Hepatitis C virus treatment with glecaprevir and pibrentasvir in patients co-prescribed carbamazepine: Three case reports.

BACKGROUND: Highly effective and well-tolerated direct-acting antiviral (DAA) therapies have revolutionised the management of hepatitis C virus (HCV); however, niche populations face treatment barriers. DAAs co-prescribed with several first-generation anti-epileptic drugs (AEDs) are contraindicated due to drug-drug interactions. A common example is carbamazepine whereby steady-state carbamazepine reduces the maximum concentration and area under the curve of velpatasvir, glecaprevir and pibrentasvir due to potent cytochrome P450 (CYP) 3A4 induction. Carbamazepine also induces P-glycoprotein which reduces glecaprevir and pibrentasvir's area under curve to infinite time. Sofosbuvir-velpatasvir and glecaprevir-pibrentasvir are contraindicated in patients who are co-prescribed carbamazepine due to the risk of reduced DAA therapeutic effect and consequently, virological treatment failure. This presents a challenge for patients in whom carbamazepine substitution is medically unfeasible, impractical or unacceptable. However, the properties of current generation DAA therapies, including high-potency non-structural protein 5A inhibitory effect, may be sufficient to overcome reduced bioavailability arising from carbamazepine related CYP 3A4 and P-glycoprotein induction. CASE SUMMARY: We present a case series of three patients with non-cirrhotic, treatment-naïve, genotype 1a, 1b, and 3a HCV who were treated with a 12 wk course of glecaprevir-pibrentasvir, while co-prescribed carbamazepine for seizure disorders. Glecaprevir-pibrentasvir combination therapy was chosen due to its potent in vitro activity and low barrier to pan-genotypic resistance associated variants. DAA therapy was dose-separated from carbamazepine to maximise time to peak concentration, and taken with meals to improve absorption. Sustained virological response at 12 wk was achieved in each patient with no adverse outcomes. CONCLUSION: DAA therapies, including glecaprevir-pibrentasvir, warrant consideration as a therapeutic agent in people with HCV who are co-prescribed carbamazepine, particularly if AED substitution is not feasible.

Hepatitis C virus in people with serious mental illness: an analysis of the care cascade at a tertiary health service with a pilot 'identify and treat' strategy.

BACKGROUND: People with serious mental illness (SMI) are underserved from a hepatitis C virus (HCV) screening and treatment perspective. AIMS: To examine the HCV care cascade in people with SMI and to pilot a supported HCV treatment integration programme. METHODS: HCV prevalence was retrospectively analysed from 4492 consecutive individuals admitted to a tertiary hospital mental health service between January 2017 and December 2018. Subcohort analysis of screening patterns and predictors of seropositive infection was performed. Referral pathways and community care integration were analysed for HCV-positive individuals, and a prospective community-based 'identify and treat' HCV programme was assessed. RESULTS: Screening for HCV had been performed in 18.6% (835/4492) of the cohort. Seroprevalence was 4.6% (207/4492). HCV seropositivity was associated with age >40 years (odds ratio (OR) = 9.30; confidence interval (CI) 3.69-23.45; P < 0.01), injecting drug use (OR = 24.26; CI 8.99-65.43; P < 0.01) and previous incarceration (OR = 12.26; CI 4.51-33.31; P < 0.01). In a cohort of treatment-eligible individuals, 43.3% (90/208) had neither been referred to specialist services or general practitioners for HCV management. Amongst those referred to specialist services, 64.7% (57/88) did not attend scheduled follow up, and 48.3% (15/31) of attendees were lost to follow up. Through an intensified community access programme, 10 people were successfully treated for HCV, although 22 could not be engaged. CONCLUSION: People with SMI are underserved by traditional models of HCV healthcare. Intensified community-based support can partially bolster the treatment cascade, although investment in innovative screening and management strategies are required to achieve healthcare parity.

Liver stiffness (Fibroscan®) is a predictor of all-cause mortality in people with non-alcoholic fatty liver disease.

