Effect of nitric oxide delivery via cardiopulmonary bypass circuit on postoperative oxygenation in adults undergoing cardiac surgery (NOCARD trial): a randomised controlled trial.

BACKGROUND: Cardiac surgery involving cardiopulmonary bypass induces a significant systemic inflammatory response, contributing to various postoperative complications, including pulmonary dysfunction, myocardial and kidney injuries. OBJECTIVE: To investigate the effect of Nitric Oxide delivery via the cardiopulmonary bypass circuit on various postoperative outcomes. DESIGN: A prospective, single-centre, double-blinded, randomised controlled trial. SETTING: Rabin Medical Centre, Beilinson Hospital, Israel. PATIENTS: Adult patients scheduled for elective cardiac surgery were randomly allocated to one of the study groups. INTERVENTIONS: For the treatment group, 40 ppm of nitric oxide was delivered via the cardiopulmonary bypass circuit. For the control group, nitric oxide was not delivered. OUTCOME MEASURES: The primary outcome was the incidence of hypoxaemia, defined as a paO2/FiO2 ratio less than 300 within 24 h postoperatively. The secondary outcomes were the incidences of low cardiac output syndrome and acute kidney injury within 72 h postoperatively. RESULTS: Ninety-eight patients were included in the final analysis, with 47 patients allocated to the control group and 51 to the Nitric Oxide group. The Nitric Oxide group exhibited significantly lower hypoxaemia rates at admission to the cardiothoracic intensive care unit (47.1 vs. 68.1%), P = 0.043. This effect, however, varied in patients with or without baseline hypoxaemia. Patients with baseline hypoxaemia who received nitric oxide exhibited significantly lower hypoxaemia rates (61.1 vs. 93.8%), P = 0.042, and higher paO2/FiO2 ratios at all time points, F (1,30) = 6.08, P = 0.019. Conversely, this benefit was not observed in patients without baseline hypoxaemia. No significant differences were observed in the incidence of low cardiac output syndrome or acute kidney injury. No substantial safety concerns were noted, and toxic methaemoglobin levels were not observed. CONCLUSIONS: Patients with baseline hypoxaemia undergoing cardiac surgery and receiving nitric oxide exhibited lower hypoxaemia rates and higher paO2/FiO2 ratios. No significant differences were found regarding postoperative pulmonary complications and overall outcomes. TRIAL REGISTRATION: This trial was registered at ClinicalTrials.gov (NCT04807413).

Comparison of different definitions of metabolic syndrome and their associations with non-alcoholic fatty liver disease: a retrospective study.

Background: Metabolic syndrome (MetS) is considered an important risk factor for non-alcoholic fatty liver disease (NAFLD). The aim of this study was to measure the prevalence of MetS based on six different MetS definitions and compare the performance of various definitions for identifying diabetes, hypertension, and dyslipidemia among NAFLD patients. Methods: The definitions compared were those developed by the World Health Organization (WHO), National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III), International Diabetes Federation (IDF), American Association of Clinical Endocrinologists (AACE), American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI), and Interim Joint Statement "harmonized" criteria. Receiver operator characteristic (ROC) curves were plotted for the six MetS definitions with NAFLD diagnosis. The diagnosis for NAFLD was established based on liver imaging or biopsy compatible with fatty liver disease. Results: A total of 500 NAFLD patients were analyzed. The mean age was 61.2 (SD 13.2) years, and BMI was 32.7 (SD 8.0) kg/m2. The most prevalent MetS component was dyslipidemia (83%), followed by hypertension (60%), obesity (61%), and diabetes (57%). The prevalence of MetS according to the WHO, NCEP/ATP-III, IDF, AACE, AHA/NHLBI, and harmonized criteria was 69%, 59%, 54%, 64%, 78%, and 79%, respectively. The highest area under the ROC curve for diabetes and hypertension was with the WHO definition (0.7405) and (0.8120), respectively. Conclusions: The prevalence of MetS in NAFLD patients varies according to the definitions of MetS employed. The modified WHO definition appeared to be most useful for the screening of MetS in NAFLD patients.

Insulin secretion in liver transplant recipients following conversion to a prolonged release tacrolimus formulation.

