[Evaluation of the efficacy of medial open wedge high tibial osteotomy combined with anterior cruciate ligament reconstruction in the treatment of varus knee osteoarthritis with anterior cruciate ligament injury].

Objective: To evaluate the efficacy of medial open wedge high tibial osteotomy (MOWHTO) combined with anterior cruciate ligament (ACL) reconstruction in the treatment of varus knee osteoarthritis (OA) with ACL injury. Methods: A follow-up study. The study retrospectively analyzed the patients underwent MOWHTO combined with ACL reconstruction for treatment of varus knee OA with ACL injury in Tianjin Hospital between April 2018 and September 2022. The preoperative and postoperative posterior slope angle (PSA), hip-knee-ankle angle (HKA), visual analog scale (VAS) pain scores, Lysholm score, International Knee Documentation Committee (IKDC) score, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, and Tegner score were compared. The follow-up indicators were recorded at 6 weeks, 3 months and 1 year after operation, and the complications were recorded. Results: The study included 32 patients (23 males, 9 females) with a mean age of (50.7±8.4) years. The mean follow-up time was (21.2±4.8) months. PSA increased from 9.2°±1.8° preoperatively to 11.1°±2.4° postoperatively, and HKA increased from 168.7°±2.2° to 181.5°±2.2° (both P<0.01). The indicators such as VAS score (6.8±1.1 vs 1.8±0.4), Lysholm score (52.6±7.1 vs 82.0±6.4), IKDC score (64.7±6.2 vs 80.3±10.0), WOMAC score (51.8±6.3 vs 81.8±6.5), and Tegner score (1.9±0.6 vs 5.0±1.0) were all improved after the operation (all P<0.01). Complications occurred in 5 patients (15.6%), including hematomas, sensory abnormalities, intermuscular vein thrombosis and correction angle loss. Conclusion: MOWHTO combined with ACL reconstruction is a safe and effective approach for the treatment of varus knee OA with ACL injury.

The JNK signaling pathway against titanium-particle-induced osteoclastogenesis and bone resorption in vivo.

OBJECTIVE: The c-Jun N-terminal kinases (JNK) signaling pathway may be involved in the regulation of osteoclast development. The purpose of this investigation was to investigate whether SB600125, a JNK inhibitor, could attenuate titanium-particle-induced inflammatory osteolysis in vivo. MATERIALS AND METHODS: A total of 45 mice were randomly divided into a Sham group, a Titanium group, and a Titanium + JNK inhibitor group, 15 mice per group. After establishing an air pouch bone graft model, we injected phosphate-buffered saline (PBS), titanium particles, or titanium particles + JNK inhibitor into the air pouch of the three groups. The pouch membranes containing bone implants were taken for morphological and molecular analysis 14 days after the mice were sacrificed. RESULTS: General morphological structure observation results, Hematoxylin and Eosin (H&E)-Stained Sections, anti-tartaric acid phosphatase (TRAP) staining, and the transmission electron microscope showed that SB600125, by inhibiting the expression of JNK, attenuated titanium particle-induced inflammatory osteolysis (p<0.05). Immunohistochemical appearance results and reverse transcription-polymerase chain reaction (RT-PCR) results showed SB600125 reduced expression of IL-6, and TNF-α in osteolytic sites stimulated with wear debris (p<0.05). The Western blot results showed the expression of the p-JNK protein in the titanium particle + SB600125 group was significantly reduced compared to the titanium particle stimulation group (p<0.05). CONCLUSIONS: Interfering with the JNK signaling pathway may be beneficial in reducing osteolysis, providing a therapeutic target for preventing and treating aseptic loosening caused by debris-induced inflammatory osteolysis.

[Expression of SOX10 and GATA3 in breast cancer and their significance].

