Role of upfront autologous transplant for peripheral T-cell lymphoma patients achieving a complete remission with first-line therapy: a systematic review and meta-analysis.

There is currently no consensus on the role of upfront autologous transplantation (ASCT) for patients with peripheral T-cell lymphomas (PTCL), especially in patients achieving first complete remission (CR1) following chemotherapy, and data in the literature is conflicting. A systematic review and meta-analysis was performed to address this question. We searched key databases from January 2000 to February 2022. Six prospective and eleven retrospective studies were included among 2959 unique records. Median follow up in these studies ranged from 22 to 94 months. There was a trend towards benefit in PFS (HR = 0.80, 95% CI 0.62-1.05, p = 0.11) and OS (HR = 0.79, 95% CI 0.57-1.09, p = 0.15) in the ASCT compared to chemotherapy only group. Importantly, in transplant eligible patients in CR1, a significant benefit was demonstrated in both OS (HR = 0.59, 95% CI 0.36-0.95, p = 0.03) and PFS (HR = 0.61, 95% CI 0.47-0.81, p = 0.0004) in the ASCT group. Amongst the nodal PTCL subgroups, ASCT showed a significant PFS benefit for the AITL subgroup (HR = 0.43, 95% CI 0.20-0.94, p < 0.03) but not PTCL-NOS or ALK-ve ALCL subgroups. Our findings support upfront ASCT for transplant eligible PTCL patients achieving CR1 post chemotherapy. In particular, patients with AITL exhibited a significantly better PFS after upfront ASCT.

Smoking cessation in dental setting: a narrative review on dental professionals' attitude, preparedness, practices and barriers.

Integration of smoking cessation program into routine oral health care has been advocated by World Health Organization since it brings extensive benefits to oral health. By tobacco cessation, patients are less prone to progression of periodontal disease, have less future tooth loss, have reduced risks of oral mucosal lesions and head and neck cancers. Evidence indicates that dentists are in a favorable position to deliver effective smoking cessation advice to improve patients' oral health. This article aims to present the current situation of smoking cessation in dental setting, including dental management of smoking patients, perceptions of dentists and dental students towards smoking cessation, challenges dental professionals face when carrying out cessation interventions. Patients' perspectives are also evaluated to provide a clearer picture of smoking cessation practice in the dental field. Review of past surveys show most patients welcome smoking cessation advice from dental practitioners. Meanwhile dentists may have wrong assumption that patients would disapprove them if they advise patient to quit smoking. On top of that, main obstacles identified are lack of training, inadequate treatment time and insufficient knowledge towards smoking cessation guidelines and referral routes. With regard to the potential barriers, evidence demonstrates that more trainings on smoking cessation strategies are needed. Future research in this aspect is also indicated to further foster the practice of smoking cessation counselling in dental setting.

Ultrasonographic Tissue Perfusion in Peri-implant Health and Disease.

Color flow ultrasonography has played a crucial role in medicine for its ability to assess dynamic tissue perfusion and blood flow variations as an indicator of a pathologic condition. While this feature of ultrasound is routinely employed in various medical fields, its intraoral application for the assessment of tissue perfusion at diseased versus healthy dental implants has never been explored. We tested the hypothesis that quantified tissue perfusion of power Doppler ultrasonography correlates with the clinically assessed inflammation of dental implants. Specifically, we designed a discordant-matched case-control study in which patients with nonadjacent dental implants with different clinical diagnoses (healthy, peri-implant mucositis, or peri-implantitis) were scanned and analyzed with real-time ultrasonography. Forty-two posterior implants in 21 patients were included. Ultrasound scans were obtained at the implant regions of midbuccal, mesial/distal (averaged as interproximal), and transverse to compute the velocity- and power-weighted color pixel density from color velocity (CV) and color power (CP), respectively. Linear mixed effect models were then used to assess the relationship between the clinical diagnoses and ultrasound CV and CP. Overall, the results strongly suggested that ultrasound's quantified CV and CP directly correlate with the clinical diagnosis of dental implants at health, peri-implant mucositis, and peri-implantitis. This study showed for the first time that ultrasound color flow can be applicable in the diagnosis of peri-implant disease and can act as a valuable tool for evaluating the degree of clinical inflammation at implant sites.

