The aim of the study was to compare the gut microbiomes from obese and lean patients with or without NASH to outline phenotypic differences.
We performed a cross-sectional pilot study comprising ...biopsy-proven NASH patients grouped according to BMI. Microbiome DNA was extracted from stool samples, and PCR amplification was performed using primers for the V4 region of the 16S rRNA gene. The amplicons were sequenced using the Ion PGM Torrent platform, and data were analyzed using QIIME software. Macronutrient consumption was analyzed by a 7-day food record. Liver fibrosis ≥ F2 was associated with increased abundance of Lactobacilli (p = 0.0007). NASH patients showed differences in Faecalibacterium, Ruminococcus, Lactobacillus and Bifidobacterium abundance compared with the control group. Lean NASH patients had a 3-fold lower abundance of Faecalibacterium and Ruminococcus (p = 0.004), obese NASH patients were enriched in Lactobacilli (p = 0.002), and overweight NASH patients had reduced Bifidobacterium (p = 0.018). Moreover, lean NASH patients showed a deficiency in Lactobacillus compared with overweight and obese NASH patients. This group also appeared similar to the control group with regard to gut microbiome alpha diversity. Although there were qualitative differences between lean NASH and overweight/obese NASH, they were not statistically significant (p = 0.618). The study limitations included a small sample size, a food questionnaire that collected only qualitative and semi-quantitative data, and variations in group gender composition that may influence differences in FXR signaling, bile acids metabolism and the composition of gut microbiota.
Our preliminary finding of a different pathogenetic process in lean NASH patients needs to be confirmed by larger studies, including those with patient populations stratified by sex and dietary habits.
•The gut microbiota in NAFLD have provided new insight in it pathogenesis and may explain the observed phenotypic differences.•We compared the gut microbiome from obese patients with or without NASH versus Lean patients with or without NASH.•Different pathogenesis can be suggested in lean NASH and fibrosis score F2 was associated with gut microbiome composition.
Compositional and functional alterations of the gut microbiota are involved in the pathogenesis of several gastrointestinal diseases. Rifaximin is often used to induce disease remission due to its ...eubiotic effects on the gut microbiota. To investigate the correlation between changes in the gut microbiota composition and symptoms improvement in patients who present a clinical response to rifaximin treatment. Patients with ulcerative colitis (UC), Crohn's disease (CD), irritable bowel syndrome (IBS) and diverticular disease (DD) undergoing rifaximin treatment for clinical indication were enrolled in the study. Rifaximin was administered at the dose of 1,200 mg/day for 10 days. Faecal samples were collected at baseline and at the end of treatment; clinical improvement was assessed by Mayo score for UC, CD Activity Index (CDAI) for CD, IBS severity scoring system (IBS-SSS) for IBS and global symptomatic score (GSS) for DD. Twenty-five patients were included in the analysis and a clinical improvement was recorded for 10/25 (40%) of them. Microbial alpha diversity showed a slight increase in clinical responders (
=0.271), while it decreased in patients who did not improved (
=0.05). A significant post-treatment increase in
abundance was observed in patients with a positive response (log
FC 1.959,
=0.042).
abundance decreased in both groups, whereas
decreased only in patients who clinically improved. Clinical improvement consequent to rifaximin treatment is associated with an increase in
abundance. Achieving a positive shift in the gut microbiota composition seems a key event to obtain a clinical benefit from treatment.
Prevalence and clinical impact of increased liver function tests in patients affected by Coronavirus disease 2019 (COVID-19) is controversial.
This observational study evaluates the prevalence of ...transaminases elevation in hospitalized patients affected by COVID-19 and investigates the presence of factors associated with hepatocellular injury and with mortality.
Data of 292 adult patients with confirmed COVID-19 admitted to the Ente Ospedaliero Cantonale (Switzerland) were retrospectively analyzed.
Transaminases were increased in about one-third of patients on hospital admission and two-thirds of patients during the hospital stay. On hospital admission, transaminases were more commonly elevated in younger patients, who also reported elevated C reactive protein and a higher degree of respiratory failure. Independent factors associated with abnormal transaminases during hospitalization were drugs, in particular paracetamol (OR=2.67; 95% CI=1.38–5.18; p = 0.004) and remdesivir (OR=5.16; 95% CI=1.10–24.26; p = 0.04). Mortality was independently associated to age (OR = 1.09; 95% CI=1.05–1.13; p<0.001), admission to intensive care unit (OR=5.22; 95% CI=2.28–11.90; p<0.001) and alkaline phosphatase peak (OR=1.01; 95% CI=1.00- 1.01; p = 0.01).
