinfection was intermediate. Multi-sexual practice was significantly associated with HIV-HBV coinfection. Screening of all HIV-positive patients for HBV and HCV and health education regarding the transmission modes should be considered.

The association of the hepatitis B virus infection and diffuse large B-cell lymphoma.

OBJECTIVES: To investigate the basic characteristics of patients with diffuse large B-cell lymphoma (DLBCL) and whether hepatitis B surface antigen positive (HBsAg [+]) affects the survival of patients with DLBCL. METHODS: The study was carried out at Affiliated Hospital of Hebei University, Baoding, China, including 602 DLBCL cases from January 2011 to December 2021. We analyzed patients' general clinical data and applied multivariate and univariate Cox analyses to assess the factors influencing their survival times. RESULTS: The HBsAg(+) and HBsAg(-) groups comprised 154 (25.6%) and 448 (74.4%) of the 602 cases, respectively. HBsAg(+) cases tended to be later-stage (III-IV) with higher international prognostic index (IPI) points (3-5) and a greater tendency toward B symptoms, impaired liver function, and recurrence than HBsAg(-) cases (all p<0.05). After follow-up, 194 (32.2%) patients died. The median overall survival (OS) and 5-year OS rates in the HBsAg(+) and HBsAg(-) groups were 16.5 months (42%) and 35 months (63%), respectively. Cox analyses indicated that HBsAg(+) affected the prognosis of DLBCL cases (HR=1.46, 95%CI=1.07-1.99, p=0.017). CONCLUSION: The HBsAg(+) seems to be an independent hazard factor for the worse prognosis of DLBCL patients; hence, a focus on these patients in clinic is required.

Case report: Recombinant human type II tumour necrosis factor receptor-antibody fusion protein induced occult hepatitis B virus reactivation leading to liver failure.

Recombinant human type II tumour necrosis factor receptor-antibody fusion protein (rh TNFR:Fc) is an immunosuppressant approved for treating rheumatoid arthritis (RA). This case report describes a case of hepatitis B reactivation in a patient with drug-induced acute-on-chronic liver failure. A 58-year-old woman with a history of RA was treated with rh TNFR:Fc; and then subsequently received 25 mg rh TNFR:Fc, twice a week, as maintenance therapy. No anti-hepatitis B virus (HBV) preventive treatment was administered. Six months later, she was hospitalized with acute jaundice. HBV reactivation was observed, leading to acute-on-chronic liver failure. After active treatment, the patient's condition improved and she recovered well. Following careful diagnosis and treatment protocols are essential when treating RA with rh TNFR:Fc, especially in anti-hepatitis B core antigen antibody-positive patients, even when the HBV surface antigen and the HBV DNA are negative. In the case of HBV reactivation, liver function parameters, HBV surface antigen and HBV DNA should be closely monitored during treatment, and antiviral drugs should be used prophylactically when necessary, as fatal hepatitis B reactivation may occur in rare cases. A comprehensive evaluation and medication should be administered in a timely manner after evaluating the patient's physical condition and closely monitoring the patient.

The Adaptive Immune Response in Hepatitis B Virus-Associated Hepatocellular Carcinoma Is Characterized by Dysfunctional and Exhausted HBV-Specific T Cells.

This systematic review investigates the immunosuppressive environment in HBV-associated hepatocellular carcinoma (HCC), characterized by dysfunctional and exhausted HBV-specific T cells alongside an increased infiltration of HBV-specific CD4+ T cells, particularly regulatory T cells (Tregs). Heightened expression of checkpoint inhibitors, notably PD-1, is linked with disease progression and recurrence, indicating its potential as both a prognostic indicator and a target for immunotherapy. Nevertheless, using PD-1 inhibitors has shown limited effectiveness. In a future perspective, understanding the intricate interplay between innate and adaptive immune responses holds promise for pinpointing predictive biomarkers and crafting novel treatment approaches for HBV-associated HCC.

Non-Invasive Diagnostic Tests for Portal Hypertension in Patients with HBV- and HCV-Related Cirrhosis: A Comprehensive Review.

