Velacur ACE outperforms FibroScan CAP for diagnosis of MASLD.

BACKGROUND: As the prevalence of metabolic dysfunction-associated steatotic liver disease increases, it is imperative to have noninvasive alternatives to liver biopsy. Velacur offers a non-invasive, point-of-care ultrasound-based method for the assessment of liver stiffness and attenuation. The aim of this study was to perform a head-to-head comparison of liver stiffness and liver fat determined by Velacur and FibroScan using MRI-based measurements as the reference standard. METHODS: This prospective cross-sectional study included 164 adult participants with well-characterized metabolic dysfunction-associated steatotic liver disease. Patients underwent a research exam including Velacur, FibroScan and contemporaneous magnetic resonance elastography, and magnetic resonance imaging proton density fat fraction (MRI-PDFF) scans. The primary outcome was the presence of advanced fibrosis (>F2) as measured by magnetic resonance elastography and the presence of liver fat (>5%) as measured by MRI-PDFF. RESULTS: The mean age and body mass index were 57±12 years and 30.6±4.8 kg/m2, respectively. The mean liver stiffness on magnetic resonance elastography was 3.22±1.39 kPa and the mean liver fat on MRI-PDFF was 14.2±8%. The liver stiffness assessments by Velacur and FibroScan were similar for the detection of advanced fibrosis (AUC 0.95 vs. 0.97) and were not statistically different (p=0.43). Velacur was significantly better than FibroScan (AUC 0.94 vs. 0.79, p=0.01), for the detection of MRI-PDFF >5% (diagnosis of metabolic dysfunction-associated liver disease). CONCLUSIONS: Velacur was superior to FibroScan for liver fat detection with MRI-PDFF as the reference. Velacur and FibroScan were not statistically different for liver stiffness assessment as defined by magnetic resonance elastography.

Prolonged and Recurrent Intrahepatic Cholestasis of Pregnancy.

Intrahepatic cholestasis of pregnancy is one of the most common disorders of pregnancy, which typically resolves in the postpartum period. Intrahepatic cholestasis is characterized by elevated bile acid levels that present as pruritus. The maternal clinical significance of recurrent and prolonged cholestasis is unknown. We discuss the longest reported case of postpartum cholestasis of 125 weeks.

Efficacy and safety of semaglutide in non-alcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease. The prevalence and disease burden of NAFLD are projected to exponentially increase resulting in significant healthcare expenditures and lower health-related quality of life. To date, there are no approved pharmacotherapies for NAFLD or non-alcoholic steatohepatitis (NASH). Semaglutide has glycemic and weight loss benefits that may be advantageous for patients with NAFLD. AIM: To investigate the efficacy and safety of semaglutide in patients with NAFLD. METHODS: MEDLINE, CENTRAL, and EMBASE were searched from inception to May 1, 2023, to identify eligible randomized controlled trials (RCTs). Meta-analysis was performed using random effects model expressing continuous outcomes as mean differences (MD) or standardized MDs (SMD), and dichotomous outcomes as odds ratios (OR) with 95% confidence intervals (CI). Statistical heterogeneity was assessed using the Cochran's Q test and I2 statistic. RESULTS: Three RCTs involving 458 patients were included. Semaglutide increased the likelihood of NASH resolution (OR: 3.18, 95%CI: 1.70, 5.95; P < 0.001), improvement in steatosis (OR: 2.83, 95%CI: 1.19, 6.71; P = 0.03), lobular inflammation (OR: 1.81, 95%CI: 1.11, 2.96; P = 0.02), and hepatocellular ballooning (OR: 2.92, 95%CI: 1.83, 4.65; P < 0.001), but not fibrosis stage (OR: 0.71, 95%CI: 0.15, 3.41; P = 0.67). Radiologically, semaglutide reduced liver stiffness (SMD: -0.48, 95%CI: -0.86, -0.11; P = 0.01) and steatosis (MD: -4.96%, 95%CI: -9.92, 0.01; P = 0.05). It also reduced alanine aminotransferase (MD: -14.06 U/L, 95%CI: -22.06, -6.07; P < 0.001) and aspartate aminotransferase (MD: -11.44 U/L, 95%CI: -17.23, -5.65; P < 0.001). Semaglutide led to improved cardiometabolic outcomes, including decreased HgA1c (MD: -0.77%, 95%CI: -1.18, -0.37; P < 0.001) and weight loss (MD: -6.53 kg, 95%CI: -11.21, -1.85; P = 0.006), but increased the occurrence of GI-related side effects (OR: 3.72, 95%CI: 1.68, 8.23; P = 0.001). Overall risk of serious adverse events was similar compared to placebo (OR: 1.40, 95%CI: 0.75, 2.62; P < 0.29). CONCLUSION: Semaglutide is effective in the treatment of NAFLD while maintaining a well-tolerated safety profile. Future studies are required to evaluate its effects on fibrosis regression and different phases of NAFLD.

