Exploring autoantibodies as predictors of severe fibrosis or cirrhosis in metabolic dysfunction associated with steatotic liver disease.

Background: Metabolic dysfunction associated steatotic liver disease (MASLD) and metabolic dysfunction associated steatohepatitis (MASH) are rapidly growing public health concerns. Identifying predictive markers for advanced liver disease in MASLD patients is crucial for early intervention. This study investigates the association between autoantibody positivity and risk for severe fibrosis or cirrhosis across various subgroups. Methods: We conducted a retrospective study of adult patients diagnosed with MASLD between 1994 and 2019. Autoantibody status (anti-nuclear and anti-smooth muscle antibodies) was assessed using laboratory studies. Hepatic fibrosis or cirrhosis was determined histologically or through accepted non-invasive measures. Logistic regression analyses were employed to evaluate the association between autoantibody positivity and severe fibrosis or cirrhosis. Patients with comorbid viral and alcohol liver disease were assessed separately. Results: Among 2,749 MASLD patients, 1,425 (51.8%) were male and 1,324 (48.2%) were female, with a mean age of 58.7 years. A total of 541 (19.7%) patients tested positive for autoantibodies. Autoantibody positivity was associated with a higher risk of severe fibrosis or cirrhosis in MASLD patients (odds ratio 1.28, 95% CI [1.0-1.6]). This association persisted across various subgroups, including those with concurrent hepatitis B and C virus infections. In contrast, in alcohol liver disease, autoantibody-positive patients exhibited a lower risk. Conclusion: Autoantibody positivity emerges as a potential predictive marker for advanced liver disease in MASLD patients, facilitating risk stratification and tailored interventions. This study highlights the clinical relevance of autoantibodies in MASLD and underscores the need for prospective validation and mechanistic investigations to refine risk assessment and management strategies.

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.

Nationwide retrospective study of hepatitis B virological response and liver stiffness improvement in 465 patients on nucleos(t)ide analogue.

BACKGROUND: Hepatitis B virus (HBV) nucleos(t)ide analog (NA) therapy reduces liver disease but requires prolonged therapy to achieve hepatitis B surface antigen (HBsAg) loss. There is limited North American real-world data using non-invasive tools for fibrosis assessment and few have compared 1st generation NA or lamivudine (LAM) to tenofovir disoproxil fumarate (TDF). AIM: To assess impact of NA on virological response and fibrosis regression using liver stiffness measurement (LSM) (i.e., FibroScan®). METHODS: Retrospective, observational cohort study from the Canadian HBV Network. Data collected included demographics, NA, HBV DNA, alanine aminotransferase (ALT), and LSM. Patients were HBV monoinfected patients, treatment naïve, and received 1 NA with minimum 1 year follow-up. RESULTS: In 465 (median 49 years, 37% female, 35% hepatitis B e antigen+ at baseline, 84% Asian, 6% White, and 9% Black). Percentage of 64 (n = 299) received TDF and 166 were LAM-treated with similar median duration of 3.9 and 3.7 years, respectively. The mean baseline LSM was 11.2 kPa (TDF) vs 8.3 kPa (LAM) (P = 0.003). At 5-year follow-up, the mean LSM was 7.0 kPa in TDF vs 6.7 kPa in LAM (P = 0.83). There was a significant difference in fibrosis regression between groups (i.e., mean -4.2 kPa change in TDF and -1.6 kPa in LAM, P < 0.05). The last available data on treatment showed that all had normal ALT, but more TDF patients were virologically suppressed (< 10 IU/mL) (n = 170/190, 89%) vs LAM-treated (n = 35/58, 60%) (P < 0.05). None cleared HBsAg. CONCLUSION: In this real-world North American study, approximately 5 years of NA achieves liver fibrosis regression rarely leads to HBsAg loss.

The Effects of Pathogen-Associated Molecular Patterns on Peripheral Blood Monocytes in Patients with Non-alcoholic Fatty Liver Disease.