Background: Post liver transplant diabetes mellitus (PLTDM) occurs in 10-40% of liver transplant recipients and is associated with increased morbidity and mortality. An important cause of PLTDM is tacrolimus induced, concentration-dependent, inhibition of insulin secretion. Objective: To determine if a newly licenced formulation of tacrolimus (Envarsus-PA), which achieves peak tacrolimus concentrations 20-30% lower than other tacrolimus formulations has less of an inhibitory effect on insulin secretion. Methods: Homeostatic model assessment (HOMA) for insulin secretion (HOMA-S) values and c-peptide levels were determined in 19 adult liver transplant recipients while being maintained on immediate- or slow-release tacrolimus formulations and repeated a minimum of 30 days following conversion to Envarsus-PA. Results: Insulin secretion was unchanged following conversion to Envarsus-PA (HOMA-S pre-conversion: 154 ± 133 vs. 129 ± 75, post-conversion [p = 0.32], and c-peptide levels; 1059 ± 602 and 934 ± 463 respectively, p = 0.42). Fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) levels were also unchanged (FBG 5.7 ± 0.8 pre-conversion vs. 5.6 ± 0.7 post-conversion; p = 0.36 and HbA1c 4.9±1.2 pre-conversion versus 5.5±0.2 post-conversion, p = 0.34). Conclusions: Envarsus-PA had no significant effect on insulin secretion or glucose homeostasis beyond that associated with other tacrolimus formulations in adult liver transplant recipients.

Binge drinking does not appear to have an adverse effect on non-alcoholic fatty liver disease: Findings from a study of four First Nations communities.

BACKGROUND: Binge drinking and non-alcoholic fatty liver disease (NAFLD) are common health problems throughout the world. However, the impact of binge drinking on NAFLD has yet to be described. The objective of this study was to document the extent of liver disease in community-based NAFLD patients who self-reported monthly binge drinking and compare the findings to NAFLD patients from the same communities who denied binge drinking (controls). METHODS: The study was undertaken in four Manitoba First Nations communities where the sale and consumption of alcoholic beverages are prohibited but visits to urban centres are common. Binge drinkers were retrospectively matched 1:2 by age, sex, and body mass index (BMI) with controls. NAFLD was diagnosed by ultrasonographic features of excess fat in the liver in individuals with no alternative, non-metabolic explanation for fatty infiltration of the liver. Hepatic inflammation and function were determined by standard liver biochemistry testing and fibrosis by FIB-4 levels and hepatic elastography. RESULTS: Of 546 NAFLD patients, 88 (16%) attested to binge drinking. The mean age of binge drinkers was 40 (SD 13) years; 51% were male; and the mean BMI was 34 (SD 7). Compared with controls, binge drinkers had similar liver biochemistry results (alanine and aspartate aminotransferases: 41 [SD 39] and 36 [SD 30] versus 36 [SD 36] and 31 [SD 27] U/L, p = 0.35 and p = 0.37, respectively), FIB-4 values (0.75 [SD 0.55] versus 0.72 [SD 0.44], p = 0.41, respectively), and hepatic elastrography (6.6 [SD 3.9] versus 6.2 [SD 2.9] kPa, p = 0.37, respectively) findings. CONCLUSIONS: In this study population, monthly binge drinking did not appear to impact the severity of NAFLD.

Clinical Outcomes and Quantitative HBV Surface Antigen Levels in Diverse Chronic Hepatitis B Patients in Canada: A Retrospective Real-World Study of CHB in Canada (REVEAL-CANADA).