Objective: To investigate the expression characteristics of SOX10 and GATA3 in breast cancer and the value of their combination. Methods: A total of 360 breast cancer specimens with SOX10 immunohistochemical staining were collected from the Department of Pathology in Shenzhen People's Hospital from 2018 to 2021, including 268 cases with simultaneous SOX10 and GATA3 staining. The expression of SOX10 and GATA3 in primary and metastatic breast cancer was detected, and the correlations between SOX10 and GATA3 and the molecular types and clinicopathological features of breast cancer were compared, and the distribution differences among each group were statistically analyzed. Results: The overall expression of SOX10 and GATA3 in breast cancer were 25.8%(93/360) and 81.7%(219/268), and that in triple negative breast cancer (TNBC) were 83.3%(80/96) and 42.7%(32/75), respectively. SOX10 was strongly associated with TNBC (P<0.001), whereas GATA3 was highly expressed in luminal A, luminal B and HER2 over expression breast cancers (P<0.001). The expression of SOX10 and GATA3 was negatively correlated in TNBC, and the combined expression rates of SOX10 and GATA3 in breast cancer and TNBC could reach 97.8% (262/268) and 94.7%(71/75), respectively. In addition, the expression of SOX10 was closely correlated with high histological grade, high Ki-67 proliferation index and lymph node metastasis, and negatively correlated with AR. The expression of GATA3 was correlated with low histological grade and lymph node metastasis, and positively correlated with AR, and the difference was statistically significant. Conclusions: SOX10 is a sensitive marker of TNBC, while GATA3 is highly expressed in non-triple negative breast cancer. The two complementary, combined application of SOX10-GATA3 can improve the detection rate of breast cancer, especially TNBC. SOX10 is associated with malignant characteristics of the tumor, suggesting that SOX10 can be used as a prognostic marker and potential therapeutic target for breast cancer.

[Analysis of complications after medial opening wedge high tibial osteotomy].

Objective: To analyze the incidence of recent complications in patients with osteoarthritis of the knee (OA) after medial opening wedge high tibial osteotomy(MOWHTO) and its influence on clinical effect. Methods: The clinical data of 131 patients with knee OA who received MOWHTO at Department of Sports Medicine and Arthroscopy,Tianjin Hospital from April 2017 to September 2018 were analyzed retrospectively. There were 75 males and 56 females, aged (62.8±5.1) years (range:48 to 70 years). Complications and clinical outcomes of patients were recorded and the proximal medial angle of tibia (MPTA), the International Knee Documentation Committee Subjective Knee Form (IKDC), the Western Ontario and McMaster Universities(WOMAC) Osteoarthritis Index and Knee Injury and Osteoarthritis Outcome score(KOOS) were collected before and 1 year after operation and compared between complication group and non-complication group. Data were analyzed by paired-samples t test, independent samples t test and χ(2) test. Results: The follow-up time was (18.5±3.4) months (range:13 to 22 months). Complications occurred in 22 patients(16.8%), including 8 cases(6.1%) of hematoma, 5 cases(3.8%) of neurosensory abnormality, 4 cases(3.1%) of intramuscular venous thrombosis, 2 cases(1.5%) of deep venous thrombosis, 3 cases(2.3%) of loss of correction angle, 3 cases(2.3%) of superficial infection, 2 cases(1.5%) of deep infection, 2 cases(1.5%) of delayed union of fracture, 1 case(0.8%) of postoperative stiffness, 1 case (0.8%) of hinge point cortex fracture. There were no significant difference in MPTA ((86.5±2.0)° vs. (86.7±2.1)°, t=-0.41, P=0.68) , IKDC ((86.4±4.8) vs.(85.5±6.9), t=0.74, P=0.50) , WOMAC ((87.7±6.5) vs. (86.1±5.8), t=1.16, P=0.25). There were no significant difference in knee scores except for the KOOS pain score ((79.4±4.4) vs. (87.2±5.9), t=-5.90, P<0.01) and sports and recreation score ((83.2±3.0) vs. (88.0±4.7), t=-6.14, P<0.01) . Conclusion: Short-term complications of MOWHTO can be managed appropriately through early diagnosis and individualized treatment and have no significant negative effect on knee function recovery of patients.

[Analysis of influencing factors on hepatic encephalopathy in patients with non-cirrhotic portal hypertension].