Clinically significant portal hypertension (CSPH) in patients with compensated advanced chronic liver disease indicates an increased risk of decompensation and death. While invasive methods like hepatic venous-portal gradient measurement is considered the gold standard, non-invasive tests (NITs) have emerged as valuable tools for diagnosing and monitoring CSPH. This review comprehensively explores non-invasive diagnostic modalities for portal hypertension, focusing on NITs in the setting of hepatitis B and hepatitis C virus-related cirrhosis. Biochemical-based NITs can be represented by single serum biomarkers (e.g., platelet count) or by composite scores that combine different serum biomarkers with each other or with demographic characteristics (e.g., FIB-4). On the other hand, liver stiffness measurement and spleen stiffness measurement can be assessed using a variety of elastography techniques, and they can be used alone, in combination with, or as a second step after biochemical-based NITs. The incorporation of liver and spleen stiffness measurements, alone or combined with platelet count, into established and validated criteria, such as Baveno VI or Baveno VII criteria, provides useful tools for the prediction of CSPH and for ruling out high-risk varices, potentially avoiding invasive tests like upper endoscopy. Moreover, they have also been shown to be able to predict liver-related events (e.g., the occurrence of hepatic decompensation). When transient elastography is not available or not feasible, biochemical-based NITs (e.g., RESIST criteria, that are based on the combination of platelet count and albumin levels) are valid alternatives for predicting high-risk varices both in patients with untreated viral aetiology and after sustained virological response. Ongoing research should explore novel biomarkers and novel elastography techniques, but current evidence supports the utility of routine blood tests, LSM, and SSM as effective surrogates in diagnosing and staging portal hypertension and predicting patient outcomes.

Hepatitis B-related hepatocellular carcinoma: classification and prognostic model based on programmed cell death genes.

Instruction: Hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma (HCC). Programmed cell death (PCD) is a critical process in suppressing tumor growth, and alterations in PCD-related genes may contribute to the progression of HBV-HCC. This study aims to develop a prognostic model that incorporates genomic and clinical information based on PCD-related genes, providing novel insights into the molecular heterogeneity of HBV-HCC through bioinformatics analysis and experimental validation. Methods: In this study, we analyzed 139 HBV-HCC samples from The Cancer Genome Atlas (TCGA) and validated them with 30 samples from the Gene Expression Omnibus (GEO) database. Various bioinformatics tools, including differential expression analysis, gene set variation analysis, and machine learning algorithms were used for comprehensive analysis of RNA sequencing data from HBV-HCC patients. Furthermore, among the PCD-related genes, we ultimately chose DLAT for further research on tissue chips and patient cohorts. Besides, immunohistochemistry, qRT-PCR and Western blot analysis were conducted. Results: The cluster analysis identified three distinct subgroups of HBV-HCC patients. Among them, Cluster 2 demonstrated significant activation in DNA replication-related pathways and tumor-related processes. Analysis of copy number variations (CNVs) of PCD-related genes also revealed distinct patterns in the three subgroups, which may be associated with differences in pathway activation and survival outcomes. DLAT in tumor tissues of HBV-HCC patients is upregulated. Discussion: Based on the PCD-related genes, we developed a prognostic model that incorporates genomic and clinical information and provided novel insights into the molecular heterogeneity of HBV-HCC. In our study, we emphasized the significance of PCD-related genes, particularly DLAT, which was examined in vitro to explore its potential clinical implications.

Management of Psoriasis Patients with Serious Infectious Diseases.

The management of patients affected by moderate-to-severe psoriasis may be challenging, in particular in patients with serious infectious diseases [tuberculosis (TB), hepatitis B and C, HIV, COVID-19]. Indeed, these infections should be ruled out before starting and during systemic treatment for psoriasis. Currently, four conventional systemic drugs (methotrexate, dimethyl fumarate, acitretin, cyclosporine), four classes of biologics (anti-tumour necrosis factor alpha, anti-interleukin (IL)12/23, anti-IL-17s, and anti-IL-23], and two oral small molecules (apremilast, deucravacitinib) have been licensed for the treatment of moderate-to-severe psoriasis. Each of these drugs is characterized by a unique safety profile which should be considered before starting therapy. Indeed, some comorbidities or risk factors may limit their use. In this context, the aim of this manuscript was to evaluate the management of patients affected by moderate-to-severe psoriasis with serious infectious diseases.

Impact of hepatic inflammation and fibrosis on the recurrence and long-term survival of hepatitis B virus-related hepatocellular carcinoma patients after hepatectomy.

