Distinct histopathological features of post-COVID-19 cholangiopathy (preprint)

Background: Cholangiopathy has been described in survivors of severe COVID-19, presenting significant clinical parallels to the pre-pandemic condition of secondary sclerosing cholangitis in critically ill patients (SSC-CIP).  Aim: Herein, we examined the liver histopathology of individuals with persistent cholestasis following severe COVID-19.  Methods: Post-COVID-19 cholestasis liver samples were subjected to routine staining techniques and cytokeratin 7 immunostaining, and the portal and parenchymal changes were semi-quantitatively analyzed.  Results: All ten patients, five men, median age 56, interquartile range (IQR) 51–60, requiring mechanical ventilation. The median and IQR liver enzyme concentrations proximal to biopsy were in IU/L: ALP, 605 (390–1,105); GGT, 925 (776–2,169); ALT, 92 (86–110); AST, 90 (68–108); and bilirubin, 3 (1–6) mg/dL. Imaging revealed intrahepatic bile duct anomalies and biliary casts. Biopsies were performed at a median of 203 (150–249) days after molecular confirmation of infection. Portal and periportal fibrosis, moderate-to-severe ductular proliferation, and bile duct dystrophy were found in all patients, while hepatocyte biliary metaplasia was observed in all tested cases. Mild-to-severe parenchymal cholestasis and bile plugs were observed in nine and six cases. Mild swelling of the arteriolar endothelial cells was observed in five patients. A thrombus in a small portal vein branch and mild periductal fibrosis were observed in one case each. One patient developed multiple small biliary infarctions. Ductopenia was not observed in any patient.  Conclusions: The alterations were similar to those observed in SSC-CIP; however, pronounced swelling of endothelial cells, necrosis of the vessel walls, and thrombosis in small vessels were notable.

Impact of progressive familial intrahepatic cholestasis on caregivers: caregiver-reported outcomes from the multinational PICTURE study.

BACKGROUND: Progressive familial intrahepatic cholestasis (PFIC) is a spectrum of rare genetic diseases characterized by inadequate bile secretion that requires substantial ongoing care, though little research is published in this area. We report health-related quality of life (HRQoL) and work productivity outcomes from the retrospective, cross-sectional PICTURE study investigating the burden of PFIC on caregivers. Information from caregivers of patients with PFIC 1 or 2 in Germany, the United Kingdom and the United States from September 2020 to March 2021 was included. RESULTS: The PICTURE study sample comprised HRQoL responses from 22 PFIC caregivers. Patients were on average 8.2 years old; most caregivers were 30-49 years old (68%) and mothers (77%). Median CarerQoL-7D score was 67.7/100; mean CarerQoL-VAS score for general happiness was 5.7/10 (SD 2.1). Most caregivers reported fulfilment in their caregiving responsibilities, but problems with mental and physical health, finances, and relationships. When stratified by patient's PFIC type, mean CarerQoL-7D and CarerQoL-VAS scores suggested worse HRQoL outcomes with PFIC2 versus PFIC1 (59.4 vs. 71.2, and 5.3 vs. 6.5, respectively). Additionally, more caregivers reported impact on sleep in the PFIC2 versus PFIC1 subgroup (93% vs. 75%). When stratified by history of PFIC-related surgeries, mean CarerQoL-7D and VAS scores were higher among those whose children had no specified surgeries (67.7 vs. 59.0/100 and 6.2 vs. 5.2/10, respectively). Nearly all caregivers reported an impact of caregiving responsibilities on sleeping (86%) and on personal relationships (82%). No caregivers reported having formal care support. Most caregivers were employed (73%); a third reported mean productivity loss of 12.9 days (SD 19.3) over the last 3 months, and a mean of 2.8 (SD 9.5) missed years of employment during their career. A higher number of workdays were missed by PFIC 2 caregivers compared to PFIC1 over last 3 months (16 days vs. 3 days). CONCLUSIONS: The PICTURE study has demonstrated the prevalent, comprehensive, and meaningful burden that caring for an individual with PFIC has on caregivers. Despite fulfilment from caregiving, the breadth and depth of these responsibilities reduced caregiver reported HRQoL including mental and physical health, productivity, career prospects, sleep, relationships and finances.

