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1.
Medicine (Baltimore) ; 100(42): e27436, 2021 Oct 22.
Article in English | MEDLINE | ID: mdl-34678872

ABSTRACT

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.


Subject(s)
End Stage Liver Disease/ethnology , End Stage Liver Disease/etiology , End Stage Liver Disease/surgery , Liver Transplantation/statistics & numerical data , Referral and Consultation/statistics & numerical data , Adult , Age Factors , Aged , Body Mass Index , British Columbia/epidemiology , Ethnicity , Female , Humans , Male , Middle Aged , Risk Factors , Severity of Illness Index , Socioeconomic Factors , Time Factors , Waiting Lists/mortality
2.
IEEE Trans Med Imaging ; 40(2): 648-660, 2021 02.
Article in English | MEDLINE | ID: mdl-33108283

ABSTRACT

Magnetic resonance elastography (MRE) is commonly regarded as the imaging-based gold-standard for liver fibrosis staging, comparable to biopsy. While ultrasound-based elastography methods for liver fibrosis staging have been developed, they are confined to a 1D or a 2D region of interest and to a limited depth. 3D Shear Wave Absolute Vibro-Elastography (S-WAVE) is a steady-state, external excitation, volumetric elastography technique that is similar to MRE, but has the additional advantage of multi-frequency excitation. We present a novel ultrasound matrix array implementation of S-WAVE that takes advantage of 3D imaging. We use a matrix array transducer to sample axial multi-frequency steady-state tissue motion over a volume, using a Color Power Angiography sequence. Tissue motion with the frequency components {40,50,60} and {45,55,65} Hz are acquired over a (90° lateral) × (40° elevational) × (16 cm depth) sector with an acquisition time of 12 seconds. We compute the elasticity map in 3D using local spatial frequency estimation. We characterize this new approach in tissue phantoms against measurements obtained with transient elastography and MRE. Six healthy volunteers and eight patients with chronic liver disease were imaged. Their MRE and S-WAVE volumes were aligned using T1 to B-mode registration for direct comparison in common regions of interest. S-WAVE and MRE results are correlated with R2 = 0.92, while MRE and TE results are correlated with R2 = 0.71. Our findings show that S-WAVE with matrix array has the potential to deliver a similar assessment of liver fibrosis as MRE in a more accessible, inexpensive way, to a broader set of patients.


Subject(s)
Elasticity Imaging Techniques , Humans , Liver/diagnostic imaging , Liver Cirrhosis/diagnostic imaging , Magnetic Resonance Imaging , Transducers , Ultrasonography
3.
World J Hepatol ; 12(9): 558-573, 2020 Sep 27.
Article in English | MEDLINE | ID: mdl-33033565

ABSTRACT

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.

4.
Ann Hepatol ; 18(4): 651-654, 2019.
Article in English | MEDLINE | ID: mdl-31056363

ABSTRACT

Rapid overcorrection of chronic hyponatremia can lead to osmotic demyelination syndrome or central pontine myelinolysis (CPM), a diagnosis often triggered by observing the characteristics of neurological abnormalities developed as a result of CPM. However, anyone with chronic hyponatremia and overcorrection of serum sodium is at risk of physiological CPM despite the lack of clinical symptoms. We report an adult patient who presented as post-op delirium, had incidental finding of CPM by magnetic resonance imaging (MRI) of the head after a liver transplant. Despite his non-typical presentation, the patient had the typical risk factors of CPM such as chronic hyponatremia, rapid overcorrection of serum sodium and cirrhosis undergoing a transplant. As hyponatremia and neurological disorder such encephalopathy simultaneously affect patients with cirrhosis, CPM may be more common than once thought in the chronic liver disease population and inappropriate hyponatremia management has important medical consequences that can go unnoticed.


Subject(s)
Delirium/diagnosis , Fluid Therapy/methods , Hyponatremia/therapy , Incidental Findings , Liver Cirrhosis, Biliary/surgery , Liver Transplantation , Myelinolysis, Central Pontine/diagnostic imaging , Postoperative Complications/diagnostic imaging , Delirium/complications , Fluid Therapy/adverse effects , Humans , Hyponatremia/blood , Liver Cirrhosis, Biliary/blood , Magnetic Resonance Imaging , Male , Middle Aged , Myelinolysis, Central Pontine/complications , Myelinolysis, Central Pontine/etiology , Preoperative Care
5.
Transplant Direct ; 5(3): e429, 2019 Mar.
Article in English | MEDLINE | ID: mdl-30882034

ABSTRACT

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.

