Thrombotic sinusoiditis and local diffuse intrasinusoidal coagulation in the liver of subjects affected by COVID-19: the evidence from histology and scanning electron microscopy.

OBJECTIVE: Liver injury has been reported in patients with COVID-19. This condition is characterized by severe outcome and could be related with the ability of SARS-CoV-2 to activate cytotoxic T cells. The purpose of this study is to show the histological and scanning electron microscopy features of liver involvement in COVID-19 to characterize the liver changes caused by the activation of multiple molecular pathways following this infection. PATIENTS AND METHODS: Liver biopsies from 4 patients (3 post-mortems and 1 in vivo) with COVID-19 were analyzed with histology and by scanning electron microscopy. RESULTS: The liver changes showed significant heterogeneity. The first case showed ground glass hepatocytes and scattered fibrin aggregates in the sinusoidal lumen. The second evidenced intra-sinusoidal thrombi. The third was characterized by sinusoidal dilatation, atrophy of hepatocytes, Disse's spaces dilatation and intra-sinusoidal aggregates of fibrin and red blood cells. The fourth case exhibited diffuse fibrin aggregates in the dilated Disse spaces and microthrombi in the sinusoidal lumen. CONCLUSIONS: In COVID-19-related liver injury, a large spectrum of pathological changes was observed. The most peculiar features were very mild inflammation, intra-sinusoidal changes, including sinusoidal dilatation, thrombotic sinusoiditis and diffuse intra-sinusoidal fibrin deposition. These findings suggested that a thrombotic sinusoiditis followed by a local diffuse intra-vascular (intra-sinusoidal) coagulation could be the typical features of the SARS-CoV-2-related liver injury.

Steadily high IDDM incidence over 4 years in Sardinia.

OBJECTIVE: To verify whether the high incidence of insulin-dependent diabetes mellitus (IDDM) in Sardinia is an epidemic outbreak or a steady phenomenon. RESEARCH DESIGN AND METHODS: All newly diagnosed cases of IDDM with onset in patients 0-29 years of age between 1 January 1989 and 31 December 1992 among residents in Sardinia were obtained from the Sardinian IDDM Incidence Registry. The local IDDM patient association (Associazione Diabete Infantile Giovanile) served as the secondary and independent source. RESULTS: The completeness of ascertainment was 91%. The age-standardized mean annual incidence of IDDM (per 100,000) was 34.4 in the 0- to 14-year-old age-group and 26.2 in the entire 0- to 29-year-old range, respectively. Men-to-women ratios were 1.38 and 1.55, respectively. Seasonal variation in incidence was observed, with a peak in fall and winter and a nadir in summer. CONCLUSIONS: Sardinia has a very high and steady IDDM incidence rate, which is up to fivefold that of other Italian regions and Mediterranean countries and approaches the Finnish top rate in the world. Interaction between the genetic peculiarity of Sardinians and still unidentified powerful environmental agents is likely to account for the phenomenon.

[Late onset Wilson's disease]. / Morbo di Wilson ad esordio tardivo.

BACKGROUND: Wilson's disease (W.D.) is a metabolic disorder that occurs predominantly in children, adolescents, young adults and, rarely, in patients over 35 years. AIMS: In order to verify the prevalence of the clinical presentation of W.D. in adulthood, we analyzed a wide number of clinical presentation of W.D. with particular attention to the age of onset and to the evolutive stage of liver disease at presentation. PATIENTS: Our study is relative to 11 Sardinian adult subjects, aged 36-57 years, 6 males and 5 females, selected from a series of 120 patients affected by W.D. The only criterion utilized to select the patients was their age at presentation, with a cut off of 35 years. METHODS: Liver biopsies were routinely processed and stained with rhodanine, rubeanic acid, orcein and Timm's methods. On the basis of the histological picture, liver biopsies were subdivided into four evolutive stages: stage I = steatosis; stage II = interface hepatitis; stage III = bridging fibrosis; stage IV = cirrhosis. Molecular characterization of W.D. for gene mutations in the Sardinian population was performed in 7 out of 11 cases (-441/-427 del, 5' UTR and 3436 G > A Exon 16). RESULTS: 3 patients showed histological features of the first evolutive stage, 2 of the second, 1 of the third, and 5 of the fourth stage. Histochemistry for copper resulted positive in 9 of 11 cases at least with one of the four employed methods. In the seven patients in whom molecular characterization was perfomed, the gene mutation of W.D. was the same observed more frequently in the Sardinian population (-441/-427 del, 5'UTR). CONCLUSIONS: Our data show that: 1) W.D. with late onset is not rare in Sardinian population; 2) in spite of the late clinical presentation, W.D. may present in the first (3/10) and in the second evolutive stage (2/10) with mild to moderate changes of the liver architecture; 3) patients may show, at presentation, a severe liver disease, characterized by bridging fibrosis or cirrhosis; 4) from a practical point of view, we ask to consider the diagnosis the W.D. in all patients with chronic liver disease of unknown etiology, even if aged over 35 years.