Background: Innate immune responses to gut-derived pathogen-associated molecular patterns (PAMPs) have been implicated in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). Whether NAFLD patients have increased sensitivity to PAMP exposure has yet to be reported. Methods: Peripheral blood mononuclear cell (PBMC)/monocytes were exposed to lipopolysaccharide (LPS), Pam3CSK4, or BSA conjugated palmitate in vitro. Changes in toll-like receptors (TLR), cytokines, and chemokine receptors (CR) expressions were documented by flow cytometry and/or enzyme-linked immunoabsorbent assays (ELISAs). Results: TLR2 and TLR4 expression were similar at baseline and increased to a similar extent (TLR2) or remained unchanged (TLR4) following PAMP exposure in NAFLD and healthy control (HC) monocytes. Proinflammatory IL-1ß and IL-6 levels were similar at baseline but increased in a concentration-dependent manner to a greater extent in NAFLD PBMCs. CCR1 and CCR2 expressions at baseline were similar and decreased to a similar extent in NAFLD and HC monocytes. The extent of PAMP-induced proinflammatory cytokine release correlated with evidence of hepatocyte injury (CK18M30 levels). Discussion: NAFLD patients have increased proinflammatory cytokine responses following exposure to PAMPs relative to HC subjects. This response is concentration-dependent and correlates with the extent of hepatic injury.

Molecular epidemiology and clinical characteristics of hepatitis D virus infection in Canada.

Background & Aims: HDV affects 4.5-13% of chronic hepatitis B (CHB) patients globally, yet the prevalence of HDV infection in Canada is unknown. To investigate the prevalence, genotype, demographics, and clinical characteristics of HDV in Canada, we conducted a retrospective analysis of (1) HDV antibody and RNA positivity among referred specimens, and (2) a cross-sectional subset study of 135 HDV seropositive +/-RNA (HDV+) patients compared with 5,132 HBV mono-infected patients in the Canadian HBV Network. Methods: Anti-HDV IgG-positive specimens collected between 2012 and 2019 were RNA tested and the genotype determined. Patients enrolled in the Canadian HBV Network were >18 years of age and HBsAg-positive. Clinical data collected included risk factors, demographics, comorbidities, treatment, fibrosis assessment, and hepatic complications. Results: Of the referred patients, 338/7,080 (4.8%, 95% CI 4.3-5.3) were HDV seropositive, with 219/338 RNA-positive (64.8%, 95% CI 59.6-69.7). The HDV+ cohort were more likely to be born in Canada, to be White or Black/African/Caribbean than Asian, and reporting high-risk behaviours, compared with HBV mono-infected patients. Cirrhosis, complications of end-stage liver disease, and liver transplantation were significantly more frequent in the HDV+ cohort. HDV viraemia was significantly associated with elevated liver transaminases and cirrhosis. Five HDV genotypes were observed among referred patients but no association between genotype and clinical outcome was detected within the HDV+ cohort. Conclusions: Nearly 5% of the Canadian HBV referral population is HDV seropositive. HDV infection is highly associated with risk behaviours and both domestic and foreign-born patients with CHB. HDV was significantly associated with progressive liver disease highlighting the need for increased screening and surveillance of HDV in Canada. Lay summary: Evidence of HDV infection was observed in approximately 5% of Canadians who were infected with HBV referred to medical specialists. HDV-positive patients were more likely to be male, born in Canada, or White or Black/African/Caribbean compared to Asian, and to have reported high-risk activities such as injection or intranasal drug use or high-risk sexual contact compared with patients infected with only HBV. Patients infected with HDV were also more likely to suffer severe liver disease, including liver cancer, compared with HBV mono-infected patients.

Comparison of growth features and cancer stem cell prevalence in intrahepatic and extrahepatic cholangiocarcinoma cell lines.

