Faculty Bibliography

BACKGROUND:Primary care practitioners (PCPs) and diabetologists are at the frontline of potentially encountering patients with NASH. Identification of those at high risk for adverse outcomes is important. AIM/OBJECTIVE:To provide practical guidance to providers on how to identify these patients and link them to specialty care. METHODS:US members of the Global Council on NASH evaluated the evidence about NASH and non-invasive tests and developed a simple algorithm to identify high-risk NASH patients for diabetologists and primary care providers. These tools can assist frontline providers in decision-making and referral to gastroenterology/hepatology practices for additional assessments. RESULTS:The presence of NASH-related advanced fibrosis is an independent predictor of adverse outcomes. These patients with NASH are considered high risk and referral to specialists is warranted. Given that staging of fibrosis requires a liver biopsy, non-invasive tests for fibrosis would be preferred. Consensus recommendation from the group is to risk-stratify patients based on metabolic risk factors using the FIB-4 as the initial non-invasive test due to its simplicity and ease of use. A FIB-4 score ≥1.3 can be used for further assessment and linkage to specialty care where additional technology to assess liver stiffness or serum fibrosis test will be available. CONCLUSION/CONCLUSIONS:Due to the growing burden of NAFLD and NASH, PCPs and diabetologists are faced with increased patient encounters in their clinical practices necessitating referral decisions. To assist in identifying high-risk NASH patients requiring specialty care, we provide a simple and easy to use algorithm.

Chronic hepatitis B virus (HBV) infection represents a major global health problem, affecting an estimated 257-291 million persons worldwide and is associated with substantial morbidity and mortality because of clinical complications, such as liver cirrhosis and hepatocellular carcinoma. Despite existing resources for vaccination, screening, and treatment, the burden of chronic HBV remains significant within the United States (US). Both the World Health Organization (WHO) and US Department of Health and Human Services (DHHS) have articulated formal hepatitis elimination plans, although an updated assessment of the epidemiology and prevalence of chronic HBV is needed to inform these initiatives. The Chronic Liver Disease Foundation (CLDF), a nonprofit 501(c)(3) educational organization dedicated to raising awareness of liver disease, partnered with a panel of leading US hepatologists to conduct an updated literature review to develop a contemporary HBV prevalence range estimate. Panel members researched and evaluated the peer-reviewed literature on HBV prevalence and, in May 2019, discussed their findings during a live HBV epidemiology workshop. The panel proposed an overall estimated prevalence for chronic HBV infection in the US of 1.59 million persons (range 1.25-2.49 million). This review provides a summary of the workshop findings and conclusions, which may serve to inform future initiatives focused on HBV screening and prevention in the US.

Background: Alpha-1 antitrypsin deficiency (AATD) arises from inherited autosomal co-dominant SERPINA1 mutations that lead to liver and lung disease. Clinical manifestations within the liver are variable and include chronic hepatitis, cirrhosis, and the development of hepatocellular carcinoma. While the risk of liver disease with homozygous AATD is established, the prevalence of clinically significant liver disease in heterozygotes is not well described. Accumulating evidence suggests that heterozygous AATD (HAATD) acts as a co-factor for other liver diseases, but little is known about its effect on pathologic fibrosis. We investigate the stage of liver fibrosis in patients with histologic evidence of HAATD compared to controls with a wide range of chronic liver diseases.
Design(s): Our database was retrospectively searched to obtain 23 liver biopsy and resection specimens with evidence of chronic liver disease and intracytoplasmic alpha1 anti-trypsin (AAT) globules stained by immunohistochemistry. The group with histologic evidence of possible HAATD was compared to control cases of liver biopsies obtained from patients with chronic liver disease without evidence of AAT globules. Clinicopathologic data included age, gender, race, genotype, chronic liver disease type (chronic cholestatic disease, fatty liver disease, Hepatitis B or C, auto-immune hepatitis, hemochromatosis, and unknown cause), liver disease stage, and clinical follow-up. Statistical analyses were performed to assess correlation between clinicopathologic variables and disease groups.
Result(s): Compared to controls, subjects in the HAATD cohort had a higher rate of stage 4 fibrosis (52.17% vs 21.67%, p = 0.017). The control specimens were relatively evenly distributed among stages 1-4 fibrosis (Table). Of the 7 HAATD patients who underwent subsequent genetic testing, 6 patients were found to have heterozygous SERPINA1 mutations (5 PI*MZ, 1 PI*SZ). There were no significant differences in age, race, or gender between control and HAATD groups. (Table presented)
Conclusion(s): Histologic and immunohistochemical evidence of AAT globules was associated with a higher stage of concurrent liver disease. These results add to the growing body of literature which suggests that HAATD may potentiate the progression of concurrent liver diseases. In addition, histologic and immunohistochemical evidence of AAT globules may be useful in the early diagnosis of HAATD