6.
Saudi J Gastroenterol ; 25(1): 67-70, 2019.
Article in English | MEDLINE | ID: mdl-30117491

ABSTRACT

Acute hepatitis A viral (HAV) infection is rare in the liver transplant population due to recommended pre-transplant vaccinations. We report a case of acute hepatitis A infection in a liver transplant recipient. This individual had immunity to hepatitis A with protective IgG antibodies and presented with abnormal liver biochemistry in the post-transplant in-patient setting. Hepatitis A infection was confirmed by positive HAV IgM whereas other etiologies, including acute cellular rejection, were ruled out by laboratory tests and liver biopsies. He was treated conservatively with supportive care and liver enzymes recovered to normal baseline. Despite adequate pre-transplant immunity, in the post-transplant setting there may be loss of protective immunity due to profound immunosuppression and hence hepatitis A should remain an important differential diagnosis in the setting of acute hepatitis.


Subject(s)
Hepatitis A Virus, Human/immunology , Hepatitis A/immunology , Liver Transplantation/adverse effects , Liver/virology , Acute Disease , Diagnosis, Differential , Hepatitis A/epidemiology , Humans , Immunoglobulin G/immunology , Immunoglobulin M/immunology , Immunosuppression Therapy/adverse effects , Liver/chemistry , Liver/enzymology , Liver Transplantation/statistics & numerical data , Male , Middle Aged , Palliative Care/methods , Treatment Outcome , Vaccination/standards , Vaccination Coverage/standards
7.
Transplant Direct ; 4(3): e347, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29707618

ABSTRACT

BACKGROUND: The goal of treating chronic hepatitis C virus (HCV) infection is sustained virologic response (SVR). There is concern that despite achieving SVR, replication-competent HCV may be sequestered at low levels within the liver and could theoretically reactivate with immunosuppression. We report transplantation of a HCV-seropositive liver donor, who achieved SVR, into a seronegative patient without HCV reactivation despite profound immunosuppression. METHOD: Retrospective chart review. RESULTS: We present a 21-year-old male who was HCV seronegative and received a liver transplant from a donor who had been treated for HCV and achieved SVR. The liver recipient, despite developing severe acute graft rejection and undergoing intense immunosuppression with T cell-depleting antibodies, did not become HCV RNA-positive with a follow up period of 8 months. The recipient was HCV seronegative before transplant, but became HCV seropositive immediately posttransplant. The antibodies were undetectable after 97 days, in keeping with a passive antibody transmission or B lymphocyte transmission with the graft. CONCLUSIONS: To the best of our knowledge, this is the first reported case of an HCV seropositive liver allograft transplanted into an HCV-negative recipient who subsequently received intense immunosuppression. This case, therefore, is an encouraging and novel step in liver transplantation, and demonstrates that SVR may be closer to a true "cure" of HCV in the donor population and that, even in circumstances of very potent immunosuppression in the recipient, this SVR is sustained.

8.
Exp Clin Transplant ; 16(5): 550-553, 2018 10.
Article in English | MEDLINE | ID: mdl-28847263

ABSTRACT

OBJECTIVES: There is a clear lack of clinical evidence guiding immunosuppressive management in long-term stable liver transplant recipients. As a result, anecdotal experience suggests wide variability across transplant centers. We aimed to identify patterns of immunosuppression practices in liver transplant centers across Canada and the United States. MATERIALS AND METHODS: From February 9 to May 31, 2015, we invited clinicians from all liver transplant centers in Canada and the United States to answer a 6-question survey generated using SurveyMonkey. RESULTS: Seventeen respondents from 15 liver transplant centers completed the survey. Although immun-suppressive practices are relatively uniform for induction and early maintenance therapy, significant variations exist in the management of long-term immunosuppression in stable transplant recipients with a relative lack of minimization protocols. CONCLUSIONS: Our survey confirms a wide variability in immunosuppression practices across Canadian and US liver transplant centers. Research and practice priorities include design of pragmatic randomized controlled trials and development of clinical practice guidelines to standardize immunosuppressive management of long-term stable liver transplant recipients with a focus on immunosuppression minimization.