COVID-19 and Liver Disease: An Evolving Landscape.

The COVID-19 pandemic has resulted in significant worldwide morbidity and mortality. In this review, we examine the intricate relationships between COVID-19 and liver diseases. While respiratory manifestations of COVID-19 are well known, its impact and consequences in patients with liver diseases remain an area of ongoing investigation. COVID-19 can induce liver injury through various mechanisms and is associated with higher mortality in individuals with preexisting chronic liver disease. Mortality increases with the severity of chronic liver disease and the level of care required. The outcomes in patients with autoimmune hepatitis remain unclear, whereas liver transplant recipients are more likely to experience symptomatic COVID-19 but have comparable outcomes to the general population. Despite suboptimal immunological response, COVID-19 vaccinations are safe and effective in liver disease, although cases of autoimmune hepatitis-like syndrome have been reported. In conclusion, COVID-19 has significant implications in liver diseases; early recognition and treatments are important for improving patient outcomes.

Review of liver transplantation candidacy and outcomes among patients who use cannabis: Is it time for a change in policy?

Background: Recreational cannabis was legalized in Canada in 2018. A controversial contraindication for liver transplantation is cannabis. There is currently no consensus regarding cannabis use in liver transplant candidates. We aim to investigate liver transplantation candidacy and outcomes among cannabis users. Methods: English peer-reviewed studies on PubMed and Google Scholar were searched on September 9, 2022, using keywords including "cannabis," "liver transplantation," and their synonyms. Titles and abstracts were screened, followed by full texts. Reference lists were reviewed. Studies that investigated liver transplantation candidacy and outcomes among cannabis users were included. Results: The proportion of patients listed for liver transplantation was significantly less among cannabis users than among non-users. Time to listing was longer for cannabis users than non-users. The incidence of delisting was similar. There is an inconsistency between transplant centres regarding transplantation candidacy for cannabis users. While only 14% of Canadian centres had a policy in place and preferred candidates to abstain or decrease cannabis use before transplantation, a third of Canadian centres rejected cannabis users. Observational studies failed to demonstrate significant differences in patient survival between pre-transplantation cannabis users and non-users. However, self-reported mental health ratings were worse in post-transplantation cannabis users than in non-users and former users. Conclusions: Current observational data do not support a link between cannabis use and poor patient survival post-transplantation. However, high-quality prospective studies are needed to better elucidate the impact of cannabis use on liver transplantation outcomes. Liver transplant candidacy should be evaluated through a multidisciplinary and comprehensive approach considering all relevant psychosocial factors.

Albuminuria post-liver transplant is a predictor of kidney disease progression and mortality.

BACKGROUND: Albuminuria is a marker of chronic kidney disease (CKD) associated with an increased risk of end-stage kidney disease (ESKD) and mortality in the general population, but it is uncertain whether the same association exists in liver transplant (LT) recipients. This study examined the association between albuminuria and kidney failure and mortality in LT recipients.METHODS: Retrospective cohort study of 294 adults who received a LT between January 1, 1989, and December 31, 2011, in British Columbia, Canada. Cox multivariable regression was used to determine the association between ACR and a primary combined outcome of mortality, doubling of serum creatinine, or ESKD; and a secondary outcome of a decrease in estimated glomerular filtration rate (eGFR) ≥30%. RESULTS: At baseline, mean eGFR was 67 (SD 20.9) mL/min/1.73 m2, and 10% had severe albuminuria (ACR >30 mg/mmol). The primary outcome occurred in 20.4% (60) of patients and was associated with ACR >30 mg/mmol (HR 2.77, 95% CI 1.28-6.04; P = 0.01). A decline in eGFR ≥30% occurred in 21.8% (64) of patients, and was associated with ACR >30 mg/mmol (HR 4.77, 95% CI 2.31-9.86; P < 0.0001). CONCLUSIONS: Severe albuminuria (ACR >30 mg/mmol) was associated with an increased risk of loss of kidney function and mortality after LT. Prospective studies are needed to determine if specific interventions directed at reducing albuminuria can improve long-term outcomes in LT recipients.