BACKGROUND: Hepatitis B surface antigen (HBsAg) loss is associated with improved clinical outcomes for individuals with chronic hepatitis B (CHB); however, the effects of varying HBsAg levels on clinical outcomes in diverse cohorts are understudied. METHODS: In this cross-sectional, multicentre, retrospective study, the data on adult subjects enrolled in the Canadian HBV Network with CHB seen from 1 January 2012 to 30 January 2021 with the treatment and virologic data within 1 year of HBsAg testing were analyzed. Patients were tested for HBsAg using qualitative (for HBsAg-negative samples) and/or commercial quantitative assays. Fibrosis or hepatic necroinflammation was determined by the liver stiffness measurement (LSM). The baseline data were summarized using descriptive statistics and compared by using univariable/multivariable analyses. RESULTS: This study included 844 CHB patients, with a median age of 49.6 years (IQR 40.1-60.5), and 37% were female. In total, 751 patients (78.6%) had known ethnicity data, and 76.7% self-reported as Asian, 11.4% as Black, 6.8% as White, and 4.8% as other. Among the 844 patients, 237 (28.0%) were HBsAg (-) (1000 IU/mL. Overall, 80% (682) had known HBeAg status at the last follow-up, and the majority (87.0%) were HBeAg-negative. In addition, 54% (461/844) had prior antiviral therapy, 19.7% of which (16.3, 23.7, n = 91) were HBsAg (-). The treated patients had a lower risk of cirrhosis (16.46, 95% CI 1.89-143.39, p = 0.01) or HCC (8.23, 95% CI 1.01-67.39, p = 0.05) than the untreated patients. A lower proportion of the HBsAg-loss group had cirrhosis (5.7% vs. 10.9%, p = 0.021) and HCC (0.9% vs. 6.2%, p = 0.001). CONCLUSION: In this retrospective, ethnically diverse cohort study, CHB patients who received antiviral therapy and/or had HBsAg loss were less likely to develop cirrhosis and HCC, confirming the results of the studies in less diverse cohorts. No association was found between the qHBsAg level and fibrosis determined with LSM. Individuals who achieved HBsAg loss had low-level qHBsAg within 1 year of seroclearance.

Post-transplant diabetes mellitus in Canadian liver and renal transplant recipients.

BACKGROUND: Post-transplant diabetes mellitus (PTDM) occurs in 10%-40% of liver and renal transplant recipients. Whether the risk factors for PTDM in liver and renal transplant recipients are similar and whether Indigenous Canadians, who have a high underlying prevalence of diabetes mellitus (DM), are at increased risk of developing PTDM have yet to be determined. OBJECTIVE: To describe and compare those variables associated with PTDM in adult Canadian liver and renal transplant recipients. METHODS: A retrospective chart review of adult liver and renal transplant recipients attending four transplant follow-up clinics in three Canadian provinces was undertaken. RESULTS: De novo PTDM was diagnosed in 184/905 (20.3%) liver and 179/390 (45.9%) renal transplant recipients. Older age, higher pre-transplant BMI, underlying immune-mediated liver disease, lower trough tacrolimus levels and longer duration of follow-up were independently associated with PTDM in liver transplant recipients and non-Caucasian race, higher pre-transplant BMI, and incidence of organ rejection in renal transplant recipients. Compared with Caucasians, Indigenous Canadians who had undergone renal transplantation had a significantly increased prevalence of PTDM (56.5% versus 40.0%, p = 0.035). The prevalence of PTDM in liver transplant recipients was similar in Indigenous Canadians and Caucasians (27.9% versus 20.1%, p = 0.215). CONCLUSIONS: The variables associated with PTDM differ in liver and renal transplant recipients. Compared with Caucasians, Indigenous Canadians undergoing renal transplantation are at increased risk of developing PTDM.

Unconjugated hyperbilirubinemia may exacerbate certain underlying chronic liver diseases.

BACKGROUND: Negative correlations have been described between elevated serum unconjugated bilirubin levels and the prevalence/severity of various chronic inflammatory conditions. Whether a similar association exists for patients with unconjugated hyperbilirubinemia (UCB) and underlying chronic liver diseases (CLD) has yet to be reported. The aim of this study was to document hepatic necro-inflammatory disease activity and fibrosis in CLD patients with and without UCB and otherwise normal liver function tests (albumin and INR). METHODS: Necro-inflammatory disease activity was assessed by serum aminotransferase levels and fibrosis by APRI and FIB-4 calculations. UCB patients were matched 1:2 by age, gender, and underlying CLD to patients with normal bilirubin levels. RESULTS: From a database of 9,745 CLD patients, 208 (2.1%) had UCB and 399 served as matched controls. Overall, UCB patients had significantly higher serum aminotransferase levels, APRI, and FIB-4 scores. The differences were driven by patients with underlying chronic viral or immune mediated liver disorders rather than non-alcoholic fatty liver disease, alcohol-related liver disease, or 'other' CLDs. CONCLUSIONS: These results suggest UCB is associated with increased rather than decreased hepatic necro-inflammatory disease activity and fibrosis in patients with certain CLDs.

