Rosen, Charles B.

Mutations in the hepatocyte nuclear factor‐1‐beta (HNF1B) gene cause a variety of diseases in different organ systems. Mutations have been described as causing neonatal cholestasis, maturity‐onset diabetes of the young (type 5), cortical renal cysts, urogenital abnormalities, liver dysfunction, and atrophy of the pancreas. We describe a male patient who presented with cholestatic liver disease in infancy which progressed by age 14 to end‐stage liver disease due to HNF1B disease. He subsequently underwent liver transplantation at age 15 and then developed diabetes requiring insulin which did not resolve after cessation of corticosteroids. To our knowledge, this is the first case reported of liver transplantation for decompensated cirrhosis secondary to HNF1B disease.

Background. Portopulmonary hypertension (POPH), pulmonary arterial hypertension (PAH) that develops in the setting of portal hypertension, affects 5%–6% of patients with liver disease and is associated with significant morbidity and mortality. A mean pulmonary arterial pressure (mPAP) threshold of 35 mm Hg is used to stratify perioperative risk and liver transplant eligibility in treated POPH patients but does not take into account the specific factors that contribute to the pressure elevation. Methods. In this case series, we describe the characteristics and posttransplant outcomes of patients with treated POPH and an mPAP ≥35 mm Hg and pulmonary vascular resistance (PVR) <250 dynes-s-cm−5 at or just before liver transplantation (LT). We also describe the effect of PAH therapy on pulmonary hemodynamics in patients with POPH. Results. Sixteen patients were included. All patients were on PAH therapy at the time of LT. PAH therapy resulted in a decrease of mPAP (median 18.4%; interquartile range [IQR] 8.9%–27.0%) with a reduction in PVR (median 50.5%; IQR, 45.4%–70.7%), and an increase in both cardiac output (CO) (median 28.1%; IQR 5.7%–63.8%) and PAWP (median 50.0%; IQR 16.7%–108.3%) before LT. One year posttransplant survival was 69% (11/16); however, only 1 death was attributed to POPH. At 1-year posttransplant, 63.6% (7/11) of patients were weaned off all PAH therapy with clinical and echocardiographic resolution of POPH. Conclusions. In treated POPH patients with an mPAP ≥35 mm Hg and PVR < 250 dynes-s-cm−5 before LT, 1-year posttransplant survival was 69% and the majority of patients were able to discontinue PAH therapy.

Selected patients with unresectable perihilar cholangiocarcinoma (pCCA) derive long-term benefits from liver transplantation. Between 1993–2019, our group at Mayo Clinic performed 237 transplants for pCCA. With this experience, we note that two distinct patient populations comprise this group of pCCA patients: those with underlying primary sclerosing cholangitis (PSC) and those without identifiable risk factors termed sporadic or de novo pCCA. Long-term survival after transplant is better in PSC patients (74% five-year survival) than in those with de novo pCCA (58% five-year survival). Herein, we review the likely clinical factors contributing to the divergence in outcomes for these two patient populations. We also offer our insights on how further advances may improve patient selection and survival, focusing on the de novo pCCA patient population.

Background. Portopulmonary hypertension (POPH) is the presence of pulmonary arterial (PA) hypertension in patients with portal hypertension and is associated with significant morbidity and mortality. In a cohort of POPH patients, we describe the clinical outcomes of POPH patients who underwent liver transplantation (LT). Methods. Retrospectively collected data from a prospectively assembled cohort of all consecutive POPH adults evaluated in 3 transplant centers from 1996 to 2019. Results. From a cohort of 228 POPH patients, 50 patients underwent LT. Significant hemodynamic improvement after PA-targeted therapy was observed, with 58% receiving only monotherapy pretransplant. After LT, 21 (42%) patients were able to discontinue and remained off PA-targeted therapy. The 1-, 3-, and 5-y unadjusted survival rates after LT were 72%, 63%, and 60%, respectively. An elevated pulmonary vascular resistance (PVR) before LT was associated with worse survival rate (HR, 1.91; 95% CI, 1.07-3.74, P = 0.04). No survival difference was observed in those granted MELD exception or transplants performed before or after the year 2010. Conclusions. Significant number of POPH patients discontinued PA-targeted therapy after LT. Higher PVR before LT was associated with worse survival, as was monotherapy use. Despite effective PA-targeted therapies, POPH survival outcomes after LT in our cohort were modest and may reflect the need for more aggressive therapy.

Background and Aims Early detection of perihilar cholangiocarcinoma (CCA) among patients with primary sclerosing cholangitis (PSC) is important to identify more people eligible for curative therapy. While many recommend CCA screening, there are divergent opinions and limited data regarding the use of ultrasound or magnetic resonance imaging (MRI) for early CCA detection, and it is unknown whether there is benefit in testing asymptomatic individuals. Our aims were to assess the diagnostic performances and prognostic implications of ultrasound and MRI‐based CCA detection. Approach and Results This is a multicenter review of 266 adults with PSC (CCA, n = 120) who underwent both an ultrasound and MRI within 3 months. Images were re‐examined by radiologists who were blinded to the clinical information. Respectively, MRI had a higher area under the curve compared with ultrasound for CCA detection: 0.87 versus 0.70 for the entire cohort; 0.81 versus 0.59 for asymptomatic individuals; and 0.88 versus 0.71 for those listed for CCA transplant protocol. The absence of symptoms at CCA diagnosis was associated with improved 5‐year outcomes including overall survival (82% vs. 46%, log‐rank P < 0.01) and recurrence‐free survival following liver transplant (89% vs. 65%, log‐rank P = 0.04). Among those with asymptomatic CCA, MRI detection (compared with ultrasound) was associated with reduction in both mortality (hazard ratio, 0.10; 95% confidence interval, 0.01‐0.96) and CCA progression after transplant listing (hazard ratio, 0.10; 95% confidence interval, 0.01‐0.90). These benefits continued among patients who had annual monitoring and PSC for more than 1 year before CCA was diagnosed. Conclusions MRI is superior to ultrasound for the detection of early‐stage CCA in patients with PSC. Identification of CCA before the onset of symptoms with MRI is associated with improved outcomes.