Liver steatosis is highly prevalent and is associated with metabolic risk factors and liver fibrosis in adult patients with type 1 Gaucher disease.

BACKGROUND AND AIMS: Gaucher disease (GD) is associated with peculiar metabolic abnormalities (ie hypermetabolic state, peripheral insulin resistance, dyslipidaemia), partially reverted by enzyme replacement therapy (ERT) at the expense of weight gain. Such metabolic alterations together with an unhealthy lifestyle acquired by an ageing GD population may favour the development of liver steatosis. We aimed at evaluating the prevalence of significant liver steatosis and at identifying the factors associated with liver steatosis in a cohort of patients with type 1 GD. METHODS: Twenty adult type 1 GD patients from an Italian academic referral centre were prospectively submitted to vibration-controlled transient elastography (Fibroscan®) with controlled attenuation parameter (CAP); significant steatosis was defined as CAP values ≥250 dB/min. RESULTS: Median CAP values were 234 [165-358] dB/min and 8 patients (40%) had significant steatosis. Significant steatosis was associated with indices of adiposity (weight, BMI and waist circumference), high blood pressure, insulin resistance and metabolic syndrome. GD-related variables and dose and duration of ERT were not associated with significant steatosis. In the subgroup of 16 patients on stable ERT for at least 24 months, CAP resulted significantly and positively associated with liver stiffness (rho 0.559, P = .024). CONCLUSIONS: Significant steatosis is highly prevalent in adult type 1 GD patients and is strongly associated with a worse metabolic profile, featuring metabolic dysfunction-associated fatty liver disease (MAFLD). MAFLD may determine liver fibrosis progression in GD patients on stable ERT and may be a risk factor for long-term liver-related complications.

Investigating Acute Hepatitis after SARS-CoV-2 Vaccination or Infection: A Genetic Case Series.

(1) Background: Despite the advantages of COVID-19 vaccination, rare cases of acute hepatitis developing after the administration of the COVID-19 vaccine or the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have been reported. The aim of the study is to describe a case series of patients who experienced the onset of acute hepatitis, with or without autoimmune features, following SARS-CoV-2 vaccination or infection and to hypothesize a genetic susceptibility in the pathogenesis. (2) Methods: A group of patients with acute onset hepatitis following SARS-CoV-2 vaccination or infection were evaluated in our hepatology outpatient clinic, where they underwent biochemical and autoimmune tests. Hepatitis A (HAV), B (HBV), and C virus (HCV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human immunodeficiency virus (HIV) infections were excluded. Patients with a diagnosis of autoimmune hepatitis (AIH) or drug-induced liver injury (DILI) underwent HLA typing and histological testing. (3) Results: Five patients experienced new-onset AIH after COVID-19 vaccination, one of which developed mild symptoms after vaccination that strongly worsened during subsequent SARS-CoV-2 infection. One patient had AIH relapse after COVID-19 vaccination while on maintenance immunosuppressive treatment. All of them had HLA DRB1 alleles known to confer susceptibility to AIH (HLA DRB1*03,*07,*13,*14), and in three of them, HLA DRB1*11 was also detected. Two patients developed acute hepatitis without autoimmune hallmarks which resolved spontaneously, both positive for HLA DRB1*11. (4) Conclusions: An association between AIH and COVID-19 vaccine or infection can be hypothesized in individuals with a genetic predisposition. In patients without autoimmune features and spontaneous improvement of hypertransaminasemia, the diagnosis of drug-induced liver injury (DILI) is probable. Further studies are needed to determine the presence of an actual association and identify a possible role of HLA DRB1*11 in the pathogenesis of acute liver injury after SARS-CoV2 vaccination or infection.

Osteochondritis Dissecans of the Knee: Etiology and Pathogenetic Mechanisms. A Systematic Review.

OBJECTIVE: The purpose of this manuscript is to analyze the evidence regarding etiopathogenesis of knee osteochondritis dissecans (OCD) lesions through a systematic review, so to summate the current understanding of the origin and progression of this pathologic articular processes. DESIGN: A systematic review of the literature was performed on the PubMed and Cochrane databases on October 2017 by 2 independent authors and included all levels of evidence. This included all English language literature, pertaining specifically to etiopathology of knee OCD with exclusions for review articles and expert opinion. Of 965 identified records, 154 full-text articles were assessed for eligibility and 86 studies met the inclusion criteria. RESULTS: According to these studies, the etiology of OCD can be of a biological or mechanical origin: 40 articles proposed a biological hypothesis, including genetic causes (27), ossification center deficit (12), and endocrine disorders (9); conversely, 52 articles supported a mechanical hypothesis, including injury/overuse (18), tibial spine impingement (5), discoid meniscus (16), and biomechanical alterations (20) as the cause of the onset of OCD. The pathogenic processes were investigated by 36 of these articles, with a focus on subchondral bone fracture and ischemia as the ultimate events leading to OCD. CONCLUSIONS: Biological and mechanical factors are found to result in subchondral bone remodeling alterations, acting independently or more likely synergically in the progression of knee OCD. The former includes genetic causes, deficit of ossification centers and endocrine disorders; the latter, tibial spine impingement, discoid meniscus, and biomechanical alterations, together with injuries and overuse. The resultant subchondral bone ischemia and/or fracturing appears to determine the onset and progression of OCD. LEVEL OF EVIDENCE: Systematic review of level II-IV studies, level IV.

Osteochondritis Dissecans of the Knee - Conservative Treatment Strategies: A Systematic Review.