Objective: To investigate the incidence of hepatic encephalopathy (HE) in patients with non-cirrhotic portal hypertension (NCPH) and to explore its risk factors. Methods: The incidence rate of HE in 150 cases with NCPH was evaluated in two hospitals, and 188 cases of compensated cirrhosis patients were taken as control. Logistic regression was used to screen for independent risk factors for HE in patients with NCPH. Results: The incidence of overt hepatic encephalopathy (OHE) in patients with NCPH was not statistically significantly different from that in patients with cirrhosis (4.7% vs. 6.9%, P = 0.682). The incidence of mild hepatic encephalopathy (MHE) was significantly lower than that of cirrhosis patients (32.7% vs. 46.3%, P < 0.05). The presence of upper gastrointestinal bleeding, infection and portosystemic venous shunt were the main independent factors for HE in NCPH patients (OR > 1, P < 0.05). Conclusion: HE is one of the important complications of NCP, and may be influenced by factors such as upper gastrointestinal bleeding, infection and portosystemic venous shunt.

[Effect of several human metabolic compounds for trapping Culex pipiens quinquefasciatus].

OBJECTIVE: To evaluate the indoor effect of six human metabolic compounds for trapping adult Culex pipiens quinquefasciatus. METHODS: The effects of six human metabolic compounds alone (acetic acid, propionic acid, octanoic acid, lactic acid, 1-octene-3-alcohol and urea alone), liquid lactic acid, acetic acid, propionic acid, octanoic acid, lactic acid or 1-octene-3-alcohol in combination with urea at an equal mass ratio, and lactic acid-urea combinations at various mass ratios, for trapping Cx. p. quinquefasciatus were examined using the trapping method, while the dechlorinated water served as a control. RESULTS: The indoor mosquito-trapping efficacy of the six human metabolic compounds was all superior to the dechlorinated water. Acetic acid, propionic acid, octanoic acid, or 1-octene-3-alcohol combined with urea at a mass ratio of 1∶1 had a comparable mosquito-trapping efficacy with acetic acid, propionic acid, octanoic acid, or 1-octene-3-alcohol alone (all P values > 0.05). The lactic acidurea combination at a mass ratio of 1∶1 had a significantly higher mean cumulative trapping capacity [(35.60 ± 8.11) mosquitoes] than lactic acid [(20.80 ± 8.53) mosquitoes], urea [(17.00 ± 7.18) mosquitoes] or dechlorinated water alone (7.20 ± 2.68) (all P values < 0.05). In addition, the lactic acid-urea combinations at mass ratios of 1∶1, 1∶2, 1∶3, 1∶4 or 1∶5 all had significantly greater mosquito-trapping efficacies than lactic acid, urea or dechlorinated water alone (all P values < 0.05), and the optimal combination (lactic acid-urea at a 1∶4 mass ratio) had a mean cumulative trapping capacity of (56.20 ± 9.88) mosquitoes, which was significantly superior to lactic acid [(17.00 ± 3.94) mosquitoes], urea [(16.40 ± 3.78) mosquitoes] or dechlorinated water alone [(7.40 ± 3.44) mosquitoes] (all P values < 0.05). CONCLUSIONS: The lactic acid-urea combination remarkably increases the indoor trapping capability of Cx. p. quinquefasciatus, and this combination has a weak smell, which is suitable to be used at home and office environments.

[The surgical management of upper parapharyngeal regions].