Questionnaire survey on knowledge, attitudes, and behaviour towards viral hepatitis among the Hong Kong public.

INTRODUCTION: We aimed to identify gaps in knowledge, attitudes, and behaviours towards viral hepatitis among the Hong Kong public and provide insights to optimise local efforts towards achieving the World Health Organization's viral hepatitis elimination target. METHODS: A descriptive, cross-sectional, self-reported web-based questionnaire was administered to 500 individuals (aged ≥18 years) in Hong Kong. Questionnaire items explored the awareness and perceptions of viral hepatitis-related liver disease(s) and associated risk factors in English or traditional Chinese. RESULTS: The majority (>80%) were aware that chronic hepatitis B and/or C could increase the risks of developing liver cirrhosis, cancer, and/or failure. Only 55.8% had attended health screenings in the past 2 years, and 67.6% were unaware of their family's history of liver diseases. Misperceptions surrounding the knowledge and transmission risks of viral hepatitis strongly hint at the presence of social stigmatisation within the community. Many misperceived viral hepatitis as airborne or hereditary, and social behaviours (casual contact or dining with an infected person) as a transmission route. Furthermore, 62.4% were aware of hepatitis B vaccination, whereas 19.0% knew that hepatitis C cannot be prevented by vaccination. About 70% of respondents who were aware of mother-to-child transmission were willing to seek medical consultation in the event of pregnancy. Gaps in knowledge as well as the likelihood of seeking screening were observed across all age-groups and education levels. CONCLUSIONS: Comprehensive hepatitis education strategies should be developed to address gaps in knowledge among the Hong Kong public towards viral hepatitis, especially misperceptions relevant to social stigmatisation and the importance of preventive measures, including vaccination and screening, when exposed to risk factors.

Review article: long-term safety of oral anti-viral treatment for chronic hepatitis B.

BACKGROUND: Safety profile of nucleos(t)ide analogues is an important issue in view of its widespread use for decades in patients with chronic hepatitis B (CHB). AIM: To review and evaluate the latest evidence on the safety profiles of the six approved nucleoside analogues. METHODS: Relevant articles related to nucleoside analogue safety were selected for review following extensive language- and date-unrestricted, electronic searches of the literature. RESULTS: Nephrotoxicity has been well reported in patients receiving older generations of nucleotide analogues, namely adefovir dipivoxil and tenofovir disoproxil fumarate (TDF). Yet risks of renal failure and renal replacement therapy were similar in patients treated with nucleoside analogues versus nucleotide analogues in real-life setting. Bone toxicity is closely related to nucleoside analogue effect on renal proximal tubular and phosphaturia. Real-life data demonstrated increased risk of hip fracture in patients receiving adefovir but not TDF. The newly approved tenofovir alafenamide (TAF) has improved renal and bone safety profiles compared to TDF. Long-term use of nucleoside analogues eg entecavir does not increase the risk of other cancers. Muscular toxicity may be seen in telbivudine-treated patients so regular monitoring is advised. Peripheral neuropathy and lactic acidosis are rare adverse events. Latest international guidelines support the use of TDF, telbivudine and lamivudine during pregnancy; breastfeeding is not contraindicated during TDF therapy. CONCLUSIONS: Long-term safety profile of nucleoside analogues is now better defined with more data from large real-life cohorts and clinical trials with long-term follow-up. The new nucleotide analogue, TAF is now available with favourable renal and bone safety profiles.

