Overall, this article details the estimated shortage of hepatologists in the coming years.
One of the more interesting suggestions in this article is the need to change the name of specialty training from “transplant hepatology” to “advanced hepatology” to more accurately reflect the type of liver conditions managed by hepatologists.
In 2018, the adult and pediatric workforce included 7,296 and 824 hepatology providers, respectively, composed of hepatologists, gastroenterologists, and advanced practice providers whose practice was ≥50% hepatology
The modeling analysis projects that in 2023, 2028, and 2033, there will be shortages of 10%, 23%, and 35% adult hepatology providers, respectively, and 19%, 20%, and 16% pediatric hepatology providers, respectively
The authors note that there are many challenges when predicting workforce needs. The main reasons for the predicted shortfall with hepatology include the following:
Older age of current clinicians
Increasing amount of liver disease (~34% increase from 2018 to 2033), particularly fatty liver disease. This is happening among adults and children.
“We pooled data from 8 phase 2 or phase 3 trials of treatment-naïve patients with HCV genotype 1 to 6 infections, without cirrhosis or with compensated cirrhosis, who received 8 weeks of glecaprevir/pibrentasvir.” (n=1248) Key finding: Overall rates of sustained virologic response at post-treatment week 12 were 97.6% (1218 of 1248) in the intention to treat (ITT) and 99.3% (1218 of 1226) in the modified ITT populations.
This review discussed the use of SMOFlipid that includes soybean, medium-chain triglycerides, olive and fish oils. Key points:
“Lipid minimization strategies have also been shown to reverse IFALD [intestinal failure associated liver disease]. There are, however, considerable concerns regarding adequate weight gain, compromise to neurodevelopment, and EFAD [essential fatty acid deficiency]”
“Thee is actually considerable safety data for CLE [composite lipid emulsion] in neonates, albeit over the short term.”
“In Canada, CLE is currently the lipid emulsion of choice for all infants at risk of IFLAD.”
Methods: “We collected information on weight-adjusted, submaximal physical work capacity (PWC), ultrasound-determined hepatic steatosis, iron indices, and hematologic and metabolic parameters from 390 female and 458 male participants of the Raine Study—a longitudinal study of disease development … in Western Australia”
Key finding: “Fourteen percent of the cohort had NAFLD. PWC was significantly reduced in adolescents with NAFLD compared to adolescents without NAFLD (reduction of 0.17 W/kg, P = .0003, adjusted for sex and body mass index [BMI])… we found NAFLD to be associated with decreased cardiorespiratory fitness, independent of BMI. The relationship between transferrin saturation and PWC in adolescents with NAFLD indicates that functional iron deficiency might contribute to reductions in cardiorespiratory fitness.”
“Thousands of Georgia’s poor and uninsured adults who meet a work or activity requirement will soon be eligible for Medicaid, with perhaps 50,000 added to the rolls within two years…And more than 350,000 very poor, uninsured Georgia adults still won’t meet Georgia’s requirements for Medicaid”
“At the same time, the 400,000 Georgians who bought individual health insurance plans on the federal healthcare.gov Affordable Care Act shopping website will find they can’t do that anymore. Instead they will be directed to contact information for private brokers or insurance companies”
Methods: The authors linked prospectively collected data from national health care registries maintained for all adults in England on hospital attendances, imaging and endoscopic evaluations, surgical procedures, cancer, and deaths.
Over 10 years, we identified 284,560 incident cases of IBD nationwide; of these, 2588 patients developed PSC. This study excluded patients <18 years of age.
Development of PSC was associated with increased risk of death and CRC (hazard ratios [HRs], 3.20 and 2.43, respectively; P < .001) and a lower median age at CRC diagnosis (59 y vs 69 y without PSC; P < .001)
Compared to patients with IBD alone, patients with PSC-IBD had a 4-fold higher risk of CRC if they received a diagnosis of IBD at an age younger than 40 years
Development of PSC also increased risks of cholangiocarcinoma (HR, 28.46), hepatocellular carcinoma (HR, 21.00), pancreatic cancer (HR, 5.26), and gallbladder cancer (HR, 9.19) ( P < .001 for all)
The greatest difference in mortality between the PSC-IBD alone group vs the IBD alone group was for patients younger than 40 years
Patients with PSC-UC had >40% risk of colonic resection compared to patients with IBD alone (aHR 1.65)
My take: This study shows the impact the added diagnosis of PSC has for patients with IBD. One of the limitations in assessing outcomes is determining whether someone with IBD has PSC as there are a lot of patients with IBD who have asymptomatic changes in their biliary tree.
This was a prospective study of 180 severely obese patients with biopsy-proven NASH.
NASH: At 5 years after bariatric surgery, NASH was resolved, without worsening fibrosis, in samples from 84% of patients (n = 64; 95% confidence interval, 73.1%-92.2%).