Subject(s)
Graft Rejection/prevention & control , Graft Survival/drug effects , Immunosuppressive Agents/therapeutic use , Liver Transplantation/trends , Practice Patterns, Physicians'/trends , Graft Rejection/immunology , Health Care Surveys , Healthcare Disparities/trends , Humans , Immunosuppressive Agents/adverse effects , Liver Transplantation/adverse effects , North America , Time Factors , Treatment Outcome
9.
Ann. hepatol ; 16(2): 230-235, Mar.-Apr. 2017. tab
Article in English | LILACS | ID: biblio-887227

ABSTRACT

ABSTRACT Background. Chronic renal failure (CRF) is a significant cause of morbidity and mortality in post-liver transplantation (LT) recipients. The risk factors associated with the development of renal dysfunction are not clearly elucidated. Objectives. To examine the risk factors in the development of CRF in these patients. Material and methods. Retrospective case-cohort of liver transplant patients without baseline kidney dysfunction who developed chronic renal failure during their follow-up. Results. Of 370 patients, 254 met the inclusion criteria. 30% (76) of these patients had CRF of which 57% (43) were male. Age, estimated glomerular filtration rate (eGFR) at discharge, and HCV infection were found to be risk factors for CRF post-LT. The odds ratio of developing CRF was 1.4 (0.6-3.3) in males with HCV, 1.6 (0.7-3.9) in females without HCV and 4.4 (1.5-13.2) among females with HCV when compared to men without HCV. Conclusions. In this cohort of LT receipients of a major Canadian city, age, eGFR, and HCV infection were risk factors for CRF. Female gender and HCV increased this odds by a factor of more than 4.


Subject(s)
Humans , Liver Transplantation/adverse effects , Hepatitis C/complications , Kidney Failure, Chronic/etiology , Time Factors , British Columbia , Chi-Square Distribution , Logistic Models , Odds Ratio , Sex Factors , Retrospective Studies , Risk Factors , Treatment Outcome , Hepatitis C/diagnosis , Risk Assessment , Glomerular Filtration Rate , Kidney/physiopathology , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/physiopathology
10.
Ann. hepatol ; 16(2): 207-214, Mar.-Apr. 2017. tab, graf
Article in English | LILACS | ID: biblio-887224

ABSTRACT

ABSTRACT Background. Patients with chronic hepatitis B virus (HBV) are often treated with nucleoside/nucleotide antiviral agents and metabolic bone toxicity is a possible concern. Objective. To determine the relationships between fibroblast growth factor 23 (FGF23), a phosphaturic hormone, bone mineral density (BMD), and bone biochemical abnormalities in these patients. Material and methods. This is a cross-sectional observational study comparing HBV-infected subjects treated for at least one year with tenofovir (TDF), lamuvidine (LVD), entacavir (ETV), or not treated (CON). Patients with abnormalities in either calcium (Ca), phosphate (PO4), intact parathyroid hormone (iPTH) or FGF23 were further evaluated with BMD by DXA. Results. No difference in liver enzymes or renal function seen among groups, but hypophosphatemia was seen in all groups with the highest incidence with TDF treatment (14%). FGF 23 levels were found to be elevated in 11.1% of TDF patients, 2.77% amongst controls. No elevations were found in the LVD or ETV groups. Among a subset of subjects (FGF23, PO4, and/or Ca abnormalities) who underwent further evaluation, 67% had insufficient 25-OH vitamin D, and 30% had elevated 24 h urinary Ca or PO4 excretion. No patients with FGF23 abnormalities had urine abnormalities. 40% had low DXA Z-score (<-2) at spine or hip but there was no difference between control and antiviral treatment groups and the mean FRAX score was 2.33% for major osteoporotic fractures and 0.29% for hip fracture. Conclusion. Abnormalities in bone metabolism, particularly involving vitamin D insufficiency, in HBV-treated subjects were observed with a small increased likelihood in TDF treated patients.