Liver Transplant Recipients Speak Out on Public Awareness and Education Surrounding Alcohol-Related Health Effects: A Survey Study.

BACKGROUND: Compared to other recreational substances in Canada, alcohol consumption incurs the highest healthcare costs. Liver transplant recipients are unique stakeholders as members of the general public with lived experiences of liver disease. We sought to explore their perspectives on the current state of public education on alcohol-related health effects. METHODS: The most recent 400 liver transplant recipients at Vancouver General Hospital, Canada, were invited to participate in an anonymous online survey on alcohol-related health effects by mail, email, and phone. RESULTS: Of 372 contacted patients, 212 (57%) completed the survey. Most patients were between 60-79 years, 63% were male, and 69% were Caucasian. The most common liver conditions leading to transplant were viral hepatitis (33%), alcohol-related liver disease (16%), autoimmune liver disease (14%), and non-alcoholic fatty liver disease (15%). Most patients knew that alcohol leads to liver failure (85%), but fewer knew about alcohol leading to cancer (54%), heart disease (50%), and damage to other organs (58%). Most common sources of information included public media (61%), family and friends (52%), and physicians (49%), with narrative comments about learning of alcohol-related health effects after liver diagnosis. Most patients believed that public health education at a middle/high school level would have long-term efficacy (72%) compared to health warning labels (33%) and safety messaging in commercials (39%). Current public education was felt to be adequate by only 20% of patients and 73% of patients supported health warning labels. CONCLUSIONS: Liver transplant patients reported a high, but not universal, awareness of alcohol-related health effects. A majority thought that current public health efforts were inadequate; it is critical to implement public health interventions to ensure consumers are able to make an informed decision on alcohol consumption.

Impact of Hepatitis B Virus Infection, Non-alcoholic Fatty Liver Disease, and Hepatitis C Virus Co-infection on Liver-Related Death among People Tested for Hepatitis B Virus in British Columbia: Results from a Large Longitudinal Population-Based Cohort Study.

Data on the contribution of hepatitis B virus (HBV) infection and related comorbidities to liver-related mortality in Canada are limited. We assessed the concurrent impact of HBV infection, non-alcoholic fatty liver disease (NAFLD), and hepatitis C virus (HCV) coinfection on liver-related deaths in British Columbia (BC), Canada. We used data from the BC Hepatitis Testers Cohort (BC-HTC). We used Fine-Gray multivariable sub-distributional hazards models to assess the effect of HBV, NAFLD, and HCV coinfection on liver-related mortality, while adjusting for confounders and competing mortality risks. The liver-related mortality rate was higher among people with HBV infection than those without (2.57 per 1000 PYs (95%CI: 2.46, 2.69) vs. 0.62 per 1000 PYs (95%CI: 0.61, 0.64), respectively). Compared with the HBV negative groups, HBV infection was associated with increased liver-related mortality risk in almost all of the subgroups: HBV mono-infection (adjusted subdistribution hazards ratio (asHR) of 3.35, 95% CI 3.16, 3.55), NAFLD with HBV infection, (asHR 12.5, 95% CI 7.08, 22.07), and HBV/HCV coinfection (asHR 8.4, 95% CI 7.62, 9.26). HBV infection is associated with a higher risk of liver-related mortality, and has a greater relative impact on people with NAFLD and those with HCV coinfection. The diagnosis and treatment of viral and fatty liver disease are required to mitigate liver-related morbidity and mortality.

Berberine Ursodeoxycholate for the Treatment of Primary Sclerosing Cholangitis: The Search for the Elusive Pharmacologic Holy Grail Will Need to Continue.

