Assessment of birth cohort screening of chronic hepatitis C in colorectal cancer screening patients in British Columbia.

Background: Since 2018, British Columbia (BC) has recommended chronic hepatitis C (HCV) screening for those born between 1945 and 1964, with a provincial prevalence of 2.31%. Combining HCV and colorectal cancer (CRC) screening can facilitate specialist referrals and follow-up. We assessed HCV screening uptake among CRC screening patients following the release of BC's birth cohort guidelines and examined the COVID-19 pandemic's impact on HCV screening practices. Methods: A retrospective review was conducted on patients referred to Vancouver Coastal Health Authority's CRC screening program. Two groups, Cohort A (October-December 2019) and Cohort B (December 2021), were studied to identify pandemic-related changes. Data on demographics, liver disease history, hepatitis B or HIV co-infection rates, and initial anti-hepatitis C and ribonucleic acid (RNA) testing dates were collected. Statistical analyses were performed with Stata 15.1. Results: A total of 579 patients were referred for the CRC screening program, of whom 465 were born between 1945 and 1964 and were included in the study. Among the 348 patients in cohort A, 144 (41%, 95% CI 36%-47%) were screened for HCV infection. Of these, four (1.2%) were positive for anti-hepatitis C, and one patient had positive RNA levels. Similar proportions of screenings were observed in cohort B (47.8%, 95% CI 39%-57%). Of those with liver disease, 66% had been screened for HCV. Conclusion: Birth cohort screening for HCV has been underutilized in British Columbia. Combining HCV and CRC screening could provide a practical approach to linking patients to health care.

Exception points for liver transplantation: A Canadian review.

Background: Exception points for liver transplant (LT) allocation are used to account for mortality risk not reflected by scoring systems such as the Model for End-Stage Liver Disease with sodium (MELD-Na). Currently, there is no formal policy regarding exception points in Canada, and differences across the country are not well understood. As such, a review of the criteria and exception points granted throughout the country for LT was conducted. Methods: Seven LT centres in five provinces were surveyed (Vancouver, Edmonton, London, Toronto, Montréal, Halifax) regarding the indications and criteria for exception points granted, the number of points granted, how points would be accrued, and the maximum points granted. Results: Programs in British Columbia and Nova Scotia grant variable exception points based on the median MELD-Na score with modifications; Alberta, Ontario, and Quebec grant exception points using specific values based on the indication. Overall, there was significant heterogeneity regarding exception points granted nationally with agreement only for awarding exception points for hepatopulmonary syndrome and polycystic liver disease. The second most common agreed-upon indications for exception points were portopulmonary hypertension and recurrent cholangitis offered by four provinces. Quebec had the most formal criteria for non-cirrhosis-based conditions. Conclusions: There is substantial variance across the country regarding the indications for granting exception points as well as the number of points granted. Future work on developing a national consensus will be important for the development of equity in LT across Canada.

Treatment journey of patients with hepatocellular carcinoma using real-world data in British Columbia, Canada.

Aim: This study examined treatment patterns, survival outcomes and healthcare costs related to hepatocellular carcinoma (HCC) in British Columbia. Methods: The study utilized data from two physician databases (HCC and MOTION) and the provincial British Columbia transplant database. Results: The analysis revealed diverse treatment approaches and identified the varying treatment journeys of patients. Liver transplant and systemic therapies demonstrated improved survival rates. However, there was a scarcity of Canadian-specific cost data. Conclusion: The research emphasizes the complexities of managing HCC and underscores the need for personalized treatment strategies to enhance patient outcomes. These findings contribute valuable insights into HCC management and provide a foundation for future studies and interventions aimed at optimizing care and resource allocation.

This study looked at how people diagnosed with liver cancer in British Columbia were treated, how long they lived and how much treatment cost. Treatment records were reviewed, and depending on the extent of the disease, treatments could include surgery, treatments directed at the liver and/or anti-cancer therapy. The average survival time varied from 21­33 months, with an average cost per patient of $94,000. This helps us understand the patient journey and future studies would include current treatment options.

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.

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.