BACKGROUND AND AIMS: Progressive liver fibrosis related to non-alcoholic fatty liver disease (NAFLD) is associated with all-cause and liver-related mortality. We assessed vibration-controlled transient elastography (VCTE) as a predictor of mortality. METHOD: Data from patients who underwent VCTE for NAFLD at four large health services in Victoria, Australia between the years 2008 and 2019 were linked to state-wide data registries. Cause of death (COD) and predictors of all-cause mortality were subsequently analysed using descriptive statistics and Cox-proportional regression analysis. RESULTS: Of 7079 VCTE records submitted for data linkage, 6341 were matched via data registry linkage. There were 217 deaths over a 22 653 person-year follow-up. COD included malignancies other than hepatocellular carcinoma (HCC) (18.0%, n = 39), sepsis (16.1%, n = 35), decompensated liver disease (15.2%, n = 33), cardiac disease (15.2%, n = 33) and HCC 6.0% (n = 13). Controlled attenuation parameter (CAP) was not associated with mortality in univariable analysis (HR = 1.00, CI 1.0-1.0, p = .488). Increased liver stiffness measurement (LSM) (HR 1.02 per kiloPascal, CI 1.01-1.03, p < .001), Charlson comorbidity index (CCI) (HR 1.32 for each point, CI 1.27-1.38, p < .001) and age (HR 1.05 per annum, CI 1.03-1.07, p < .001) were each associated with higher rates of all-cause mortality in multivariable analysis. LSM ≥10 kPa suggestive of compensated advanced chronic liver disease (cACLD) was associated with mortality in multivariable analysis (HR 2.31, CI 1.73-3.09, p < .001). CONCLUSION: VCTE LSM, in addition to age and CCI, is independently associated with increased all-cause mortality in a large cohort with NAFLD.

Integrating Hepatitis C Virus Treatment Programs Within Community Mental Health.

Conventional models of health care for the hepatitis C virus (HCV) underserve people with serious mental illness. In a 6-month proof-of-concept study, colocated HCV care coordination was assessed within community mental health settings. The program, which relied on referrals to a visiting hepatologist and was augmented by a part-time nurse practitioner, received 18 referrals for HCV management. From this group, 11 individuals achieved sustained virological response at 12 weeks after direct-acting antiviral therapy. Seven individuals declined treatment or were lost to follow-up. Overall, colocated integrated services may play an important role in HCV health care parity for people with serious mental illness.

Determinants of Hepatitis C Virus Prevalence in People With Serious Mental Illness: A Systematic Review and Meta-Analysis.

Objective: To perform a meta-analysis of hepatitis C virus (HCV) prevalence in people with serious mental illness (SMI) and to systematically review barriers to care with the contention that both individual complications and HCV community transmission can be reduced with enhanced health care strategies.Data Sources: PubMed, Scopus, Embase, CINAHL, and Web of Science were searched for articles published in English between April 21, 1989, and July 1, 2020. The terms Hepatitis C Virus, HCV, HCV seroprevalence, and HCV prevalence were cross-referenced with serious mental illness, severe mental illness, psychiatric illness, mental illness, and psychiatric patients.Study Selection: We identified 230 titles after removing duplicates. The final analysis included 36 publications drawn from prospective and large retrospective cohort studies that cross-sectionally screened for HCV in people with SMI ≥ 18 years of age.Data Extraction: Pooled HCV prevalence was analyzed, with random effects modeling due to significant attributable study heterogeneity. Demographic data and HCV risk factors were subanalyzed. Qualitative and semiqualitative data relating to control cohort prevalence and the HCV care cascade were also extracted.Results: The pooled HCV prevalence was 8.0% (95% CI, 6.0%-9.0%). Subanalysis of prospective studies (n = 9,015 individuals) demonstrated a similar prevalence, 8.0% (CI, 5.0%-11.0%), to retrospective studies (n = 289,247), 8.0% (CI, 6.0%-10.0%). HCV was 3.0- to 11.3-fold higher in people with SMI relative to controls. Semiqualitative analysis of seropositive cases showed that (1) 20.0%-58.1% did not have an identified HCV risk factor; (2) 12.5%-100% of cases were not previously known to have HCV; and (3) the majority, 57.0%-96.6%, of people with SMI were receptive to HCV screening.Conclusions: People with SMI have high HCV seroprevalence and should be recognized as a priority group for HCV screening and health care access.

