Presence of autoantibodies in serum does not impact the occurrence of immune checkpoint inhibitor-induced hepatitis in a prospective cohort of cancer patients.

PURPOSE: Immune checkpoint inhibitor (ICI)-induced hepatitis belongs to the frequently occurring immune-related adverse events (irAEs), particularly with the combination therapy involving ipilimumab and nivolumab. However, predisposing factors predicting the occurrence of ICI-induced hepatitis are barely known. We investigated the association of preexisting autoantibodies in the development of ICI-induced hepatitis in a prospective cohort of cancer patients. METHODS: Data from a prospective biomarker cohort comprising melanoma and non-small cell lung cancer (NSCLC) patients were used to analyze the incidence of ICI-induced hepatitis, putatively associated factors, and outcome. RESULTS: 40 patients with melanoma and 91 patients with NSCLC received ICI between July 2016 and May 2019. 11 patients developed ICI-induced hepatitis (8.4%). Prior to treatment, 45.5% of patients in the hepatitis cohort and 43.8% of the control cohort showed elevated titers of autoantibodies commonly associated with autoimmune liver diseases (p = 0.82). We found two nominally significant associations between the occurrence of ICI-induced hepatitis and HLA alleles associated with autoimmune liver diseases among NSCLC patients. Of note, significantly more patients with ICI-induced hepatitis developed additional irAEs in other organs (p = 0.0001). Neither overall nor progression-free survival was affected in the hepatitis group. CONCLUSION: We found nominally significant associations of ICI-induced hepatitis with two HLA alleles. ICI-induced hepatitis showed no correlation with liver-specific autoantibodies, but frequently co-occurred with irAEs affecting other organs. Unlike other irAEs, ICI-induced hepatitis is not associated with a better prognosis.

[Abdominal Pain Caused by Viral Infection Is Not Always Trivial]. / Bauchschmerzen bei viralem Infekt sind nicht immer trivial.

Abdominal Pain Caused by Viral Infection Is Not Always Trivial Abstract. We report on a 28-year-old previously healthy patient with initially elevated temperature and cough and developing most severe epigastric pain and peritonism in the right upper abdomen. A "bedside" sonography revealed a portal vein thrombosis, the CT additionally partial thromboses of the vena lienalis, vena mesenterica superior. During the examination, a SARS-CoV-2 infection (IgM, IgG) was confirmed. Currently (pandemic), extrapulmonary thromboembolism must also be considered. For this purpose, sonography is the appropriate "search method" - it can be used from "head to toe", immediately and at the "bedside".

[Sonographic Wall Changes of the Stone-Free Gall Bladder - a Diagnostic and Therapeutic Dilemma]. / Sonografische Wandveränderungen der steinfreien Gallenblase ­ ein diagnostisches und therapeutisches Dilemma.

Sonographic Wall Changes of the Stone-Free Gall Bladder - a Diagnostic and Therapeutic Dilemma Abstract. Various diseases frequently cause sonographic abnormalities of the gallbladder wall and its surroundings. The interpretation of these abnormalities is often a great challenge for the treating physician and will be briefly discussed here. In our patient these abnormalities are due to hepatitis A, which is responsible for multiple extrahepatic manifestations. Considering this etiology, gallbladder resection should be avoided in order to minimize unnecessary complications.

Controlled attenuation parameter for the assessment of liver steatosis in comparison with liver histology: a single-centre real life experience.

BACKGROUND AND AIMS: Accurate diagnosis and staging of non-alcoholic fatty liver disease are essential for the management of this disorder. Controlled attenuation parameter (CAP) has been suggested as a new noninvasive measurement made during transient elastography to assess liver steatosis. The aim of this study was to evaluate CAP as a diagnostic tool for identifying the presence and degree of hepatic steatosis in consecutive patients in an outpatient liver unit of a tertiary centre. METHODS: Between March 2015 and August 2016, all patients who underwent liver biopsy underwent liver stiffness measurement with simultaneous CAP determination using the FibroScan® M or XL probe. Steatosis, inflammatory activity and fibrosis were assessed using the histological SAF scoring system. In addition, fibrosis was scored according to the METAVIR system, and body mass index (BMI) and the underlying liver disease were also recorded. RESULTS: 224 patients were included in the analysis; 146 (65.2%) were male. Steatosis grades were distributed as follows: S0 n = 85 (37.9%), S1 n = 82 (36.6%), S2 n = 33 (14.7%), S3 n = 24 (10.7%). Mean BMI was 26.8 kg/m2, for the S0 group 24.9 kg/m2, S1 26.5 kg/m2, S2 27.3 kg/m2 and S3 32.5 kg/m2. The CAP differed significantly between steatosis groups S0 to S3. The area under receiver operating characteristics curve for S0 vs S1–S3 was 0.78, for S0/1 vs S2/3 0.83 and for S0–2 vs S3 0.82. Calculated cut-off values were 258.5 dB/m for S0 vs S1–3, 282.5 dB/m for S0/1 vs S2/3 and 307.5 dB/m for S0–2 vs S3. CONCLUSIONS: CAP values are strongly associated with the degree of steatosis irrespective of the underlying liver disease. Integrating CAP measurements in the standard work-up may identify patients with NAFLD.  .