Laboratory parameter-based machine learning model for excluding non-alcoholic fatty liver disease (NAFLD) in the general population.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) affects 20%-40% of the general population in developed countries and is an increasingly important cause of hepatocellular carcinoma. Electronic medical records facilitate large-scale epidemiological studies, existing NAFLD scores often require clinical and anthropometric parameters that may not be captured in those databases. AIM: To develop and validate a laboratory parameter-based machine learning model to detect NAFLD for the general population. METHODS: We randomly divided 922 subjects from a population screening study into training and validation groups; NAFLD was diagnosed by proton-magnetic resonance spectroscopy. On the basis of machine learning from 23 routine clinical and laboratory parameters after elastic net regulation, we evaluated the logistic regression, ridge regression, AdaBoost and decision tree models. The areas under receiver-operating characteristic curve (AUROC) of models in validation group were compared. RESULTS: Six predictors including alanine aminotransferase, high-density lipoprotein cholesterol, triglyceride, haemoglobin A1c , white blood cell count and the presence of hypertension were selected. The NAFLD ridge score achieved AUROC of 0.87 (95% CI 0.83-0.90) and 0.88 (0.84-0.91) in the training and validation groups respectively. Using dual cut-offs of 0.24 and 0.44, NAFLD ridge score achieved 92% (86%-96%) sensitivity and 90% (86%-93%) specificity with corresponding negative and positive predictive values of 96% (91%-98%) and 69% (59%-78%), and 87% of overall accuracy among 70% of classifiable subjects in the validation group; 30% of subjects remained indeterminate. CONCLUSIONS: NAFLD ridge score is a simple and robust reference comparable to existing NAFLD scores to exclude NAFLD patients in epidemiological studies.

Significant positive association of endotoxemia with histological severity in 237 patients with non-alcoholic fatty liver disease.

BACKGROUND: Patients with nonalcoholic steatohepatitis (NASH) have gut dysbiosis and intestinal bacterial overgrowth. AIM: To test the hypothesis that endotoxemia is associated with the histological severity of nonalcoholic fatty liver disease (NAFLD) and determine factors associated with endotoxemia. METHODS: The endotoxemia markers lipopolysaccharide-binding protein (LBP) and endotoxin levels were measured in 237 NAFLD patients 1 day before liver biopsy. Biomarkers of liver injury and transient elastography were performed as additional markers of disease severity. RESULTS: A total of 114/237 (48%) patients had NASH and 80/237 (34%) had F2-4 fibrosis. LBP was correlated with lobular inflammation (P=.001), while both LBP (P=.0004) and endotoxin levels (P=0.008) were correlated with fibrosis. LBP was also correlated with cytokeratin-18 fragments (P=.002) and aspartate aminotransferase-to-alanine aminotransferase ratio (P=.006), and both LBP (P=.019) and endotoxin (P=.006) were correlated with liver stiffness measurement by transient elastography. LBP was increased in patients with NASH (15.3±4.6 vs 13.8±3.3 µg/mL; P=.005) and F2-4 fibrosis (15.4±4.4 vs 14.0±3.7 µg/mL; P=.008). Interestingly, patients harbouring the TM6SF2 rs58542926 T allele that predispose to NAFLD/NASH had higher LBP level. By multivariate analysis, gender, higher body mass index and glycated haemoglobin, and TM6SF2 variants were independent factors associated with increased LBP level. CONCLUSIONS: Endotoxemia is positively associated with NASH and significant fibrosis. The association between TM6SF2 and endotoxemia warrants further investigations. The findings may shed light on the pathogenesis of NASH and inform a novel treatment target.

Long-term use of oral nucleos(t)ide analogues for chronic hepatitis B does not increase cancer risk - a cohort study of 44 494 subjects.

BACKGROUND: Patients with chronic hepatitis B (CHB) need long-term antiviral treatment with nucleos(t)ide analogues (NA). Animal studies suggest that some NA may increase cancer risk, but human data are lacking. AIM: To investigate cancer risks in patients with or without NA treatment. METHODS: We conducted a territory-wide cohort study using the database from Hospital Authority in Hong Kong. The diagnosis of CHB and various malignancies was based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes between 2000 and 2012. Patients exposed to any of the oral NA for CHB were included. The primary outcome was incident cancers. A 3-year landmark analysis, with follow-up up to 7 years, was used to evaluate the relative risk of cancers in treated and untreated patients. RESULTS: A total of 44 494 patients (39 712 untreated and 4782 treated) were included in the analysis. During 194 890 patient-years of follow-up, hepatocellular carcinoma developed in 402 (1.0%) untreated patients and 179 (3.7%) treated patients, while other cancers developed in 528 (1.3%) and 128 (2.7%) patients respectively. After propensity score weighting, treated patients had similar risks of all malignancies [weighted hazard ratio (wHR): 1.01, 95% CI: 0.82-1.25, P = 0.899], lung/pleural cancers (wHR: 0.82, 95% CI: 0.52-1.31, P = 0.409) and urinary/renal malignancies (wHR: 1.04, 95% CI: 0.38-2.81, P = 0.944) when compared with untreated patients. CONCLUSIONS: Oral nucleos(t)ide analogue treatment does not appear to increase cancer risk in patients with chronic hepatitis B. Given the beneficial effect on liver outcomes, our data support the current practice of long-term anti-viral therapy.

