[Prevalence and epidemiological characteristics of major chronic diseases in people living with HIV in Taizhou, Zhejiang Province, 1998-2022].

Objective: To understand the prevalence of major chronic diseases of diabetes, cardiovascular disease and malignant tumor in people living with HIV in Taizhou. Methods: The data were collected from China Information System for Disease Control and Prevention and Taizhou Chronic Disease Information Management System. A total of 5 126 people living HIV under follow-up in Taizhou from 1998 to 2022 were included in the analysis. Software SAS 9.4 was used for χ2 test, trend analysis and logistic regression analysis. Results: In the 5 126 people living with HIV, the reported prevalence rates of diabetes,cardiovascular disease and malignant tumor were 10.28% (527/5 126),3.98% (204/5 126) and 6.01% (308/5 126), respectively. 37.00% (195/527) and 48.58% (256/527), 40.20% (82/204) and 48.53% (99/204), 37.66% (116/308) and 48.38% (149/308) were diagnosed as diabetes, cardiovascular disease and malignant tumor before and after confirmation of HIV infection. From 2013 to 2022, the proportion of HIV infected people diagnosed with diabetes, cardiovascular disease and malignant tumor after confirmation increased (trend χ2=79.98,P<0.001; trend χ2=17.44,P<0.001; trend χ2=32.06,P<0.001). Based on the analysis on the factors for complicated chronic diseases in people living with HIV, it was found that women under 60 years old (aOR=0.66, 95%CI: 0.50-0.86) and those with access to antiviral treatment for >5 years before 2016 (aOR=0.54,95%CI:0.37-0.78) were less likely to develop complicated chronic diseases, and those under 60 years old with initial CD4+T lymphocytes counts <200 cells/µl (aOR=1.32, 95%CI: 1.02-1.70), those aged 40-49 and 50-59 years (aOR=2.88, 95%CI:2.20-3.79; aOR=5.43, 95%CI: 4.10-7.21) as well as those without a record of treatment medication use after 2016 (aOR=1.95,95%CI:1.20-3.16) were more likely to develop complicated chronic diseases. The probability of developing complicated chronic diseases might increase with age in people living with HIV. Conclusions: From 1998 to 2022, there was a certain proportion of complicated chronic diseases among HIV infected individuals in Taizhou, and the proportion of diagnosed cases increased after HIV infection was confirmed. It is necessary to conduct early chronic disease screening, behavior intervention and standardized management in people living with HIV.

[Analysis on death causes of HIV/AIDS patients in Taizhou, Zhejiang Province, 1998-2022].

Objective: To understand the incidence and causes of HIV/AIDS death patients in Taizhou from 1998 to 2022. Methods: The data were collected from the AIDS Integrated Prevention and Control Information System of China Information System for Diseases Control and Prevention and Taizhou Chronic Disease Information Management System. By the end of 2022, a total of 5 126 HIV/AIDS patients living in Taizhou for a long time were included, SAS 9.4 was used for Kruskal-Wallis test, χ2 test and trend analysis. Results: From 1998 to 2022, a total of 796 HIV/AIDS patients died, with a fatality rate of 15.53% (796/5 126), in whom 52.26% (416/796) died within one year after confirmation. The proportion of HIV/AIDS patients who died within one year decreased (trend χ2=5.60, P<0.001). For the constituent of death causes, there were 140 (17.59%) deaths of AIDS, 237 (29.77%) deaths of malignant tumors, 99 (12.44%) deaths of cardiovascular disease, 58 (7.29%) deaths caused by injuries, 160 (20.10%) deaths due to other causes, and 102 (12.81%) deaths due to unknown causes. The constituent ratio of deaths of malignant tumor, cardiovascular disease and other causes increased over time (trend χ2=1.92, P=0.028; trend χ2=2.81, P=0.003; trend χ2=2.07, P=0.020). There were differences in the distribution of death causes in HIV/AIDS cases in terms of age, occupation, marital status, ethnic group, educational level and mode of transmission (all P<0.05). The average age of the death cases due to cardiovascular disease was higher than other death cases, the cases who died from AIDS had shorter survival time and the lower initial CD4+T cells after confirmation compared with all other death cases, and the time interval from confirmation to treatment in HIV/AIDS patients with unknown death causes was longer than those of all other death cases (all P<0.05). Conclusions: The constituent ratio of non-AIDS related deaths in HIV/AIDS patients in Taizhou was relatively high and showed an upward trend during 1998-2022. It is necessary to further strengthen the early screening, prevention and treatment of chronic non infectious diseases.

