Purpose of review SARS-CoV2 is a b-coronavirus, isolated for the first time in Wuhan in December 2019. Bilateral interstitial pneumonia is the hallmark of this disease. Liver is the second viral target for frequency and AST and ALT elevation is a common finding. From February 2020, two different cholangiopathies have been reported in COVID-19 patients. The aim of this article is to review the cases so far described in order to share information and awareness about these new clinical entities.Recent findings SARS-CoV2 seems to trigger autoimmunity and two cases of primary biliary cholangitis (PBC) have been developed after viral infection while more than 30 patients have showed a rapidly progressing cholangiopathy with features of secondary sclerosing cholangitis (SSC). For what concerns SSC pathogenesis, a theory combining multiple hits is the most recognized. SummaryTwo different cholangiopathies have been reported in patients after severe-COVID-19. Attention should be paid to the development of cholestasis in ICU setting but above all after discharge and liver function tests should be, therefore, periodically performed. No treatment strategies are available and liver transplantation remains the last option in individuals with liver failure because of SSC. Other efforts are necessary to better understand the pathogenesis and to expand therapeutic options. Keywords cholangiopathy, coronavirus disease 2019, primary biliary cholangitis, secondary sclerosing cholangitis LIVER DISEASE IN CORONAVIRUS DISEASE 2019During COVID-19 hospitalization, a variable percentage of patients, ranging from 14 to 76%, develops transaminase alterations with a greater
To the Editor:We would like to present the case of a female patient who developed primary biliary cholangitis (PBC) concomitant with Guillain-Barré syndrome (GBS) during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. 1 A 44-year-old obese and hypertensive woman already suffering from Hashimoto's thyroiditis, was admitted to hospital with fever, cough and dyspnoea on March 18, 2020. Chest X-rays showed bilateral interstitial pneumonia and she had a positive SARS-CoV-2 nasopharyngeal swab. Because of clinical deterioration, the patient was intubated and treated in the intensive care unit with mechanical ventilation and the following drugs in chronological order: tocilizumab, ceftriaxone, azithromycin, darunavir/cobicistat, anakinra, remdesivir and fluconazole. After 2 weeks of mechanical ventilation, the patient's condition began to improve. She was extubated but, because of respiratory worsening, non-invasive ventilation was initiated. Then, she experienced a rapid cognitive deterioration (Glasgow coma scale 3) with good oxygen saturation and was reintubated. In the following days the state of consciousness improved with complete recovery, but she displayed a proximal hyposthenia at the 4 limbs without altered sensitivity; osteo-tendon reflexes were absent at the upper limbs, weakly evocable the patellars, present at the heels. The electromyography showed signs of radiculo-neuropathy with prevalent interesting of the proximal section of the four limbs and diffuse signs of active neurogenic sufferance with modest re-innervating activity. An acute motor axonal neuropathy (AMAN) subtype of GBS was diagnosed and the patient was treated with intravenous immunoglobulins with a progressive clinical improvement enabling transfer to a rehabilitation ward.During the hospitalization in intensive care, an important rise in serum gamma-glutamyltransferase (GGT) was observed with initially normal levels of alkaline phosphatase (AP) that progressively increased later (Fig. 1A). Serum bilirubin was normal or slightly augmented while alanine aminotransferase (ALT) tended to fluctuate between normal and slightly increased levels (28-120 IU/L, normal range 1-31). The patient had no history of previous increases in cholestastic indexes (last blood exams in 2015, including GGT and AP, were normal) or symptoms before COVID-19 infection. Family history was negative for autoimmune and hepato-biliary diseases; clinical examination was unremarkable. An abdominal ultrasound showed a slightly enlarged liver with moderate steatosis and a mildly enlarged spleen. Liver stiffness measured with Fibroscan was 9.1 kPa. Serology for hepatotropic viruses was negative, immunoglobulins were normal, while total cholesterol was slightly augmented (251 mg/dl, normally <200) as was low-density lipoprotein (LDL) cholesterol (174 mg/dl, normal <110). The patient tested positive for anti-nuclear (titre 1:160, cytoplasmic pattern) and anti-mitochondrial (titre 1:640) autoantibodies, but negative for anti-smooth muscle, anti-liver kidne...