Subject(s)
Humans , Antiviral Agents/therapeutic use , Phosphates/blood , Bone and Bones/drug effects , Calcium/blood , Lamivudine/therapeutic use , Hepatitis B, Chronic/drug therapy , Fibroblast Growth Factors/blood , Tenofovir/therapeutic use , Guanine/analogs & derivatives , Antiviral Agents/adverse effects , Time Factors , Vitamin D Deficiency/chemically induced , Bone and Bones/metabolism , Bone and Bones/diagnostic imaging , Biomarkers/blood , Absorptiometry, Photon , Bone Density/drug effects , Cross-Sectional Studies , Risk Factors , Treatment Outcome , Bone Remodeling/drug effects , Hepatitis B, Chronic/diagnosis , Hepatitis B, Chronic/blood , Fractures, Bone/chemically induced , Tenofovir/adverse effects , Guanine/adverse effects , Guanine/therapeutic use
11.
Ann Hepatol ; 16(2): 207-214, 2017.
Article in English | MEDLINE | ID: mdl-28233741

ABSTRACT

BACKGROUND: Patients with chronic hepatitis B virus (HBV) are often treated with nucleoside/nucleotide antiviral agents and metabolic bone toxicity is a possible concern. OBJECTIVE: To determine the relationships between fibroblast growth factor 23 (FGF23), a phosphaturic hormone, bone mineral density (BMD), and bone biochemical abnormalities in these patients. MATERIAL AND METHODS: This is a cross-sectional observational study comparing HBV-infected subjects treated for at least one year with tenofovir (TDF), lamuvidine (LVD), entacavir (ETV), or not treated (CON). Patients with abnormalities in either calcium (Ca), phosphate (PO4), intact parathyroid hormone (iPTH) or FGF23 were further evaluated with BMD by DXA. RESULTS: No difference in liver enzymes or renal function seen among groups, but hypophosphatemia was seen in all groups with the highest incidence with TDF-treatment (14%). FGF 23 levels were found to be elevated in 11.1% of TDF patients, 2.77% amongst controls. No elevations were found in the LVD or ETV groups. Among a subset of subjects (FGF23, PO4, and/or Ca abnormalities) who underwent further evaluation, 67% had insufficient 25-OH vitamin D, and 30% had elevated 24 h urinary Ca or PO4 excretion. No patients with FGF23 abnormalities had urine abnormalities. 40% had low DXA Z-score (&lt;-2) at spine or hip but there was no difference between control and antiviral treatment groups and the mean FRAX score was 2.33% for major osteoporotic fractures and 0.29% for hip fracture. CONCLUSION: Abnormalities in bone metabolism, particularly involving vitamin D insufficiency, in HBV-treated subjects were observed with a small increased likelihood in TDF treated patients.


Subject(s)
Antiviral Agents/therapeutic use , Bone and Bones/drug effects , Calcium/blood , Fibroblast Growth Factors/blood , Guanine/analogs & derivatives , Hepatitis B, Chronic/drug therapy , Lamivudine/therapeutic use , Phosphates/blood , Tenofovir/therapeutic use , Absorptiometry, Photon , Adult , Aged , Antiviral Agents/adverse effects , Biomarkers/blood , Bone Density/drug effects , Bone Remodeling/drug effects , Bone and Bones/diagnostic imaging , Bone and Bones/metabolism , Cross-Sectional Studies , Female , Fibroblast Growth Factor-23 , Fractures, Bone/chemically induced , Guanine/adverse effects , Guanine/therapeutic use , Hepatitis B, Chronic/blood , Hepatitis B, Chronic/diagnosis , Humans , Lamivudine/adverse effects , Male , Middle Aged , Risk Factors , Tenofovir/adverse effects , Time Factors , Treatment Outcome , Vitamin D Deficiency/chemically induced
12.
Ann Hepatol ; 16(2): 230-235, 2017.
Article in English | MEDLINE | ID: mdl-28233746

ABSTRACT

BACKGROUND: Chronic renal failure (CRF) is a significant cause of morbidity and mortality in post-liver transplantation (LT) recipients. The risk factors associated with the development of renal dysfunction are not clearly elucidated. OBJECTIVES: To examine the risk factors in the development of CRF in these patients. MATERIAL AND METHODS: Retrospective case-cohort of liver transplant patients without baseline kidney dysfunction who developed chronic renal failure during their follow-up. RESULTS: Of 370 patients, 254 met the inclusion criteria. 30% (76) of these patients had CRF of which 57% (43) were male. Age, estimated glomerular filtration rate (eGFR) at discharge, and HCV infection were found to be risk factors for CRF post-LT. The odds ratio of developing CRF was 1.4 (0.6-3.3) in males with HCV, 1.6 (0.7-3.9) in females without HCV and 4.4 (1.5-13.2) among females with HCV when compared to men without HCV. CONCLUSIONS: In this cohort of LT receipients of a major Canadian city, age, eGFR, and HCV infection were risk factors for CRF. Female gender and HCV increased this odds by a factor of more than 4.


