A randomized phase 2b study of subcutaneous PD-L1 antibody ASC22 in virally-suppressed, HBeAg negative chronic hepatitis B patients.

BACKGROUND AIMS: Studies have shown that blocking the PD-1/PD-L1 pathway may lead to a potential cure for HBV infections. ASC22 (Envafolimab) is a humanized, single-domain PD-L1 antibody administered subcutaneously. This study aimed to evaluate the efficacy and safety of ASC22 in virally suppressed chronic hepatitis B (CHB) patients on nucleos(t)ide analogs (NAs). APPROACH AND RESULTS: This randomized, single-blind, phase IIb trial enrolled CHB patients in two cohorts for a 24-week treatment with ASC22 or placebo (PBO) once every 2 weeks and 24-week follow-up. In total, 60, 59, and 30 patients were treated with 1.0, 2.5 mg/kg ASC22 and PBO, respectively. The mean HBsAg changes from baseline at week 24 and 24 week follow-up periods were -0.309 (p<0.001) and -0.272 (p<0.023) log10 IU/mL in the 1.0 mg/kg ASC22 group, -0.231 (p=0.007) and -0.205 (p=0.12) log10 IU/mL in the 2.5 mg/kg ASC22 group, and-0.003 and -0.063 log10 IU/mL in the PBO group, respectively (ITT population). Three out of ten patients with baseline HBsAg levels ≤100 IU/mL in the 1.0 mg/kg group obtained on-treatment HBsAg loss. Most AEs were mild (97.9%). There were no study drug-related serious AEs in the 1.0 mg/kg ASC22 group. CONCLUSIONS: Subcutaneous administration of 1.0 mg/kg ASC22 Q2W for 24 weeks was shown to be safe and well tolerated in virally suppressed CHB patients on NAs and can induce HBsAg decline, especially in patients with HBsAg ≤100 IU/mL.

Cutaneous Deep Ulcerations as Initial Presentations of Granulomatosis with Polyangiitis: Two Case Reports and Differential Diagnosis.

Background: Granulomatosis with polyangiitis (GPA) is an antineutrophil-cytoplasmic-antibody (ANCA)-associated small-vessel vasculitis characterized by necrotizing granulomatous inflammation. Symptoms of skin involvement can appear in 30-50% of patients with GPA, and may present as the initial presentation. Case Presentation: We describe two patients who presented with multiple deep, large, nonhealing skin ulcers postoperatively with purulent drainage and fever. Both patients were diagnosed with GPA after an extensive evaluation, including histopathology. Infectious, connective tissue disease and malignant etiologies were excluded. Their cANCA and PR3-ANCA levels were positive. Patient 2 was diagnosed early and recovered well after treatment with corticosteroids and rituximab; however, Patient 1 had a poor prognosis due to a long disease course. Conclusions: Diseases with multiple deep, large skin ulcers and fever can be infectious or noninfectious. Atypical manifestations may lead to missed diagnosis and misdiagnosis. GPA may initially present in a localized form before progressing to a generalized disease. The two cases we have highlighted will prompt clinicians to nevertheless call for a low threshold for diagnosis.

Shear wave elastography may be sensitive and more precise than transient elastography in predicting significant fibrosis.

BACKGROUND: Noninvasive measurements including transient elastography (TE) and two-dimensional shear wave elastography (SWE) have been used clinically instead of liver biopsy for regular assessment of liver fibrosis in chronic hepatitis B (CHB) patients. AIM: To investigate the diagnostic efficiency of SWE compared to TE by assessing independent influencing factors and performance for diagnosing significant fibrosis based on our cohort of treatment-naive CHB patients. METHODS: Fifty-four treatment-naive CHB patients who underwent liver biopsy to determine whether to initiate antiviral therapy were enrolled. SWE, TE, serum tests and liver biopsy were performed for all participants. The fibrosis-4 and aspartate aminotransferase to platelet ratio index scores were also calculated. Potential independent influencing factors on SWE and TE values were analyzed. Based on liver pathology results, the agreement and correlation were determined, and a comparison of the two methods was performed. RESULTS: There were 27 cases (50%) of mild fibrosis (F0-F2) and 27 (50%) cases of significant fibrosis (F3-F6); fibrosis was assessed with the Ishak scoring system. Multivariate linear regression analyses revealed that the fibrosis stage was the only factor that affected the SWE values (P < 0.001), whereas the total bilirubin level (P = 0.013) and fibrosis stage (P = 0.037) were independent factors that affected TE values. Orthogonal partial least squares discriminant analysis showed that the number of independent factors (VIP > 1) was higher for TE than SWE. Bland-Altman analysis showed satisfactory agreement between liver stiffness measurements (LSMs) of SWE and TE. Both SWE and TE could significantly discriminate significant fibrosis from mild fibrosis (P < 0.001). SWE exhibited a higher correlation with LSMs of liver fibrosis than TE (r = 0.65 and 0.50, P < 0.001). The diagnostic performance of SWE was better than that of TE for significant fibrosis (F > 2). The areas under the receiver operating characteristic curves of SWE and TE were 0.786 and 0.714, respectively. The optimal LSM cutoff values of SWE and TE were 9.05 kPa and 8.15 kPa, respectively. CONCLUSION: Compared to the TE value, the SWE value was less affected by other factors. SWE may be more sensitive and precise than TE in predicting significant fibrosis (> F2) in CHB patients.