Objective: To find proper the surgical approval and evaluate clinical efficacy to treat the tumor of upper parapharyngeal space involving the base of skull and intracranial skull. Method: The data of 9 cases from June 2013 and June 2018 were analyzed retrospectively including schwannoma in 6 cases, pleomorphic adenoma in 2 cases and hemangioma in 1 case. All cases received preoperative high resolution CT and MRI, some cases also did the DSA examination. Tumor invaded top of nasopharyngeal in 4 cases, the base of skull in 3 cases, and intraskull in 2 cases. 9 cases were treated with surgery alone. Surgical approach: transcervical approach (n=1), transcervical approach and mandibular fracture surgery(n=2), transoral approach(n=3), transnasal transpterygoid approach(n=2), transparotid gland approach(n=1). Result: Tumors in 8 cases were completely removed, and 1 case was performed by partial excision. Hemorrhage(>500 ml) occurred in 2 cases, tongue deflection and cerebrospinal fluid leakage occurred in 1 case. No death, tumor recurrence and wound infection was found. Conclusion: The position of benign upper parapharyngeal space tumors is deep and tumor often invade in the base of the skull and brain tissue. It is close to the important nerve, vessels of the skull base and meninges. The appropriate surgical approach should be selected according to the individual situation. The main point of the operation is complete the tumor resection with preserving or reconstructing the important function of the blood vessel and nerve.

Generic velpatasvir plus sofosbuvir for hepatitis C virus infection in patients with or without human immunodeficiency virus coinfection.

BACKGROUND: Data are limited regarding the effectiveness and safety of generic velpatasvir plus sofosbuvir (VEL/SOF) for hepatitis C virus (HCV) in patients with or without human immunodeficiency virus (HIV) coinfection. AIM: To evaluate the effectiveness and safety of generic VEL/SOF-based therapy for HCV infection in patients with or without HIV coinfection in Taiwan. METHODS: Sixty-nine HIV/HCV-coinfected and 159 HCV-monoinfected patients receiving 12 weeks of generic VEL/SOF with or without ribavirin (RBV) for HCV were prospectively enrolled. The anti-viral responses and the adverse events (AEs) were compared between the two groups. The characteristics potentially related to sustained virological response 12 weeks off therapy (SVR12 ) were analysed. RESULTS: The SVR12 was achieved in 67 HIV/HCV-coinfected patients (97.1%; 95% CI: 90.0%-99.2%) and in 156 HCV-monoinfected patients (98.1%; 95% CI: 94.6%-99.4%) receiving VEL/SOF-based therapy, respectively. The SVR12 rates were comparable between HIV/HCV-coinfected and HCV-monoinfected patients, regardless of pre-specified baseline characteristics. One hundred twenty-two (53.5%) and seven (3.1%) patients had baseline resistance-associated substitutions (RASs) in HCV NS5A and NS5B regions, but the SVR12 rates were not affected by the presence or absence of RASs. One (1.4%) and five (3.1%) patients in the HIV/HCV-coinfected and HCV-monoinfected groups had serious AEs. No patient died or discontinued treatment due to AEs. The eGFR remained stable throughout the course of treatment in HIV/HCV-coinfected patients receiving anti-retroviral therapy containing tenofovir disoproxil fumarate (TDF). CONCLUSIONS: Generic VEL/SOF-based therapy is well-tolerated and provides comparably high SVR12 rates for HCV infection in patients with and without HIV coinfection.

Fibrosis-4 index predicts cirrhosis risk and liver-related mortality in 2075 patients with chronic HBV infection.

BACKGROUND: Fibrosis-4 index (FIB-4) is a surrogate marker for hepatic fibrosis in hepatitis B virus (HBV) carriers. AIM: To investigate whether FIB-4 index stratifies the risks of adverse liver events. METHODS: A total of 2075 treatment-naïve, noncirrhotic the patients with chronic HBV infection were included. Most of them (82.1%) were HBeAg-negative patients and their baseline FIB-4 levels were explored to stratify the risks of cirrhosis, cirrhosis-related complications and liver-related mortality. RESULTS: During a mean follow-up period of 15.47 years, we found a higher baseline FIB-4 index was associated with increased incidence rates of cirrhosis in addition to the common host and viral factors. Patients with FIB-4 >1.29, compared to those with FIB-4 <1.29, were associated with increased risks of cirrhosis, cirrhosis-related complications and liver-related mortality with the hazard ratio (95% confidence interval) of 6.19 (4.76-8.05), 6.88, (3.68-12.86) and 7.79, (4.54-13.37) respectively. Within the first 3 years of follow-up, FIB-4 remained stable and its kinetics were consistently associated with the develoopment of adverse liver events. Furthermore, FIB-4 index of 1.29 was able to stratify all the risks of adverse liver events even in HBeAg-negative patients with a low risk of disease progression (HBV DNA <2000 IU/mL, HBsAg <1000 IU/mL and ALT <40 U/L). Only 1 patient with FIB-4 index <1.29 developed cirrhosis but not other events within 15 years of follow-up. CONCLUSIONS: In noncirrhotic patients with chronic HBV infection, a higher FIB-4 index was associated with increased risks of adverse liver events. FIB-4 index <1.29 is useful for the prediction of the lowest risks of disease progression.