BACKGROUND: Underlying liver disease is correlated with hepatocellular carcinoma (HCC) development in patients with hepatitis B virus (HBV) infection. However, the impact of hepatic inflammation and fibrosis on the patients' prognoses remains unclear. METHODS: The clinicopathological data of 638 HBV-infected patients with early-stage HCC between 2017 and 2019 were prospectively collected. Hepatic inflammation and fibrosis were evaluated by experienced pathologists using the Scheuer score system. Survival analysis was analyzed using the Kaplan-Meier analysis. RESULTS: Application of the Scheuer scoring system revealed that 50 (7.9%), 274 (42.9%), and 314 (49.2%) patients had minor, intermediate, and severe hepatic inflammation, respectively, and 125 (15.6%), 150 (23.5%), and 363 (56.9%) patients had minor fibrosis, advanced fibrosis, and cirrhosis, respectively. Patients with severe hepatitis tended to have a higher rate of HBeAg positivity, higher HBV-DNA load, elevated alanine aminotransferase (ALT) levels, and a lower proportion of capsule invasion (all Pp < 0.05). There were no significant differences in the recurrence-free and overall survival among the three groups (P = 0.52 and P = 0.66, respectively). Patients with advanced fibrosis or cirrhosis had a higher proportion of HBeAg positivity and thrombocytopenia, higher FIB-4, and larger tumor size compared to those with minor fibrosis (all P < 0.05). Patients with minor, advanced fibrosis, and cirrhosis had similar prognoses after hepatectomy (P = 0.48 and P = 0.70). The multivariate analysis results indicated that neither hepatic inflammation nor fibrosis was an independent predictor associated with prognosis. CONCLUSIONS: For HBV-related HCC patients receiving antiviral therapy, hepatic inflammation and fibrosis had little impact on the post-hepatectomy prognosis.

Hepatitis B and hepatitis C virus infections and associated factors among prisoners in Gondar City, Northwest Ethiopia.

BACKGROUND: Globally, hepatitis B virus (HBV) and hepatitis C virus (HCV) cause considerable morbidity and mortality from their acute and chronic infections. The transmission of the viruses within the prisons is high due to overcrowding, and other risk behaviors such as drug use, and unsafe sexual practices. This study aimed at determining the prevalence and associated factors of HBV and HCV infections among prisoners in Gondar city, Northwest Ethiopia. METHODS: A cross-sectional study was conducted in the Gondar City Prison Center from May 1, 2022, to July 30, 2022. A total of 299 prison inmates were selected by using a systematic random sampling technique. A semi-structured questionnaire was used to collect data on sociodemographic, clinical, behavioral and prison related factors. Five milliliters of blood sample were collected, and the serum was separated from the whole blood. The serum was tested for HBV surface antigen (HBsAg) and anti-HCV antibody by using an Enzyme-Linked Immunosorbent Assay (ELISA). Data was entered using EpiData version 4.6.0 and exported to SPSS version 20 for analysis. Logistic regression analysis was done to assess the association between the independent variables and HBV and HCV infections. P-values < 0.05 were considered statistically significant. RESULTS: The overall seroprevalence of HBV or HCV infections was 10.4%. The seroprevalence of HBV and HCV infections was 7.0% and 4.0%, respectively. It has been demonstrated that having several heterosexual partners, sharing sharp materials in prison, having longer imprisonment, and having a body tattoo are significantly associated with HBV infection. The presence of a body tattoo, a history of surgical procedures, and previous imprisonment are associated risk factors for HCV infection. CONCLUSION: The prevalence of HBV and HCV were high-intermediate and high, respectively. Therefore, preventative and control initiatives are needed in prisons to decrease the rate of infection and transmission.

Changing etiological spectrum of acute liver failure.

BACKGROUND AND OBJECTIVES: Acute liver failure (ALF) is an uncommon but potentially dramatic syndrome characterized by massive hepatic necrosis and has a very high mortality rate of 50% to 75% without liver transplantation. This study is aimed at analyzing the etiological spectrum of ALF patients and compare these with ALF mimics such as malaria, dengue fever and other tropical infectious diseases. METHODS: The study population included patients who presented with ALF and ALF mimics in a tertiary care center over two years. We retrospectively analyzed the patient case files and a comparison was made concerning the baseline demographic details, clinical profile, laboratory values and outcomes. RESULTS: Sixty-three patients were assessed, with 32 in ALF and 31 in ALF mimics group. The most common cause for ALF was hepatitis A virus (25%), followed by hepatitis B virus (18.7%), drug-induced liver injury (12.7%), autoimmune hepatitis (12.5%), hepatitis E virus (9.3%) and Wilson's disease (6.25%). In the ALF mimics group, malaria (58.06%) was the most common cause, followed by dengue fever (16.1%), leptospirosis (12.9%) and scrub typhus (12.9%). Patients in the ALF mimics group had significantly higher incidence of fever (p = 0.001), hepatosplenomegaly (p = 0.01), anemia (p = 0.02) and shorter jaundice to encephalopathy duration (p = 0.032) as compared to the ALF group, while higher transaminase levels (p = 0.03), bilirubin (p = 0.01), prothrombin time (p = 0.01), serum ammonia (p = 0.02) and mortality (p = 0.02) were observed in ALF patients. CONCLUSIONS: The most common cause for ALF was hepatitis A virus, followed by hepatitis B virus, while in ALF mimics it was malaria followed by dengue fever, in our study. Patients of ALF mimics can have similar presentation, but a high index of suspicion and awareness is required to identify the common infectious ALF mimics for early diagnosis.

