Mang Ma - Academia.edu (original) (raw)

Papers by Mang Ma

Canadian liver journal, Feb 1, 2021

BackgroundMultidisciplinary care has the potential to improve outcomes among patients with cirrho... more BackgroundMultidisciplinary care has the potential to improve outcomes among patients with cirrhosis, yet its impact on this population remains unclear, with existing studies demonstrating discrepant results. Using data from the multidisciplinary outpatient Cirrhosis Care Clinic (CCC) at the University of Alberta Hospital, we aimed to evaluate acute care utilization and survival outcomes of patients followed by the CCC compared with those receiving standard care (SC).MethodsWe performed a retrospective chart review of 212 patients with cirrhosis admitted to University of Alberta Hospital between 2014 and 2015. CCC patients (n = 36) were followed through the CCC before index admission. SC patients (n = 176) were managed outside of the CCC. Readmission time in hospital was collected until 1 year, death, or liver transplant.ResultsCCC patients had more advanced liver disease (higher prevalence of ascites, encephalopathy, and varices). Despite this, acute care utilization was significantly lower among CCC patients (adjusted length of stay lower by 3 days, p = 0.03, and adjusted survival days spent in hospital lower by 9%, p = 0.02). CCC patients also had improved 1-year transplant-free survival, with an adjusted 1-year relative risk reduction of 53% (p = 0.03). Total mean cost of care was lower in the CCC group by $2,280 per patient-month of life.DiscussionFor patients admitted with cirrhosis, specialized post-discharge multidisciplinary outpatient care is associated with decreased acute care utilization, improved 1-year transplant-free survival probability, and the potential for cost savings to the system.

Journal of Hepatology, Jun 1, 2023

Annals of Hepatology, Mar 1, 2023

World Journal of Gastroenterology, Aug 21, 2022

JHEP reports, May 1, 2022

Background & Aims HDV affects 4.5–13% of chronic hepatitis B (CHB) patients globally, yet the... more 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.

Clinical and Investigative Medicine

Purpose: There is a need for effective and affordable treatments that achieve hepatitis B virus (... more Purpose: There is a need for effective and affordable treatments that achieve hepatitis B virus (HBV) functional cure and prevent long-term complications. The use of immune-modulators combined with HBV antivirals is a promising therapeutic strategy to achieve these goals. Based on ribavirin (RBV) monotherapy data, we hypothesized that RBV could improve virological responses when used in combination with tenofovir. Methods: In this randomized, open label, controlled pilot trial, we evaluated RBV (n=4) dosed for the initial 24 weeks of treatment versus no RBV (n=4) in tenofovir recipients dosed over 48 weeks. Results: Although well tolerated and safe in combination with tenofovir, RBV demonstrated no beneficial effects on virologic, biochemical or immunological markers of chronic HBV infection over 48 weeks of serial evaluation. Conclusions: Our data does not suggest a HBV-specific immunomodulatory effect or an impact of RBV on HBV virological and antigen suppression.

The American Journal of Gastroenterology, Oct 1, 2016

Journal of Crohn's and Colitis, 2013

World Journal of Hepatology

BACKGROUND Hepatitis C virus (HCV) can lead to chronic liver damage resulting in cirrhosis and he... more BACKGROUND Hepatitis C virus (HCV) can lead to chronic liver damage resulting in cirrhosis and hepatocellular carcinoma. Spontaneous clearance of HCV has been documented after an acute infection in 20%-45% of individuals. However, spontaneously resolved chronic hepatitis C following liver transplant (LT) is rare and has been documented only in a few case reports. The phenomenon of spontaneous clearance of chronic hepatitis C occurs together with other meaningful events, which are typically associated with significant changes in the host immunity. CASE SUMMARY We report three cases of spontaneous resolution of chronic hepatitis C following liver transplantation. These patients either failed or had no HCV treatment prior to transplant, but had spontaneous resolution of HCV post-LT as documented by undetectable polymerase chain reaction (PCR). Diagnosis of HCV was based on viremia through PCR or liver biopsy. All three patients currently undergo surveillance and have no recurrence of HCV. CONCLUSION Examining each patient’s clinical course, we learned about many viral, host and cellular-factors that may have enhanced the host’s immunity leading to spontaneous clearance of HCV. Though HCV treatment has excellent cure rates, understanding this mechanism may provide clinicians with insights regarding timing and duration of treatment.