On hospital admission, factors associated with liver damage were linked to demographic and clinical characteristics (age, inflammation and hypoxia) while, during hospitalization, drug treatment was related to development and progression of hepatocellular damage. Mortality was associated with alkaline phosphate peak value.
Liver involvement of SARS-CoV-2 infection has been reported in several papers, but without homogeneous findings. We aimed to systematically review the prevalence of liver involvement in patients with ...SARS-CoV-2 infection at their hospital admission, and its correlation with disease severity and clinical outcomes in patients with or without pre-existing chronic liver disease.
We systematically searched PubMed, Embase, Web of Science, Medline, PMC, clinical trial registries, and other Coronavirus family publications for studies reporting data on SARS-CoV-2 infection or COVID-19 and liver function tests (LFTs) alterations, as well as clinical course of patients with chronic liver disease or cirrhosis. Case reports, preprints, editorials, reviews were excluded. We also revised literature to describe the background of liver involvement during SARS-CoV-2 infection.
36 studies, including 20724 patients with SARS-CoV-2 infection, were included. The pooled prevalence of LFTs abnormalities at admission was 46.9% (AST 26.5%, ALT 22.8%, GGT 22.5%, ALP 5.7%, tBIL 8.0%). ALT, AST, tBIL were independent predictors of disease severity (ALT OR 1.54, 95% CI 1.17-2.03; AST OR 3.17, 95% CI 2.10-4.77; tBIL OR 2.32, 95% CI 1.18-4.58) and in-hospital mortality (ALT OR 1.48, 95% CI 1.12-1.96; AST OR 4.39, 95% CI 2.68-7.18; tBIL OR 7.75, 95% CI 2.28-26.40). Heterogeneity among studies was high. The few available data also reported that COVID-19 was associated with increased risk of liver decompensation and mortality in patients with liver cirrhosis.
LFTs alterations were reported in up to 47% of unselected patients with COVID-19 and were associated with severe disease or in-hospital mortality. In cirrhotic patients, COVID-19 was associated with high risk of liver decompensation or mortality.
We report the case of an 84-year-old man with asymptomatic chronic hepatitis C virus (HCV) infection treated with direct antiviral agents. At the end of the antiviral therapy laboratory tests showed ...an abrupt increase in cholestasis parameters and aminotransferases, associated with anti-mitochondria antibodies positivity. Therefore, primary biliary cholangitis (PBC) was diagnosed. The patient was treated with ursodeoxycholic acid achieving a good biochemical response. This is the second case described in literature of PBC onset after HCV eradication with an interferon-free antiviral regimen. In both cases an autoimmune damage of cholangiocytes secondary to the immunological derangement caused by virus clearance may be hypothesized. Indeed, according to the hygiene hypothesis, when two different triggers act simultaneously on the immune system they tend to be mutually inhibitory, and an immune tolerance develops; when one of these triggers disappears (as HCV in this case), the immune system may mount a response against self-antigens, causing autoimmune disorders such as PBC.
Background
Hepatitis B virus (HBV) reactivation is commonly observed in HBsAg-positive hematologic patients undergoing immunosuppressive chemotherapy. Recent guidelines recommend antiviral ...prophylaxis to be continued for up to 12 months after the discontinuation of the anticancer regimen.
Case Presentation
We report a case of a patient who underwent antiviral prophylaxis for 26 months after the discontinuation of a rituximab-containing chemotherapy regimen for a lymphoma and was admitted in the infectious diseases department with a 3-day history of jaundice, itching, and dark urine. After excluding other possible causes of acute liver damage, HBV reactivation was suspected. HBV-DNA was 4497000 IU/mL. Following reintroduction of entecavir, we observed a steady decline of ALT, AST, bilirubin and HBV-DNA serum levels, with a rapid resolution of acute hepatitis and an improvement in clinical conditions; one year after the event of HBV reactivation and beginning of antiviral therapy, the patient was virologically suppressed.