Historical epidemiology of hepatitis C virus in select countries-volume 4.

Due to the introduction of newer, more efficacious treatment options, there is a pressing need for policy makers and public health officials to develop or adapt national hepatitis C virus (HCV) control strategies to the changing epidemiological landscape. To do so, detailed, country-specific data are needed to characterize the burden of chronic HCV infection. In this study of 17 countries, a literature review of published and unpublished data on HCV prevalence, viraemia, genotype, age and gender distribution, liver transplants and diagnosis and treatment rates was conducted, and inputs were validated by expert consensus in each country. Viraemic prevalence in this study ranged from 0.2% in Hong Kong to 2.4% in Taiwan, while the largest viraemic populations were in Nigeria (2 597 000 cases) and Taiwan (569 000 cases). Diagnosis, treatment and liver transplant rates varied widely across the countries included in this analysis, as did the availability of reliable data. Addressing data gaps will be critical for the development of future strategies to manage and minimize the disease burden of hepatitis C.

Strategies to manage hepatitis C virus infection disease burden-Volume 4.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 17 countries in Africa, Asia, Europe, Latin America and the Middle East, and interventions for achieving the Global Health Sector Strategy on viral hepatitis targets-"WHO Targets" (65% reduction in HCV-related deaths, 90% reduction in new infections and 90% of infections diagnosed by 2030) were considered. Scaling up treatment and diagnosis rates over time would be required to achieve these targets in all but one country, even with the introduction of high SVR therapies. The scenarios developed to achieve the WHO Targets in all countries studied assumed the implementation of national policies to prevent new infections and to diagnose current infections through screening.

The present and future disease burden of hepatitis C virus infections with today's treatment paradigm: Volume 4.

Factors influencing the morbidity and mortality associated with viremic hepatitis C virus (HCV) infection change over time and place, making it difficult to compare reported estimates. Models were developed for 17 countries (Bahrain, Bulgaria, Cameroon, Colombia, Croatia, Dominican Republic, Ethiopia, Ghana, Hong Kong, Jordan, Kazakhstan, Malaysia, Morocco, Nigeria, Qatar and Taiwan) to quantify and characterize the viremic population as well as forecast the changes in the infected population and the corresponding disease burden from 2015 to 2030. Model inputs were agreed upon through expert consensus, and a standardized methodology was followed to allow for comparison across countries. The viremic prevalence is expected to remain constant or decline in all but four countries (Ethiopia, Ghana, Jordan and Oman); however, HCV-related morbidity and mortality will increase in all countries except Qatar and Taiwan. In Qatar, the high-treatment rate will contribute to a reduction in total cases and HCV-related morbidity by 2030. In the remaining countries, however, the current treatment paradigm will be insufficient to achieve large reductions in HCV-related morbidity and mortality.

Chronologic changes in serum hepatitis B virus DNA, genotypes, surface antigen mutants and reverse transcriptase mutants during 25-year nationwide immunization in Taiwan.