ABSTRACT: Effective pharmacologic treatment of primary sclerosing cholangitis (PSC) remains elusive. Ursodeoxycholic acid (UDCA) is known to improve liver biochemistry, specifically serum alkaline phosphatase, in patients with PSC but has not been shown to favourably alter the natural history. Similarly, many immunomodulatory medications have been studied for the treatment of PSC, but none has been demonstrated to be of unequivocal benefit. In this issue of the Journal, a pilot study of a ursodeoxycholate berberine salt vs placebo is reported. Although improvement in serum alkaline phosphatase is reported, without a control arm with UDCA monotherapy, it is not possible to determine whether this study drug is beneficial over UDCA by itself. More study in the PSC therapeutic arena is needed.

Isolated Hepatic Chronic Ductopenic Rejection Requiring Liver Retransplant in the Absence of Kidney Graft Rejection After Combined Liver-Kidney Transplant: A Case Report.

The liver is considered the most immunotolerant organ among all solid-organ transplants. Liver transplant recipients have a lower incidence of rejection and better outcomes after episodes of rejection, with spontaneous operational tolerance developing in up to 20%. In multiorgan transplants, a protective effect of the liver allograft on simultaneously transplanted organs from the same donor has been demonstrated. We describe an unusual case of isolated liver allograft rejection in a patient with polycystic liver and kidney disease who received a combined liver-kidney transplant from the same donor. After initial discharge from the hospital, our patient had 2 episodes of biopsy-proven late acute cellular rejections, despite higher levels of immunosuppression required for her kidney allograft, which were addressed with pulsed steroid therapy. She had no evidence of ischemic cholangiopathy on imaging. Later, a subsequent liver biopsy demonstrated features consistent with chronic ductopenic rejection. She was eventually listed for liver retransplant and has recently received a second liver transplant while continuing to have no concerns with her kidney allograft function. Examination of the explanted liver confirmed graft loss from chronic ductopenic rejection. The exact reasons why our patient developed acute graft rejection progressing to chronic end-stage rejection of the liver allograft despite not developing graft rejection in the kidney allograft from the same donor remains elusive. Our experience demonstrates that graft tolerance in multiorgan transplant recipients can be organ specific and despite the belief of "immunologic privilege," isolated liver allograft rejection can occur in multiorgan transplant, resulting in graft loss.

Emerging Systemic Therapies in Advanced Unresectable Biliary Tract Cancer: Review and Canadian Perspective.

Biliary tract cancer (BTC) is a group of rare and aggressive malignancies with a dismal prognosis. There is currently a significant lack in effective treatment options for BTC, with gemcitabine-cisplatin remaining the first-line standard of care treatment for over a decade. A wave of investigational therapies, including new chemotherapy combinations, immunotherapy, and biomarker-driven targeted therapy have demonstrated promising results in BTC, and there is hope for many of these therapies to be incorporated into the Canadian treatment landscape in the near future. This review discusses the emerging therapies under investigation for BTC and provides a perspective on how they may fit into Canadian practice, with a focus on the barriers to treatment access.

Clinical characterization of patients with primary biliary cholangitis: A report from multiple Canadian centres.

Background: Primary biliary cholangitis (PBC) is a rare, chronic autoimmune, cholestatic liver disease affecting approximately 318 per million Canadians. There is limited information regarding the characterization of this patient population in Canada. Consequently, we aim to describe a cohort of PBC patients managed across liver centres serving this type of population. Methods: A cross-sectional examination of 1,125 PBC patient charts at 15 liver centres across Canada was conducted between January 2016 and September 2017. Results: Data from 1,125 eligible patients were collected from 7 Canadian provinces. The patient population was largely female (90.2%), had a median overall age of 61.3 years, and a median overall time since diagnosis of 6.4 years. Of the patients included in the study, 89% were on ursodeoxycholic acid (UDCA) therapy at a median dose of 14.0 mg/kg/day and 4.4% were previously treated with UDCA, whereas 6.6% were never treated with UDCA. Of the patients with available data (n = 1067), 289 (27.1%) presented with alkaline phosphatase (ALP) levels ≥200 IU/L and/or total bilirubin levels ≥21 µmol/L. Assessment of UDCA treatment response revealed that 26.6% and 38.3% of patients were inadequate responders according to the Toronto and Paris-II criteria, respectively. Mortality occurred in 1.2% (14) of patients, with liver-related adverse outcomes being more commonly observed in patients who discontinued UDCA compared to those who are currently on treatment (36.3% and 19.6%, respectively). Conclusion: This study showed that Canadian PBC patients present with demographics and features commonly reported in the literature for this disease. Over one third of PBC patients had inadequate response to UDCA treatment or were not currently being treated with UDCA. Consequently, there is a significant unmet therapeutic need in this Canadian PBC population.