Background Children affected by neurodevelopmental disability could experience early pubertal changes at least 20 times more than the general population. Limited data about central precocious puberty (CPP) among children affected by cerebral palsy (CP) are available. Methods This is a longitudinal, observational, retrospective, case-control study involving 22 children affected by CPP and CP (group A), 22 paired with CP but without CPP (group B), and 22 children with CPP without CP. Auxological, biochemical, and instrumental data were collected at diagnosis of CPP and at 2 follow-up visits. Results No differences were detected between groups A (at baseline) and B. At diagnosis of CPP, height SDS adjusted for target height (H-TH SDS) was significantly reduced in A than in C (−0.63 ± 1.94 versus 1.56 ± 1.38), while basal LH and oestradiol levels were significantly elevated in A than in C. During follow-up, despite an effective treatment, growth impairment deteriorated in A than in C (Δ H-SDS from diagnosis of CPP to last follow-up: −0.49 ± 0.91 versus 0.21 ± 0.33, p = 0.023). Conclusions Diagnosis of CPP could be partially mislead in CP due to growth failure that got worse during follow-up despite therapy. CPP in CP seems to progress rapidly along time supporting the hypothesis of a more intense activation of hypothalamic-pituitary-gonadal-axis in these patients.
The hepatitis B virus is responsible for most of the chronic liver disease and liver cancer worldwide. As actual therapeutic strategies have had little success in eradicating the virus from hepatocytes, and as lifelong treatment is often required, new drugs targeting the various phases of the hepatitis B virus (HBV) lifecycle are currently under investigation. In this review, we provide an overview of potential future treatments for HBV.
ObjectiveTo evaluate tocilizumab (TCZ) efficacy in refractory Behcet's Disease (BD) patients.MethodsMulticenter study of 30 patients fulfilling the International Criteria for BD and treated with TCZ at different European referral centres. The clinical response was evaluated at 6 months (M6) from TCZ initiation.ResultsNinety percent of BD patients were refractory or intolerant to anti-TNF-α agents. Overall, TCZ was effective in 25 (83%) BD patients of whom 18 (60%) and 7 (23%) were complete and partial responders, respectively. The complete response was of 67%, 60% and 42% in patients with uveitis (18/30), neurological (5/30) and muco-cutaneous and/or articular (7/30) manifestations, respectively. TCZ had a significant steroid-sparing effect allowing to decrease the median daily prednisone dose from 20mg/day [10-40] to 9mg [5-13] at 6 months (p < 0.001). The number of BD patients needing concomitant DMARDs therapy fell from 7 (23%) to 4 (13%) at 6 months. Mild to moderate side effects were observed in 6 (20%) patients and 3 (10%) presented serious adverse events [pneumonia, intestinal perforation, and septicemia] requiring therapy discontinuation in 2 cases.ConclusionTCZ seems an effective alternative to anti-TNF-α agents in BD uveitis and neurological manifestations.
Purpose From the beginning of the Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV2) pandemic, different cases of a cholangiopathy with features of secondary sclerosing cholangitis in critically ill patients (SSC-CIP) have been reported. Patients developing it are generally recovering from severe Coronavirus disease 19 (COVID-19) and required intensive care unit (ICU) admission and mechanical ventilation. Many of them have been administered with ketamine during their ICU stay. The pathogenesis of this novel disease is still debated, and, since prognosis is poor, efforts are needed in order to better understand it. Patients and Methods In this review, we focused our attention on COVID-19 SSC clinical, imaging, and histology findings in order to clarify the different pathogenetic options, particularly in regard of the ischemic-direct viral damage and ketamine-related theories, beginning with a recapitulation of SSC-CIP and ketamine-induced cholangiopathy in abusers. The research has been conducted using PubMed and Google Scholar databases. Key-words were “Secondary Sclerosing Cholangiopathy”, “SSC-CIP”, “Secondary Sclerosing Cholangiopathy in critically ill patients”, “Ketamine and cholangiopathy”, “Ketamine abusers and liver disease”, “Ketamine-related cholangiopathy”, “SARS-CoV2 infection and liver disease”, “post Covid-19 secondary sclerosing cholangitis”, “Covid-19 cholangiopathy”. Results Many authors, based on the clinical, histological, imaging, and prognostic features of the disease, have pointed out the similarities between post COVID-19 SSC and SSC-CIP; however, peculiar features in the former were not previously observed. Therefore, a direct viral cytopathic action and SARS-CoV2-related coagulopathy are considered the most likely causes. On the other hand, ketamine, with the available data, cannot be surely linked as the main determinant cause of cholangiopathy. Moreover, ketamine-induced cholangitis (KIC) presentation is different from post COVID-19 SSC. Its role as a cofactor precipitating the disease cannot be ruled out. Conclusion Post COVID-19 SSC is a rare clinical entity following severe COVID-19 disease. The most accepted theory is that a sum of different insults determines the disease: biliary ischemia, direct viral damage, toxic bile, possibly worsened by ketamine and hyperinflammation due to the cytokine storm. Given the severe prognosis of the disease, with persistent cholangiopathy, organ failure, and orthotopic liver transplantation (OLT), further study on this novel clinical entity is needed.
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