Social determinants and spatio-temporal variation of Ischemic Heart Disease in Manitoba.

INTRODUCTION: The aim was to study any spatial and/or temporal patterns of ischemic heart disease (IHD) prevalence and measure the effects of selected social determinants on these spatial and space-time patterns. METHODS: Data were obtained from the Population Research Data Repository housed at the Manitoba Centre for Health Policy to identify persons who were diagnosed with IHD between 1995 and 2018. These persons were geocoded to 96 geographic regions of Manitoba. An area-level socioeconomic factor index (SEFI-2) and the proportion of the population who was Indigenous were calculated for each geographic region using the 2016 Canadian Census data. Associations between these factors and IHD prevalence were measured using Bayesian spatial Poisson regression models. Temporal trends and spatio-temporal trends were measured using Bayesian spatio-temporal Poisson regression models. RESULTS: Univariable models showed a significant association with increased regional Indigenous population proportion associated with a higher prevalence of IHD (RR: 0.07, 95% CredInt: (0.05, 0.10)) and for SEFI-2 (RR: 0.17, 95% CredInt: (0.11, 0.23)). Using a multivariable model, after accounting for the proportion of the population that was Indigenous, there was no evidence of an association between IHD prevalence and area-level socioeconomic factor. Spatio-temporal models showed no significant overall temporal trend in IHD prevalence, but there were significant spatially varying temporal trends within the 96 regions. CONCLUSIONS: Association between Indigenous population proportion and IHD is consistent with previous research. No significant overall temporal trend was measured. However, regions with significantly increasing trends and significantly decreasing trends in IHD prevalence were identified.

Low serum alkaline phosphatase levels in patients with chronic liver diseases: Possible contributions to disease pathogenesis.

OBJECTIVES: A low serum alkaline phosphatase (ALP) level is an uncommon finding in patients with chronic liver disease (CLD). The prevalence of this finding and whether low ALP expression influences CLD remain to be determined. The objectives of this study were: (1) to document the prevalence of low serum ALP levels in adult CLD patients and (2) compare features of CLD in patients with low versus normal or elevated serum ALP levels. METHODS: An adult, outpatient liver disease database was searched for patients with low serum ALP levels (<40 IU/L). Hepatic inflammation, function, fibrosis and disease severity were determined by serum aminotransferases, albumin, bilirubin and INR levels, Fib-4 calculations and MELD scores respectively. RESULTS: Of 19,037 patients entered into the database, 47 (0.25%) had consistently low serum ALP levels, 51 (0.27%) low levels on the majority and 469 (2.44%) on the minority of determinations. Patients with consistently low levels were matched (1:2) by age, gender and nature of the underlying liver disease to patients with normal or elevated serum ALP levels. Matched patients with consistently low ALP levels had significantly lower serum aminotransferase and bilirubin levels at their initial visit and throughout the follow-up period (p < 0.05 respectively) while Fib-4 levels and MELD scores were similar at the initial and last follow-up visit. CONCLUSIONS: These results establish the prevalence of low serum ALP levels in adult CLD patients and describe a hitherto unreported association between low serum ALP levels and less biochemical evidence of active disease.

The impact of primary biliary cholangitis on non-alcoholic fatty liver disease.

BACKGROUND: The impact of chronic cholestatic liver diseases such as primary biliary cholangitis (PBC) on non-alcoholic fatty liver disease (NAFLD) has yet to be described. OBJECTIVES: To document and compare the severity and course of liver disease in patients with NAFLD/PBC versus NAFLD alone. METHODS: In this retrospective, case-control study 68 adult NAFLD/PBC patients were matched 1:2 for age and sex with 136 NAFLD alone patients. Disease activity and severity were documented by serum aminotransferases, albumin, bilirubin and international normalized ratio (INR) values and hepatic fibrosis by Fib-4 and aspartate aminotransferase/platelet ratio indices (APRI). RESULTS: On presentation (baseline), NAFLD/PBC patients had similar serum aminotransferase, albumin and bilirubin levels but lower INR values than NAFLD alone patients. Fib-4 and APRI levels were similar. Despite longer follow-up (favouring more advanced disease) in NAFLD/PBC patients, serum aminotransferases and bilirubin values were similar but albumin and INR levels significantly lower in NAFLD/PBC versus NAFLD alone patients at the end of follow-up. NAFLD/PBC patients also had significantly lower and less worsening of Fib-4 values at the end of follow-up. Transition from intermediate Fib-4 levels to those compatible with no or limited fibrosis was higher in NAFLD/PBC patients. CONCLUSION: These findings suggest PBC does not adversely affect the severity or course of NAFLD.