BACKGROUND:The use of direct acting antivirals (DAA) has expanded transplantation from hepatitis C viremic donors (HCV-VIR). Our team has conducted an open-label, prospective trial to assess outcomes transplanting HCV-viremic hearts. Glecaprevir/Pibrentasvir (GLE/PIB) was our sole DAA. METHODS:Serial quantitative hepatitis C virus (HCV) RNA PCR was obtained to assess HCV viral titers. Between January 2018 to June 2019, a total of 50 recipients were transplanted. Of these, 22/50 (44%) were from HCV-VIR, the remaining 28 from non-viremic (HCV NON-VIR) donors. An 8 week course of GLE/PIB was initiated at 1 week post-transplant. RESULTS:There was no difference in demographic or clinical parameters between groups. All 22 recipients of HCV-VIR transplants became viremic. GLE/PIB was effective in decreasing viremia to undetectable levels by 6 weeks post-transplant in all patients. The median time to first undetectable HCV quantitative PCR was (4.3 weeks, IQR: 4-5.7 weeks). All patients demonstrated sustained undetectable viral load through 1 year follow up. There was no difference in survival at one year between HCV NON-VIR 28/28: (100%) vs. HCV-VIR 21/22 (95%) recipients. CONCLUSIONS:Our center reports excellent outcomes in transplanting utilizing hearts from HCV-VIR donors. No effect on survival or co-morbidity was found. An 8 week GLE/PIB course was safe and effective when initiated approximately 1 week post-transplant.

The aim of this study was to evaluate changes in noninvasive tests of fibrosis (NITs) to understand the natural history of cirrhosis regression following removal of the causative exposure. In this ongoing, prospective cirrhosis registry study, 1574 subjects with HCV cirrhosis who achieved SVR via sofosbuvir (SOF)-based regimens were enrolled. Routine assessments included semi-annual Child-Pugh- Turcotte (CPT) scoring and measurement of the Enhanced Liver Fibrosis (ELF) test, as well as annual liver stiffness measurement by transient elastography (LS by TE). Logistic regression was used to identify predictors of fibrosis improvement as defined by NITs. As of May 2019, median duration of follow-up was 123 weeks (IQR 96, 168). At week 144, 49% of those with baseline CPT class B/C had improved CPT class, while 98% of those with baseline CPT class A remained in CPT class A. During follow-up, changes in ELF and LS by TE suggested fibrosis improvement in an increasing proportion of patients with both F3 and F4 fibrosis at enrollment (Figure). ELF score improved by >=0.5 units at week 144 in 27% and 47% of patients with baseline F3 (ELF 9.8-11.3) and F4 (ELF > 11.3) fibrosis, respectively. Predictors of ELF improvement included higher ELF (p<0.001) and AST (p = 0.049), and lower platelets (p = 0.02) and BMI (p = 0.10) at registry baseline. In patients with cirrhosis in whom HCV has been eradicated by SOF-based therapy, NITs suggest significant fibrosis improvement in 25-50% of patients within 3 years. Associations between reductions in these NITs and improvements in clinical outcomes require evaluation during longerterm follow-up