Liver fibrosis and fatty liver in Asian HIV-infected patients.

BACKGROUND: Little is known about the importance of liver fibrosis and fatty liver in HIV-monoinfected individuals without hepatitis virus co-infection, particularly among the Asian population. AIM: To evaluate prevalence and risk factors for liver fibrosis and fatty liver in Asian HIV-monoinfected individuals. METHODS: Eighty asymptomatic HIV-monoinfected individuals (tested negative for HBV/HCV) were compared with 160 matched HIV-uninfected healthy controls. Transient elastography and proton-magnetic resonance spectroscopy ((1) H-MRS) were performed to measure liver stiffness and hepatic steatosis respectively. Blood samples were analysed for metabolic profiles and markers of steatohepatitis (e.g. cytokeratin-18). RESULTS: All HIV-infected individuals (mean ± s.d. age 54 ± 11 years, male 93%, Chinese 94%; diagnosis median duration 8 (IQR 4-13 years) were stable on anti-retrovirals (PI-based 58.7%, NNRTI-based 25.0% integrase-inhibitors 16.3%); diabetes, dyslipidaemia, and metabolic syndrome were common. Fatty liver disease was detected in 28.7%. There was significantly higher degree of liver stiffness [4.9 (IQR 4.1-6.2) kPa vs. 4.2 (IQR 3.6-5.0) kPa, P < 0.001], and greater proportions developed significant fibrosis (7.0 kPa, 14.3% vs. 3.1%, P = 0.001) and cirrhosis (10.3 kPa, 5.2% vs. 0.6%, P = 0.040) compared with controls. HIV infection was an independent risk factor for significant fibrosis (adjusted OR 4.00, 95% CI 1.29-12.41, P = 0.016). HIV-infected individuals with fatty liver had excessive liver stiffness and fibrosis. Two cases of asymptomatic hepatocellular carcinoma were detected. CONCLUSIONS: HIV-monoinfected patients are at risk for liver fibrosis and cirrhosis. HIV-related mechanisms and fatty liver disease may play important roles. Screening and intervention to prevent severe outcomes should be considered.

Anodic aluminum oxide-epoxy composite acoustic matching layers for ultrasonic transducer application.

The goal of this work is to demonstrate the application of anodic aluminum oxide (AAO) template as matching layer of ultrasonic transducer. Quarter-wavelength acoustic matching layer is known as a vital component in medical ultrasonic transducers to compensate the acoustic impedance mismatch between piezoelectric element and human body. The AAO matching layer is made of anodic aluminum oxide template filled with epoxy resin, i.e. AAO-epoxy 1-3 composite. Using this composite as the first matching layer, a ∼12MHz ultrasonic transducer based on soft lead zirconate titanate piezoelectric ceramic is fabricated, and pulse-echo measurements show that the transducer exhibits very good performance with broad bandwidth of 68% (-6dB) and two-way insertion loss of -22.7dB. Wire phantom ultrasonic image is also used to evaluate the transducer's performance, and the results confirm the process feasibility and merit of AAO-epoxy composite as a new matching material for ultrasonic transducer application. This matching scheme provides a solution to address the problems existing in the conventional 0-3 composite matching layer and suggests another useful application of AAO template.

Oral nucleos(t)ide analogues reduce recurrence and death in chronic hepatitis B-related hepatocellular carcinoma.

