Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment.

BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens. METHODS: We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP. RESULTS: We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose. CONCLUSIONS: Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.

Segmental quantification of hepatic lipid content based on volumetric MRI data in patients with suspected iron overload.

PURPOSE: To investigate the segmental distribution of hepatic fat fraction, determined with MRI (MR proton density fat fraction, short MR-PDFF) in patients suspected of having liver iron overload. METHODS: The liver of 44 patients examined with MRI using a 3D multi-echo gradient-echo sequence was segmented semiautomatically and subdivided into nine segments (segment 4 divided in 4a and 4b). Segmental fat content was determined on MR-PDFF maps. Whole-liver steatosis grades were compared to those found in individual segments. Segmental MR-PDFF differences were tested for statistical significance. RESULTS: The most common diseases were thalassemia, various forms of anemia, and hereditary hemochromatosis. No patients suffered from fat metabolism disease. Iron overload was present in 37/44 (84 %) patients. For the whole liver, 22 patients showed a steatosis grade of 0, 21 patients were graded S1, and one patient had a steatosis grade of 2. The grade of steatosis was underestimated in 5 of 21 patients (24 %) in segment 8 and in 8 of 21 patients (38 %) in segment 7. Highly significant segmental MR-PDFF differences were detected with p < 0.00 001, e. g., comparing segment 2 to 5. Segments 1 to 3 had the highest fat content, segments 7 and 8 had the lowest. CONCLUSION: Our results suggest that the storage of fat in the liver is inhomogeneous, so that segment-wise differing fat concentrations were found. Fat distribution in patients with suspected hepatic iron overload was similar to living liver donors. However, it showed significant differences compared with the values published for NAFLD patients, which were less pronounced in the group with high average hepatic MR-PDFF values than in the group with normal lipid content. In patients suspected of having iron overload, segment 8, which is mainly targeted for biopsy, and segment 7 may underestimate steatosis grade. KEY POINTS: · A volumetric analysis of 3D MRI data of patients with suspected hepatic iron overload yielded a markedly elevated MR proton density fat fraction (MR-PDFF) in hepatic segments 1 to 3.. · This hepatic fat distribution, observed for the whole patient cohort, is similar to healthy living liver donors.. · The subgroup of patients with a high average MR-PDFF ≥ 6.5 % shows this effect with lower segmental deviations.. · In patients without fat metabolic disorders, the steatosis grade may be underestimated when taking biopsies in segment 8 or 7..

Blood-Based Targeted Metabolomics Discriminate Patients with Alcoholic Liver Cirrhosis from Those with Non-Cirrhotic Liver Damage: An Explorative Study.

BACKGROUND: Early detection of liver cirrhosis is crucial for secondary prevention of complications. However, noninvasive blood-based patient monitoring tools are lacking. In this explorative study, we conducted a targeted metabolomic analysis in order to identify possible serum markers indicating alcoholic liver cirrhosis (aLiC) with or without hepatocellular carcinoma (HCC). METHODS: Venous blood of 30 individuals was collected: healthy controls ("Con", n = 12), patients with aLiC without and with HCC ("aLiC": n = 6 and "aLiC + HCC": n = 6), and patients with other liver diseases ("oLiD": n = 6). A targeted metabolomic analysis was conducted using the AbsoluteIDQ® p180 Kit (Biocrates Life Sciences®, Innsbruck, Austria). Statistical analysis was performed by applying a one-way ANOVA on all subgroups followed by a t test for pairwise comparison of subgroups and logistic regression analysis. RESULTS: ANOVA revealed 29 metabolites that significantly discriminate between the different cohorts. Among these analytes, 25 were significantly altered in Con versus aLiC, as indicated by t test, most importantly SM C18:1 (p < 0.001), SM C20:2 (p = 0.001), SM (OH) C22:2 (p < 0.001), lysoPC a C20:4 (p < 0.001), and PC aa C36:5 (p < 0.001). To a similar extent, the metabolites discriminated also between the oLiD and aLiC but less between the Con or oLiD and aLiC + HCC cohorts. Most of these analytes were either lyso- and phosphatidylcholines or sphingomyelins. Results were not significant for comparison of Con versus oLiD and aLiC versus aLiC + HCC. CONCLUSION: Decreased lyso- and phosphatidylcholine as well as sphingomyelin species in venous blood could help to detect liver cirrhosis in patients with non-cirrhotic liver disease.