Elevated serum ferritin in non-alcoholic fatty liver disease is not predictive of fibrosis.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is common with widely ranging severity. Non-invasive risk scores for risk stratification are recommended but misclassify a significant proportion of patients. In situations where non-invasive risk scores do not provide guidance, referral is typically made to a Hepatologist for transient elastography or liver biopsy. Serum ferritin is elevated in many patients with NAFLD related to dysmetabolic and inflammatory hyperferritinemia. Ferritin is widely available and part of a standard workup for chronic liver disease. METHODS: To explore the association of ferritin and risk of fibrosis in NAFLD, we reviewed patients diagnosed with NAFLD at the hepatology clinic of the Vancouver General Hospital between the years of 2015 and 2018. We collected data on 317 patients retrospectively assessing for a relationship between serum ferritin and elastography score. RESULTS: Two hundred twenty-four patients were included in the final analysis. Median ferritin was 145 µg/L (IQR 62-311). Median liver stiffness was 5.2 kPa with 14.3% of patients having liver stiffness ≥8.7 kPa and 17.4% ≥ 8.0 kPa. ROC curve analysis using a liver stiffness ≥8.0 kPa as a cutoff for F2 fibrosis showed an AUROC of 0.54 for serum ferritin levels. At a cut-off of both 300 µg/L; and 450 µg/L median liver stiffness did not differ significantly in those with ferritin above the cutoff (ferritin ≥300 µg/L; p = 0.099, ferritin ≥450 µg/L; p = 0.12). Ferritin was significantly higher in male patients (198 versus 91 µg/L; p = 0.0001). There was a weak linear association between AST and ferritin levels. CONCLUSION: In this cohort of 224 patients with NAFLD, serum ferritin was not predictive of significant liver fibrosis.

Outcomes of liver transplant recipients with high MELD scores: an experience from a Canadian centre.

BACKGROUND: The frequency with which patients with high Model for End-Stage Liver Disease (MELD) scores undergo liver transplantation has been increasing. Canadian literature regarding the outcomes of liver transplantation in recipients with high MELD scores is limited. The primary objective of this study was to assess patient and graft survival among recipients with high (> 35) and low (≤ 35) MELD scores. Secondary objectives were to potentially identify independent predictors of graft failure and patient mortality. METHODS: We conducted a retrospective chart review of patients undergoing liver transplantation at a single Canadian centre from 2012 to 2017. RESULTS: A total of 332 patients were included in the study: 280 patients had a MELD score of 35 or lower, and 52 had a MELD score above 35. Patients with high MELD scores had higher rates of pretransplant acute kidney injury and dialysis (p < 0.001), admission to the intensive care unit (ICU) or intubation (p < 0.001), intraoperative blood product transfusions (p < 0.001) and post-transplantation acute kidney injury and dialysis (p < 0.001), as well as longer ICU (p < 0.001) and hospital stays (p = 0.002). One- and 3-year patient survival in recipients with MELD scores of 35 or lower was 93.1% and 84.9% versus 85.0% and 80.0% in recipients with MELD scores above 35 (p = 0.37). One- and 3-year graft survival in recipients with MELD scores of 35 or lower was 91.7% and 90.9% versus 77.2% and 72.8% in recipients with MELD scores above 35 (p < 0.001). Prior liver transplant was an independent predictor of patient mortality, and no independent predictors of graft failure were identified. When MELD was replaced with D-MELD (donor age × recipient MELD), it predicted graft failure but not patient survival. CONCLUSION: No difference in patient mortality was found between MELD groups. Graft survival was significantly lower in recipients with MELD scores above 35. D-MELD may potentially be used as an adjunct in determining risk of graft failure in recipients with high MELD scores.

COVID-19 infection immediately post-transplant in an unvaccinated patient: Clinical observations and ethical implications.

We report the case of a 28-year-old woman who presented with acute liver failure from suspected drug-induced liver injury. She was not vaccinated against COVID-19 and expressed considerable reluctance to become vaccinated, prompting discussions within the transplant group regarding her candidacy. She received a liver transplant and acquired COVID-19 immediately post-operatively that was treated with sotrovimab. She recovered well and was discharged shortly following her transplant. This case suggests that unwillingness to receive COVID-19 vaccination pre-transplant should not represent an absolute contraindication to a life-saving liver transplantation.

End stage liver disease etiology & transplantation referral outcomes of major ethnic groups in British Columbia, Canada: A cohort study.

