Immunosuppression induces regression of fibrosis in primary biliary cholangitis with moderate-to-severe interface hepatitis.

BACKGROUND: In patients with primary biliary cholangitis (PBC) treated with ursodeoxycholic acid (UDCA), the presence of moderate-to-severe interface hepatitis is associated with a higher risk of liver transplantation and death. This highlights the need for novel treatment approaches. In this study, we aimed to investigate whether combination therapy of UDCA and immunosuppressant (IS) was more effective than UDCA monotherapy. METHODS: We conducted a multicenter study involving PBC patients with moderate-to-severe interface hepatitis who underwent paired liver biopsies. Firstly, we compared the efficacy of the combination therapy with UDCA monotherapy on improving biochemistry, histology, survival rates, and prognosis. Subsequently we investigated the predictors of a beneficial response. RESULTS: This retrospective cohort study with prospectively collected data was conducted in China from January 2009 to April 2023. Of the 198 enrolled patients, 32 underwent UDCA monotherapy, while 166 received combination therapy, consisting of UDCA combined with prednisolone, prednisolone plus mycophenolate mofetil (MMF), or prednisolone plus azathioprine (AZA). The monotherapy group was treated for a median duration of 37.6 months (IQR 27.5-58.1), and the combination therapy group had a median treatment duration of 39.3 months (IQR 34.5-48.8). The combination therapy showed a significantly greater efficacy in reducing fibrosis compared to UDCA monotherapy, with an 8.3-fold increase in the regression rate (from 6.3% to 52.4%, P < 0.001). Other parameters, including biochemistry, survival rates, and prognosis, supported its effectiveness. Baseline IgG >1.3 × ULN and ALP <2.4 × ULN were identified as predictors of regression following the combination therapy. A predictive score named FRS, combining these variables, accurately identified individuals achieving fibrosis regression with a cut-off point of ≥ -0.163. The predictive value was validated internally and externally. CONCLUSION: Combination therapy with IS improves outcomes in PBC patients with moderate-to-severe interface hepatitis compared to UDCA monotherapy. Baseline IgG and ALP are the most significant predictors of fibrosis regression. The new predictive score, FRS, incorporating baseline IgG and ALP, can effectively identify individuals who would benefit from the combination therapy.

Effects of Psychological Nursing Combined with Comprehensive Nursing on Gastrointestinal Bleeding and Nutritional Status in Cirrhosis.

Objective: Cirrhosis of the upper GIB is a surgical emergency, PN and CN can reduce the risk of gastrointestinal bleeding, but there is a lack of analysis on PN combined with CN in Cirrhotic patients. This work explored the effects of psychological nursing (PN) combined with comprehensive nursing (CN) on gastrointestinal bleeding (GIB) and nutritional status of patients with cirrhosis. Methods: Total 80 patients with GIB and cirrhosis who received emergency treatment in the Affiliated Hospital of Shaoxing University from October 2019 to October 2022 were randomly rolled into two groups. Patients in the control group (Ctrl group) received CN (n = 40 cases), and those in the experimental group (Exp group) received PN combined CN (n = 40 cases). The Model for end-stage liver disease (MELD) score, self-rating anxiety scale (SAS), self-rating depression scale (SDS), SCL-90, complication rate, and nursing satisfaction of patients from different groups were analyzed and compared. MELD score effectively predicts short - and medium-term mortality in end-stage liver disease. SAS consisted of 20 questions related to anxiety symptoms, four-level scoring method was adopted. The SCL-90 scale included four aspects: somatic symptoms, interpersonal relationships, psychological emotions, and psychological needs. Results: The results disclosed that after nursing intervention, SAS, SDS, and MELD scores in the Exp group were remarkably lower than those in the Ctrl group (P < .05). The scores of SCL-90 somatic symptoms, interpersonal relationships, psychological emotion, and psychological needs of participants in the Exp group were much lower than those in the Ctrl group (P < .05). The complication rate was significantly lower in the Exp (30.0%) than in the Ctrl groups (72.5%) (P < .05). The total nursing satisfaction was increased, and it is significan higher in the Exp group (97.5%) than control group (87.5% ) (P < .05). Conclusions: In conclusion, PN combined with CN could effectively reduce the incidence of complications in patients with GIB and cirrhosis and improve nursing satisfaction. Therefore, such a method was worth promoting, which provides a reference for the clinical diagnosis and treatment of patients with GIB and cirrhosis.

MiR-155 regulates M2 polarization of hepatitis B virus-infected tumour-associated macrophages which in turn regulates the malignant progression of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) initiated by hepatitis B virus (HBV) infection is a complicated process. MiR-155 can alter the immune microenvironment to affect the host's anti-infective ability. This study investigated the mechanism by which miR-155 affects tumour-associated macrophage (TAM) polarization at a molecular level, thus affecting the malignant progression of HBV+ HCC. MiR-155 and TAM-related cytokine expression were analysed by qRT-PCR. The distribution of TAMs was detected by immunohistochemistry. The effect of the aberrant miR-155 expression on macrophage polarization was examined by flow cytometry. The targeted relationship was verified by dual-luciferase assay, and the protein level of src homology 2 domain-containing inositol polyphosphate 5-phosphatase 1 (SHIP1) was detected by western blot. The proliferation of HCC cells was examined by CCK-8 and colony formation assays. Invasion and migration of HCC cells were detected by transwell assay. In HBV+ HCC tissues, miR-155 was significantly highly expressed and the number of CD206-positive TAM (CD206+ TAM) and CD68-positive TAM (CD68+ TAM) were higher than those in HBV- HCC tissues. In addition, miR-155 overexpression significantly promoted M2-type macrophage polarization, whilst miR-155 silencing expression significantly promoted M1-type macrophage polarization. Besides, the miR-155/SHIP1 axis accelerated HCC cell invasion, proliferation and migration by inducing M2-type macrophage polarization. MiR-155 accelerates HCC cell proliferation, migration and invasion by targeting SHIP1 expression and inducing macrophage M2 polarization. This finding provides new insights into the development of novel therapeutic strategies for combatting HBV+ HCC and a new reference for exploring anti-tumour immunotherapy.