This was a population-based prospective study from Canterbury, New Zealand
Overall incidence rates were 1.93 per 100,000 for AIH (95% CI, 1.58–2.34), 0.51 per 100,000 for PBC (95% CI, 0.33–0.73), and 0.92 per 100,000 for PSC (95% CI, 0.68–1.21).
The incidence rateof AIH was significantly higher during the period of 2014–2016 (2.39 per 100,000; 95% CI, 1.76–3.23) than during the period of 2008–2010 (1.37 per 100,000; 95% CI, 0.91– 2.06) (P < .05). Incidences of PBC and PSC did not change significantly.
In 2016, prevalence values were 27.4 per 100,000 for AIH (95% CI, 23.58–32.0), 9.33 per 100,000 for PBC (95% CI, 7.13–12.05), and 13.17 per 100,000 for PSC (95% CI, 10.56–16.42).
My take: This study indicates that autoimmune hepatitis has been increasing in incidence.
This study was an analysis of data from the Scientific Registry of Transplant Recipients (2002 through 2019).
In 2002, the most common etiologies of non-acute liver failure on the liver transplant waitlist (in patients without HCC)
In 2019, among patients without HCC, NASH was the second leading indication for liver transplantation (28% of patients), after ALD (38% of patients). were chronic HCV infection (37%) and ALD (16%), whereas only 5% had NASH
HCC accounted for 27,799 patients (16.5%) and was commonly due to chronic HCV throughout study period
My take: Demand for liver transplantation has NOT improved despite curative therapy for chronic hepatitis C. This is due to increased liver failure related to fatty liver disease and alcoholic liver disease.
70 patients completed the trial (44 PSC, 24 PBC, 2 SSC) (SSC =secondary sclerosing cholangitis). Treated patients received bezafibrate 400 mg once a day for 21 days.
For the primary end point, bezafibrate led in 45% (41% PSC, 55% PBC) and placebo in 11% to >/=50% reduction of severe or moderate pruritus (P ¼ .003).
Bezafibrate also reduced serum alkaline phosphatase (35%, P ¼ .03 vs placebo) correlating with improved pruritus (VAS, P ¼ .01) suggesting reduced biliary damage.
Serum bile acids and autotaxin activity remained unchanged.
My take: While the majority of patients did not reach the primary end point, bezafibrate merits further investigation and may be a useful agent for pruritus in the setting of cholestatic liver disease. From the associated editorial (pg 649, JK Dyson et al. Bezafibrate for the Treatment of Cholestatic Pruritus: Time for a Change in Management?): “FITCH is an important study and provides novel and important data. It suggests that bezafibrate can be part of the answer to cholestatic pruritus.”
Cases of alcoholic liver disease — which includes milder fatty liver and the permanent scarring of cirrhosis, as well as alcoholic hepatitis — are up 30% over the last year at the University of Michigan’s health system, says Dr. Jessica Mellinger, a liver specialist there….
Excluding those who died within the first 3 months, the 10‐year patient survival and graft survival rates were 92.6% and 77.1%, respectively, in the PSC with IBD (PSC‐IBD) group and 97.1% and 83.2% in the isolated PSC group, respectively.
The rate of recurrent PSC was 21% in the PSC‐IBD group and 11% in the isolated PSC group
Thus, it appears that having pre-existing IBD did not significantly influence survival after transplantation.
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.
VDZ was initiated at median age of 16 years [IQR 15–18], 69% were male, 65% had large duct involvement, 19% had (Metavir F3/F4) fibrosis and 59% had ulcerative colitis.
Overall, there was a mild increase in median GGT after initiation of VDZ. Of 32 patients with abnormal GGT at baseline, 22% had a liver biochemical response (defined as GGT <50 or at least a 75% decline) after 9 to 12 months
For IBD, 32% achieved remission, 30% had a clinical response, and 38% had no response
In the discussion, the authors note that their findings are in agreement with three retrospective studies in adults which have shown that VDZ is not effective for PSC in patients with IBD.
My take: This study indicates that VDZ is not likely to help with PSC, though 62% of IBD patients had improvement in their GI disease.
EM Kim et al. Inflamm Bowel Dis 2020; 26: 1232-38.Mucosal Eosinophilia Is an Independent Predictor of Vedolizumab Efficacy in Inflammatory Bowel Diseases n=65 patients. In IBD cohort, colonic eosinophilia (340 +/- 156 vs 236 +/- 124) was associated with clinical non-response to vedolizumab (as was prior anti-TNF treatment). In those with ulcerative colitis, mean eosinophil count was 438 in nonresponders compared to 299 in responders. In those with Crohn’s disease, colonic biopsies showed a non-significant increase in eosinophil count in non-responders compared to responders: 352 vs. 232.
Crohn’s disease subjects with Pittsburgh Sleep Quality Index (PSQI) >5 more often had inflammatory phenotypes and reported increased benzodiazepine and psychiatric medication use. Crohn’s disease subjects with PSQI >5 also reported more night awakenings due to pain and bathroom use.
The PSQI correlated with HBI
PSQI >8 was predictive of surgery or hospitalization (hazards ratio 5.37; 95% confidence interval, 1.39-27.54).
My take: This study indicates that poor sleep is a marker for increased adverse outcomes/disease activity. It may be that sleep disturbance is due to increased disease activity or this may be a bidirectional issue in which poor sleep triggers more disease activity as well.