Assessment of nomogram model for the prediction of esophageal variceal hemorrhage in hepatitis B-induced hepatic cirrhosis.

BACKGROUND: Esophageal variceal (EV) hemorrhage is a life-threatening consequence of portal hypertension in hepatitis B virus (HBV) -induced cirrhotic patients. Screening upper endoscopy and endoscopic variceal ligation to find EVs for treatment have complications, contraindications, and high costs. We sought to identify the nomogram models (NMs) as alternative predictions for the risk of EV hemorrhage. METHODS: In this case-control study, we retrospectively analyzed 241 HBV-induced liver cirrhotic patients treated for EVs at the Second People's Hospital of Fuyang City, China from January 2021 to April 2023. We applied univariate analysis and multivariate logistic regression to assess the accuracy of various NMs in EV hemorrhage. The area under the curve (AUC) and calibration curves of the receiver's operating characteristics were used to evaluate the predictive accuracy of the nomogram. Decision curve analysis (DCA) was used to determine the clinically relevant of nomograms. RESULTS: In the prediction group, multivariate logistic regression analysis identified platelet distribution and spleen length as independent risk factors for EVs. We applied NMs as the independent risk factors to predict EVs risk. The NMs fit well with the calibration curve and have good discrimination ability. The AUC and DCA demonstrated that NMs with a good net benefit. The above results were validated in the validation cohort. CONCLUSION: Our non-invasive NMs based on the platelet distribution width and spleen length may be used to predict EV hemorrhage in HBV-induced cirrhotic patients. NMs can help clinicians to increase diagnostic performance leading to improved treatment measures.

Current status of liver transplantation for human immunodeficiency virus-infected patients in mainland China.

According to the report from the Chinese Center for Disease Control and Prevention, the prevalence of human immunodeficiency virus (HIV) infection exceeded 1.2 million individuals by the year 2022, with an annual increase of about 80000 cases. The overall prevalence of hepatitis B surface antigen among individuals co-infected with HIV reached 13.7%, almost twice the rate of the general population in China. In addition to the well-documented susceptibility to opportunistic infections and new malignancies, HIV infected patients frequently experience liver-related organ damage, with the liver and kidneys being the most commonly affected. This often leads to the development of end-stage liver and kidney diseases. Therefore, organ transplantation has emerged as an important part of active treatment for HIV infected patients. However, the curative effect is not satisfactory. HIV infection has been considered a contraindication for organ transplantation. Until the emergence of highly active anti-retroviral therapy in 1996, the once intractable replication of retrovirus was effectively inhibited. With prolonged survival, the failure of important organs has become the main cause of death among HIV patients. Therefore, transplant centers worldwide have resumed exploration of organ transplantation for HIV-infected individuals and reached a positive conclusion. This study provides an overview of the current landscape of HIV-positive patients receiving liver transplantation (LT) in mainland China. To date, our transplant center has conducted LT for eight end-stage liver disease patients co-infected with HIV, and all but one, who died two months postoperatively due to sepsis and progressive multi-organ failure, have survived. Comparative analysis with hepatitis B virus-infected patients during the same period revealed no statistically significant differences in acute rejection reactions, cytomegalovirus infection, bacteremia, pulmonary infections, acute kidney injury, new-onset cancers, or vascular and biliary complications.

Liver Disease-Associated Glomerulopathies.