[Application of two kinds of electrophysiological monitoring techniques for the prediction of facial nerve outcomes after vestibular Schwannoma surgery].

Objective: To investigate the application of transcranial facial nerve motor evoked potential (FNMEP) and direct nerve electrical stimulation (DNES) for the prediction of facial nerve function after vestibular schwannoma surgery. Methods: The clinical data of 106 patients who underwent vestibular schwannoma surgery under electrophysiological monitoring of facial nerve between 2017 and 2021 were retrospectively examined, and there were 57 males and 49 females, with a mean age of (51±11) years. Neuroelectrophysiological monitoring was performed in all patients during the operation. After the tumor was removed, FNMEP and DNES were used for electrophysiological evaluation of facial nerve function. The amplitude ratios of FNMEP to baseline (M1) and the brainstem segment to the internal auditory canal segment of DNES (M2) were recorded after the tumor was removed, respectively. The correlation between these two ratios and facial nerve function at 1 day, 1 month and 3 months after the operation were compared. According to the House-Brackmann (HB) scale, Grade Ⅰ-Ⅱ refers to good facial nerve function, and grade Ⅲ-Ⅵ refers to moderate and severe facial nerve dysfunction. Non-parameter Spearman correlation coefficient was used to evaluate the correlation between M1 and M2 and facial nerve function at 1 day, 1 month and 3 months after operation, and the receiver operating characteristic (ROC) curves were plotted to verify the diagnostic efficacy of M1 and M2 for predicting the prognosis of postoperative facial nerve function. Results: Among 106 patients, 102 cases (96.3%) underwent total tumor resection, 4 patients (3.7%) underwent subtotal resection, 104 patients (98.1%) had anatomical preservation of facial nerves, and there were no deaths reported. All patients could evoke reliable FNMEP and 2 patients could not evoke DNES in the brainstem segment of the facial nerve. There were 81 (76.4%), 99 (93.4%) and 103 patients (97.2%) with satisfactory function of facial nerve at 1 day, 1 month and 3 months after surgery, respectively. M1 had large absolute values of Spearman correlation coefficient at 1 day (ρ=|-0.648|) and 1 month (ρ=|-0.552|) after surgery (both P<0.001), while M2 showed a greater absolute value of Spearman correlation coefficient at 3 months (ρ=|-0.395|) than that of M1 (ρ=|-0.378|) (P<0.001). Cut-off value of M1 was 0.58 (sensitivity=0.92, specificity=0.64), and that of M2 was 0.36 (sensitivity=0.64, specificity=1.00). Meanwhile, M1<0.58 or M2<0.36 suggested moderate and severe impairment of facial nerve function. Conclusions: Both FNMEP and DNES during vestibular schwannoma surgery can effectively evaluate the postoperative facial nerve function. FNMEP is better than DNES in predicting the early postoperative facial nerve function, but DNES is better for predicting the long-term postoperative facial nerve function.

[Neurocognitive impairment and characteristics of neurocognitive performance among people with HIV on antiretroviral treatment].

Objective: Using two measuring tools to examine the prevalence and correlates of neurocognitive impairment (NCI) as well as characteristics of neurocognitive performance among people with HIV (PWH) on antiretroviral treatment (ART). Methods: A total of 2 250 treated PWH from the Comparative HIV and Aging Research in Taizhou (CHART) were recruited in Taizhou, Zhejiang province. The Chinese version of the Mini-mental State Examination (MMSE) and the International HIV Dementia Scale (IHDS) were used to evaluate their neurocognitive performance. Cluster analysis was conducted on the seven cognitive domains in the scale. Results: Among 2 250 treated PWH, 48.0% (1 080/2 250) were aged 45 to 89, 79.2% (1 782/2 250) were male, and 37.8% (852/2 250) had primary school education or below. The prevalence of neurocognitive impairment judged by MMSE and IHDS among HIV-infected people was 14.3% (321/2 250) and 31.8% (716/2 250), respectively. Aged 60 to 89 (aOR=2.63, 95%CI:1.52-4.56), depressive symptoms (aOR=5.58, 95%CI:4.20-7.40) and treatment with EFV (aOR=2.86, 95%CI:1.89-4.34) were main risk factors of NCI diagnosed by MMSE. Male (aOR=0.71, 95%CI:0.51-1.00), overweight (aOR=0.63, 95%CI:0.44-0.89), and high education level (aOR=0.11, 95%CI:0.05-0.25) were protective factors of NCI diagnosed by MMSE. Aged 60 to 89 (aOR=3.10, 95%CI:2.09-4.59), depressive symptoms (aOR=1.78, 95%CI:1.44-2.20) and treatment with EFV (aOR=1.79, 95%CI:1.41-2.29) were risk factors of NCI diagnosed by IHDS. Male (aOR=0.75, 95%CI:0.58-0.97), underweight (aOR=0.67, 95%CI:0.47-0.96), baseline CD4+ T lymphocyte (CD4) counts ≥350 cells/µl (aOR=0.69, 95%CI:0.53-0.91) and high education level (aOR=0.23, 95%CI:0.14-0.39) were protective factors of NCI diagnosed by IHDS. The neurocognitive performance of HIV-infected people can be divided into four main types. Among four types, age, gender, education level, alcohol drinking, depressive symptoms, waist-to-hip ratio, hypertension, diabetes, baseline CD4 counts and treatment with EFV were different statistically (all P<0.05). Conclusions: There are four main types of neurocognitive performance in treated PWH. The prevalence of NCI is high among this population, underscoring the need for tailored prevention and intervention.