ABSTRACT: Liver disease etiology and transplantation outcomes may vary by ethnicity. We aimed to determine if disparities exist in our province.We reviewed the provincial database for liver transplant referrals. We stratified cohorts by ethnicity and analyzed disease etiology and outcomes.Four thousand nine hundred sixteen referrals included 220 South Asians, 413 Asians, 235 First Nations (Indigenous), and 2725 Caucasians. Predominant etiologies by ethnicity included alcohol (27.4%) and primary sclerosing cholangitis (PSC) (8.8%) in South Asians, hepatitis B (45.5%) and malignancy (13.9%) in Asians, primary biliary cholangitis (PBC) (33.2%) and autoimmune hepatitis (AIH) (10.8%) in First Nations, and hepatitis C (35.9%) in Caucasians. First Nations had lowest rate of transplantation (30.6%, P = .01) and highest rate of waitlist death (10.6%, P = .03). Median time from referral to transplantation (268 days) did not differ between ethnicities (P = .47). Likelihood of transplantation increased with lower body mass index (BMI) (hazard ratio [HR] 0.99, P = .03), higher model for end stage liver disease (MELD) (HR 1.02, P < .01), or fulminant liver failure (HR 9.47, P < .01). Median time from referral to ineligibility status was 170 days, and shorter time was associated with increased MELD (HR 1.01, P < .01), increased age (HR 1.01, P < .01), fulminant liver failure (HR 2.56, P < .01) or South Asian ethnicity (HR 2.54, P < .01). Competing risks analysis revealed no differences in time to transplant (P = .66) or time to ineligibility (P = .91) but confirmed increased waitlist death for First Nations (P = .04).We have noted emerging trends such as alcohol related liver disease and PSC in South Asians. First Nations have increased autoimmune liver disease, lower transplantation rates and higher waitlist deaths. These data have significance for designing ethnicity specific interventions.

Review article: comprehensive analysis of cirrhotic cardiomyopathy.

BACKGROUND: Patients with cirrhosis are at risk of developing cirrhotic cardiomyopathy. This syndrome is unique to cirrhosis and is generally defined as subnormal cardiac function in the absence of prior heart disease. There is no systematic or comprehensive review of cirrhotic cardiomyopathy to date. AIMS: To comprehensively review the literature on the definition, pathogenic mechanisms, diagnostic criteria, prevalence, management and influence on liver transplantation including reversibility of cirrhotic cardiomyopathy. METHODS: Electronic searches of the EMBASE, MEDLINE, EBM Reviews-Cochrane Central Register of Controlled Trials, EBM Reviews-Cochrane Database of Systematic Reviews and Google Scholar databases were conducted. MeSH terms focused on cirrhosis, cardiomyopathy, medication classes and epidemiology. Literature up to August 2020 was reviewed. RESULTS: New diagnostic criteria for the definition of cirrhotic cardiomyopathy have recently been published, consisting of systolic and diastolic dysfunction parameters as assessed by echocardiographic methods. The roles of electrocardiographic disturbances and biomarkers in the definition criteria remain unclear. Pathogenic mechanisms underlying cirrhotic cardiomyopathy are likely related to the inflammatory phenotype of cirrhosis. Prevalence rates of 26%-81% in cirrhotic patients are reported. Several medical therapies have been proposed, but none with clear evidence of efficacy. The presence of cirrhotic cardiomyopathy complicates the liver transplantation process with a higher risk of adverse cardiovascular events post-transplant. Complete reversibility of the syndrome after transplantation remains controversial but most studies suggest that it does not occur at least within the first post-operative year. CONCLUSIONS: Cirrhotic cardiomyopathy is a clinically relevant syndrome that affects morbidity and mortality in patients with cirrhosis.

Occult Hepatitis B Reactivation after Liver Transplant: The Role of a Novel Mutation in the Surface Antigen.