Intrahepatic cholestasis of pregnancy resistant to both therapeutic plasma exchange and albumin dialysis.

Intrahepatic cholestasis in pregnancy (ICP) represents, depending on its severity, a serious risk for the fetus. Those cases with unusually high bile acid levels may be resistant to pharmaceutical treatment and can be treated with plasma exchange or albumin dialysis. However, the success rate of these therapeutic options and the factors influencing therapeutic response are unknown. Furthermore, if these options fail to improve ICP and serum bile acid levels are very high (>200 µm/L), there are no clear recommendations when delivery should be planned. Here, we report a patient with severe ICP resistant to both therapeutic plasma exchange and albumin dialysis. Caesarean section was performed at 32 weeks of gestation followed by rapid remission of ICP.

Maternal and fetal effects of COVID-19 virus on a complicated triplet pregnancy: a case report.

BACKGROUND: Coronavirus disease 2019 (COVID-19), the global pandemic that has spread throughout the world, is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Given the limited scientific evidence on the manifestations and potential impact of this virus on pregnancy, we decided to report this case. CASE PRESENTATION: The patient was a 38 year-old Iranian woman with a triplet pregnancy and a history of primary infertility, as well as hypothyroidism and gestational diabetes. She was hospitalized at 29 weeks and 2 days gestational age due to elevated liver enzymes, and finally, based on a probable diagnosis of gestational cholestasis, she was treated with ursodeoxycholic acid. On the first day of hospitalization, sonography was performed, which showed that biophysical scores and amniotic fluid were normal in all three fetuses, with normal Doppler findings in two fetuses and increased umbilical artery resistance (pulsatility index [PI] > 95%) in one fetus. On day 4 of hospitalization, she developed fever, cough and myalgia, and her COVID-19 test was positive. Despite mild maternal symptoms, exacerbated placental insufficiency occurred in two of the fetuses leading to the rapid development of absent umbilical artery end-diastolic flow. Finally, 6 days later, the patient underwent cesarean section due to rapid exacerbation of placental insufficiency and declining biophysical score in two of the fetuses. Nasopharyngeal swab COVID-19 tests were negative for the first and third babies and positive for the second baby. The first and third babies died 3 and 13 days after birth, respectively, due to collapsed white lung and sepsis. The second baby was discharged in good general condition. The mother was discharged 3 days after cesarean section. She had no fever at the time of discharge and was also in good general condition. CONCLUSIONS: This was a complicated triplet pregnancy, in which, after maternal infection with COVID-19, despite mild maternal symptoms, exacerbated placental insufficiency occurred in two of the fetuses, and the third fetus had a positive COVID-19 test after birth. Therefore, in cases of pregnancy with COVID-19 infection, in addition to managing the mother, it seems that physicians would be wise to also give special attention to the possibility of acute placental insufficiency and subsequent fetal hypoxia, and also the probability of vertical transmission.

COVID-19 is a risk factor for severe liver damage for patients with intrahepatic cholestasis of pregnancy: a case report (preprint)

Background: Patients with intrahepatic cholestasis of pregnancy (ICP) may present with slight liver damage. In the global outbreak, the number of pregnant women infected with coronavirus disease 2019 (COVID-19) is increasing. For the pregnant patients with ICP, COVID-19 may cause severe liver damage.Case presentation: A 31-year-old pregnant woman was admitted with fever and respiratory symptoms to Tongji Hospital in Wuhan amid the outbreak of COVID-19. Her chest CT scan showed an infection with viral pneumonia as multiple ground glass opacities in both lungs were spotted. Laboratory tests revealed increased white blood cell (WBC) count and decreased lymphocyte count. The levels of serum total bile acid (TBA) were highly elvated. So were the indices of liver function, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), alkaline phosphatase (AKP), 𝛄-glutamyltranspeptidase (𝛄-GT), and lactate dehydrogenase (LDH). The patient was later diagnosed of COVID-19 with comorbid ICP, presenting severe liver damage. Through timely termination of pregnancy and effective treatments, the prognoses of the patient and the fetus were well improved.Conclusions: This case highlights that COVID-19 may be a risk factor of severe liver damage for patients with ICP.Timely termination of pregnancy and effective symptomatic treatments are helpful to improve the progonosis.