[Correlation between HIV infection, club drug use and anal canal human papillomavirus infection in men who have sex with men in Taizhou].

Objective: To explore the correlation between club drug use and anal canal human papillomavirus (HPV) infection in HIV-negative and HIV-positive men who have sex with men (MSM) in Taizhou. Methods: A cross-sectional survey was conducted in Taizhou. HIV-negative MSM were recruited by convenient sampling in voluntary counseling and testing clinics of Taizhou prefectural CDC from August 2016 to October 2017, and HIV-positive MSM were recruited through the routine follow-up and management by Taizhou prefectural CDC from August 2016 to June 2019. A face-to-face questionnaire interview was conducted to collect the information about the socio-demographic characteristics, sexual orientation, sexual behavior, club drug use and other information of the participants. Anal canal swabs were collected for HPV genotyping. The correlation between club drug use and the prevalence of HPV infection were evaluated with χ2 test and logistic regression analysis. Results: A total of 69 HIV-negative and 345 HIV-infected MSM were included. The prevalence of any type of anal canal HPV infection in HIV-negative MSM (27.5%, 19/69) was lower than that in HIV-positive MSM (66.4%, 229/345) (χ2=36.114,P<0.001). The prevalence of self-reported club drug use in HIV-negative MSM was higher (17.4%, 12/69) than that in HIV-positive MSM (7.0%, 24/345) (χ2=7.886, P=0.005). For HIV-negative MSM, the prevalence of club drug use was higher in MSM who had homosexual group sex (P=0.036); the prevalence of HPV infection was 50.0% (6/12) in club drug users and 22.8% (13/57) in non-club drug users (χ2=3.674, P=0.055). For HIV-positive MSM, the prevalence of HPV infection was 70.8% (17/24) in club drug users and 66.0% (212/321) in non-club drug users (χ2=0.230, P=0.632). Multivariable logistic regression model showed that HPV infection in MSM was positively correlated with HIV infection (OR=5.42, 95%CI: 2.92-10.06), and the association between HPV infection and club drug use (OR=1.66, 95%CI: 0.75-3.71) was not significant. Conclusions: HIV infection was positively correlated with anal canal HPV infection in MSM in Taizhou. Club drug use was positively correlated with high-risk sexual behaviors, while its association with HPV infection needs further study.

[Prevalence of alcohol use and related factors in HIV positive and HIV negative males].