Excellent outcome of direct antiviral treatment for chronic hepatitis C in Switzerland.

BACKGROUND: The introduction of direct acting antivirals (DAAs) for the therapy of chronic hepatitis C (CHC) has revolutionised treatment and marks a paradigm shift in the approach to this disease, rendering interferon-based therapies obsolete. AIMS OF THE STUDY: We retrospectively and prospectively evaluated treatment results after the introduction of DAA in Switzerland in a cohort of patients with CHC. METHODS: We examined 565 patients who received DAA treatment for CHC between November 2013 and June 2016 with regard to HCV genotype, fibrosis stadium, treatment and outcome. In addition, outcome of re-treatment and resistance-associated substitutions (RAS) in patients that did not achieve sustained virological response (SVR) were evaluated. The majority of patients participate in the Swiss Hepatitis C Cohort Study. Data were evaluated in an intention-to-treat and a modified intention-to-treat analysis. RESULTS: Overall SVR rate for all patients was 94% (530 of 565, 95% CI 92-96%). Of 350 patients with HCV genotype 1 CHC, 335 achieved SVR, resulting in an SVR rate of 96% (335 of 350, 95% CI 94-98%). Patients with HCV genotype 2 achieved SVR in 94% (48 of 51, 95% CI 87-100%). Patients with HCV genotype 3 showed SVR of 92% (98 of 107, 95% CI 87-97%). In patients with HCV genotype 4, the SVR rate was substantially lower at 85% (49 of 57, 95% CI 76-94%). The rate of advanced liver fibrosis (Metavir F3/F4) assessed by means of liver biopsy or Fibroscan® in the entire patient population was 71% (404 of 565). Out of 35 patients that did not achieve SVR after DAA treatment, 32 had a relapse and 3 patients showed viral breakthrough. In 17 of 35 cases (49%) patients were treatment naïve and 21 of 35 patients (60%) were cirrhotic. RAS genotyping of HCV was performed in 14 patients. Nine of these 14 patients (60%) carried mutations in the NS5A region of the virus genome. Twenty-seven percent of patients who experienced treatment failure were not treated with recommended regimens as a result of drug availability and reimbursement limitations. CONCLUSION: In Switzerland, novel DAA treatments for CHC reflect the positive results from registration trials. Genotypes 2 and 4 remained more difficult to treat between 2014 and 2016. Patients who experienced a relapse after DAA treatment in Switzerland predominantly showed mutations in the NS5A region of the virus genome. DAA treatment limitations in Switzerland did prevent optimal treatment regimens in some patients.

Direct antiviral agent treatment of chronic hepatitis C results in rapid regression of transient elastography and fibrosis markers fibrosis-4 score and aspartate aminotransferase-platelet ratio index.

BACKGROUND: Novel direct antiviral agents (DAA) targeting hepatitis C virus (HCV) have revolutionized the treatment of chronic hepatitis C infection (CHC). Rates of sustained virological response (SVR) to treatment have drastically improved since introduction of DAA. Transient Elastography (TE) is an ultrasound based, non-invasive technique to assess liver stiffness (LS). We examined the changes in TE values and fibrosis scores FIB-4 and APRI after DAA treatment of CHC. METHODS: 549 patients who received a DAA based treatment for CHC were screened and 392 were included. TE values recorded prior to therapy and within 18 months after therapy were evaluated. In addition, FIB-4 and APRI scores were calculated and histopathological results were recorded if available. RESULTS: Median TE prior to DAA treatment was 12.65 kPa (IQR 9.45-19.2 kPa) and decreased to 8.55 kPa (IQR 5.93-15.25) post-treatment. This finding is statistically significant (P<.001) and equals a TE regression of 32.4% after DAA treatment. Median FIB-4 and APRI values significantly decreased from 2.54 (IQR 1.65-4.43) and 1.10 (IQR 0.65-2.43) to 1.80 (IQR 1.23-2.84, P<.001) and 0.43 (IQR 0.3-0.79, P<.001) respectively. CONCLUSION: Patients with SVR after DAA therapy showed significant regression of TE values. Rapid decrease in TE was in concordance with regression of validated fibrosis scores FIB-4 and APRI. It remains to be examined whether this indicates a true regression of fibrosis or merely resolution of chronic liver inflammation with subsequent improvement of TE values and laboratory parameters.