Spontaneous Flares of Chronic Hepatitis B Virus in Hepatitis Be Antigen Negative Carriers Who Subsequently Clear Hepatitis B Surface Antigen.

BACKGROUND: Acute exacerbations of chronic hepatitis B virus (HBV) infections can occur in HBV-infected, hepatitis e antigen (HBeAg)-negative patients in the absence of recent withdrawal of antiviral or immunosuppressive therapies. Whether these spontaneous "flares" predict subsequent loss of hepatitis B surface antigen (HBsAg) has yet to be determined. OBJECTIVES: To document the percent of patients who experience spontaneous HBV flares and severity of the flares in chronic HBeAg-negative carriers. METHODS: A retrospective review of an HBV database identified and followed HBeAg-negative patients for biochemical evidence of flares (ALT > 5× normal) and subsequent HBsAg status. Patients that subsequently cleared HBsAg were matched 1:1 with those who remained HBsAg positive. RESULTS: Of 1299 HBeAg-negative patients followed for 10.2 ± 6.1 years, 88 (6.8%) developed spontaneous HBV flares. Flares occurred in 14/115 (12.2%) patients who subsequently cleared HBsAg and 4/111 (3.6%) matched patients who remained HBsAg positive (p = 0.025). The severity of flares was similar in the two study cohorts. Following multivariate analyses, only low HBV-DNA levels at baseline identified patients likely to subsequently clear HBsAg. CONCLUSIONS: Although more common in patients who subsequently clear HBsAg, spontaneous HBV flares do not predict subsequent HBsAg clearance.

Chronic Liver Disease and Metabolic Comorbidities in Healthy Young Males Followed for 65 Years: The Manitoba Follow-up Study.

BACKGROUND & AIMS: The prevalence of chronic liver disease (CLD) is largely derived from cross-sectional epidemiologic surveys. The goal of this long-term, prospective study was to document the lifetime risk of developing chronic liver disease and determine the impact of common metabolic conditions associated with metabolic syndrome (MetS) on the development and outcomes of CLD. METHODS: 3,983 air force men were enrolled in the Manitoba Follow-up Study in 1948. The comprehensive database on results of routine physicals and health encounters was examined for evidence of CLD and MetS. The joint relationship between CLD and components of MetS on mortality was examined using Cox proportional hazard model. RESULTS: In 65 follow-up years, 5.2% of men developed CLD and 6.4% MetS. Hypertension was the strongest predictor of CLD (HR 2.958, 95% CI - 2.065 to 4.236, p < .0001), followed by insulin resistance /diabetes mellitus (IR/DM) (2.008, 95% CI - 1.332 to 3.027, p = .0009) and obesity (1.958, 95% CI - 1.419 to 2.703, p < .0001). Relative to men without MetS comorbidities, an increasing gradient of risk for CLD was apparent with increasing numbers of MetS components; the HR of 3.67, 5.97 and 14.3 for IR/DM, IR/DM + one component, and IR/DM + two or more components respectively. The relative risk of mortality in men with vs. without CLD was 3.33 (95% CI - 2.83 to 3.91, p < .0001) and 1.505 (95% CI - 1.31 to 1.73, p < .0001) in men with vs. without MetS. CONCLUSIONS: CLD and MetS independently increase the relative risk of mortality; the magnitude of the effect is greater in CLD.

Non-Wilson's Disease-Associated Hypoceruloplasminemia.