We investigated breakthrough infection and hepatitis B virus (HBV) genetic changes in immunized subjects after 25 years of a universal infant immunization. Specifically, serum HBV DNA, genotypes, surface antigen mutants and nucleoside analog-resistant (NAr) mutants were assessed in 2853 subjects (<25 years old) surveyed in 2009, and these data were compared with the data from previous serosurveys. A comparison across different age-stratified groups using the 2009 data revealed a significant increase in the seropositive rate of anti-HBc (5.51% vs 12.38%, P=.001) and HBV DNA (1.13% vs 3.96%, P=.007) between those 17-22 and 23-24 years of age, possibly due to selective infant immunization in 1984-1986. Well-characterized NAr mutants, potential NAr mutants and surface "a" determinant mutants were detected in none, 15 (45.5%) and nine (27.3%) of 33 HBV DNA-positive subjects, respectively. Of 15 immunized, HBV DNA-positive young adults (18-24 years), three (20%) carried "a" determinant mutants. Amongst 1176 HBsAg-negative subjects evaluated for occult HBV infection, those seropositive for anti-HBc had a higher seropositive rate for HBV DNA (10/110, 9.1% vs 7/1066, 0.66%; P<.001) and "a" determinant mutants (4/110, 3.6% vs 0/1066; P<.001) than those seronegative for anti-HBc. Overall, the HBsAg-positive subjects in six serosurveys showed no significant increase in genotype C frequency in the comparison between the vaccinated and unvaccinated cohorts (25/98, 25.5% versus 14/79, 17.7%, P=.188). Over the 25-year programme, there was no increase in the prevalence of genotype C in HBsAg carriers and no increase in breakthrough HBV infection or surface mutant prevalence beyond adolescence. Nucleic acid amplification should still be considered the primary screening method for occult hepatitis B detection in high-risk recipients.

Immune escape to PD-L1/PD-1 blockade: seven steps to success (or failure).

The emergence of programmed death-ligand 1 (PD-L1)/programmed death-1 (PD-1)-targeted therapy has demonstrated the importance of the PD-L1 : PD-1 interaction in inhibiting anticancer T-cell immunity in multiple human cancers, generating durable responses and extended overall survival. However, not all patients treated with PD-L1/PD-1-targeted therapy experience tumor shrinkage, durable responses, or prolonged survival. To extend such benefits to more cancer patients, it is necessary to understand why some patients experience primary or secondary immune escape, in which the immune response is incapable of eradicating all cancer cells. Understanding immune escape from PD-L1/PD-1-targeted therapy will be important to the development of rational immune-combination therapy and predictive diagnostics and to the identification of novel immune targets. Factors that likely relate to immune escape include the lack of strong cancer antigens or epitopes recognized by T cells, minimal activation of cancer-specific T cells, poor infiltration of T cells into tumors, downregulation of the major histocompatibility complex on cancer cells, and immunosuppressive factors and cells in the tumor microenvironment. Precisely identifying and understanding these mechanisms of immune escape in individual cancer patients will allow for personalized cancer immunotherapy, in which monotherapy and combination immunotherapy are chosen based on the presence of specific immune biology. This approach may enable treatment with immunotherapy without inducing immune escape, resulting in a larger proportion of patients obtaining clinical benefit.

Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update.

Worldwide, some 240 million people have chronic hepatitis B virus (HBV), with the highest rates of infection in Africa and Asia. Our understanding of the natural history of HBV infection and the potential for therapy of the resultant disease is continuously improving. New data have become available since the previous APASL guidelines for management of HBV infection were published in 2012. The objective of this manuscript is to update the recommendations for the optimal management of chronic HBV infection. The 2015 guidelines were developed by a panel of Asian experts chosen by the APASL. The clinical practice guidelines are based on evidence from existing publications or, if evidence was unavailable, on the experts' personal experience and opinion after deliberations. Manuscripts and abstracts of important meetings published through January 2015 have been evaluated. This guideline covers the full spectrum of care of patients infected with hepatitis B, including new terminology, natural history, screening, vaccination, counseling, diagnosis, assessment of the stage of liver disease, the indications, timing, choice and duration of single or combination of antiviral drugs, screening for HCC, management in special situations like childhood, pregnancy, coinfections, renal impairment and pre- and post-liver transplant, and policy guidelines. However, areas of uncertainty still exist, and clinicians, patients, and public health authorities must therefore continue to make choices on the basis of the evolving evidence. The final clinical practice guidelines and recommendations are presented here, along with the relevant background information.