BACKGROUND: In patients with chronic hepatitis B (CHB)-related hepatocellular carcinoma (HCC), high viral load was associated with tumour recurrence and deaths. AIMS: To investigate the effect of nucleos(t)ide analogues (NA) on the clinical outcomes after different HCC treatments. METHODS: A territory-wide cohort study was conducted using the database from Hospital Authority. We identified CHB patients with HCC by International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes in 2000-2012. HCC treatments, NA use and laboratory parameters were retrieved. The primary endpoint was HCC recurrence and death. A 3-month landmark analysis was used to evaluate the primary outcome in patients with or without NA treatment. RESULTS: A total of 2198 CHB patients (1230 NA-untreated and 968 NA-treated) with HCC, receiving at least one type of HCC treatment were included in the analysis. At a median follow-up of 2.8 (IQR 1.4-4.9) years, tumour recurrence and death occurred in 451 (36.7%) and 578 (47.0%) untreated patients; and in 216 (22.3%) and 301 (31.1%) NA-treated patients respectively. NA therapy reduced the risk of overall HCC recurrence [adjusted sub-hazard ratio (SHR) 0.63, 95% confidence interval (CI) 0.49-0.80; P < 0.001]. The effect was most obvious in patients undergoing resection (SHR = 0.58, 95% CI = 0.37-0.91, P = 0.018). The possibility of NA therapy reducing the risk of death (HR = 0.82, 95% CI = 0.64-1.03, P = 0.092), is most obvious in resection subgroup (HR = 0.64, 95% CI = 0.41-0.99, P = 0.050) but insignificant in the other treatment groups. CONCLUSION: Our findings show that nucleos(t)ide analogues treatment reduces the risk of HCC recurrence in patients with chronic hepatitis B treated by surgical resection.

Serum interferon-inducible protein 10 levels predict hepatitis B s antigen seroclearance in patients with chronic hepatitis B.

BACKGROUND: Hepatitis B s antigen (HBsAg) seroclearance is regarded as the optimal virological end-point. AIM: To investigate the dynamic changes in serum cytokine levels around the time of HBsAg seroclearance. METHODS: This was a case-control study. Consecutive patients with chronic hepatitis B (CHB) who lost HBsAg were matched with those remained positive for HBsAg with same age, gender, HBeAg status and presence of cirrhosis in 1:2 ratio. Relevant serum cytokines [interleukin (IL)-2, IL-3, IL-4, IL-7, IL-9, IL-10, IL-12, IL-15, IL-21 interferon-γ, tumour necrosis factor-α (TNF-α), granulocyte macrophage colony-stimulating factor (GM-CSF) and interferon-inducible protein 10 (IP-10)] were assayed at the time (Year 0) and 3 years before (Year -3) HBsAg seroclearance. RESULTS: Seventy-one and 142 CHB patients who did and did not achieve HBsAg seroclearance were included. Mean age was 48 ± 11 years; 76% were male, 20% had positive HBeAg, 99 (46%) patients received anti-viral therapy, and mean baseline HBV DNA was 3.78 ± 2.28 log IU/mL vs. 4.36 ± 2.13 log IU/mL respectively (P = 0.05). In those who achieved HBsAg seroclearance, serum IL-15 and GM-CSF levels decreased significantly from Year -3 to Year 0 (P = 0.017 and 0.05 respectively). When compared to controls, only serum IP-10 level was significantly lower at Year 0 than at Year -3 in patients with HBsAg seroclearance. Lower serum IP-10 level at Year 0 was the only factor associated with HBsAg seroclearance. There was no correlation between serum IP-10 and HBsAg levels around the time of HBsAg seroclearance. CONCLUSION: Lower serum IP-10 level at Year 0 was the only factor associated with HBsAg seroclearance.

Antiviral therapy improves post-hepatectomy survival in patients with hepatitis B virus-related hepatocellular carcinoma: a prospective-retrospective study.