Gastro Hep Advances, 2022

BACKGROUND AND AIMS: The obesity epidemic has increased the risk of nonalcoholic fatty liver dise... more BACKGROUND AND AIMS: The obesity epidemic has increased the risk of nonalcoholic fatty liver disease (NAFLD) in both the general and chronic hepatitis B (CHB) populations. Our study aims to determine the prevalence of NAFLD in patients with CHB based on controlled attenuation parameter (CAP) and the epidemiological, clinical, and virological factors associated with severe hepatic steatosis. METHODS: The Canadian Hepatitis B Network cohort was utilized to provide a cross-sectional description of demographics, comorbidities, antiviral treatment, and hepatits B virus (HBV) tests. Liver fibrosis and steatosis were measured by transient elastography and CAP, respectively. Any grade and severe steatosis were defined as CAP >248 and >280 dB/m, respectively. Advanced liver fibrosis was defined as transient elastography measurement >10.7 kPa. RESULTS: In 1178 patients with CHB (median age: 47.4%, 57.7% males, 75.7% Asian, 13% African, 6.5% White, 86% HBV e antigen negative, median HBV DNA of 2.44 log 10 IU/ mL, 42.7% receiving treatment), the prevalence of any grade and severe steatosis was 53% and 36%, respectively. In the multivariate analysis, obesity was a significant predictor for severe steatosis (adjusted odds ratio: 5.046, 95% confidence interval: 1.22-20.93). Severe steatosis was a determinant associated with viral load (adjusted odds ratio: 0.385, 95% confidence interval: 0.20-0.75, P < .01; r ¼ À0.096, P ¼ .007) regardless of antiviral therapy, age, and alanine aminotransferase levels. CONCLUSION: In this large multiethnic CHB population, hepatic steatosis is common. Severe steatosis is independently associated with higher fibrosis, but negatively with HBV DNA, regardless of antiviral therapy history.

Journal of Hepatology, 2018

American Journal of Gastroenterology, 2013

It's a routine practice to correct coagulation abnormalities and thrombocytopenia prior to liver ... more It's a routine practice to correct coagulation abnormalities and thrombocytopenia prior to liver biopsy. Diff erent cutoff and local guidelines are in place to follow pre-procedure. Although logical, the evidence behind these protocols is trace. Aim: We aimed to audit the use of coagulation factors and platelets prior to liver biopsies, to verify its impact upon the outcome and tailoring the service if no profound benefi t is observed. Methods: We audited computer-based records for clinical, histological, and radiological data of transjugular liver biopsies (TJLBs) performed in last 4 years at Manchester Royal Infi rmary, which is a tertiary care referral center for TJLBs. Laboratory values were recorded using clinical work station soft ware. Data was analyzed using Excel sheets and concluded. Results: Fift y patients were studied (28 males, 22 females), with average age of 52 years. Seventeen patients had thrombocytopenia (defi ned as platelet count <150x109/L) prior to biopsy. Median count was 47 x 109/L. Two patients transfused did not have recheck of platelets prior to the procedure, while the rest had marginal improvement. Th irty-fi ve patients had prolonged prothrombin time (PT) (defi ned as >14.5s). Median value was 17.5. Although three patients did have correction of the abnormal clotting screen with plasma, no patients experienced bleeding, even in the absence of correction of the deranged results. Conclusion: Transjugular liver biopsy is safe in wide variety of patients with liver disease and abnormal coagulation screen. Correction of thrombocytopenia prior to biopsy has no impact on clinical outcome.

American Journal of Gastroenterology, 2016

Canadian Journal of Gastroenterology, 1994

Celiac sprue is a chronic disease characterized by maldigestion and malabsorption. Whereas many d... more Celiac sprue is a chronic disease characterized by maldigestion and malabsorption. Whereas many diseases have been reported in association with celiac sprue, hemochromatosis has not. A 62-year-old man with celiac sprue and a history of iron deficiency and osteopenic bone disease who developed hemochromatosis is reported. Liver biopsy showed portal tract fibrosis, early nodule formation and increased hepatic iron storage. The patient developed hemochromatosis with hepatic injury two years after his transferrin saturation became elevated and 10 years after he had been placed on gluten-free diet. Lifelong iron accumulation was prevented by chronic malabsorption of iron but hemochromatosis became manifest when his celiac sprue was treated.

