Background: Albumin platelet product (APP) is a novel blood-based biomarker for liver fibrosis staging. This study evaluates APP's performance against Fibrosis-4 index (FIB-4), AST-platelet ratio index (APRI), and aspartate aminotransferase-alanine aminotransferase (AST/ALT) ratio in diagnosing advanced fibrosis and cirrhosis in metabolic dysfunction-associated steatotic liver disease (MASLD) patients with and without diabetes (DM). Method: Adults with MASLD/metabolic dysfunction-associated steatohepatitis (MASH) in 2010-2023 and available fibrosis staging biomarkers were included. Clinical fibrosis staging was confirmed by liver biopsy, transient elastography (FibroScan), and/or magnetic resonance elastography. Fibrosis staging-matched fibrosis biomarkers were calculated and analyzed. Results: A total of 570 patients (48.6% male) with available clinical staging and biomarkers were analyzed. DM was present in 38% of the cohort with a significantly higher prevalence among those with advanced fibrosis or cirrhosis (p < 0.001). APP and FIB-4 showed comparable diagnostic performance with areas under the curve (AUCs) of 0.85 (95% CI 0.82-0.88) and 0.84 (95% CI 0.81-0.87), both significantly outperforming APRI and AST/ALT ratio (AUC 0.76, p < 0.05). Importantly, all AUCs were significantly lower in the DM cohort. In patients with DM, APP outperformed FIB-4 in detecting cirrhosis (AUC 0.80 versus 0.76, p = 0.04) and was comparable for advanced fibrosis. In the non-DM cohort, APP and FIB4 performed similarly (AUCs 0.84-0.89, p > 0.05). Conclusion: APP outperformed FIB4 in detecting cirrhosis or advanced fibrosis among patients with DM and was comparable in non-DM patients. Revised FIB-4 thresholds may be needed in MASLD/MASH patients with DM to improve its diagnostic accuracy.

Background: Lysosomal acid lipase deficiency (LAL-D) is a rare autosomal recessive disorder caused by mutations in the LIPA gene, leading to accumulation of cholesterol esters and triglycerides, particularly in the liver and spleen. The disease manifests as either severe infantile Wolman disease or the milder chronic cholesteryl ester storage disease (CESD). Enzyme replacement therapy (ERT) with sebelipase alfa (Kanuma) has shown potential in reducing hepatic and lipid abnormalities.Methods: We present a case of a 41-year-old female with biopsy-confirmed CESD and cirrhosis, diagnosed in childhood. She was enrolled in the 2015 phase 3 clinical trial for Kanuma and continued on biweekly ERT thereafter. Serial liver imaging and biopsies were performed between 2002 and 2023 to monitor fibrosis progression or regression.Results: Initial fibrosis staging progressed to cirrhosis (Metavir F4) by 2016. Despite persistently elevated lipid levels (LDL 3.81 mmol/L in 2025), MR elastography and liver biopsy in 2023 demonstrated regression of fibrosis to stage 1-2 and histologic signs of cirrhosis reversal while she was taking Kanuma. This occurred in the absence of significant hepatic steatosis or iron overload.Conclusions: This case highlights the potential for long-term Kanuma therapy to reverse liver fibrosis in LAL-D, even with ongoing dyslipidemia. While early initiation of ERT may optimize outcomes, this case supports its continued use in advanced disease stages. Further research is needed to assess the long-term metabolic and histologic benefits of ERT in LAL-D patients.

Background Older adults with cirrhosis have complex medical needs that are not satisfied by organ specific management. Interdisciplinary approach may mitigate comorbidity and improve patient satisfaction. Methods A pilot study consisted of dual specialist interdisciplinary referral pathway and mixed virtual care delivery model are prospectively evaluated in older adults (65 years and older) with cirrhosis during the COVID-19 pandemic between September and December 2022. Participant attitudes towards telemedicine were surveyed. Results 68 participants with cirrhosis were consecutively assessed by hepatology. The mean age was 73 years. 39 (57%) screened positive for one or more geriatric syndrome(s). Comprehensive geriatric assessments were conducted via telemedicine in 18 participants, with additional referrals to physiotherapy and nutritional education. Compared to a historic cohort matched for age, sex, and Child-Pugh class, acute health service utilization measured by ER visits among those received dual specialist interdisciplinary consultation were lowered by 1.11 per patient at three-month follow up period (p = .0006, 95% CI 0.47–1.74). Majority participants (87.6%) preferred telemedicine or mixed method visits. Conclusion An interdisciplinary approach to older adults with cirrhosis will likely be beneficial, and routine screening for geriatric syndrome may lead to reduced acute health-care utilization in the short term. Telemedicine and virtual screening tools in seniors should be fully explored to improve access to care.