Complete mitochondrial genome of the Chinese Hwamei Garrulax canorus (Aves: Passeriformes): the first representative of the Leiothrichidae family with a duplicated control region.

The Chinese Hwamei Garrulax canorus, a member of the family Leiothrichidae, is commonly found in central and southern China, northern Indochina, and on Hainan Island. In this study, we sequenced the complete mitochondrial genome of G. canorus. The circular mitochondrial genome is 17,785 bp in length and includes 13 protein-coding genes, 22 transfer RNA (tRNA) genes, and two ribosomal RNA genes. In addition, two copies of highly similar putative control regions were observed in the mitochondrial genome. As found in other vertebrates, most of the genes are coded on the H-strand, except for one protein-coding gene (nad6; NADH dehydrogenase subunit 6) and eight tRNA genes (tRNA(Gln), tRNA(Ala), tRNA(Asn), tRNA(Cys), tRNA(Tyr), tRNA(Ser(UCN)), tRNA(Pro), and tRNA(Glu)). All the protein-coding genes start with ATG, with the exception of cox1 (cytochrome oxidase subunit 1), which starts with GTG. All tRNA genes have the potential to fold into the typical clover-leaf structure. Conserved sequences in three domains were observed in the two putative control regions. These results provide basic information for future phylogenetic analyses among species of the order Passeriformes.

Increased risk of hepatocellular carcinoma in chronic hepatitis C patients with new onset diabetes: a nation-wide cohort study.

BACKGROUND: The impact of diabetes for hepatocellular carcinoma (HCC) development in chronic hepatitis C (CHC) patients remains controversial. AIM: To investigate the risk of HCC in CHC patients who develop new onset diabetes. METHODS: We conducted a nation-wide cohort study by using Taiwanese National Health Insurance Research Database, which comprised of data from >99% of entire population. Among randomly sampled one million enrollees, 6251 adult CHC patients were identified from 1997 to 2009. Diabetes was defined as new onset in the patient who was given the diagnosis in the years 1999-2009 but not in 1997-1998. The cohorts of CHC with new onset diabetes (n = 1100) and 1:1 ratio age-, gender-, and inception point (onset date of diabetes) matched nondiabetes (n = 1087) were followed up from the inception point until the development of HCC, withdrawal from insurance, or December 2009. RESULTS: After adjustment for competing mortality, patients with new onset diabetes had a significantly higher cumulative incidence of HCC (Relative Risk = 1.544, 95% CI = 1.000-2.387, modified log-rank test, P = 0.047) as compared to those without. After adjustment for age, gender, cirrhosis, hyperlipidaemia, CHC treatment, diabetes treatment, comorbidity index, obesity and statins therapy by Cox proportional hazard model, diabetes was still an independent predictor for HCC (hazard ratio (HR) = 1.906, 95% CI = 1.102-3.295, P = 0.021). The risk for HCC was increased in those who were 40-59 years old, independent of other variables (HR = 3.086, 95% CI = 1.045-9.112, P = 0.041), and after adjustment for competing mortality (modified log-rank test, P = 0.009). CONCLUSION: Chronic hepatitis C patients who develop diabetes are at an increased risk of hepatocellular carcinoma over time.

Increased risk of hepatocellular carcinoma in chronic hepatitis B patients with new onset diabetes: a nationwide cohort study.

