Leveraging opportunities for treatment/user simplicity (LOTUS): Navigating the current treatment landscape for achieving hepatitis C virus elimination among persons who inject drugs.

All-oral, direct-acting antivirals can cure hepatitis C virus (HCV) in almost all infected individuals; yet, many individuals with chronic HCV are not treated, and the incidence of acute HCV is increasing in some countries, including the United States. Strains on healthcare resources during the COVID-19 pandemic negatively impacted the progress toward the World Health Organization goal to eliminate HCV by 2030, especially among persons who inject drugs (PWID). Here, we present a holistic conceptual framework termed LOTUS (Leveraging Opportunities for Treatment/User Simplicity), designed to integrate the current HCV practice landscape and invigorate HCV treatment programs in the setting of endemic COVID-19: (A) treatment as prevention (especially among PWID), (B) recognition that HCV cure may be achieved with variable adherence with evidence supporting some forgiveness for missed doses, (C) treatment of all persons with active HCV infection (viremic), regardless of acuity, (D) minimal monitoring (MinMon) during treatment, and (E) rapid test and treat (TnT). The objective of this article is to review the current literature supporting each LOTUS petal; identify remaining gaps in knowledge or data; define the remaining barriers facing healthcare providers; and review evidence-based strategies for overcoming key barriers.

The impact of an educational program on HCV patient outcomes using boceprevir in community practices (OPTIMAL trial).

OBJECTIVES: Although effective, direct acting antiviral (DAA) therapies for genotype 1 (GT 1) hepatitis C virus (HCV) have been associated with compliance challenges. Additionally, treatment at predominantly community-based centers has been associated with low retention of patients on treatment and higher dropout rates. The OPTIMAL Phase IV interventional trial (ClinicalTrials.gov Identifier: NCT01405027) was designed to evaluate the impact of an education program for community investigator (CI) sites participating in a Chronic Liver Disease Foundation study treating chronic GT 1 HCV patients. METHODS: This physician educational program was administered by 22 Hepatology Centers of Educational Expertise (HCEE) academic sites to 33 CI sites asked to participate from December 2011 to July 2012. The HCEE mentors from DAA-experienced academic sites educated those at CI sites on therapeutic management, practice, and patient outcomes through a series of four standardized educational sequence visits regarding the use of first generation HCV protease inhibitors and the overall treatment of HCV. RESULTS: Treatment duration compliance rates for patients treated at CI sites versus those treated at HCEE academic sites were evaluable in 77 of 84 HCEE academic site patients, 102 of 113 patients treated at CI sites, and 179 of 197 overall patients. The treatment duration compliance rates for patients treated at HCEE academic sites, CI sites and overall were 85.4 ± 25.39%, 83.8 ± 27.37%, and 84.5 ± 26.48%, respectively, and did not differ statistically between the groups (p = 0.49). Almost half (47%) of the patients in the study achieved a sustained virological response for 24 weeks (SVR24) regardless of the type of site (p = 0.64). Safety profiles were similar at both HCEE and CI sites. CONCLUSIONS: These results demonstrated that education of CI sites unfamiliar with DAAs resulted in patient outcomes consistent with those observed at DAA-experienced academic sites.

Managing patients with hepatitis­B-related or hepatitis­C-related decompensated cirrhosis.

Treatment of patients with hepatitis-B-related or hepatitis-C-related decompensated cirrhosis should focus on controlling the complications of cirrhosis, surveillance for hepatocellular carcinoma and, if applicable, preparation for orthotopic liver transplant. Interferon-based regimens for the treatment of hepatitis C have been somewhat successful in patients with cirrhosis, although treatment of patients with decompensated cirrhosis should be approached with caution. Given the potential for exacerbation of decompensation and poor tolerance of adverse effects, treatment should be reserved for those patients awaiting liver transplantation. Eradication of HCV before liver transplantation reduces the chances of recurrent hepatitis C infection after transplant. HBV can be treated with few adverse effects in patients with decompensated cirrhosis. This treatment is associated with improvement in decompensation in some patients. Hepatocellular carcinoma remains a significant risk in all patients with cirrhosis, and control of or eradication of HBV or HCV does not remove this risk.

Inherited metabolic disease of the liver.

PURPOSE OF REVIEW: The past decade has seen extraordinary growth in our understanding of the pathophysiology of Wilson disease, genetic hemochromatosis and alpha-1 antitrypsin deficiency as we continue to elucidate the molecular and cellular machinery involved in their pathogenesis. The continued progress in the elaboration of the molecular biology, genetics, epidemiology, and management of these prototypical inherited metabolic diseases will be the focus of this review. RECENT FINDINGS: Wilson disease and genetic hemochromatosis involve defects in metal transport with copper and iron accumulation in hepatocytes, respectively. In alpha-1 antitrypsin deficiency, hepatocytes accumulate defective alpha-1 antitrypsin that misfolds. As a more complete picture of the molecular biology of the proteins and genes involved in transport has evolved, so has our understanding of the etiopathogenesis of these disorders and the variety of phenotypes observed. Finally, new ideas regarding the clinical management of these disorders will emerge with elucidation of the cellular basis for these diseases. SUMMARY: The recent developments detailed in this article have important implications for the future diagnosis and treatment of these diseases. Recent discoveries link molecular defects with alterations in the functional machinery of the cell, and provide new avenues for advancing the diagnosis and treatment of these disorders.

Inherited metabolic liver disease.

PURPOSE OF REVIEW: The past decade has seen understanding of the molecular machinery involved in the pathogenesis of genetic hemochromatosis, Wilson's disease, and alpha1-antitrypsin deficiency grow significantly. This year has seen further progress in elaborating the molecular biology, genetics, epidemiology, and management of these inherited metabolic diseases. RECENT FINDINGS: Both Wilson's disease and genetic hemochromatosis involve defects in the transport of heavy metals and their accumulation in hepatocytes. In alpha1-antitrypsin deficiency, intrahepatocyte accumulation of defective alpha(1)-antitrypsin occurs. As a more complete picture of the molecular biology of proteins and genes involved in transport has evolved, so has our understanding of their interactions. The molecular genetics of these diseases explains the different phenotypes seen. Finally, the elucidation of the molecular pathophysiology of these diseases has led to new ideas in their clinical management. SUMMARY: The recent developments detailed in this article have important implications for the future. Recent research has elegantly shifted the paradigm in our understanding to one focused on defects in the genetic machinery of the cell and on how better comprehension of these defects can lead to potential new therapies.