Background: Steatotic liver disease (SLD) may be caused by cardiometabolic risk factors, drugs/toxins, viral hepatitis, genetic diseases, malnutrition, or panhypopituitarism. SLD can advance to steatohepatitis with resulting lipid accumulation, inflammation, and hepatocellular damage. SLD is associated with pituitary dysfunction, in particular growth hormone deficiency, as insulin resistance leads to lipid buildup and oxidative stress. Growth hormone replacement may improve liver steatosis and fibrosis in patients with hypopituitarism. Case: We report a case of a 20-year-old man who was referred to Hepatology with abnormal liver enzymes. He had panhypopituitarism from a resected pituitary mass, for which he was treated with levothyroxine, hydrocortisone, growth hormone, and testosterone. He presented with elevated liver enzymes, normal liver function, obesity, dyslipidemia, and had no extrahepatic manifestations of chronic liver disease. Work-up for secondary causes of liver disease, including infectious, autoimmune, drug-induced, and genetic causes, were negative. An abdominal ultrasound revealed moderate hepatic steatosis with mild hepatomegaly and splenomegaly. His liver enzymes remained elevated, and his biochemical liver function remained normal despite withdrawal of hepatotoxic medications. Liver biopsy showed grade II/III steatohepatitis with stage III-IV fibrosis. The biopsy results suggested that panhypopituitarism, with growth hormone deficiency and related metabolic dysfunction, caused his liver disease. Conclusions: This is a unique case of an aggressive form of SLD due to panhypopituitarism, and treating growth hormone deficiency with hormone replacement did not improve liver enzymes or liver damage. Physicians should recognize SLD as a serious complication of panhypopituitarism and resulting growth hormone deficiency and follow patients closely given the risk of disease progression.

Sarcoidosis is a multi-organ inflammatory disease that can have hepatic involvement in up to 80% of cases. Rarely, sarcoidosis can manifest with only confined disease to the liver. While most patients with hepatic sarcoidosis are clinically silent, certain cases can have insidious onset leading to cirrhosis and secondary complications. Here, we describe three cases of isolated hepatic sarcoidosis to illustrate the range of presentations that may be associated with this condition. Clinicians should be vigilant in consideration of hepatic sarcoidosis as a culprit when investigating patients with undifferentiated liver disease.

BACKGROUND: Persons with primary biliary cholangitis (PBC) experience significantly higher rates of mental distress and impaired health related quality of life (HrQoL) than the general population. Given limited evidence, but a high need, our primary aim was to assess feasibility and acceptability of a 12-week, online, mind-body wellness program in people with PBC. METHODS: This was a single-group, sequential mixed-methods, pre-post feasibility, and acceptability study. Core program components included follow-along movement, meditation and breathwork videos, and cognitive behavioural therapy informed activities. This was supplemented by weekly phone check-ins. Feasibility was assessed by recruitment, adherence, and retention. The pre-post exploratory efficacy assessment included surveys for fatigue, perceived stress, anxiety, depression, HrQoL, and resilience. A qualitative descriptive approach with semi-structured interviews evaluated study experiences. RESULTS: Thirty-two participants were recruited within 30 days and 29 (91%) were retained to end-of-study. Of these, 25 (86%) adhered to carrying out the mind-body practice at least 2-3 days per week. Feedback supported acceptability (satisfaction score 90%). Significant improvements were observed in fatigue (13%, p = 0.004), anxiety (30%, p = 0.005), depression (28%, p = 0.004), and five PBC-40 domains (itch, fatigue, cognitive, emotional, general symptoms). Qualitative interviews revealed improved stress management, better coping, and a more positive mindset. Fatigue and self-sabotaging thoughts were cited as barriers to participation. CONCLUSIONS: These findings suggest that a 12-week online mind-body intervention is feasible and acceptable in patients with PBC. After iterative refinement, a randomized controlled trial will be designed using this feedback.

Managed alcohol programs aim to reduce health and social harms associated with severe alcohol use disorder. Here, we describe a young man with severe alcohol use disorder enrolled in a managed alcohol program, who was admitted to hospital with acute liver injury. Fearing that alcohol was contributing, the inpatient care team discontinued the managed alcohol dose in hospital. He was ultimately diagnosed with cephalexin-induced liver injury. After consideration of risks, benefits, and alternative options, the patient and care team jointly decided to restart managed alcohol after hospital discharge. With this case, we describe managed alcohol programs and summarize the emerging evidence-base, including eligibility criteria and outcome measures; we explore clinical and ethical dilemmas in caring for patients with liver disease within managed alcohol programs; and we emphasize principles of harm reduction and patient-centered care when establishing treatment plans for patients with severe alcohol use disorder and unstable housing.