INTRODUCTION AND AIM: Low serum ceruloplasmin levels can occur in patients without Wilson's disease (WD) liver disorders. When present, extensive, costly, and potentially harmful additional investigations for WD may be undertaken. The purpose of this study was to document the prevalence of low serum ceruloplasmin levels in adult patients without WD and describe the features commonly associated with this finding. MATERIALS AND METHODS: Serum ceruloplasmin levels were measured by an enzymatic assay in 3040 adult patients attending an urban, liver diseases outpatient clinic. RESULTS: A total of 122 (4.0%) patients without WD had serum ceruloplasmin levels less than the lower limit of normal documented at their initial visit. Their mean age was 44 ± 14 years, and 80 (66%) were men. The Model for End-stage Liver Disease (MELD) score was 9.0 ± 4.0. Approximately, one half (65/122, 53%) had underlying viral hepatitis (52% hepatitis B and 48% hepatitis C). When compared with 64 MELD-matched control patients with normal or elevated serum ceruloplasmin levels, there were no significant differences in liver enzyme/function tests, ferritin, creatinine values, or survival. However, the low serum ceruloplasmin cohort patients were younger (43 ± 14 versus 52 ± 13 years, p = 0.0002), less often men (66% vs. 88%, p = 0.001), and viral hepatitis was significantly more common (53% versus 27%, p = 0.0005). CONCLUSION: Low serum ceruloplasmin levels were documented in 4.0% of adult patients without WD attending this urban liver diseases outpatient clinic. These patients tend to be younger, less often men, and more often have viral hepatitis as the underlying cause of their liver disease.

The effects of hyperthermia on human hepatocellular carcinoma stem and mature cancer cells.

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) can recur following radiofrequency ablation and other hyperthermic treatment modalities. Cancer stem cells (CSCs) are a subpopulation of HCC cells that are difficult to eradicate and largely responsible for tumor recurrences. Thus, the principal objective of this study was to determine whether human HCC CSCs are relatively thermal-resistant compared to non-stem or mature cancer cells (MCCs). MATERIALS AND METHODS: Epithelial cell adhesion molecule (EpCAM) positive enriched CSCs and EpCAM- MCCs were derived from a human HCC cell line using fluorescence activated cell sorting. Each cell population was exposed to 65°C heat for 0-16min and survival documented at various time points. RESULTS: Cell survival curves were similar in CSC and MCCs throughout the 16min heat exposure period. Maximum killing was obtained after 12-14min of heat exposure. Cytoprotective, heat shock proteins-70 (HSP70) and -90 (HSP90) mRNA expression were not disproportionately increased in CSCs. CONCLUSIONS: These results suggest that human HCC CSCs are not more thermal resistant than MCCs and therefore, do not support the hypothesis that HCC recurrences following hyperthermic treatment reflect CSC thermal-resistance.

Serum immunoglobulin A levels and alcohol-induced liver disease.

Background: Recent data suggest intestinal immunity including immunoglobulin A (IgA) may contribute to the pathogenesis of alcohol-induced liver disease (ALD). Methods: We documented serum IgA levels in ALD patients and determined whether those with elevated levels of IgA (E-IgA) had similar, more, or less advanced disease and different rates of progression than those with normal levels of IgA (N-IgA). Standard liver function tests (bilirubin, international normalized ratio [INR], and albumin), model for end-stage liver disease (MELD), and Fibrosis-4 (FIB-4) scores were used as indicators of disease severity. Results: From the study centre's clinical database, we identified 175 adult patients with ALD, 107 (61%) with E-IgA and 68 (39%) with N-IgA. Gender distribution and mean age of the two cohorts were similar. E-IgA patients had biochemical evidence of more advanced liver disease (higher serum bilirubin and INR and lower albumin levels) than N-IgA patients (ps < .05). E-IgA patients also had significantly higher median MELD and FIB-4 scores (ps < .01). A higher percentage of E-IgA patients had FIB-4 values in keeping with advanced fibrosis or cirrhosis (55% versus 28%, p = .02). After mean follow-up periods of approximately 4 years, liver biochemistry and MELD and FIB-4 scores changed to similar extents in the two cohorts. Conclusions: Serum IgA levels were increased in approximately 70% of ALD patients. Although these patients had biochemical and non-invasive indicators of more advanced disease, elevations in serum IgA levels do not predict disease progression; therefore, IgA is unlikely to be of importance in the pathogenesis of ALD.