Subject(s)
Hepatitis C/complications , Kidney Failure, Chronic/etiology , Liver Transplantation/adverse effects , Adult , Aged , British Columbia , Chi-Square Distribution , Female , Glomerular Filtration Rate , Hepatitis C/diagnosis , Humans , Kidney/physiopathology , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/physiopathology , Logistic Models , Male , Middle Aged , Odds Ratio , Retrospective Studies , Risk Assessment , Risk Factors , Sex Factors , Time Factors , Treatment Outcome
13.
Nephrol Dial Transplant ; 32(1): 35-41, 2017 01 01.
Article in English | MEDLINE | ID: mdl-26481484

ABSTRACT

Historically, standard treatment of hepatitis C virus (HCV) infection in patients with renal impairment has been limited by low cure rates and poor tolerability. The introduction of direct-acting antivirals (DAAs) has revolutionized the treatment of HCV with impressive cure rates >90% and low rates of adverse events. Despite these major advancements, treatment of patients with HCV and advanced chronic kidney disease (CKD) is a major challenge due to the lack of efficacy and safety data in this patient population. The purpose of this review is to summarize the available data for efficacy and safety of the following DAAs in treating HCV patients with advanced Stage 4 and 5 CKD: simeprevir, sofosbuvir, ledipasvir, ombitasvir, paritaprevir, dasabuvir, grazoprevir, elbasvir and daclatasvir.


Subject(s)
Antiviral Agents/therapeutic use , Hepacivirus/drug effects , Hepatitis C/drug therapy , Renal Insufficiency, Chronic/drug therapy , Hepatitis C/complications , Humans , Renal Insufficiency, Chronic/virology
14.
Exp Clin Transplant ; 15(6): 693-695, 2017 Dec.
Article in English | MEDLINE | ID: mdl-27001306

ABSTRACT

Hepatopulmonary syndrome and portopulmonary hypertension are complications of portal hypertension with opposing mechanisms that can coexist. Moderate portopulmonary hypertension, which is a contraindication to a liver transplant, must be managed with pulmonary vasodilators to normalize pulmonary arterial pressures before a transplant listing. Concomitant hepatopulmonary syndrome complicates the management of portopulmonary hypertension, as pulmonary vasodilators can theoretically exacerbate the intrapulmonary dilatation believed to cause hepatopulmonary syndrome. We describe a case of a post-liver transplant patient with concomitant hepatopulmonary syndrome and portopulmonary hypertension safely treated with sildenafil.


Subject(s)
Antihypertensive Agents/therapeutic use , Hemodynamics/drug effects , Hepatopulmonary Syndrome/surgery , Hypertension, Portal/drug therapy , Hypertension, Pulmonary/drug therapy , Liver Transplantation/adverse effects , Sildenafil Citrate/therapeutic use , Vasodilator Agents/therapeutic use , Antihypertensive Agents/adverse effects , Female , Hepatopulmonary Syndrome/diagnosis , Hepatopulmonary Syndrome/etiology , Hepatopulmonary Syndrome/physiopathology , Humans , Hypertension, Portal/diagnosis , Hypertension, Portal/etiology , Hypertension, Portal/physiopathology , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/physiopathology , Liver Circulation/drug effects , Middle Aged , Pulmonary Circulation/drug effects , Sildenafil Citrate/adverse effects , Treatment Outcome , Vasodilator Agents/adverse effects
15.
J Clin Transl Hepatol ; 4(3): 192-205, 2016 Sep 28.
Article in English | MEDLINE | ID: mdl-27777888