Aim of the study: Intra- and extrahepatic cholangiocarcinoma (I-CCA and E-CCA respectively) exhibit different growth features that contribute to different clinical outcomes. Cancer stem cells (CSCs) influence tumor growth and thereby may be responsible for these differences. The aim of this study was to document and compare the growth features of human I-CCA and E-CCA cell lines and determine whether any differences observed could be explained by differences in the prevalence and/or stem cell surface marker (SCSM) expression profiles of CSCs within the tumor cell lines. Material and methods: Six CCA cells lines, three I-CCA and three E-CCA, were studied. Tumor cell growth features including cell proliferation, colony/spheroid formation, migration and invasion were documented. CSC prevalence and SCSM expression profiles were examined by flow cytometry. Results: I-CCA cells had significantly increased proliferative activity, shorter doubling times and were more invasive than E-CCA cells, while colony/spheroid formation and migration were similar in the two cell populations. There were no significant differences in CSC prevalence rates or SCSM expression profiles. Conclusions: These findings suggest that I-CCA cells proliferate at a more rapid rate and are more invasive than E-CCA cells but the differences cannot be explained by differences in the prevalence or SCSM expression profiles of CSCs within the tumor cell population.

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.

Fibroblast Growth Factor 19 Induced Changes in Non-malignant Cholangiocytes.

BACKGROUND AND AIMS: Fibroblast growth factor (FGF)19 has been implicated in the pathogenesis of murine hepatocellular carcinoma. Whether it plays a role in the development or course of human cholangiocarcinoma remains to be determined. The aim of this study was to determine whether prolonged exposure to FGF19 results in the transformation of non-malignant human cholangiocytes into cells with malignant features. METHODS: Human SV-40 transfected non-malignant H69 cholangiocytes were cultured with FGF19 (0-50 ng/mL) for 6 weeks, followed by 6 weeks with medium alone. Cell proliferation, invasion, stem cell surface markers, oncofetoprotein expression, state of differentiation, epithelial-mesenchymal transition (EMT) and interleukin (IL)-6 expression were documented at various time intervals throughout the 12-week period. RESULTS: FGF19 exposure was associated with significant increases in cell proliferation, de-differentiation, EMT and IL-6 expression. However, each of these effects returned to baseline or control values during the 6-week FGF19 free follow-up period. The remaining cell properties remained unaltered. CONCLUSIONS: Six weeks of FGF19 exposure did not result in the acquisition of permanent malignant features in non-malignant, human cholangiocytes.

Pharmacokinetics of a once-daily tacrolimus formulation in first nations and caucasian liver transplant recipients.

Patient ethnicity may influence the pharmacokinetics (PK) of tacrolimus. Because the Canadian First Nations (FN) constitute a large and increasing segment of the liver transplant population, we undertook to determine whether PK differences exist for a once-daily, extended release formulation of tacrolimus (Advagraf) in FN compared to Caucasian (CAUC) liver transplant recipients. Following achievement of a steady state with Advagraf, blood samples were drawn at 0, 1, 2, 4, 6, 8 and 24 hours for whole blood tacrolimus levels by commercial immunoassay and CYP3A4 and CYP3A5 allele analyses were performed by polymerase chain reactions. Nineteen subjects participated in the study (7 FN and 12 CAUC). The FN cohort had significantly higher AUC (214 ± 48 versus 168 ± 25, P < 0.05), Cmax (16.7 ± 4.4 ng/ml versus 11.3 ± 1.7 ng/ml, P < 0.05), Cmin (6.1 ± 1.0 ng/ml versus 4.7 ± 0.5 ng/ml, P < 0.05) and shorter Tmax (1.6 ± 0.2 hours versus 2.8 ± 0.3 hours, P < 0.05) values than CAUCs. CYP3A4 genotypes were C/C in both cohorts, while the CYP3A5 *1/*3 allele was present in 2/5 FN and 0/9 CAUC. The results of this study indicate that once-daily, extended release Advagraf results in higher blood tacrolimus levels and shorter times to Cmax in FN compared to CAUC liver transplant recipients.

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.

Efficacy and Safety of Cenicriviroc in Patients With Primary Sclerosing Cholangitis: PERSEUS Study.