Efficacy of Retreatment After Failed Direct-acting Antiviral Therapy in Patients With HCV Genotype 1-3 Infections.

Hepatitis C virus infection is causing chronic liver disease, cirrhosis, and hepatocellular carcinoma. By combining direct-acting antivirals (DAAs), high sustained virologic response rates (SVRs) can be achieved. Resistance-associated substitutions (RASs) are commonly observed after DAA failure, and especially nonstructural protein 5A (NS5A) RASs may impact retreatment options.1-3 Data on retreatment of DAA failure patients using first-generation DAAs are limited.4-7 Recently, a second-generation protease- and NS5A-inhibitor plus sofosbuvir (voxilaprevir/velpatasvir/sofosbuvir [VOX/VEL/SOF]) was approved for retreatment after DAA failure.8 However, this and other second-generation regimens are not available in many resource-limited countries or are not reimbursed by regular insurance, and recommendations regarding the selection of retreatment regimens using first-generation DAAs are very important. This study aimed to analyze patients who were re-treated with first-generation DAAs after failure of a DAA combination therapy.

IgG4-Related Diseases in the Gastrointestinal Tract: Clinical Presentation, Diagnosis and Treatment Challenges.

BACKGROUND: IgG4-related diseases are a rare but an important entity. Due to the variable clinical presentation, this multiorgan disease was attributed to single-organ systems for many years. Also, it often remains a challenge to differentiate between IgG4-related diseases and malignancies. The pathogenesis seems to be a mixture of Th1- and Th2- immune responses, whereas the role of the non-pathogenic IgG4 antibodies is still unclear. Histopathological characteristics are a lymphoplasmacellular infiltrate with IgG4+ plasma cells, a storiform fibrosis and an obliterative phlebitis. This can lead to the functional destruction of every organ affected. In most cases, glucocorticoid treatment leads to remission and is used as maintenance therapy as well. Immune modulatory therapies are employed in case of steroid resistance. However, a majority of patients achieve remission without any therapy. SUMMARY: In this study, we review the current state-of-the-art regarding pathophysiology, diagnostics, organ manifestation and therapeutic approaches. Key Messages: While the diagnosis of IgG4-related diseases is still challenging, there have been significant improvements in diagnostic as well as in therapeutic approaches. This is partially due to a better understanding of the pathophysiology of the disease but also due to improved imaging modalities and novel, more targeted therapies.

High Prognostic Value of Mini-Laparoscopy for Advanced Liver Disease-Related Complications in Patients with HCV Infection.

BACKGROUND/AIM: The assessment of advanced chronic liver disease (ACLD) is a prerequisite for therapy and surveillance in patients with chronic hepatitis C infection. Mini-laparoscopy-assisted liver biopsies facilitate both histological and macroscopical evaluation of liver fibrosis. This study is aimed at investigating the prognostic significance of the laparoscopic assessment for the cumulative incidence of ACLD-related events. PATIENTS AND METHODS: We performed a single center, retrospective analysis of 94 patients with either macroscopically or/and microscopically assessed advanced fibrosis/cirrhosis caused by chronic hepatitis C infection. The patients' data, the respective laboratory results, and follow-up period were evaluated in the outpatient clinic. RESULTS: The group with both macro- and microscopic diagnosed ACLD showed a significantly higher number of decompensating events (n = 7) compared with the other 2 groups (n = 0 in the group with only histological and n = 1 in the group with only laparoscopic diagnosis of advanced liver disease). The results were not affected by the successful treatment of the hepatitis C virus. In the Cox-regression analysis, the spleen size (>120 mm) was significantly associated with the incidence of ACLD-related events. CONCLUSIONS: Assessment of ACLD in chronic hepatitis C by mini-laparoscopy-assisted liver biopsies may facilitate the selection of patients with a poor prognosis, irrespective of achieving a sustained virological response following treatment. Follow-up of these patients should be intensified to treat decompensation early.