Fibrosis: Fibrosis decreased, compared with baseline, in samples from 70.2% of patients (95% CI, 56.6%-81.6%). Fibrosis disappeared from samples from 56% of all patients (95% CI, 42.4%-69.3%) and from samples from 45.5% of patients with baseline bridging fibrosis.
My take: This study showed that patients with NASH who underwent bariatric surgery had resolution of NASH in liver samples from 84% of patients 5 years later. The reduction of fibrosis was progressive, beginning during the first year and continuing through 5 years.
Background: As of April 1, 2019, an estimated 103,000 kidney, 13,500 liver, and 3,800 heart transplant (HT) candidates are awaiting transplantation
Seventy‐seven patients who were HCV negative underwent solid organ transplantation from a donor who was HCV viremic. Only one has been a HCV-treatment nonresponder (though several have not completed SVR12).
“Our study is the largest to describe a real‐world experience of the transplantation of HCV‐viremic organs into recipients who are aviremic. In carefully selected patients, the use of HCV‐viremic grafts in the DAA era appears to be efficacious and well tolerated.”
This was an open‐label, single‐arm, multicenter, international pilot study; adults with recent HCV (duration of infection < 12 months) received glecaprevir/pibrentasvir 300/120 mg daily for 6 weeks.
At baseline, median estimated duration of infection was 29 weeks (range 13, 52) and median HCV RNA was 6.2 log10 IU/mL (range 0.9, 7.7). SVR12 in the intention‐to‐treat and per‐protocol populations was achieved in 90% (27/30) and 96% (27/28), respectively.
This is a lengthy article with extensive recommendations –here are a few:
Consider etiologies unrelated to COVID‐19, including other viruses such as hepatitis A, B and C, when assessing patients with COVID‐19 and elevated liver biochemistries.
Consider other causes of elevated liver biochemistries, including myositis (particularly when AST>ALT), cardiac injury, ischemia, and cytokine release syndrome.
Generally, this article supports continuation of ongoing treatments in those with liver disease who are without active infection. “Do not reduce immunosuppression or stop mycophenolate for asymptomatic posttransplant patients without known COVID‐19”
A recent open-label randomized controlled study (M Bazinet et al. Gastroenterol 2020; 158: 2180-94. https://doi.org/10.1053/j.gastro.2020.02.058) showed that the addition of nucleic acid polymers (NAPs) which inhibit assembly and secretion of hepatitis B virus (HBV) subviral particles significantly improved outcomes in a phase 2 HBV trial (n=40).
NAP therapy was administered intravenously once a week.
During the first 24 weeks of tenofovir (TDF) and peg-Interferon (pegIFN) administration, significantly higher proportions of patients in NAP groups had decreases in HBsAg to below 1 IU/mL (P < .001 vs control) and HBsAg seroconversion (P = .046 vs control).
At the time patients completed the TDF + pegIFN + NAP regimen, HBsAg levels were 0.05 IU/mL or lower in 24/40 participants
During 48 weeks of treatment-free follow-up, virologic control persisted in 13 of 40 participants (2 lost to follow-up after 24 weeks), whereas functional cure persisted in 14 of 40 participants (all completing 48 weeks of follow-up) with persistent HBsAg seroconversion
The associated editorial (pg 2051-4 by D Durantel, T Asselah) makes the following points:
The authors call for larger multicenter studies with longer followup. They note that more evaluation is needed to determine if seroconversion is sustained.
It remains unclear whether PEG-IFN is needed. TDF/NAP therapy without PEG-IFN was not studied.
They state that more information about flares during treatment are needed. In this study, flares were safe and associated with beneficial outcomes. It is not clear if therapy flares would be detrimental in those with advanced fibrosis.
Optimistically, they state that there are multiple competing therapies being studied (eg. small interfering RNA, and small molecule HBs-RNA destabilizer) which could be more easily administered.
My take (borrowed from authors): In a phase 2 randomized trial, “we found that addition of NAPs to TDF + pegIFN did not alter tolerability and significantly increased rates of HBsAg loss and HBsAg seroconversion during therapy and functional cure after therapy.”
A related commentary (Gastroenterol 2020; 158: 2028-32) calls for investment/study of treatment for immune-tolerant patients along with curative therapy when it becomes available. The authors also argue for a study of long-term viral suppression with either entecavir or tenofovir alafenamide.
Plus one: N Rodriguez-Baez et al. JPGN 2020; 71: 99-105. This study examined liver histology from 134 liver biopsies from treatment-naive children with chronic hepatitis B infection. 60% acquired infection vertically, 69% were HBeAg-positive. Interface hepatitis was mild in 31%, moderate in 61% and severe in 6%; lobular inflammation was mild in 54%, moderate in 29% and severe in 7%. Fibrosis: 18% had no fibrosis, 59% had portal fibrosis without bridging, 19% had bridging fibrosis and 4% had cirrhosis. Alanine amnotransferase was a fairly good indicator of the severity of hepatic inflammation and extent of fibrosis.