The aim of this study is to evaluate the cumulative probability of recurrence and admission rates in an inflammatory bowel disease (IBD) inception cohort diagnosed in 2003-2004. Data on medications, phenotypes and surgery for 513 individuals with ulcerative colitis (UC, n=300) and Crohn's disease (CD, n=213) were obtained from medical records and linked to population-based health administrative database information. The admission rates and cumulative probability of recurrences were estimated, and the association with the baseline factors and medication was tested. The cumulative risk of first recurrence after 1, 5 and 7 years was 40%, 63%, and 66% in CD patients and 51%, 75%, and 79% in UC patients, respectively. The cumulative risk of first surgical relapse was 6%, 18%, and 23% at 1, 5 and 7 years in CD respectively. One hundred and CD patients (66%) and 142 UC patients (47%) had at least one IBD-related hospitalisation. The hospitalisation rate decreased from 7.0 days/person-year in year one to 0.9 day at year 5 in CD, and from 4.7 days to 0.4 days for UC patients. Age above 40, current smoking, stricturing behaviour, and disease localisation (colonic, ileocolonic, and upper-GI) at diagnosis were predictors of recurrence in CD. In UC, age above 40 and former smoker status were predictors of recurrence and left-sided and extensive colitis were predictors of first-time hospitalisation. In an era of improved treatment options, the recurrence rates, but not the surgery or hospitalisation rates, have decreased for CD but not for UC. The phenotypic characteristics at diagnosis predict the risk of recurrence and hospitalisation.

The aim of this study is to characterize cell type-specific transcriptional signatures in non-alcoholic steatohepatitis (NASH) to improve our understanding of the disease. We performed single-cell RNA sequencing on liver biopsies from 10 patients with NASH. We applied weighted gene co-expression network analysis and validated our findings using a publicly available RNA sequencing data set derived from 160 patients with non-alcoholic fatty liver disease (NAFLD) and 24 controls with normal liver histology. Our study provides a comprehensive single-cell analysis of NASH pathology in humans, describing 19,627 single-cell transcriptomes from biopsy-proven NASH patients. Our data suggest that the previous notion of ”NASH-associated macrophages” can be explained by an up-regulation of normally existing subpopulations of liver macrophages. Similarly, we describe two distinct populations of activated hepatic stellate cells, associated with the level of fibrosis. Finally, we find that the expression of several circulating markers of NAFLD are co-regulated in hepatocytes together with predicted effector genes from NAFLD genome-wide association studies (GWAS), coupled to abnormalities in the complement system. In sum, our single-cell transcriptomic data set provides insights into novel cell type-specific and general biological processes associated with inflammation and fibrosis, emphasizing the importance of studying cell type-specific biological processes in human NASH.

Background: Patients with cirrhosis and portal hypertension face a high risk of complications. Besides their anti-inflammatory and antifibrotic effects, statins may reduce portal pressure and thus the risk of complications and mortality. We aimed to investigate the effects of atorvastatin on hospital admissions, mortality, inflammation, and lipidomics in cirrhosis with portal hypertension. Methods: We performed a double-blinded, randomized, placebo-controlled clinical trial among patients with cirrhosis and portal hypertension. Atorvastatin (10–20 mg/d) was administered for 6 months. We measured splanchnic hemodynamics, analyzed inflammatory markers, and performed lipidomics at baseline and after 6 months. Results: Seventy-eight patients were randomized, with 38 patients allocated to atorvastatin and 40 patients to placebo. Fifty-nine patients completed 6 months of intervention. Comparisons between changes in each group were calculated. Liver-related complications and mortality were similar between the groups. The HVPG and Model for End-stage Liver Disease score did not change between groups (p=0.95 and 0.87, respectively). Atorvastatin decreased 3 of 42 inflammatory markers, CD62-L-selectin, matrix metalloproteinases-2, and TNF-α (p-values: 0.005, 0.011, and 0.023, respectively), while lipidomics was not significantly changed. Conclusions: In patients with cirrhosis, atorvastatin was safe to use, but did not reduce mortality, the risk of liver-related complications, or the HVPG. Atorvastatin induced minor anti-inflammatory effects and minor effects on lipids during a 6-month treatment period.

Roux-en-Y gastric bypass (RYGB) improves, and can sometimes resolve, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) but data based on histological assessment for the efficacy of sleeve gastrectomy (SG) in resolving NAFLD are sparse. Consequently, we aimed to compare the efficacy of RYGB vs. SG on NAFLD 12 months after surgery. In a prospective cohort study, 40 patients with obesity underwent bariatric surgery (16 RYGB and 24 SG). During surgery, a liver biopsy was taken and repeated 12 months later. NAFLD severity was evaluated using the NAFLD Activity Score (NAS) and Kleiner Fibrosis score. RYGB and SG patients were comparable at baseline. Mean (standard deviation, SD) NAS was 3.3 (0.9) in RYGB and 3.1 (1.4) in SG (p = 0.560) with similar degrees of steatosis, inflammation, and ballooning. Two RYGB patients, and six SG patients, had NASH (p = 0.439). Twelve months after surgery, NAS was significantly and comparably (p = 0.241) reduced in both RYGB (−3.00 (95% CI −3.79–−2.21), p < 0.001) and SG (−2.25 (95% CI −2.92–−1.59), p < 0.001) patients. RYGB patients had significantly more reduced (p = 0.007) liver steatosis (−0.91 (95% CI −1.47–−1.2) than SG patients (−0.33 (95% CI −0.54–−0.13) and greater improvement in the plasma lipid profile. Fibrosis declined non-significantly. NASH was resolved in seven of eight patients without a worsening of their fibrosis. RYGB and SG have similar beneficial effects on NAS and NASH without the worsening of fibrosis. RYGB is associated with a more pronounced reduction in liver steatosis.

Summary: Background: Liver fibrosis accumulation is considered a turnover disease, with formation exceeding degradation, although this hypothesis has never been tested in humans.Aims: To investigate extracellular matrix (ECM) remodelling in a biopsy‐controlled study of alcohol‐related liver disease (ALD) patients.Methods: We evaluated the relationship between formation and degradation of four collagens as a function of histological fibrosis, inflammation and steatosis in 281 patients with ALD and 50 matched healthy controls. Post hoc, we tested the findings in a cohort of patients with alcohol‐related cirrhosis and assessed the collagens' prognostic accuracy. We assessed the fibrillar collagens type III (PRO‐C3/C3M) and V (PRO‐C5/C5M), the basement membrane collagen IV (PRO‐C4/C4M), and the microfilament interface collagen VI (PRO‐C6/C6M).Results: Mean age was 54 ± 6 years, 74% male, fibrosis stage F0/1/2/3/4 = 33/98/84/18/48. Compared to controls, patients with ALD had higher levels of type III collagen formation and degradation, with the highest concentrations in those with cirrhosis (PRO‐C3 = 8.2 ± 1.7 ng/mL in controls, 14.6 ± 13.5 in ALD, 34.8 ± 23.1 in cirrhosis; C3M 7.4 ± 1.9 in controls, 9.3 ± 4.4 in ALD, 14.0 ± 5 in cirrhosis). ECM remodelling became increasingly imbalanced in higher stages of liver fibrosis, with formation progressively superseding degradation. This was particularly pronounced for type III collagen. We observed similar imbalance for inflammatory severity, but not steatosis.Conclusions: ALD is characterised by both elevated collagen formation and degradation, which becomes increasingly imbalanced with more severe disease. Net increase in fibrillar collagens contributes to fibrosis progression. This has important implications for monitoring and very early identification of patients at highest risk of progressing to cirrhosis.