ABSTRACT

Aims: To systematically evaluate the literature for evidence to support the use of bile acids in non-cholestatic liver conditions. Methods: Searches were conducted on the databases of Medline (1948-March 31, 2015), Embase (1980-March 31, 2015) and the Cochrane Central Register of Controlled Trials, and on Google and Google Scholar to identify articles describing ursodeoxycholic acid (UDCA) and its derivatives for non-cholestatic hepatic indications. Combinations of the following search terms were used: ursodeoxycholic acid, ursodiol, bile acids and/or salts, non alcoholic fatty liver, non alcoholic steatohepatitis, fatty liver, alcoholic hepatitis, alcohol, liver disease, autoimmune, autoimmune hepatitis, liver transplant, liver graft, transplant rejection, graft rejection, ischemic reperfusion injury, reperfusion injury, hepatitis B, hepatitis C, viral hepatitis, chronic hepatitis, acute hepatitis, transaminases, alanine transaminase, liver enzymes, aspartate aminotransferase, gamma-glutamyl transferase, gamma-glutamyl transpeptidase, bilirubin, alkaline phosphatase. No search limits were applied. Additionally, references of the included studies were reviewed to identify additional articles. Results: The literature search yielded articles meeting inclusion criteria for the following indications: non-alcoholic fatty liver disease (n = 5); alcoholic liver disease (n = 2); autoimmune hepatitis (n = 6), liver transplant (n = 2) and viral hepatitis (n = 9). Bile acid use was associated with improved normalization of liver biochemistry in non-alcoholic fatty liver disease, autoimmune hepatitis and hepatitis B and C infections. In contrast, liver biochemistry normalization was inconsistent in alcoholic liver disease and liver transplantation. The majority of studies reviewed showed that normalization of liver biochemistry did not correlate to improvement in histologic disease. In the prospective trials reviewed, adverse effects associated with the bile acids were limited to minor gastrointestinal complaints (most often, diarrhea) and did not occur at increased frequency as compared to controls. As administration of bile acids was often limited to durations of 12 months or less, long-term side effects for non-cholestatic indications cannot be excluded. Conclusions: Based on the available literature, bile acids cannot be widely recommended for non-cholestatic liver diseases at present.

16.
Can J Infect Dis Med Microbiol ; 2016: 8372835, 2016.
Article in English | MEDLINE | ID: mdl-27366182

ABSTRACT

Although major advances have occurred in treating patients with hepatitis C virus (HCV) with the development of new direct-acting antivirals (DAAs), treatment of liver transplant recipients with HCV, human immunodeficiency virus (HIV) coinfection, and renal disease is challenging due to the lack of efficacy and safety data in this population. We report a case of successful HCV therapy in a postliver transplant HIV coinfected patient, with stage 4 chronic kidney disease, using an all-oral regimen of simeprevir, sofosbuvir, and ribavirin. The 51-year-old male achieved SVR24, and no specific HIV-related or transplant-related adverse events were documented during the treatment period. The new DAAs show promise for HIV coinfected patients and those with severe to end-stage renal disease (ESRD); however, robust clinical trials or large cohort studies will need to be conducted to confirm the efficacy and safety of these newer agents in this setting.

17.
Can J Gastroenterol Hepatol ; 29(2): 72-6, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25803016

ABSTRACT

BACKGROUND: The cost of liver biopsy (LB) is publicly funded in British Columbia, while the cost of transient elastography (FibroScan [FS], Echosens, France) is not. Consequently, there is regional variation regarding FS access and monitoring of liver disease progression. OBJECTIVE: To evaluate patient preference for FS versus LB and to assess the willingness to self-pay for FS. METHODS: Questionnaires were distributed in clinic and via mail to LB-experienced and LB-naive patients who underwent FS at Vancouver General Hospital, Vancouver, British Columbia. RESULTS: The overall response rate was 76%. Of the 422 respondents, 205 were LB-experienced. The mean age was 53.5 years, 50.2% were male, 54.7% were Caucasian, 38.2% had hepatitis C and 26.3% had an annual household income >$75,000. Overall, 95.4% of patients preferred FS to LB. FS was associated with greater comfort than LB, with the majority reporting no discomfort during FS (84.1% versus 7.8% for LB), no discomfort after (96.2% versus 14.6% LB) and no feelings of anxiety after FS explanation (78.2% versus 12.7% LB). FS was also associated with greater speed, with the majority reporting short test duration (97.2% versus 48.3% LB) and short wait for the test result (95.5% versus 30.2% LB). Most (75.3%) respondents were willing to self-pay for FS, with 26.3% willing to pay $25 to $49. Patients with unknown liver disease preferred LB (OR [FS preference] 0.20 [95% CI 0.07 to 0.53]). CONCLUSIONS: FS was the preferred method of assessing liver fibrosis among patients, with the majority willing to self-pay. To ensure consistency in access, provincial funding for FS is needed. However, LB remains the procedure of choice for individuals with an unknown diagnosis.