A 45-year-old female presented to hospital with confusion and visual disturbances. She had undergone a liver transplant 3 years prior for cirrhosis secondary to primary biliary cholangitis. Computed tomography and magnetic resonance imaging of the brain showed features consistent with posterior reversible encephalopathy syndrome. Her medications included tacrolimus, sirolimus, and prednisone. She reported smoking 4 grams of cannabis per day. Following cessation of tacrolimus, the patient's encephalopathy and visual disturbances resolved. To our knowledge, this case represents the longest time elapsed from liver transplantation to the development of tacrolimus-associated posterior reversible encephalopathy syndrome in the literature. This case highlights the potential danger of cannabis use in transplant recipients who are on immunosuppressants such as tacrolimus. Clinicians should have a high index of suspicion for posterior reversible encephalopathy syndrome in post-transplant patients presenting with altered mental status, even years after liver transplantation, and be familiar with potential interactions between cannabis and immunosuppressants.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is becoming the most common cause of liver disease as well as the most common indication for liver transplantation in Canada. Treatment options are limited as there are currently no approved medications to treat NAFLD. There are many molecules in development and prospects for a treatment in the near future. As therapeutic options for the treatment of NAFLD expand, there will be a large number of patients who may undergo liver biopsy to risk stratify those patients at highest risk of progression of their fibrosis. Accordingly, it is important to validate the safety of liver biopsy in this patient population. Methods: A retrospective chart review was performed on all patients with NAFLD who underwent outpatient elective percutaneous and transjugular liver biopsies at a tertiary care hospital from 2010 to 2020. We excluded inpatient biopsies, surgical biopsies, allograft biopsies, and targeted liver biopsies. We collected gender, age, and pre-biopsy platelets/INR/PTT. For each biopsy reviewed, we recorded the route used to obtain the biopsy (percutaneous or transjugular), indication for the liver biopsy, and the results of the biopsy. We recorded all complications up to one week post-procedure. Results: There were 582 biopsies reviewed in total, 540 (92.8%) percutaneous and 42 (7.2%) transjugular. The mean age was 53.1 (±11.2). There was an even proportion of males to females (291 each). The mean fibrosis stage was 1.9 (±1.4), platelet count was 223.9 (±83.7), INR 1 (±0.1), and PTT 31 (±3.9). There were no mortalities related to liver biopsy observed in our study period. Major complications occurred in 8 out of 582 biopsies (1.4%). Bleeding accounted for 6 of the major complications observed, while infection and pneumoperitoneum each occurred once. We did not identify any statistically significant associations between fibrosis stage, age, sex, platelet count, INR and major complication rates. Conclusion: This is the first study to evaluate the complication of outpatient liver biopsies in patients with NAFLD. We found that major complications occurred in 1.4% of all biopsies. There were no mortalities observed in our study. Our results are consistent with previous studies examining complication rates in heterogenous populations and support the overall safety of liver biopsies.

BACKGROUND: With new treatments for non-alcoholic fatty liver disease (NAFLD) on the horizon, it will be important to risk-stratify patients based on degree of fibrosis to allocate treatment to those at highest risk. No studies have examined the complication rates of liver biopsies in patients with NAFLD in the outpatient setting. METHODS: We conducted a retrospective chart review of all outpatient elective liver biopsies for NAFLD at a tertiary care centre over a 10-year period. Demographic variables and stage of fibrosis were recorded. Complications up to 1-week post-procedure were recorded. We used univariate logistic regression models to estimate the odds of major complications by fibrosis stage, age, sex, platelets, and international normalized ratio (INR). RESULTS: There were 582 biopsies reviewed in total. The mean age was 53 years. There was an even proportion of males to females. The mean fibrosis stage was 1.9; platelet count was 223.9, INR was 1, and partial thromboplastin time (PTT) was 31. Major complications occurred in 8 out of 582 biopsies (1.4%). Bleeding accounted for 6 of the major complications observed, while infection and pneumoperitoneum each occurred once. There were no statistically significant associations between age (odds ratio [OR] 0.97, 95% CI 0.92-1.03), female sex (OR 1.00, 95% CI 0.25-4.04), platelet count <150 (OR 0.59, 95% CI [-inf.], 3.86), INR >1.3 (OR 0.47, 95% CI 0.057-3.85), fibrosis stage, and complication rate. CONCLUSIONS: Our results are consistent with previous studies examining complication rates in other patient populations and clinical settings and support the overall safety of liver biopsies.