Hepatitis B virus (HBV) and hepatitis C virus (HCV) infect a significant number of individuals globally and their extra-hepatic manifestations, including glomerular disease, are well established. Additionally, liver disease-associated IgA nephropathy is the leading cause of secondary IgA nephropathy with disease course varying from asymptomatic urinary abnormalities to progressive kidney injury. Herein we provide an updated review on the epidemiology, pathogenesis, clinical manifestations, and treatment of HBV- and HCV-related glomerulonephritis as well as IgA nephropathy in patients with liver disease. The most common HBV-related glomerulonephritis is membranous nephropathy, although membranoproliferative glomerulonephritis and podocytopathies have been described. The best described HCV-related glomerulonephritis is cryoglobulinemic glomerulonephritis occurring in about 30% of patients with mixed cryoglobulinemic vasculitis. The mainstay of treatment for HBV-GN and HCV-GN is antiviral therapy, with significant improvement in outcomes since the emergence of the direct-acting antivirals. However, cases with severe pathology and/or a more aggressive disease trajectory can be offered a course of immunosuppression, commonly anti-CD20 therapy, particularly in the case of cryoglobulinemic glomerulonephritis.

Burden, Outcome, and Comorbidities of Extrahepatic Manifestations in Hepatitis B Virus Infections.

Hepatitis B virus (HBV) infections affect approximately 296 million people around the world, and the prevalence of any past or present HBV infection during the years 2015-2018 was as high as 4.3%. Acute HBV infection often presents with nonspecific symptoms and is usually self-limited, but 5% of patients can have persistent infections leading to chronic HBV infection and the risk of turning into chronic HBV infection is significantly higher in babies with vertical transmission (95%). Patients with chronic HBV infection are usually asymptomatic, but 15 to 40% of chronic HBV carriers develop cirrhosis and/or hepatocellular carcinoma. In addition to liver-related disorders, HBV is also associated with several extrahepatic complications, including glomerulonephritis, cryoglobulinemia, neurologic disorders, psychological manifestations, polyarthritis, and dermatologic disorders. Making the diagnosis of HBV can be challenging since patients with chronic infections can remain symptom-free for decades before developing cirrhosis or hepatocellular carcinoma, and patients with acute HBV infection may have only mild, nonspecific symptoms. Therefore, understanding how this virus causes extrahepatic complications can help clinicians consider this possibility in patients with diverse symptom presentations. The pathophysiology of these extrahepatic disorders likely involves immune-related tissue injury following immune complex formation and inflammatory cascades. In some cases, direct viral infection of extrahepatic tissue may cause a clinical syndrome. Currently, the American Association for the Study of Liver Diseases recommends treatment of chronic HBV infections with interferon therapy and/or nucleos(t)ide analogs, and this treatment has been reported to improve some extrahepatic disorders in some patients with chronic HBV infection. These extrahepatic complications have a significant role in disease outcomes and increase medical costs, morbidity, and mortality. Therefore, understanding the frequency and pathogenesis of these extrahepatic complications provides important information for both specialists and nonspecialists and may help clinicians identify patients at an earlier stage of their infection.

Patients undergoing liver resection for non-alcoholic fatty liver disease-related hepatocellular carcinoma and those for viral hepatitis-related hepatocellular carcinoma have similar survival outcomes.

Numerous studies have compared outcomes of liver resection (LR) of patients with non-alcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) to those of patients with non-NAFLD-related HCC. However, results have been inconsistent. We aim to clarify this issue. We enrolled 801 patients with hepatitis B virus (HBV)-related HCC, 433 patients with hepatitis C virus (HCV)-related HCC, and 128 patients with NAFLD-related HCC undergoing LR. Overall survival (OS) and disease-free survival (DFS) of patients with different etiologies of chronic liver disease was compared using the Kaplan-Meier estimator and log-rank test after propensity score matching (PSM). After PSM, 83 patients remained in each group. The groups did not differ significantly in age, sex, the proportion of patients with pathological American Joint Committee on Cancer stage 1, tumor size > 50 mm, receipt of major resection, alpha-fetoprotein (AFP) ≥ 20 ng/ml, presence of cirrhosis, model for end-stage liver disease (MELD) score, and American Society of Anesthesiologists (ASA) classification. The five-year OS of patients with HBV-, HCV-, and NAFLD-related HCC was 78%, 75%, and 78%, respectively (p = 0.789). The five-year DFS of the HBV, HCV, and NAFLD groups was 60%, 45%, and 54%, respectively (p = 0.159). Perioperative morbidity was noted in 17 (20.5%) in the HBV group, 22 (26.5%) in the HCV group, and 15 (18.1%) in the NAFLD group (p = 0.398). The five-year OS, DFS, and perioperative morbidity of patients undergoing LR for NAFLD-related HCC and those for viral hepatitis-related HCC was similar.

What Is Hepatitis D Infection?

This JAMA Patient Page describes hepatitis D infection and its risk factors, outcomes of acute and chronic infection, diagnosis, treatment, and prevention.