Subject(s)
Biopsy/psychology , Elasticity Imaging Techniques/psychology , Fees and Charges , Financing, Personal , Liver Cirrhosis/diagnosis , Patient Preference/psychology , Adult , Biopsy/economics , British Columbia , Elasticity Imaging Techniques/economics , Female , Humans , Liver/pathology , Male , Middle Aged , Patient Preference/economics , Surveys and Questionnaires
18.
Ann Pharmacother ; 49(6): 674-87, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25770114

ABSTRACT

OBJECTIVE: Review pharmacokinetics of new direct-acting antivirals (DAAs) for hepatitis C (HCV) infection and interactions with concomitant immunosuppressant and antiretroviral therapies (ART). DATA SOURCES: MEDLINE (1948-January 2015), EMBASE (1964-January 2015), International Pharmaceutical Abstracts (1970-January 2015), Google, and Google Scholar were searched combining the terms simeprevir, sofosbuvir, ledipasvir, daclatasvir, paritaprevir, ABT-450, ombitasvir, dasabuvir, pharmacokinetics, drug interaction, drug metabolism, HIV, antiretroviral, immunosuppressant, transplant. Articles, conference proceedings, abstracts, and product monographs were reviewed. STUDY SELECTION AND DATA EXTRACTION: Literature on pharmacokinetic or pharmacodynamic interactions with DAAs and immunosuppressants or ART was considered for inclusion. Pertinent information was extracted and summarized in the review. In the absence of data, pharmacokinetic and pharmacodynamic principles were used to predict the likelihood of interactions. DATA SYNTHESIS: DAA pharmacokinetics are reviewed and drug interaction data are presented with provision of management strategies. Fixed-dose combination paritaprevir/ritonavir/ombitasvir plus dasabuvir is most susceptible to drug interactions with immunosuppressants and ART mainly due to the influence of ritonavir on multiple enzymes. Simeprevir is also prone to drug interactions because of cytochrome P450(CYP) 3A4, CYP1A2, P-glycoprotein, and OATP1 involvement and is not recommended for use in combination with several HIV antiretrovirals (ARVs). Close therapeutic drug monitoring of calcineurin inhibitors is required with concomitant simeprevir. Few clinically significant interactions are expected with sofosbuvir or ledipasvir. Limited data suggest that daclatasvir may be coadministered with immunosuppressants but requires dose adjustments with certain ARVs. CONCLUSIONS: None of the DAAs are completely free of drug interactions. Awareness and management of drug interactions is critical to optimize outcomes and minimize adverse effects in these patient populations.


Subject(s)
Antiviral Agents/pharmacokinetics , HIV Infections/drug therapy , Hepatitis C/drug therapy , Anti-HIV Agents/therapeutic use , Antiviral Agents/therapeutic use , Drug Interactions , Humans , Immunosuppressive Agents/therapeutic use
19.
Ann Hepatol ; 14(1): 137-40, 2015.
Article in English | MEDLINE | ID: mdl-25536653

ABSTRACT

Renal dysfunction frequently occurs in liver transplant recipients and is associated with increased morbidity and mortality. BK virus is a human polyoma virus that reactivates during immunocompromised states and is a known cause of renal allograft dysfunction in renal transplant recipients. However, BK nephropathy of native kidneys is rare in non-renal transplant recipients. There is no published data linking BK virus and renal dysfunction in liver transplant recipients. We describe the first confirmed case of native polyomavirus BK nephropathy in a liver transplant recipient. BK nephropathy should be considered in the differential diagnosis of new renal failure in liver transplant recipients.