Objective: To understand the prevalence of alcohol use and related factors in HIV positive and HIV negative males. Methods: Baseline data were from the prospective cohort study of comparative HIV and aging research in Taizhou of Zhejiang province from January to December, 2017. The information about alcohol use in the last month was collected through a face-to-face questionnaire interview. Participants were categorized into non-current drinkers, light/moderate drinkers and heavy drinkers according to the US National Institute on Alcoholism and Alcohol Abuse (NIAAA) standard. Results: A total of 1 367 HIV positive males and 2 418 HIV negative males were included. Current alcohol use rate (35.2%, 481/1 367) and heavy alcohol use rate (5.0%, 24/481) were significantly lower in HIV positive males than in HIV negative males (48.0%, 1 161/2 418; 23.5%, 273/1 161), but the proportion of drinking wine and yellow rice wine were significantly higher (21.8%, 105/481; 9.1%, 44/481) in HIV positive males than in HIV negative males (13.5%, 157/1 161; 5.8%, 67/1 161). The multivariate multinomial logistic regression analysis results showed that larger waist circumference, current smoking and regular physical exercise were associated with heavy alcohol use behavior in HIV positive males, and age ≥30 years, current smoking, regular physical exercise, higher score of depressive symptoms, heterosexual transmission route and baseline CD(4)(+)T cells counts of 200-499 cells/µl were significantly associated with mild/moderate alcohol use behavior in HIV positive males. Conclusions: The alcohol use rate was significantly lower in HIV positive males than in HIV negative males in Taizhou. It is important to strengthen intervention on alcohol drinking behavior and chronic disease risk factors, such as larger waist circumference, smoking and so on.

[Effect of JAZF1 over-expression on high-fat diet-induced non-alcoholic fatty liver disease].

Objective: To investigate the effects of juxtaposed with another zinc finger gene 1 (JAZF1) over-expression on the levels of pro-inflammatory cytokines in high-fat diet (HFD)-induced mouse fatty liver and its associated mechanisms. Methods: Twenty male C57BL/6J (3 weeks old) and 10 male JAZF1 transgenic (JAZF1-Tg) mice were randomly divided into three groups: wide-type with normal diet (NF group,n= 10), wide-type with high-fat diet (HF group,n= 10), and JAZF1-Tg with high-fat diet (HJ group,n= 10). All mice were fed with the corresponding diet for 12 weeks, and their food consumption and body weight were measured periodically. After 12 weeks, fasting blood glucose (FBG), insulin (INS), total cholesterol (TC), triglyceride (TG), free fatty acids (FFA), and alanine aminotransferase (ALT) in the blood and liver tissue from each group were measured. TG concentration in liver tissue was determined using an enzymatic assay, and the mRNA expression of tumor necrosis factor-α(TNF-α), monocyte chemoattractant protein-1 (MCP-1), and interleukin-8 (IL-8) in the liver was measured by RT-PCR. In addition, the expression of p-JNK/JNK, p-p-38 MAPK/p-38 MAPK, p-ERK/ERK, IκBα, andß-actin (reference) in the liver was determined using Western blot.. Results: (1) Body weight, FBG, INS, TC, and ALT were significantly reduced in the HJ group compared with those of the HF group (31.19±0.81 vs 36.07±1.43, 6.94±0.32 vs 8.14±0.36, 31.09±2.12 vs 45.21±3.34, 3.05±0.07 vs 3.81±0.08, 54.75±4.92 vs 68.09±5.15, respectively;P< 0.05). There were no significant differences in TG and FFA between the HJ and HF groups (0.72±0.05 vs 0.81±0.03, 0.81±0.4 vs 0.87±0.03; bothP> 0.05). (2) There was no significant difference in liver TG concentration between the HJ and HF groups (35.49±3.17 vs 38.26±3.59,P> 0.05). (3) Compared with the HF group, the HJ group had significantly reduced mRNA expression of TNF-α, MCP-1, and IL-8 (2.54TNF-αvs 8.64±0.73, 1.19±0.73,vs 3.93±0.18, 5.09±0.48 vs 9.09±0.89; allP< 0.01), significantly reduced protein expression of p-JNK and p-p-38 MAPK (0.92±0.06 vs 1.51±0.01, 1.07±0.04 vs 1.45±0.04; bothP< 0.01), and significantly increased protein expression of IκBα(0.99±0.06 vs 0.79±0.05,P< 0.01) in liver tissue. However, no significant difference was observed in the p-ERK level between the HJ and HF groups (P> 0.05). Conclusion: Upregulation of JAZF1 expression can significantly inhibit the expression of TNF-α, MCP-1, and IL-8 in the liver of mice on HFD. This attenuation may be closely associated with the reduced activation of the JNK, p-38 MAPK, and NF-κB pathways.

Prescribing Pattern of Antidepressants in Children and Adolescents: Findings from the Research on Asia Psychotropic Prescription Pattern.