Non-alcoholic fatty liver disease (NAFLD) in Filipino North American patients: Results from a multi-ethnic cohort.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is more prevalent in certain ethnicities due to a combination of genetic, environmental, and metabolic factors. North American Filipino populations may have lifestyle and metabolic risk factors for NAFLD; however, the prevalence of NAFLD in this group is unknown. We sought to determine whether Filipino patients are over-represented in a multi-ethnic NAFLD cohort and describe their clinical presentation, primarily compared to other ethnicities in the same geographical region and secondarily compared to Manila-based Filipino patients. METHODS: A cross-sectional study was conducted with patients with NAFLD who were followed at the Hepatology Clinic at Vancouver General Hospital, Canada, from January 2015 to August 2018. Data were extracted for clinicodemographic data, ethnicity, anthropometric measures, blood work, and transient elastography (TE). External comparison data was obtained online from the Metro Vancouver census and a NAFLD study conducted in Manila, Philippines. RESULTS: Of 317 patients meeting inclusion criteria for the study, 224 patients had complete datasets. The mean age was 51.1 years, and 50% were female. There were 139 (62%) Caucasian and other ethnicity patients, 55 (25%) Asian patients, and 30 (13%) Filipino patients. Compared to other ethnic groups, the Filipino group had similar clinical characteristics, including NAFLD fibrosis scores and TE. Of included NAFLD patients, the proportion of Filipino patients (13.39%) was significantly greater than the proportion of Filipino residents in Metro Vancouver (5.52%, p <0.01). Our Filipino Canadians seemed to be younger, with fewer females and a lower proportion of diabetes mellitus, but a higher proportion of hypertension than the previously reported cohort from Manila. CONCLUSIONS: While Filipino patients have not previously been examined in multi-ethnic NAFLD studies, they may represent a high-risk population. Further research is needed to clarify the prevalence and presentation of NAFLD in Filipino Canadian patients, as this appears to be a significant health issue in this community.

Seroprevalence of hepatitis B in previously undiagnosed patients: A community screening study.

BACKGROUND: Forty percent of hepatitis B carriers have no knowledge of their diagnosis. A prior study in British Columbia suggested high rates of hepatitis B among immigrants. The authors undertook a large-scale screening study to validate these rates. METHODS: Attendees at Asian health fairs without knowledge of their hepatitis B status participated. They completed a questionnaire, and blood was drawn for HBV serologies. Active HBV was defined as HBV surface antigen positive. RESULTS: Of 2,726 patients, 1,704 (62.5%) were female and 1,022 (37.5%) male. Mean age was 62.7 (SD 22.1) years, and mean time of residing in Canada was 27.5 (SD 15.3) years. Most patients originated from China (1,042 patients, 38.2%) and Hong Kong (871, 31.2%). Fifty-six patients tested positive (seroprevalence rate 2.05%, 95% CI 1.52%-2.59%). Most seropositive patients were from China (28 patients, 50.0%). Mean time of residence in Canada for seropositive patients (23.8 [SD 2.1] y) was less than seronegative patients (27.6 [SD 0.3] y) (p = 0.06). There was a trend towards association of seropositivity with time of residence in Canada (OR 0.98, 95% CI 0.96-1.00, p = 0.09). 8 (14.3%) seropositive patients did not have family doctors, compared with 128 (4.8%) seronegative patients. Lack of a family doctor was strongly associated with seropositivity (OR 3.31, 95% CI 1.32-7.25, χ2 = 10.42, p = 0.001). INTERPRETATION: The authors have shown that high risk immigrant populations may have seroprevalence rates as high as 2,700 per 100,000. Lack of a family physician was associated with seropositivity. These results should be used to design improved outreach programs.