The relative expression of hepatocellular and cholestatic liver enzymes in adult patients with liver disease.

INTRODUCTION AND OBJECTIVES: Hepatocellular liver injury is characterized by elevations in serum alanine (ALT) and aspartate (AST) aminotransferases while cholestasis is associated with elevated serum alkaline phosphatase (ALP) levels. When both sets of enzymes are elevated, distinguishing between the two patterns of liver disease can be difficult. The aim of this study was to document the predicted ranges of serum ALP values in patients with hepatocellular liver injury and ALT or AST values in patients with cholestasis. MATERIALS AND METHODS: Liver enzyme levels were documented in adult patients with various types and degrees of hepatocellular (non-alcoholic fatty liver disease, hepatitis B and C, alcohol and autoimmune hepatitis) and cholestatic (primary biliary cholangitis and primary sclerosing cholangitis) disease. RESULTS: In 5167 hepatocellular disease patients with ALT (or AST) values that were normal, 1-5×, 5-10× or >10× elevated, median (95% CI) serum ALP levels were 0.64 (0.62-0.66), 0.72 (0.71-0.73), 0.80 (0.77-0.82) and 1.15 (1.0-1.22) fold elevated respectively. In 252 cholestatic patients with ALP values that were normal, 1-5× or >5× elevated, serum ALT (or AST) values were 1.13 (0.93-1.63), 2.47 (2.13-2.70) and 4.57 (3.27-5.63) fold elevated respectively. In 56 patients with concurrent diseases, ALP levels were beyond predicted values for their hepatitis in 38 (68%) and ALT (or AST) values beyond predicted values for their cholestatic disorder in 24 (43%). CONCLUSIONS: These data provide health care providers with predicted ranges of liver enzymes in patients with hepatocellular or cholestatic liver disease and may thereby help to identify patients with concurrent forms of liver disease.

Epidemiologic and clinical features of chronic hepatitis B virus infection in 8 Canadian provinces: a descriptive study by the Canadian HBV Network.

BACKGROUND: Published Canadian epidemiologic data on hepatitis B virus (HBV) infection include single-centre studies or are focused on Indigenous populations. We performed a study to characterize the demographic and clinical features, liver disease status and treatment of people with chronic hepatitis B in Canada. METHODS: In this descriptive, opportunistic, cross-sectional study, available data for people known to be monoinfected with HBV were collected by the Canadian HBV Network from existing clinical databases, with support from the National Microbiology Laboratory, Public Health Agency of Canada. Data were collected in all provinces with the exception of New Brunswick and Newfoundland and Labrador. We analyzed the data using parametric and nonparametric statistical methods, with a significance level of p < 0.05. RESULTS: In the 9380 unique patient records reviewed, the median age was 48 years, and 5193 patients (55.4%) were male. Ethnicity information was available for 7858 patients, of whom 5803 (73.8%) were Asian, 916 (11.6%) were black and 914 (11.6%) were white. Most of those tested (5556/6796 [81.8%]) were negative for HBV e-antigen, and most of those with fibrosis data (3481/4260 [81.7%]) had minimal liver fibrosis, with more advanced fibrosis noted in older people (> 40 yr). Of the 980 patients with genotype data, 521 (53.2%) had genotype B or C infection. Most of the 9241 patients with known confirmed treatment status received tenofovir disoproxil fumarate (1655 [17.9%]), lamivudine (1434 [15.5%]) or entecavir (548 [5.9%]). INTERPRETATION: Based on available data, Canadian patients with chronic hepatitis B are predominantly Asian and negative for HBV e-antigen, and have genotype B or C infection. Interprovincial variations were noted in antiviral treatment regimen. This multicentre nationwide study provides data regarding patients with chronic hepatitis B and may inform future studies on the epidemiologic features of HBV infection in Canada.

Changing incidence of reported viral hepatitis in China from 2004 to 2016: an observational study.