Primary sclerosing cholangitis (PSC) is a chronic cholestatic disease with no approved treatments. C-C chemokine receptor types 2 and 5 (CCR2/CCR5) play an important role in inflammation and fibrosis and are potential therapeutic targets for PSC. We evaluated the efficacy and safety of cenicriviroc (CVC), a dual antagonist of CCR2 and CCR5, for the treatment of PSC. This was a single-arm, open-label, exploratory study of CVC in adults with a clinical diagnosis of PSC, serum alkaline phosphatase (ALP) ≥1.5 times the upper limit of normal (ULN), with or without inflammatory bowel disease, across eight sites in the United States and Canada. The primary endpoint was percent change in ALP over 24 weeks; key secondary efficacy endpoints were proportion of participants who achieved ALP normalization and overall response (decrease to <1.5 times the ULN or 50% decrease). Of the 24 participants, 20 completed the study. The mean age was 43 years, 50% were female, and the mean body mass index was 25 kg/m2. From a median ALP baseline of 369 U/L (range: 173, 1,377 U/L), a median absolute reduction of 49.5 U/L (range: -460, 416 U/L) was achieved at week 24, corresponding to a median reduction of 18.0% (range: -46%, 89%). No participant achieved ALP normalization or a 50% decrease; 2 participants (10%) achieved a reduction in ALP to < 1.5 times the ULN, and 4 had ≥25% increase. Twenty participants (83.3%) reported at least one adverse event; most were mild to moderate in severity. The most frequent events were rash, fatigue, and dizziness. Conclusion: After 24 weeks of CVC treatment, adults with PSC achieved a modest reduction (median 18%) in the surrogate endpoint of ALP. CVC was well tolerated, and no new safety signals were observed. ClinicalTrials.gov identifier: NCT02653625.

The effects of binge drinking on healthy and diseased livers.

The estimated global prevalence of alcohol abuse is 5%-15%, with 15%-20% of these individuals being considered binge drinkers. Despite the high prevalence, the effects of binge drinking on healthy and diseased livers remain unclear. This review focuses on the effects of binge drinking in adults with otherwise healthy livers and those with a variety of common underlying chronic liver diseases.

Hepatic adenomatosis in a young woman with non-familial maturity-onset diabetes of the young type 3.

Hepatic adenomatosis (HA) is a rare condition in which multiple adenomas exist in an otherwise healthy liver. The most common subtype (H-HA) is associated with bi-allelic, somatic hepatic nuclear factor 1-alpha (HNF1A) mutations. Maturity-onset diabetes of the young type 3 (MODY3) is most often seen in young individuals with heterozygous, germline mutations in HNF1A. In this report, we describe a 17-year-old woman with H-HA and non-familial MODY3.

Liver enzymes and fibrosis markers in patients with non-alcoholic fatty liver disease and concomitant chronic viral hepatitis.

The impact of non-alcoholic fatty liver disease (NAFLD) on patients with chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections has yet to be determined. In this retrospective, cross-sectional analysis, untreated chronic HBV, hepatitis B e-antigen (HBeAg)-positive patients with NAFLD had similar liver biochemistry and FIB-4 values as age-, gender-, and viral-load-matched HBeAg-positive patients without NAFLD. Among HBeAg-negative patients with NAFLD, although liver biochemistry findings were similar, mean FIB-4 values were significantly lower (0.98, SD 1.46, versus 1.51, SD 4.04, respectively; p < 0.05) and the percentage of patients with FIB-4 values in keeping with advanced fibrosis or cirrhosis was less (0.3% versus 3.9%, p < 0.015) than that of matched HBeAg-negative patients without NAFLD. Chronic HCV-infected patients with NAFLD had higher mean serum aminotransferase values than those without NAFLD (123 U/L, SD 247, versus 90 U/L, SD 128, respectively; p < 0.05). These results suggest that NAFLD adversely affects chronic HCV infections but not HBV infections.

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.