Efficacy of ursodeoxycholic acid combined with prednisolone and immunosuppressant triple therapy in the treatment of refractory primary biliary cholangitis / Eficacia del ácido ursodesoxicólico combinado con prednisolona y triple terapia inmunosupresora en el tratamiento de la colangitis biliar primaria refractaria

Background and AIM: To explore the efficacy treatment regimen in refractory PBC. METHODS: Triple treatment including ursodeoxycholic acid, prednisolone and immunosuppressant was prescribed to 47 refractory patients. Biochemistries, immune parameters, non-invasive liver fibrosis assessments were measured during follow-up. RESULTS: Triple therapy resulted in significant decrease in ALP, GGT, ALT, AST, TBIL, ALB, IgG, IgM, APRI, FIB-4 and S-INDEX. The biochemical cumulative normalization rates of ALP and other biochemical parameters were higher in long-term follow-up. Poor outcome was observed in patients with lower ALB, higher TBIL, PT, sp100 positivity and advanced liver pathology at baseline. Osteoporosis and bone fracture were observed in 15% patients. CONCLUSIONS: Triple therapy is associated with marked decrease and normalization of ALP and other parameters. ALB, TBIL, PT, sp100 and pathology were related with poor outcome. Osteoporosis should be closely monitored

ANTECEDENTES Y OBJETIVO: Explorar el régimen de tratamiento de eficacia en PBC refractario. MÉTODOS: Se prescribió un tratamiento triple que incluyó ácido ursodesoxicólico, prednisolona e inmunosupresor a 47 pacientes refractarios. Las bioquímicas, los parámetros inmunes, las evaluaciones no invasivas de fibrosis hepática se midieron durante el seguimiento. RESULTADOS: La triple terapia resultó en una disminución significativa de ALP, GGT, ALT, AST, TBIL, ALB, IgG, IgM, APRI, FIB-4 y S-INDEX. Las tasas de normalización bioquímica acumulada de ALP y otros parámetros bioquímicos fueron mayores en el seguimiento a largo plazo. Se observó un resultado deficiente en pacientes con ALB más bajo, TBIL más alto, PT, positivo de SP100 y enfermedad hepática avanzada al inicio del estudio. La osteoporosis y la fractura ósea se observaron en el 15% de los pacientes. CONCLUSIONES: La triple terapia se asocia con una marcada disminución y normalización de ALP y otros parámetros. ALB, TBIL, PT, SP100 y la enfermedad se relacionaron con un mal resultado. La osteoporosis debe estar bajo estrecha supervisión

Efficacy of ursodeoxycholic acid combined with prednisolone and immunosuppressant triple therapy in the treatment of refractory primary biliary cholangitis.

BACKGROUND AND AIM: To explore the efficacy treatment regimen in refractory PBC. METHODS: Triple treatment including ursodeoxycholic acid, prednisolone and immunosuppressant was prescribed to 47 refractory patients. Biochemistries, immune parameters, non-invasive liver fibrosis assessments were measured during follow-up. RESULTS: Triple therapy resulted in significant decrease in ALP, GGT, ALT, AST, TBIL, ALB, IgG, IgM, APRI, FIB-4 and S-INDEX. The biochemical cumulative normalization rates of ALP and other biochemical parameters were higher in long-term follow-up. Poor outcome was observed in patients with lower ALB, higher TBIL, PT, sp100 positivity and advanced liver pathology at baseline. Osteoporosis and bone fracture were observed in 15% patients. CONCLUSIONS: Triple therapy is associated with marked decrease and normalization of ALP and other parameters. ALB, TBIL, PT, sp100 and pathology were related with poor outcome. Osteoporosis should be closely monitored.