BACKGROUND: The effect of antiviral therapy on the post-hepatectomy long-term survival in patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remains uncertain. AIM: To evaluate the effect of antiviral therapy on post-hepatectomy survival and recurrence in patients with HBV-related HCC. METHODS: This was a prospective-retrospective study of a total of 404 patients who underwent hepatectomy for HBV-related HCC in a tertiary academic hospital. Data on patient and tumour characteristics, tumour recurrence, treatment for recurrence and survival were compared between antiviral and no antiviral groups. RESULTS: Patient's and tumour characteristics were comparable between the two groups, except a higher proportion of patients with cirrhosis in the antiviral group. With a mean follow-up time of 52.4 months, antiviral group had a better 5-year overall survival (66.7% vs. 56.0%, P = 0.001) while there was no significant difference in the 5-year disease-free survival (44.7% vs. 38.1%, P = 0.166). Use of antiviral therapy was associated with better liver function reserve at the time of recurrence and a greater proportion of patients could receive curative treatment for recurrence (38.5% vs. 24.3%, P = 0.041). There was no significant different in the hazard ratios of patients who started antiviral therapy before or after operation (P = 0.054). CONCLUSIONS: Use of antiviral therapy improves the long-term post-hepatectomy survival in patients with HBV-related HCC. With a better liver function reserve at the time of recurrence, a greater proportion of patients in antiviral group could receive curative treatment for recurrence.

Combination therapy of interferon and nucleotide/nucleoside analogues for chronic hepatitis B.

Chronic hepatitis B is one of the leading causes of cirrhosis and hepatocellular carcinoma globally. At present, seven drugs, including two interferons and five oral nucleos(t)ide analogues (NAs), have been approved for the treatment of chronic hepatitis B. Interferon works by immunomodulation, but is successful in less than a third of treated patients and is a relatively weak antiviral. NAs directly suppress the hepatitis B virus but have limited durability. Based on current data, combination of NA and interferon results in greater viral suppression but does not translate to off-treatment sustained response. Concomitant or sequential treatment also does not make a difference. Combining telbivudine and interferon also runs the risk of severe peripheral neuropathy. On the other hand, interferon switch or additional therapy in patients well controlled with NAs appears to improve the durability of off-treatment response. This article reviews current data on interferon and NA combination and discusses potential future developments.

Metabolic syndrome delays HBeAg seroclearance in Chinese patients with hepatitis B.

BACKGROUND: Delayed hepatitis B e antigen (HBeAg) seroclearance increases the risk of cirrhosis and hepatocellular carcinoma (HCC). The effect of metabolic syndrome (MetS) on HBeAg seroclearance in chronic hepatitis B (CHB) patients remains unclear. AIMS: To examine the effect of MetS on HBeAg seroclearance. METHODS: A prospective cohort of 413 treatment-naïve HBeAg-positive CHB patients from 2005 to 2012 was studied. Clinical, virological and histological parameters were evaluated. The patients were classified into three groups according to the metabolic characteristics; normal, pre-MetS and MetS based on the International Diabetes Federation criteria. The primary outcome was age at HBeAg seroclearance. RESULTS: The overall HBeAg seroclearance rate was 11.4% per annum during 19 351 patient-months of follow-up with no difference in HBeAg seroclearance rates between 162 treatment-free and 251 patients receiving nucleos(t)ide analogues. Patients with pre-MetS and MetS were older when HBeAg seroclearance occurred (44 ± 12 and 53 ± 7 years, respectively) than the normal patients (37 ± 9 years, all P < 0.01). Patients with pre-MetS and MetS had more advanced liver fibrosis (33.0% and 53.1%, respectively) than the normal patients (18.4%, all P < 0.05). By the age of 50, 59.3% of the metabolic normal patients, 42.1% of the pre-MetS and 18.7% of the MetS patients had achieved HBeAg seroclearance (all P < 0.05, except P = 0.07 for pre-MetS vs. MetS). In multivariate analysis, MetS and type II diabetes at baseline were predictors of delayed HBeAg seroclearance after adjusting for viral load, anti-viral therapy and necroinflammatiom. CONCLUSION: Chinese patients with chronic hepatitis B and with pre-metabolic syndrome or metabolic syndrome have delayed HBeAg seroclearance.

Non-invasive algorithm of enhanced liver fibrosis and liver stiffness measurement with transient elastography for advanced liver fibrosis in chronic hepatitis B.