Manzano-Robleda MC, et al. This article should appeal to health insurance payers and policy makers who are in the business of management of hepatitis C infection, especially within health care systems that will not have access immediately to the newer directacting antiviral agents which were reviewed recently in the Annals of Hepatology.1 In this meta-analysis, data were extracted systematically allowing guidance regarding efficacy of treating chronic hepatitis C infection using first generation protease inhibitors (PI): boceprevir and telaprevir, no matter if patients were previously exposed to pegylated interferon plus ribavirin (PR). The results of this study may also assist clinicians the usage of old drugs with better outcomes especially when individualized treatments of hepatitis C genotype 1 are considered. The goal of this systematic analysis was to summarize the world literature for predictors of the primary outcome for sustained viral response (SVR) defined as negative viral load at week 12 or 24. After analysis of 33 studies (10,525 patients) with a meta-regression, previously treated patients exhibited greater benefit from PI + PR (RR, 3.47) but minimal adverse events (RR, 1.01) and low discontinuation rate (RR, 1.69). Furthermore, if there was any doubt about it, the study confirmed that PRtreated patients have a very low probability of achieving an SVR with a new round of PR treatment (17%), whereas treatment-naïve patients receiving PR achieved only 41% SVR. Predictors of greater SVR included IL-28 genotype TT, non-black race, low viral load, younger age, absence of cirrhosis, statin use, undetectable viral load at the first anemia episode or at week 2 of treatment, and low IL-6 levels. This type of analysis allows the identification of potential factors that may be utilized for individualized treatment of patients with better outcomes. Unfortunately, in the absence of the primary datasets from all 33 studies, more specific conclusions cannot be made regarding independent predictors of SVR. Practically, most of us have been using undetectable viral load at week-2 as a predictor of SVR especially when IL-28 genotyping is not available. The authors are right! The newer direct-acting antiviral agents will take over chronic hepatitis C infection treatment but not until payers and policy makers appreciate the advantages of direct-acting antiviral agents in spite their expense tags. Most clinicians who have been treating hepatitis C for the last two decades have moved on and will be unlikely use PI + PR as an alternative.

Manzano-Robleda MC, et al. This article should appeal to health insurance payers and policy makers who are in the business of management of hepatitis C infection, especially within health care systems that will not have access immediately to the newer directacting antiviral agents which were reviewed recently in the Annals of Hepatology.1 In this meta-analysis, data were extracted systematically allowing guidance regarding efficacy of treating chronic hepatitis C infection using first generation protease inhibitors (PI): boceprevir and telaprevir, no matter if patients were previously exposed to pegylated interferon plus ribavirin (PR). The results of this study may also assist clinicians the usage of old drugs with better outcomes especially when individualized treatments of hepatitis C genotype 1 are considered. The goal of this systematic analysis was to summarize the world literature for predictors of the primary outcome for sustained viral response (SVR) defined as negative viral load at week 12 or 24. After analysis of 33 studies (10,525 patients) with a meta-regression, previously treated patients exhibited greater benefit from PI + PR (RR, 3.47) but minimal adverse events (RR, 1.01) and low discontinuation rate (RR, 1.69). Furthermore, if there was any doubt about it, the study confirmed that PRtreated patients have a very low probability of achieving an SVR with a new round of PR treatment (17%), whereas treatment-naïve patients receiving PR achieved only 41% SVR. Predictors of greater SVR included IL-28 genotype TT, non-black race, low viral load, younger age, absence of cirrhosis, statin use, undetectable viral load at the first anemia episode or at week 2 of treatment, and low IL-6 levels. This type of analysis allows the identification of potential factors that may be utilized for individualized treatment of patients with better outcomes. Unfortunately, in the absence of the primary datasets from all 33 studies, more specific conclusions cannot be made regarding independent predictors of SVR. Practically, most of us have been using undetectable viral load at week-2 as a predictor of SVR especially when IL-28 genotyping is not available. The authors are right! The newer direct-acting antiviral agents will take over chronic hepatitis C infection treatment but not until payers and policy makers appreciate the advantages of direct-acting antiviral agents in spite their expense tags. Most clinicians who have been treating hepatitis C for the last two decades have moved on and will be unlikely use PI + PR as an alternative.