European Journal of Gastroenterology & Hepatology, 2021

Objectives The prevalence and effects of anxiety on health-related quality of life and clinical o... more Objectives The prevalence and effects of anxiety on health-related quality of life and clinical outcomes in cirrhosis are not well understood. This is increasingly relevant during COVID-19. Our aim was to use the Mini-International Neuropsychiatric Interview (MINI) to determine the prevalence of anxiety, its association with clinical outcomes in cirrhosis and to develop a rapid cirrhosis-specific anxiety screening nomogram. Methods Adults with a diagnosis of cirrhosis were prospectively recruited as outpatients at three tertiary care hospitals across Alberta and followed for up to 6 months to determine the association with unplanned hospitalization/death. The Hospital Anxiety and Depression scale (HADS) was used as a screening tool as it is free of influence from somatic symptoms. Anxiety was diagnosed using the MINI. Results Of 304 patients, 17% of patients had anxiety by the MINI and 32% by the HADS. Anxious patients had lower health-related quality of life as assessed by the chronic liver disease questionnaire (P < 0.001) and EuroQol Visual Analogue Scale (P < 0.001), and also had higher levels of frailty using the Clinical Frailty score (P = 0.004). Multivariable analysis revealed smoking and three HADS subcomponents as independent predictors of anxiety. These were used to develop a rapid screening nomogram. Conclusion A formal diagnosis of anxiety was made in approximately one in five patients with cirrhosis, and it was associated with worse HrQoL and frailty. The use of a 4-question nonsomatic symptom-based nomogram requires validation but is promising as a rapid screen for anxiety in cirrhosis.

Human Vaccines & Immunotherapeutics, 2019

Treatment of chronic hepatitis B (CHB) typically requires lifelong administration of drugs. Cohor... more Treatment of chronic hepatitis B (CHB) typically requires lifelong administration of drugs. Cohort and preclinical studies have established the link between a functional T-cell-mounted immunity and resolution of infection. TG1050 is an adenovirus 5-based vaccine that expresses HBV polymerase and domains of core and surface antigen and has shown immunogenicity and antiviral effects in mice. We performed a phase 1 clinical trial to assess safety and explore immunogenicity and early efficacy of TG1050 in CHB patients. This randomized, double blind, placebo-controlled study included two sequential phases: one single dose cohort (SD, n = 12) and one multiple (3) doses cohort (MD, n = 36). Patients, virally suppressed under nucleoside(d)tide analog NUC therapy, were randomized 1:1:1 across 3 dose levels (DL) and assigned to receive 10 9 , 10 10 , 10 11 virus particles (vp) of TG1050 and then randomized within each DL to placebo (3:1 and 9:3 vaccines/placebo in each DL, respectively, for the SD and MD cohorts). Cellular (ELISPOT) and antibody responses (anti-Adenovirus), as well as evolution of circulating HBsAg and HBcrAg, were monitored. All doses were well tolerated in both cohorts, without severe adverse event. TG1050 was capable to induce IFN-γ producing T-cells targeting 1 to 3 encoded antigens, in particular at the 10 10 vp dose. Overall, minor decreases of HBsAg were observed while a number of vaccinees reached unquantifiable HBcrAg by end of the study. In CHB patients under NUC, TG1050 exhibited a good safety profile and was capable to induce HBV-specific cellular immune response. These data support further clinical evaluation, especially in combination studies.

Liver Transplantation, 2007

Wait-listed (n ϭ 226) or post-liver transplantation (n ϭ 241) chronic hepatitis B (CHB) patients ... more Wait-listed (n ϭ 226) or post-liver transplantation (n ϭ 241) chronic hepatitis B (CHB) patients with lamivudine-resistant hepatitis B virus (HBV) were treated with adefovir dipivoxil for a median of 39 and 99 weeks, respectively. Among wait-listed patients, serum HBV DNA levels became undetectable (Ͻ1,000 copies/mL) in 59% and 65% at weeks 48 and 96, respectively. After 48 weeks, alanine aminotransferase (ALT), albumin, bilirubin, and prothrombin time normalized in 77%, 76%, 60%, and 84% of wait-listed patients, respectively. Among posttransplantation patients, serum HBV DNA levels became undetectable in 40% and 65% at weeks 48 and 96, respectively. After 48 weeks, ALT, albumin, bilirubin, and prothrombin time normalized in 51%, 81%, 76%, and 56% of posttransplantation patients, respectively. Among wait-listed patients who underwent on-study liver transplantation, protection from graft reinfection over a median of 35 weeks was similar among patients who did (n ϭ 34) or did not (n ϭ 23) receive hepatitis B immunoglobulin (HBIg). Hepatitis B surface antigen was detected on the first measurement only in 6% and 9% of patients who did or did not receive HBIg, respectively. Serum HBV DNA was detected on consecutive visits in 6% and 0% of patients who did or did not receive HBIg, respectively. Treatment-related adverse events led to discontinuation of adefovir dipivoxil in 4% of patients. Cumulative probabilities of resistance were 0%, 2%, and 2% at weeks 48, 96, and 144, respectively. In conclusion, adefovir dipivoxil is effective and safe in wait-listed or posttransplantation CHB patients with lamivudine-resistant HBV and prevents graft reinfection with or without HBIg.

Journal of Hepatology, 2017

Hepatology 28(4 Part, Dec 26, 1998