This retrospective study provides additional information on the observation that children with PSC often have subclinical disease; it is similar to a prospective study by the same group in 2018 (n=37): (prior blog post: Active Colitis More Likely in Children in Clinical Remission Who Have IBD and PSC) Key finding: Higher proportions of children with PSC-IBD had backwash ileitis, pancolitis, and rectal sparing, and more severe right-sided disease, than controls (P < .05). Conclusions: “Despite the mild clinical activity of IBD in patients with PSC, lack of symptoms does not always indicate lack of mucosal inflammation. Children with PSC-IBD have greater growth impairments compared with children with ulcerative colitis or IBD-unclassified.”
A Malian et al.Pedictors [sic] of Perianal Fistula Relapse in Crohn’s Disease. Inflamm Bowel Dis 2020; 26: 926-31. In this retrospective study with 137 patients, fistula relapse rates were not different in patients receiving infliximab or adalimumab (P = 0.66). In patients treated by anti-TNF at inclusion, discontinuation of anti-TNF therapy (odds ratio 3.49, P = 0.04), colonic location (OR 6.25, P = 0.01), and stricturing phenotype (odds ratio 4.39, P = 0.01) were independently associated with fistula relapse in multivariate analysis.
B Barberio et al. Matrix Metalloproteinase 3 Predicts Therapeutic Response in Inflammatory Bowel Disease Patients Treated with Infliximab. Inflamm Bowel Dis 2020; 26: 756-62. Retrospectively, 73 IBD patients who had received IFX for at least 1 year were enrolled: 35 patients were responders and 38 were nonresponders at 52 weeks…The MMP3 levels were similar at baseline (19.83 vs 17.92 ng/mL), but at postinduction, patients who failed to respond at 1 year had significantly higher levels than patients who responded (26.09 vs 8.68 ng/mL, P < 0.001); the difference was confirmed at week 52 (29.56 vs 11.48 ng/mL, P < 0.001)…The MMP3 serum determination may represent an early marker of response to infliximab.
A recent study (A Chandrakumar et al. J Pediatr 2019; 215: 144-51) followed 190 children with inflammatory bowel disease from 2011 to 2018 in a longitudinal population-based cohort in Manitoba and examined the development of primary sclerosing cholangitis (PSC). The diagnosis of PSC was made on discretion of the treating physician; thus, only a subset of patients underwent extensive evaluations for PSC.
9 developed PSC-UC (9/95) and overall 11 developed PSC-IBD (11/190)
Among children with PSC-UC, 8 had high GGT (>50) at baseline and only 1 had a normal GGT at baseline.
All UC patients who developed PSC were diagnosed withing 6 months of their UC diagnosis.
At baseline, 22 patients with UC had an elevated GGT and 73 had a normal GGT. Thus, about one-third of patients with an elevated GGT developed PSC (possibly more as all patients were not subjected to extensive testing)
My view: This study reinforces two concepts: 1) GGT is valuable as a screening test 2) PSC (often asymptomatic) is fairly common in UC and needs to be considered especially in the first year of diagnosis. What this study does not do is help us figure out what should be done about children with asymptomatic PSC as there are no proven therapies.
A recent clinical practice update (CL Bowlus et al. Clin Gastroenterol Hepatol 2019; 17: 2416-22) makes several recommendations on surveillance for hepatobiliary cancers in patients with primary sclerosing cholangitis (PSC).
I will highlight the most important recommendation for pediatric hepatologists:
Best practice advice 6: Surveillance for cholangiocarcinoma should not be performed in PSC patients with small-duct PSCs or those younger than age 20.
In the text, the authors note that “in pediatric PSC patients, cholangiocarcinoma is very rare, with only 8 of 781 (1%) …developing cholangiocarcinoma” (MR Deneau et al. Hepatology 2017; 66: 518-27)
Here are the other recommendations:
Best practice advice 1 Surveillance for cholangiocarcinoma and gallbladder cancer should be considered in all adult patients with PSC regardless of disease stage, especially in the first year after diagnosis and in patients with ulcerative colitis and those diagnosed at an older age.
Best practice advice 2 Surveillance for cholangiocarcinoma and gallbladder cancer should include imaging by ultrasound, computed tomography, or magnetic resonance imaging, with or without serum carbohydrate antigen 19-9, every 6 to 12 months
Best practice advice 3 Endoscopic retrograde cholangiopancreatography with brush cytology should not be used routinely for surveillance of cholangiocarcinomas in PSC.
Best practice advice 4 Cholangiocarcinomas should be investigated by endoscopic retrograde cholangiopancreatography with brush cytology with or without fluorescence in situ hybridization analysis and/or cholangioscopy in PSC patients with worsening clinical symptoms, worsening cholestasis, or a dominant stricture.
Best practice advice 5 Fine-needle aspiration of perihilar biliary strictures should be used with caution in PSC patients considered to be liver transplant candidates because of concerns for tumor seeding if the lesion is a cholangiocarcinoma.
Best practice advice 7 The decision to perform a cholecystectomy in PSC patients with a gallbladder polyp should be based on the size and growth of the polyp, as well as the clinical status of the patient, with the knowledge of the increased risk of gallbladder cancer in polyps greater than 8 mm.
Best practice advice 8 Surveillance for hepatocellular carcinoma in PSC patients with cirrhosis should include ultrasound, computed tomography, or magnetic resonance imaging, with or without α-fetoprotein every 6 months.