OBJECTIVE: Osteochondritis dissecans (OCD) lesions are a relevant problem that affects the long-term prognosis of young patients. The purpose of this study was to analyze the evidence on potential and indications of nonsurgical treatment strategies for knee OCD. DESIGN: The search was conducted on 3 medical electronic databases according to PRISMA guidelines, including reports of any level of evidence dealing with the conservative management of knee OCD. Of 1688 identified records, 55 full-text articles were screened: 27 studies met the inclusion criteria, for a total of 908 knees, and were used for the analysis. RESULTS: No high-level studies were found: 24 articles were case series and 3 case reports, reporting on different treatments summarized in (1) restriction of physical activity, (2) physiokinesitherapy and muscle-strengthening exercises, (3) physical instrumental therapies, (4) limitation of weightbearing, and (5) immobilization. The analysis showed an overall healing rate of 61.4%, with large variability (10.4%-95.8%). A conservative treatment based on restriction of sport and strenuous activities seems a favorable approach, possibly combined with physiokinesitherapy. Negative prognostic factors were also identified: larger lesion size, more severe lesion stages, older age and skeletal maturity, discoid meniscus, and clinical presentation with swelling or locking. CONCLUSIONS: The literature on conservative treatments for knee OCD is scarce. Among different non-surgical treatment options, strenuous activity restriction seems a favorable approach, whereas there is no evidence that physical instrumental therapy, immobilization, or weightbearing limitation could be beneficial. However, further studies are needed to improve treatment potential and indications for the conservative management of knee OCD.

Early Viscosupplementation After Anterior Cruciate Ligament Reconstruction: A Randomized Controlled Trial.

BACKGROUND: Hyaluronic acid (HA) has been widely used to treat osteoarthritis given its biological and mechanical properties. Because HA is an "intra-articular" treatment approach that affects the joints, it could be used in the management of acute conditions, such as during the early postsurgical phase, to reduce inflammatory stress and improve articular function. PURPOSE: The aim of the present double-blind, randomized controlled trial was to evaluate pain control and functional recovery provided by a single injection of HA performed the day after anterior cruciate ligament (ACL) reconstruction. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: The study enrolled 60 patients affected by primary, chronic, and symptomatic ACL tear requiring surgical reconstruction. All patients were treated with the same reconstructive technique and rehabilitation protocol. Exclusion criteria were (1) concurrent articular lesion requiring surgical treatment, (2) axial malalignment in the index limb, and (3) functional limitation or pain in the contralateral knee. The day after the procedure, the patients were randomized to receive a single injection of 3 mL HA or 3 mL saline solution after surgical drains were removed. All patients were evaluated at baseline and at 15, 30, 60, and 180 days and 12 months after surgery by use of the following tools: Short Form-36 Health Survey (SF-36), International Knee Documentation Committee (IKDC) subjective score, visual analog scale (VAS) for pain, VAS for general health status, and Tegner score. At each follow-up evaluation, the transpatellar circumference and active and passive range of motion (ROM) of both knees were recorded. RESULTS: No severe adverse events were documented after early viscosupplementation. A significant improvement was documented in both treatment groups. Significant differences were documented in the transpatellar circumference at 60 days and in active ROM at 30 days postoperatively; patients who received HA had better values compared with the placebo group (P = .022 and .027, respectively). No statistically relevant intergroup differences were found in the clinical scores. CONCLUSION: The study documented no adverse events and had some positive findings in terms of active ROM recovery and transpatellar circumference reduction. However, the early postoperative application of viscosupplementation did not lead to significant improvement in clinical scores after ACL reconstruction. REGISTRATION: NCT02630407 (ClinicalTrials.gov identifier).

No Effects of Early Viscosupplementation After Arthroscopic Partial Meniscectomy: A Randomized Controlled Trial.

BACKGROUND: The management of the postoperative period after knee arthroscopic surgery may be challenging because surgical trauma deeply alters the joint microenvironment, causing the release of several catabolic molecules and proinflammatory factors that might slow down functional recovery. The possibility of using hyaluronic acid (HA) to promote postoperative pain relief and expedite functional improvement seems attractive, considering its biological properties. PURPOSE: The aim of the present double-blind randomized controlled trial was to evaluate the effects, in terms of pain control and functional recovery, provided by a single HA injection performed at the end of arthroscopic meniscectomy. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 90 patients, 18 to 55 years old, were included according to the following criteria: (1) chronic, symptomatic meniscal tears requiring partial resection; (2) a healthy contralateral knee; (3) no previous surgery on the index knee; and (4) no other concurrent articular lesions requiring surgical treatment (eg, cartilage or ligament injuries). Patients were randomized into 2 treatment groups: one underwent meniscectomy alone, whereas the other also received an injection of 3 mL HA at the end of the procedure. All patients were evaluated at baseline and then at 15, 30, 60, and 180 days using the following tools: International Knee Documentation Committee (IKDC) subjective, Knee injury and Osteoarthritis Outcome Score (KOOS), visual analog scale (VAS) for pain, VAS for general health status, and Tegner scores. The transpatellar circumference and active and passive ranges of motion were also recorded during the follow-up evaluations. RESULTS: No major adverse events were reported using HA postoperatively. A statistically significant increase in all the clinical scores was reported in both treatment groups, but no significant intergroup difference was documented at any follow-up evaluation. No difference was observed also in the objective measurements. The mean time to return to full sports activity was not different between groups, and a comparable satisfaction rate was recorded in both treatment groups. CONCLUSION: Early postoperative viscosupplementation did not provide significant clinical benefits after arthroscopic meniscectomy. Despite the lack of major adverse events, the administration of a single HA injection at the end of the surgical procedure is not a successful strategy to provide either faster functional recovery or symptomatic improvement after meniscectomy. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02629380.