OBJECTIVE: Pharmacotherapy of depression in children and adolescents is complex. In the absence of research into the efficacy and safety of antidepressants in this group of patients, their off-label prescription is common. This paper aimed to illustrate the prescription pattern of antidepressants in children and adolescents from major psychiatric centres in Asia. METHODS: The Research on Asia Psychotropic Prescription Pattern on Antidepressants worked collaboratively in 2013 to study the prescription pattern of antidepressants in Asia using a unified research protocol and questionnaire. Forty psychiatric centres from 10 Asian countries / regions participated and 2321 antidepressant prescriptions were analysed. RESULTS: A total of 4.7% antidepressant prescriptions were for children and adolescents. Fluoxetine, sertraline, and escitalopram were the most common antidepressants prescribed for children and adolescents. Almost one-third (30.3%) of prescriptions were for diagnoses other than depressive and anxiety disorders. There was less antidepressant polypharmacy and concomitant use of benzodiazepine, but more concomitant use of antipsychotics in children and adolescents compared with adults. CONCLUSION: Off-label use of antidepressants in children and adolescents was reported by 40 Asian psychiatric institutions that participated in the study. In-service education and regulatory mechanisms should be reinforced to ensure efficacy and safety of antidepressants in children and adolescents.

[Effects of simvastatin nano-liposomes on osteogenic differentiation of bone marrow stromal cells].

OBJECTIVE: To investigate the effects of liposomal formulation on simvastatin nano-liposomes (SMV-liposome) promoting the osteogenic differentiation of mice bone marrow stromal cells (BMSC) analyzed by the expressions of bone morphogenetic protein 2 (BMP-2) and alkaline phosphatase (ALP). METHODS: Primary BMDC were cultured in vitro using adherence and culture of whole bone marrow method. SMV dosage was set as control group and had two different dosages in this group on the basis of the concentration of SMV. 1 µmol/L and 2 µmol/L SMV concentration were represented by SMV low dosage group (S1) and SMV high dosage group (S2), respectively. Similarly, SMV-liposome dosage was set as experimental group including two different dosages, 1 µmol/L SMV capsuled concentration as SMV-liposome low dosage group (SL1) and 2 µmol/L SMV capsuled concentration as SMV-liposome high dosage group (SL2). Besides, groups with no drug intervention in the experiments were set as blank. BMSC were treated with different concentrations of SMV and SMV-liposome for 48 h, the activity of ALP was measured using p-nitropheny-phosate method, and ALP expression in the BMSC cells was stained by BCIP/NBT alkaline phosphatase color development kit (BCIP/NBT Kit). Furthermore, BMP-2 expression in the BMSC was determined by Western Blot. RESULTS: MTT assay showed, after incubated with different concentrations of SMV and SMV-liposome, the cell viabilities of BMSC were all above 85% and had no significant difference in the groups. Compared with the same dosage of SMV in these groups, control group and experimental group had significantly elevated the specific activity of ALP, the staining of BCIP/NBTKit as well as the protein expression of BMP-2. Besides, the data showed dose-dependent elevation in the control group and experimental group, namely the high dose group had better results than the low dose group. CONCLUSION: Nano-liposomal formulation significantly enhanced SMV effects on the osteogenetic differentiation of BMSC.

Induction of anion exchanger-1 translation and its opposite roles in the carcinogenesis of gastric cancer cells and differentiation of K562 cells.

Anion exchanger-1 (AE1), an erythroid-specific membrane protein, mediates the Cl(-)/HCO(-)(3) exchange across the plasma membrane and regulates intracellular pH. We have found that AE1 was unexpectedly expressed in gastric cancer cells and participated in the tumorigenesis of the cancer. Here, we focus on the induction of AE1 expression and its role in gastric carcinogenesis as well as in the differentiation of K562 cells. The results show that expression of AE1 is not related to genetic mutation or the mRNA level, but rather, that it is modulated by miR-24. miR-24 decreases the expression of AE1 through binding to the 3'UTR of AE1 mRNA. Transfection of an miR-24 into gastric cancer cells reduced the elevation of the AE1 protein, which resulted in return of AE1-sequestrated p16 to the nucleus, thereby inhibiting proliferation of the cells. Furthermore, the miR-24 inhibitor cooperated with hemin to induce the expression of AE1 in K562 cells and differentiation of the cells, which is consistent with results obtained from the cells cultured at pH 7.6 or from forced stable expression of AE1. These findings establish a novel regulation of miR-24-related AE1 expression in gastric carcinogenesis and erythropoiesis.

Expression of anion exchanger 2 in human gastric cancer.