BACKGROUND: The accuracy of Enhanced Liver Fibrosis (ELF; ADVIA Centaur, Siemens Healthcare Diagnostics, Tarrytown, NY, USA) in assessing liver fibrosis in chronic hepatitis B (CHB) is to be determined. AIM: To derive and validate a combined ELF-liver stiffness measurement (LSM) algorithm to predict advanced fibrosis in CHB patients. METHODS: Using the data of a previously reported cohort of 238 CHB patients, an ALT-based LSM algorithm for liver fibrosis was used as a training cohort to evaluate the performance of ELF against liver histology. The best combined ELF-LSM algorithm was then validated in new cohort of 85 CHB patients not previously reported. RESULTS: In the training cohort, LSM has better performance of diagnosing advanced (≥F3) fibrosis (area under the receiver operating characteristics curve [AUROC] 0.83, 95% confidence interval [CI 0.76-0.91] than ELF (AUROC 0.69, 95% CI 0.63-0.75). The optimal cut-off values of ELF were 8.4 to exclude advanced fibrosis, and 10.8 to confirm advanced fibrosis. In the training cohort, an ELF ≤ 8.4 had a sensitivity of 95% to exclude advanced fibrosis; an ELF > 10.8 had a specificity of 92% to confirm advanced fibrosis. In the combined algorithm, low ELF or low LSM could be used to exclude advanced fibrosis as both of them had high sensitivity (≥90%). To confirm advanced fibrosis, agreement between high ELF and high LSM could improve the negative predictive value specificity (from 65% and 74% to 80%). CONCLUSIONS: An Enhanced Liver Fibrosis - liver stiffness measurement algorithm could improve the accuracy of prediction of either ELF or LSM alone. Liver biopsy could be correctly avoided in approximately 60% of patients.

Systematic review with meta-analysis: non-invasive assessment of non-alcoholic fatty liver disease--the role of transient elastography and plasma cytokeratin-18 fragments.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) affects 15-40% of the general population. Some patients have non-alcoholic steatohepatitis (NASH) and progressive fibrosis, and would be candidates for monitoring and treatment. AIM: To review current literature on the use of non-invasive tests to assess the severity of NAFLD. METHODS: Systematic literature searching identified studies evaluating non-invasive tests of NASH and fibrosis using liver biopsy as the reference standard. Meta-analysis was performed for areas with adequate number of publications. RESULTS: Serum tests and physical measurements like transient elastography (TE) have high negative predictive value (NPV) in excluding advanced fibrosis in NAFLD patients. The NAFLD fibrosis score comprises of six routine clinical parameters and has been endorsed by current American guidelines as a screening test to exclude low-risk individuals. The pooled sensitivities and specificities for TE to diagnose F ≥ 2, F ≥ 3 and F4 disease were 79% and 75%, 85% and 85%, and 92% and 92% respectively. Liver stiffness measurement often fails in obese patients, but the success rate can be improved with the use of the XL probe. A number of biomarkers have been developed for the diagnosis of NASH, but few were independently validated. Serum/plasma cytokeratin-18 fragments have been most extensively evaluated and have a pooled sensitivity of 66% and specificity of 82% in diagnosing NASH. CONCLUSIONS: Current non-invasive tests are accurate in excluding advanced fibrosis in NAFLD patients, and may be used for initial assessment. Further development and evaluation of NASH biomarkers are needed.

Reconstructive procedures for treating peri-implantitis: a systematic review.

This review aimed at evaluating the effectiveness of reconstructive procedures for treating peri-implantitis. Searches of electronic databases and cross-referencing were performed for human comparative clinical trials with ≥ 10 implants for ≥ 12 months of follow-up, reporting radiographic defect fill and at least one of the following parameters: probing depth reduction, clinical attachment level gain, bleeding on probing reduction, and mucosal recession. The searches retrieved 430 citations. Only 1 randomized controlled trial was identified, which compared reconstructive therapy and open flap debridement. Case series studies were also included to evaluate the overall performance of the reconstructive procedures. Twelve studies were finally included. Meta-analysis revealed that the weighted mean radiographic defect fill was 2.17 mm (95% confidence interval [CI]: 1.46-2.87 mm), probing depth reduction was 2.97 mm (95% CI: 2.38-3.56 mm), clinical attachment level gain was 1.65 mm (95% CI: 1.17-2.13 mm), and bleeding on probing reduction was 45.8% (95% CI: 38.5%-53.3%). Great variability in reparative outcomes was found, attributed to patient factors, defect morphology, and reconstructive agents used. Currently, there is a lack of evidence for supporting additional benefit of reconstructive procedures to the other treatment modalities for managing peri-implantitis.