Treatment of primary biliary cholangitis with ursodeoxycholic acid, prednisolone and immunosuppressants in patients not responding to ursodeoxycholic acid alone and the prognostic indicators.

BACKGROUND AND AIM: We reviewed the medical records of primary biliary cholangitis patients who were diagnosed by liver biopsy and treated with the corresponding treatment. We evaluated the therapeutic effect and long-term prognostic indicators. METHODS: This observational cohort study enrolled 80 eligible patients diagnosed by liver biopsy between December 2013 and December 2018 in our department. UDCA monotherapy or UDCA added to prednisolone and immunosuppressant triple therapy was prescribed to patients. We analyzed and compared the demographic characteristics, biochemistry profiles, immune parameters, and noninvasive liver fibrosis assessments at baseline as well as the treatment efficacy, long-term outcomes and adverse effects at baseline and at each visit between the two groups. The indicators that could affect prognosis were assessed. RESULTS: Thirty-eight primary biliary cholangitis patients received UDCA monotherapy (group A), and another 42 patients received UDCA, prednisolone and immunosuppressant triple therapy (group B). After therapy, all patients showed significant improvements in liver biochemical parameters, immune indicators, and noninvasive fibrosis indicators (Fibrosis-4 (FIB-4), aspartate aminotransferase-to-platelet ratio index (APRI)), all P values<0.0001. The Mayo score also decreased significantly after treatment (P=0.022). Triple therapy was more effective, and there was a significant difference between the two groups. In addition, multivariate analysis showed that anti-gp210 antibody positivity; antimitochondrial antibody (AMA) negativity; high alkaline phosphatase (ALP), total bilirubin (TBIL) and globulin levels; and a severe degree of fibrosis at baseline were independent predictors of a poor prognosis. CONCLUSIONS: Triple therapy was a treatment option for UDCA-refractory PBC patients. Anti-gp210 antibody positivity; AMA negativity; high ALP, TBIL and globulin levels; and a severe degree of fibrosis at baseline were associated with a poor prognosis.

A systematic review of lopinavir therapy for SARS coronavirus and MERS coronavirus-A possible reference for coronavirus disease-19 treatment option.

In the past few decades, coronaviruses have risen as a global threat to public health. Currently, the outbreak of coronavirus disease-19 (COVID-19) from Wuhan caused a worldwide panic. There are no specific antiviral therapies for COVID-19. However, there are agents that were used during the severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) epidemics. We could learn from SARS and MERS. Lopinavir (LPV) is an effective agent that inhibits the protease activity of coronavirus. In this review, we discuss the literature on the efficacy of LPV in vitro and in vivo, especially in patients with SARS and MERS, so that we might clarify the potential for the use of LPV in patients with COVID-19.

Gilbert syndrome combined with prolonged jaundice caused by contrast agent: Case report.

This case highlights a patient with Gilbert syndrome who underwent endoscopic retrograde cholangiopancreatography (ERCP) with removal of bile duct stones, who then experienced an unexplained increase in bilirubin, with total bilirubin (TBIL) levels increasing from 159.5 µmol/L to 396.2 µmol/L and to a maximum of 502.8 µmol/L after 9 d. Following the decrease in the TBIL level, enhanced magnetic resonance cholangiopancreatography (MRCP) was performed to exclude any possible remaining choledocholithiasis. Nevertheless, the serum bilirubin level increased again, with TBIL levels rising from 455.7 µmol/L to 594.8 µmol/L and a maximum level of 660.3 µmol/L with no remaining bile duct stones. A liver biopsy showed severe bile duct cholestasis with no inflammation. Based on the exclusion of other potential causes of hyperbilirubinemia and the fact that both instances of increased bilirubin occurred after ERCP and MRCP, the contrast agents iopromide and gadoterate meglumine were suspected to be the causes of the hyperbilirubinemia. As of the writing of this report, the patient's bilirubin levels have spontaneously returned to baseline levels. In summary, ERCP and MRCP utilizing the contrast agents iopromide and gadoterate meglumine may possibly induce prolonged hyperbilirubinemia.