Occult hepatitis B infection is characterized by loss of hepatitis B surface antigen (HBsAg) and persistence of low levels of hepatitis B virus (HBV) replication that may or may not be detectable in plasma/serum. We present a case of HBV reactivation in a male patient who underwent orthotopic liver transplant for hepatocellular carcinoma secondary to active hepatitis C (HCV) infection. Pre-transplant, he was HBsAg-negative and hepatitis B core antibody-positive, with an undetectable HBV viral load that was incidentally found to be positive at a very low HBV viral load on the day of transplant. Post-transplant, his HBsAg remained undetectable, with an undetectable HBV viral load, until eradication of his HCV infection with direct acting antiviral agents. After eradication of HCV, there was reactivation of HBV, with a high viral load and emergence of serum HBsAg. A deep sequencing genetic analysis of his HBV both pre- and post-transplant revealed the presence of a mutation in the "a" determinant of the HBV surface antigen. The role of HBV genotype 'a' determinant mutation in HBV reactivation post-transplant is unknown and needs further examination. Our experience suggests a possible role for antiviral prophylaxis in these patients or monitoring of HBV viral loads post-transplant.

Incidental alpha-1-antitrypsin deficiency found in post-transplant liver allografts: Report of two cases.

Alpha-1 antitrypsin deficiency is an autosomal recessive disease most commonly caused by misfolding of the Alpha-1-antitrypsin protein, which prevents its release from hepatocytes into the systemic circulation. This results in increased lifetime risk of liver and lung disease. Due to its variable penetrance, presentation and natural history, patients with alpha-1 antitrypsin deficiency are often underdiagnosed. In this report, we present two cases of alpha-1 antitrypsin deficiency in deceased-donor liver transplant allografts diagnosed post-transplant. There is currently no known adverse outcome directly linked to alpha-1 antitrypsin deficiency in the immediate post-transplant follow-up period. Thus, these allografts should not be excluded from transplantation.

Comparing the performance of Fibrosis-4 and Non-Alcoholic Fatty Liver Disease Fibrosis Score with transient elastography scores of people with non-alcoholic fatty liver disease.

Background: With the rate of non-alcoholic fatty liver disease (NAFLD) on the rise, the necessity of identifying patients at risk of cirrhosis and its complications is becoming ever more important. Liver biopsy remains the gold standard for assessing fibrosis, although costs, risks, and availability prohibit its widespread use with at-risk patients. Transient elastography has proven to be a non-invasive and accurate way of assessing fibrosis, although the availability of this modality is often limited in primary care settings. The Fibrosis-4 (FIB-4) and Non-Alcoholic Fatty Liver Disease Fibrosis Score (NFS) are scoring systems that incorporate commonly measured lab parameters and BMI to predict fibrosis. Method: In this study, we compared FIB-4 and NFS scores with transient elastography scores to assess the accuracy of these inexpensive and readily available scoring systems in detecting fibrosis. Results: Using an NFS score cut-off of -1.455 and a FibroScan score cut-off of ≥8.7 kPa, the NFS score had a negative predictive value of 94.1%. Using a FibroScan score cut-off of ≥8.7 kPa, the FIB-4 score had a negative predictive value of 91.6%. Conclusion: The NFS and FIB-4 are non-invasive, inexpensive scoring systems that have high negative predictive value for fibrosis compared with transient elastography scores. These findings suggest that the NFS and FIB-4 can provide adequate reassurance to rule out fibrosis in patients with NAFLD and can be used with select patients to circumvent the need for transient elastography or liver biopsy.

Biomarkers for hepatocellular cancer.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. If diagnosed early, curative treatment options such as surgical resection, loco-regional therapies, and liver transplantation are available to patients, increasing their chances of survival and improving their quality of life. Unfortunately, most patients are diagnosed with late stage HCC where only palliative treatment is available. Therefore, biomarkers which could detect HCC early with a high degree of sensitivity and specificity, may play a crucial role in the diagnosis and management of the disease. This review will aim to provide an overview of the different biomarkers of HCC comprising those used in the diagnosis of HCC in at risk populations, as well as others with potential for prognosis, risk predisposition and prediction of response to therapeutic intervention.

Ablative Transarterial Radioembolization Improves Survival in Patients with HCC and Portal Vein Tumor Thrombus.