Discussion
Our study demonstrates that the risk of HBV reactivation in HBsAg-positive patients with undetectable HBV-DNA can occur even after three years from the last administration of rituximab and several months after the withdrawal of prophylactic antiviral therapy in patients with hematological malignancies. This implies that a close monitoring of HBV-related markers including HBV-DNA must continue after the withdrawal of prophylactic NA therapy.
Aim
To evaluate the impact of antiplatelet therapy (APT)on the incidence of hepatocellular carcinoma (HCC) and mortality following its treatment.
Methods
A systematic literature search was performed ...using PubMed and Cochrane Central Register of Controlled Trials Databases. Two HCC clinical settings were explored: (i) incidence, and (ii) death after any HCC treatment. Odds ratios (OR) and 95% confidence intervals (95%CI) were calculated to compare the pooled data between patients who received or did not receive APT.
Results
A total of 20 studies were identified, of whom 15 focused on HCC incidence, including 2,685,009 patients, and five on post‐treatment death, including 3281 patients. APT was associated with an overall reduced risk of HCC incidence (OR: 0.63; 95%CI = 0.51–0.79; p < 0.001) as well as of post‐treatment mortality (OR: 0.54; 95%CI = 0.35–0.83; p = 0.006).
Conclusions
Current data suggest that APT correlated with higher HCC incidence and poor overall survival following tumour treatment.
The objective of this study is to find a contrast-enhanced CT-radiomic signature to predict clinical incomplete response in patients affected by hepatocellular carcinoma who underwent locoregional ...treatments.
190 patients affected by hepatocellular carcinoma treated using focal therapies (radiofrequency or microwave ablation) from September 2018 to October 2020 were retrospectively enrolled. Treatment response was evaluated on a per-target-nodule basis on the 6-months follow-up contrast-enhanced CT or MR imaging using the mRECIST criteria. Radiomics analysis was performed using an in-house developed open-source R library. Wilcoxon-Mann-Whitney test was applied for univariate analysis; features with a p-value lower than 0.05 were selected. Pearson correlation was applied to discard highly correlated features (cut-off=0.9). The remaining features were included in a logistic regression model and receiver operating characteristic curves; sensitivity, specificity, positive and negative predictive value were also computed. The model was validated performing 2000 bootstrap resampling.
56 treated lesions from 42 patients were selected. Treatment responses were: complete response for 26 lesions (46.4%), 18 partial responses (32.1%), 10 stable diseases (17.9%), 2 progression diseases (3.6%). Area-Under-Curve value was 0.667 (95% CI: 0.527-0.806); accuracy, sensitivity, specificity, positive and negative predictive values were respectively 0.66, 0.85, 0.50, 0.59 and 0.79.
This contrast-enhanced CT-based model can be helpful to early identify poor responder's hepatocellular carcinoma patients and personalize treatments.
The microbiome plays a crucial role in maintaining the homeostasis of the organism. Recent evidence has provided novel insights for understanding the interaction between the microbiota and the host. ...However, the vast majority of such studies have analyzed the interactions taking place in the intestinal tract. The biliary tree has traditionally been considered sterile under normal conditions. However, the advent of metagenomic techniques has revealed an unexpectedly rich bacterial community in the biliary tract. Associations between specific microbiological patterns and inflammatory biliary diseases and cancer have been recently described. Hence, biliary dysbiosis may be a primary trigger in the pathogenesis of biliary diseases. In particular, recent studies have suggested that microorganisms could play a significant role in the development of gallstones, pathogenesis of autoimmune cholangiopathies and biliary carcinogenesis. Moreover, the intimate connection between the biliary tract, liver and pancreas, could reveal hidden influences on the development of diseases of these organs. Further studies are needed to deepen the comprehension of the influence of the biliary microbiota in human pathology. This knowledge could lead to the formulation of strategies for modulating the biliary microbiota in order to treat and prevent these pathological conditions.
Abstract Hepatitis C virus (HCV) infection is the major indication for liver transplantation worldwide. Its recurrence is virtually universal. Once reinfection is established, progression to ...cirrhosis occurs in 25%–30% of recipients within 5 years. Several studies have attempted to identify the ideal antiviral treatment for liver transplant recipients. At present, the management of recurrent HCV infection in liver transplant recipients is based on widely accepted indications, which represent a reliable guide to identify the “ideal” candidate for therapy, when therapy should be started, and what is to be expected in terms of side effects and response to treatment.
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