Subject(s)
Graft Rejection/prevention & control , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Kidney Diseases/chemically induced , Liver Transplantation , Polyomavirus Infections/chemically induced , Tumor Virus Infections/chemically induced , BK Virus , Cholangitis, Sclerosing/complications , End Stage Liver Disease/etiology , End Stage Liver Disease/surgery , Humans , Kidney Diseases/virology , Male , Middle Aged
20.
Can J Infect Dis Med Microbiol ; 25(3): 159-62, 2014 May.
Article in English | MEDLINE | ID: mdl-25285113

ABSTRACT

BACKGROUND: The demand for definitive management of end-stage organ disease in HIV-infected Canadians is growing. Until recently, despite international evidence of good clinical outcomes, HIV-infected Canadians with end-stage liver disease were ineligible for transplantation, except in British Columbia (BC), where the liver transplant program of BC Transplant has accepted these patients for referral, assessment, listing and provision of liver allograft. There is a need to evaluate the experience in BC to determine the issues surrounding liver transplantation in HIV-infected patients. METHODS: The present study was a chart review of 28 HIV-infected patients who were referred to BC Transplant for liver transplantation between 2004 and 2013. Data regarding HIV and liver disease status, initial transplant assessment and clinical outcomes were collected. RESULTS: Most patients were BC residents and were assessed by the multidisciplinary team at the BC clinic. The majority had undetectable HIV viral loads, were receiving antiretroviral treatments and were infected with hepatitis C virus (n=16). The most common comorbidities were anxiety and mood disorders (n=4), and hemophilia (n=4). Of the patients eligible for transplantation, four were transplanted for autoimmune hepatitis (5.67 years post-transplant), nonalcoholic steatohepatitis (2.33 years), hepatitis C virus (2.25 years) and hepatitis B-delta virus coinfection (recent transplant). One patient died from acute renal failure while waiting for transplantation. Ten patients died during preassessment and 10 were unsuitable transplant candidates. The most common reason for unsuitability was stable disease not requiring transplantation (n=4). CONCLUSIONS: To date, interdisciplinary care and careful selection of patients have resulted in successful outcomes including the longest living HIV-infected post-liver transplant recipient in Canada.


HISTORIQUE: La demande d'une prise en charge définitive des maladies organiques terminales chez les Canadiens infectés par le VIH est en hausse. Jusqu'à tout récemment, malgré des données internationales faisant foi de résultats cliniques positifs, les Canadiens atteints d'une maladie hépatique terminale infectés par le VIH n'étaient pas admissibles à une transplantation, sauf en Colombie-Britannique (C.-B.), où le programme de transplantations de BC Transplant les accepte en vue d'un aiguillage, d'une évaluation, de l'inscription sur la liste d'attente et de l'exécution d'une allogreffe du foie. L'évaluation de l'expérience de la C.-B. s'impose pour déterminer les enjeux entourant la transplantation hépatique chez les patients infectés par le VIH. MÉTHODOLOGIE: Les chercheurs ont procédé à l'étude des dossiers des 28 patients infectés par le VIH qui ont été orientés vers BC Transplant pour subir une transplantation hépatique entre 2004 et 2013. Ils ont colligé les données sur l'état du VIH et de la maladie hépatique, l'évaluation initiale de la transplantation et les résultats cliniques. RÉSULTATS: La plupart des patients étaient des habitants de la C.-B. qui avaient été évalués par l'équipe multidisciplinaire de la clinique de C.-B. La majorité présentait des charges virales indétectables du VIH, prenaient des antirétroviraux et étaient infectés par le virus de l'hépatite C (n=16). Les comorbidités les plus courantes étaient l'anxiété et les troubles des humeurs (n=4), ainsi que l'hémophilie (n=4). Parmi les patients admissibles à la transplantation, quatre ont subi une transplantation consécutive à une hépatite auto-immune (5,67 ans après la transplantation), à une stéatose hépatique non alcoolique (2,33 ans), à un virus de l'hépatite C (2,25 ans) et à une co-infection par l'hépatite B et le virus delta (transplantation récente). Un patient est décédé d'une insuffisance rénale aiguë alors qu'il était en attente de transplantation. Dix sont décédés pendant la préévaluation et dix n'étaient pas des candidats adéquats pour la transplantation. La principale raison de ne pas être un candidat adéquat était une maladie stable ne nécessitant pas de transplantation (n=4). CONCLUSIONS: Jusqu'à présent, les soins interdisciplinaires et une sélection attentive des patients permettent d'obtenir des résultats positifs, y compris la présence au Canada du greffé hépatique infecté par le VIH ayant vécu le plus longtemps depuis sa transplantation.

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