Liver disease prevalence and severity in people with serious mental illness: a cross-sectional analysis using non-invasive diagnostic tools.

BACKGROUND/PURPOSE OF THE STUDY: Little is known about all-cause liver disease in people with serious mental illness (SMI), despite heightened risk factors. We, therefore, prospectively assessed liver disease by etiology and severity in a cross-sectional cohort of people with SMI at a tertiary health service. METHODS: We recruited 255 people with SMI between August 2019 and March 2020. Liver disease data were derived from structured interview, medical records, biochemical and BBV serological analyses, and vibration-controlled transient elastography (VCTE). Steatosis was determined using a threshold of ≥ 248 db/m via the controlled attenuation parameter (CAP) on VCTE. Liver disease prevalence was assessed descriptively, and predictors of metabolic-dysfunction associated fatty liver disease (MAFLD) analyzed using linear regression and multivariable analysis. Best fit modeling of non-invasive screening tests for MAFLD was also assessed. RESULTS: Valid VCTE was obtained for 252 (98.9%) participants. Median age was 40 years (IQR 31-49) with male predominance (65.9%). Hepatitis C Virus (HCV) seroprevalence was 14.7% (37/252), with four new viremic cases identified. Hepatic steatosis was diagnosed in 61.5% (155/252) of participants, with MAFLD criteria met in 59.9% (151/252) of cases. Clozapine and paliperidone were associated with hepatic steatosis (CAP + 23.3 db/m, p 0.013 and CAP + 25.5, p 0.037, respectively). Advanced liver disease, defined by LSM ≥ 8.2 kPa, was identified in 26 individuals (10.3%). MAFLD compared to no MAFLD was associated with more advanced liver disease (5.3 kPa, 4.3-6.5 versus 4.9 kPa, 3.9-5.6, p < 0.001). CONCLUSION: Liver disease is common in people with SMI and should be screened for as part of standard physical health assessment.

Acute medical stabilisation of adults with anorexia nervosa: experience of a defined interdisciplinary model of care.

BACKGROUND: Patients with anorexia nervosa (AN) are vulnerable to physiological decompensation and often require inpatient management by an eating disorders unit. AIMS: Patients admitted to an Australian tertiary medical centre for medical stabilisation of AN were assessed as part of quality assurance. Analysis included: (i) medical complications during acute inpatient stabilisation; (ii) predictors of refeeding syndrome; (iii) predictors governing length of stay (LOS); and (iv) outcomes pre- and post-implementation of multidisciplinary treatment guidelines. METHODS: A retrosepctive analysis of 95 consecutive admissions (60 individual patients) between November 2011 and August 2017 was performed. RESULTS: Patients had a median LOS of 9.6 days (interquartile range 5.8-19.7) and a mean weight gain of 1.4 kg (standard deviation 2.9). Medical complications included the following: hypoglycaemia (11.6%) and refeeding electrolyte derangement (26.3%). Advancing age (odds ratio (OR) 1.06 per year, P = 0.019), nasogastric tube requirement (OR 3.4, P = 0.014) and Code Grey(s) (security calls) (OR 7.1, P = 0.010) were associated with refeeding electrolyte derangement. Parameters associated with increased LOS included the following: lower body mass index (P = 0.029), Code Grey(s) (P = 0.029) and tachycardia (P = 0.013). Following multivariate analysis, the post-guidelines implementation group required less intravenous fluid and electrolyte replacement, though had lower rates of refeeding electrolyte derangement (OR 0.33 (0.11-0.99)). CONCLUSION: Patients with moderate to severe AN are at risk of dangerous medical complications, and older patients may have heightened predisposition to refeeding electrolyte derangement. Early identification of medically high-risk patients is imperative to implement timely, life-saving interventions.