PURPOSE: Patients with hepatocellular carcinoma and portal vein tumor thrombus have a poor prognosis and limited therapeutic options. We sought to compare survival, tolerability, and safety in such patients treated with conventional yttrium-90 transarterial radioembolization dosimetric techniques or ablative transarterial radioembolization. MATERIALS AND METHODS: This retrospective, single-center cohort study included patients with hepatocellular carcinoma and right, left, and/or main portal vein tumor thrombus, preserved liver function (Child-Pugh class ≤ B7), and good performance status (Eastern Cooperative Oncology Group score ≤ 1) treated with yttrium-90 microspheres from 2011 to 2018 with ablative intent transarterial radioembolization (A-TARE), or conventional technique (cTARE). Statistical models were used to compare overall survival, post-treatment survival, toxicities, and prognosticators of response. RESULTS: Fifty-seven patients were included (21 [36.8%] ablative and 36 [63.2%] conventional intent). Median overall survival was 15.7 months. Compared to conventional treatment, ablative radioembolization was associated with longer median overall survival (45.3 vs 18.2 months; P = 0.003), longer post-treatment survival (19.1 vs 4.9 months; P = 0.005), a 70% lower risk of death (hazard ratio 0.30; 95% confidence interval, 0.13-0.70; P = 0.005), and improved 4-year survival (53.9% vs 11.2%). Overall survival did not differ significantly between treatment with resin and glass microspheres (27.5 vs 22.2 months; P = 0.62). Acceptable hepatic toxicities were observed after yttrium-90 administration, without statistical differences between the groups. CONCLUSION: In patients with advanced hepatocellular carcinoma and portal vein tumor thrombus, A-TARE is associated with longer survival than cTARE. Neither modality is associated with deleterious effects on liver function.

Patients' Perspectives on Early Liver Transplantation in Alcohol-Related Liver Disease.

Liver transplant programs in Canada require a period of 6 months of abstinence from alcohol before considering a patient with liver disease secondary to alcohol for transplantation. Although some studies have demonstrated good outcomes following a transplant in carefully selected patients before the 6-month abstinence period has been met, there have been arguments against this, including the claim that the public has a general negative perception of those with alcohol dependence. We performed a multicenter cross-sectional survey to determine the perception of people in British Columbia, Canada, toward liver transplantation in patients with liver disease due to alcohol who have not demonstrated the capacity to remain abstinent from alcohol for 6 months. A total of 304 patient questionnaires were completed, and 83.1% agreed with a period of abstinence of 6 months. In those patients who were unlikely to survive 6 months without a transplant, 34.1% of respondents agreed with, 44.1% did not agree with, and 21.4% were neutral about, early transplantation; 42.8% would have less trust in the process of transplantation if a period of abstinence was not maintained, but relaxing the requirement for an abstinence period would not have an impact on the majority's decision to donate organs. Only 30.5% would support abandoning the abstinence criteria. Conclusion: Among patients followed at general gastroenterology, medicine, or transplant clinics, there is a willingness to relax the criteria in selected patients unlikely to survive without a transplant, although a general consensus remains in support of the existing 6-month alcohol abstinence rule. A larger scale survey of all provinces in Canada would be required to assess support for such a change in policy.

Early Persistent Progressive Acute Kidney Injury and Graft Failure Post Liver Transplantation.

BACKGROUND: Acute kidney injury (AKI) in the setting of liver transplantation is a common and multifaceted complication. Studies in the general population have demonstrated worse prognosis with AKI episodes that persist for a longer duration. Our primary objective was to evaluate the impact of early AKI episodes that are persistent or progressive in nature, on patient outcomes and graft survival. METHODS: This was a retrospective cohort study including all patients who received a liver transplant between 2011 and 2015 at our center. Moderate to severe AKI episodes (AKIN II or III) were recorded immediately before transplantation and after surgery until hospital discharge. We evaluated the incidence density rate (IDR) of graft failure and the time to graft failure in patients with persistent or progressive AKI (ppAKI) as compared to controls. RESULTS: Two hundred seventy-nine patients received 301 deceased donor liver allografts. Progressive or persistent AKI was documented in more than half of transplant cases (152/301). The rate of graft loss was 3 times higher in the ppAKI group (25%) versus the controls (8.7%). The IDR of graft failure was 13.79 per 100 case-years in the ppAKI group as compared with 3.79 per 100 case-years in the controls (IDR ratio, 3.64; 95 % confidence interval, 1.88-7.50). After adjusting for hepatic artery thrombosis, ischemic cholangiopathy, infectious complications and Model for End-stage Liver Disease, ppAKI was associated with a decreased graft survival time. CONCLUSIONS: Persistent or progressive AKI after liver transplantation is associated with an increased incidence rate of graft failure and is an independent predictor of decreased graft survival time.