BACKGROUND: Diabetes increases the risk of hepatocellular carcinoma (HCC), however, the time-relationship between hepatitis B virus and diabetes for the development of HCC remains unclear. AIM: To explore the risk of HCC in chronic hepatitis B patients with newly diagnosed diabetes. METHODS: We conducted a nationwide cohort study by using Taiwanese National Health Insurance Research Database, which covers over 99% of entire population. Among randomly sampled one million enrollees, 14 523 chronic hepatitis B patients were diagnosed in years 1997-2009. We defined new onset diabetes as patients who were given the diagnosis in the years 1999-2009, but not in 1997-1998. The cohorts of chronic hepatitis B with new onset diabetes (n = 2099) and 1:1 ratio age-, gender- and inception point (onset date of diabetes)- matched nondiabetes (n = 2080) were followed up from the inception point until development of HCC, withdrawal from insurance or December 2009. RESULTS: After adjustment for competing mortality, patients with new onset diabetes had a significantly higher cumulative incidence of HCC [relative risk = 1.628, 95% confidence interval (CI) = 1.114-2.378, modified log-rank test, P = 0.012] as compared to nondiabetes patients. After adjustment for age, gender, hyperlipidaemia, chronic hepatitis B treatment, statins therapy, cirrhosis, comorbidity index and obesity, diabetes was still an independent predictor for HCC (hazard ratio = 1.798, 95% CI = 1.194-2.707, P = 0.005). CONCLUSION: Chronic hepatitis B patients with newly diagnosed diabetes have an increased risk of hepatocellular carcinoma over time.

Higher lifetime chance of spontaneous surface antigen loss in hepatitis B carriers with genotype C infection.

BACKGROUND: Clearance of hepatitis B surface antigen (HBsAg) indicates clinical control of hepatitis B virus (HBV) infection. However, little is known about the impact of viral genomic variations on HBsAg loss. METHODS: We explored the association between viral genomic factors and HBsAg loss in 2121HBeAg-negative patients. HBV pre-core stop codon (1896) and basal core promoter (BCP) (1762/1764) sequences were determined in patients with HBV DNA ≥200 IU/mL (N = 1693). The effect of HBV genotype on HBsAg loss was further validated in the whole cohort of 3445 HBsAg carriers. RESULTS: The cumulative lifetime (age 28-75 years) incidence of HBsAg loss was 50.4% in 2121 HBeAg-negative patients. We found that genotype C, but not pre-core stop codon or BCP mutants, was associated with HBsAg loss. Compared to genotype B patients, genotype C patients had higher lifetime chance of HBsAg loss, with hazard ratio of 1.8 (95% confidence interval: 1.4-2.4). Multivariable analysis showed that male sex, elevated ALT levels, lower serum HBV DNA and HBsAg levels, and genotype C infection were associated with higher chance of HBsAg loss independently. We then performed sensitivity analysis, which re-included HBeAg-positive, cirrhotic and treatment-experienced patients, and confirmed the robustness of our results in 3445 HBsAg carriers. CONCLUSION: Genotype C infection, compared to genotype B, is associated with a higher lifetime chance of HBsAg loss in Asian HBV carriers.

Quantitative hepatitis B core antibody levels in the natural history of hepatitis B virus infection.

We previously demonstrated that pretreatment quantitative anti-hepatitis B core protein (qAnti-HBc) levels can predict the treatment response for both interferon and nucleoside analogue therapy, but the characteristics of qAnti-HBc during chronic hepatitis B virus (HBV) infection remain poorly understood. To understand this issue, the qAnti-HBc levels were evaluated in individuals with past HBV infection, occult HBV infection and chronic HBV infection in the immune tolerance phase, immune clearance phase, low-replicative phase and hepatitis B e antigen (HBeAg)-negative hepatitis phase. Individuals with hepatitis B surface antigen (n = 598, 3.74 ± 0.90 log10 IU/mL) had significantly higher (p < 0.001, approximately 1000-fold) serum qAnti-HBc levels than those who had occult HBV, and serum qAnti-HBc levels were significantly higher in the occult HBV group than in the past HBV infection group (p < 0.001). qAnti-HBc levels were positively correlated with alanine aminotransferase levels (R = 0.663, p < 0.001), and subjects with an abnormal alanine aminotransferase level had a higher qAnti-HBc level (p < 0.001). Serum qAnti-HBc level varied in different phases of HBV infection, as determined by host immune status. Serum qAnti-HBc level is strongly associated with hepatitis activity in subjects with chronic HBV infection.