OBJECTIVE: China's national hepatitis burden is high. This study aims to provide a detailed national-level description of the reported incidence of viral hepatitis in China during 2004-2016. DESIGN: Observational study. SETTING: Data were obtained from China's National Notifiable Disease Reporting System, and changing trends were estimated by joinpoint regression analysis. PARTICIPANTS: In this system, 16 927 233 reported viral hepatitis cases occurring during 2004-2016 were identified. PRIMARY OUTCOME MEASURE: Incidence rates per 100 000 person-years and changing trends were calculated. RESULTS: There were 16 927 233 new cases of viral hepatitis reported in China from 2004 to 2016. Hepatitis B (HBV) (n=13 543 137, 80.00%) and hepatitis C (HCV) (n=1 844 882, 10.90%) accounted for >90% of the cases. The overall annual percent change (APC) in reported cases of viral hepatitis and HBV were 0.3%(95% CI -2.0 to 0.8, p=0.6) and -0.2% (95% CI -1.6 to 1.2, p=0.8), respectively, showing a stable trend. HBV rates were highest in the 20-29 year old age group and lowest in younger individuals, likely resulting from the universal HBV vaccination. The reported incidence of HCV and hepatitis E (HEV) showed increasing trends; the APCs were 14.5% (95% CI 13.1 to 15.9, p<0.05) and 4.7% (95% CI 2.8 to 6.7, p<0.05), respectively. The hepatitis A (HAV) reporting incidence decreased, and the APC was -13.1% (95% CI -15.1 to -11.0, p<0.05). There were marked differences in the reporting of hepatitis among provinces. CONCLUSIONS: HBV continues to constitute the majority of viral hepatitis cases in China. Over the entire study period, the HBV reporting incidence was stable, the HCV and HEV incidence increased and the HAV incidence decreased. There were significant interprovincial disparities in the burden of viral hepatitis, with higher rates in economically less-developed areas. Vaccination is important for viral hepatitis prevention and control.

The Impact of Gender on Interferon-Associated Depression and Anxiety.

Population studies indicate women have higher prevalences of depression and anxiety than men. Interferon (IFN) is a biologic agent that can induce or exacerbate depression and/or anxiety. Whether women are more likely to experience these side effects of IFN during treatment remains to be determined. The aim of this study was to document levels of depression and anxiety in female and male patients before and during IFN-based treatment. This was a prospective open-label study in which depression was measured by Beck Depression Inventory (BDI) and anxiety by Hospital Anxiety and Depression Scale (HADS). Before treatment, the prevalence of depression was higher in females (3/13 [23%]) than males (1/25 [4%]), but the difference did not reach statistical significance (P = 0.12). Initial BDI scores were also higher in females but not significantly (P = 0.07). During treatment, BDI scores increased to a similar extent in both genders. A similar percentage of nondepressed patients at baseline developed depression (females: 50% versus males: 35%, P = 0.45). Before treatment, anxiety was significantly more common in females (7/13 [54%]) than males (3/25 [12%]) (P = 0.016) and median HADS scores were higher in females (P = 0.03). During treatment, increases in HADS scores were similar in the 2 genders. A similar percentage of patients without anxiety at baseline developed anxiety on treatment (females: 50% versus males: 23%, P = 0.31). The frequency and extent of IFN-induced/exacerbated depression and anxiety are not gender dependent.

Serial liver transaminases have no prognostic value in non-alcoholic fatty liver disease.

Background: Routine measurement of liver transaminases is common in the general monitoring of patients with non-alcoholic fatty liver disease (NAFLD), but there is little data to support the utility of this practice. The aims of this study were to determine how alanine aminotransferase (ALT) results vary over time in patients with NAFLD; and to determine if serial measurement of ALT is a useful clinical marker for progression of NAFLD. Methods: Consecutive adult patients with NAFLD were followed prospectively in a tertiary liver disease clinic over a 15-year period. Clinicodemographic characteristics and the change in liver enzymes, liver function, and histopathology were followed over time. Paired t test, chi-square test, analysis of variance (ANOVA), and logistic regression were performed to assess the relationship between ALT and severity of NAFLD, or development of cirrhosis or hepatocellular carcinoma (HCC). Results/Conclusion: A change in liver transaminases over time is not a useful metric in predicting outcomes in patients with NAFLD. Additionally, all stages of NAFLD are equally responsive to standard medical interventions of advocating for weight loss and correcting metabolic disturbances.