UNLABELLED: Anion exchanger 2 (AE2), which mediates exchange of Cl(-)/HCO3(-) across the plasma membrane, is widely expressed in body tissues. It is most abundantly expressed in stomach and is responsible for the uptake of Cl(-) ions that are destined to become HCl molecules. AIM: To determine whether AE2 expression was altered in gastric tumors. METHODS: We have studied AE2 expression in normal human gastric tissues (n =16) and in gastric tumors (n = 33) using immunohistochemistry and immunofluorescent labeling. RESULTS: In normal gastric tissue positive staining was observed in gastric fundus gland, suggesting parietal cell-related expression of AE2, and AE2 expression was localized in the nuclear membrane and even in cell nuclei. For assay of cancerous gastric tissues, specimens of human gastric cancer arising from the region of the fundus (2 cases), the body (14 cases) and the antrum (17 cases) were randomly selected. Immunohistochemical staining has showed that AE2 was down-regulated in all 14 cancerous gastric body specimens, whereas staining for AE2 in cancerous antrum was less intense and had a diffuse profile. CONCLUSIONS: The data suggest that AE2 might be associated with gastric carcinogenesis and the achlorhydria experienced by gastric cancer patients.

Soy isoflavone supplementation in postmenopausal women. Effects on plasma lipids, antioxidant enzyme activities and bone density.

OBJECTIVE: To investigate isoflavone supplementation on plasma lipids, erythrocyte antioxidant enzyme activities and bone mineral density in postmenopausal women. STUDY DESIGN: Thirty-seven postmenopausal women were given 150 mg/d of isoflavone supplements twice daily for six months. Blood was sampled before and after supplementation, at three and six months. RESULTS: There were no significant differences in plasma total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride concentrations or erythrocyte antioxidant enzyme activities after three and six months of supplementation when compared with the baseline. No significant changes were noted in calcaneus bone mineral density after supplementing isoflavones for six months. CONCLUSION: The antioxidant effect of isoflavones in normal postmenopausal women is not obvious, and supplementation with isoflavone alone may not have a hypocholesterolemic effect. Since the duration of this study was too short with respect to bone density, longer studies are needed to clarify the bone-sparing effect of isoflavone supplementation.

A history of antipsychotic drug development.

The history of antipsychotic drug development has had a long and torturous course, often based on chance findings that bear little relationship to the intellectual background driving observations. In 1891, Paul Ehrlich observed the antimalarial effects of methylene blue, a phenothiazine derivative. Later, the phenothiazines were developed for their antihistaminergic properties. In 1951, Laborit and Huguenard administered the aliphatic phenothiazine, chlorpromazine, to patients for its potential anesthetic effects during surgery. Shortly thereafter, Hamon et al. and Delay et al. extended the use of this treatment in psychiatric patients and serendipitously uncovered its antipsychotic activity. Between 1954 and 1975, about 15 antipsychotic drugs were introduced in the United States and about 40 throughout the world. Thereafter, there was a hiatus in the development of antipsychotics until the introduction of clozapine treatment in the United States in 1990 opened the era of "atypical" antipsychotic drugs, which show a reduced potential to induce extrapyramidal symptoms (EPS), an increased efficacy for the negative symptoms of schizophrenia, no elevation of prolactin after chronic use (except risperidone), and, at least for clozapine, effectiveness in some patients previously regarded as treatment-refractory. This review describes the available atypical antipsychotic drugs and their characteristics, and concludes by highlighting those in the pharmaceutical "pipeline."

Activation of the tumor necrosis factor-alpha system in the liver in chronic hepatitis B virus infection.

To determine the status of the tumor necrosis factor-alpha (TNFalpha) system in the liver in chronic hepatitis B virus (HBV) infection, hepatic expression of TNFalpha, its two receptors (TNFR-A, TNFR-B), HLA class I antigens (HLA-I), and HBV core antigen (HBcAg) were studied by immunohistochemistry in 24 patients with chronic HBV infection. TNFalpha was detected exclusively in the infiltrating mononuclear cells (MNC) in 19 of 24 patients. The expression of TNFalpha in infiltrating MNC correlated with serum markers of HBV replication and liver histology. TNFR were detected in hepatocytes, sinusoidal cells, and infiltrating MNC. The expression of TNFR correlated with liver histology (p < 0.01) but had no bearing on viral replication. There was a parallel expression of TNFalpha and TNFR (p < 0.01). Hepatocytic expression of HLA-I was increased, and this was related to liver histology but not with TNF alpha nor TNFR. These data indicate that the TNFalpha system is activated in the liver in chronic HBV infection.