Background
Adrenal rest tumor is an ectopic collection of adrenocortical cells in an extra-adrenal site, more frequently located around the kidney, retroperitoneum, spermatic cord, para-testicular ...region and broad ligament, but very rarely occurring also in the liver. Hepatic adrenal rest tumor poses a diagnostic challenge in differentiating it from hepatocellular carcinoma, particularly in a cirrhotic liver.
Case presentation
An 83-years-old male was referred to our hospital by his family doctor for hepatological evaluation due to multifactorial liver cirrhosis. Ultrasound revealed a centimetric hypoechoic nodule in the VI hepatic segment in the context of a liver with signs of cirrhosis and steatosis. The patient first underwent MRI and then CT, which showed a fat containing focal liver lesion in the subcapsular location of the right lobe, strictly adjacent to the homolateral adrenal gland. The nodule was hypervascular in the arterial phase, washed out in the portal-venous and transitional phases, resulting hypointense in the hepato-biliary phase at MR imaging. In the suspicion of a hepatocellular carcinoma, the nodule was surgically removed, and the patient’s postoperative course was unremarkable. The final histopathological diagnosis was of adrenal rest tumor of the liver.
Conclusions
Hepatic adrenal rest tumor is an extremely rare hepatic tumor, often without any clinical manifestation, that can also occur in the cirrhotic liver as in our case. Although there are not specific imaging findings, the possible diagnosis of HART should be considered when we observe a well-defined lesion in the subcapsular location of the right lobe, with fat containing, hypervascularity after contrast medium injection and vascular supply from the right hepatic artery.
Multisystem inflammatory syndrome in children (MIS-C) is a pathologic condition that has emerged during the coronavirus disease 2019 (COVID-19) pandemic. Although the epidemiological evidence of ...association between MIS-C and SARS-CoV-2 infection has been demonstrated, its pathogenic mechanism is still undefined. We describe the case of a 17-year old female, previously vaccinated against SARS-CoV-2, presenting with a history of asthenia, fever, cough, anorexia, abdominal pain, and vomiting. During the hospitalization, the patient developed bilateral conjunctivitis, hand vasculitis, cutaneous rash, and multiple pulmonary nodules, following by hepatitis and pancreatitis. As she reported a high-risk contact with a SARS-CoV-2 positive patient 10 days before admission, the epidemiological link and the clinical picture characterized by multi-system organ disfunction and inflammatory biomarkers increase led us to the diagnosis of MIS-C. Therefore, the patient was treated with intravenous immunoglobulin and corticosteroids, resulting in a rapid resolution of fever, cutaneous, and pulmonary involvement, while the recovery of hepatitis and pancreatitis was observed in the following weeks. This case leads to the discussion on whether SARS-CoV-2 immunized children and adolescents should be considered at risk of developing MIS-C and on their possible presentation with non-classic clinical features. Additionally, due to the increasing number of vaccinated children and adolescents, the issues resulting either from the diagnostic suspect of MIS-C or from the consequent need of an early therapeutic approach are discussed.
Direct-acting antivirals (DAAs) for hepatitis C virus (HCV) may induce hepatitis B virus (HBV) reactivations in co-infected patients, whose dynamics and outcomes could depend on the phase of HBV ...infection. We investigated HBsAg and HBV-DNA kinetics in fifteen untreated HBeAg Negative Infection (ENI) (4F-11M, 62.1y) and eight Nucleos(t)ide Analogs (NAs) treated Chronic Hepatitis B (CHB) (3F-6M, 54.8y) with HCV co-infection, receiving DAAs-regimens including Sofosbuvir (13) or not (10). All achieved a sustained virologic response (SVR) and normalized alanine-aminotransferase (ALT). At the direct acting antivirals’ (DAAs) baseline (BL), the HBV-DNA was undetectable (<6 IU/mL) in eight ENI and all CHB, the mean Log-HBsAg was lower in ENI than CHB (0.88 vs. 2.42, p = 0.035). During DAAs, HBV-DNA increased in untreated ENI by >1 Log in five and became detectable in two. Accordingly, mean BL Log-HBV-DNA (0.89) increased at week-4 (1.78; p = 0.100) and at the end of therapy (1.57; p = 0.104). Mean Log-HBsAg decreased at week-4 in ENI (from 0.88 to 0.55; p = 0.020) and CHB (from 2.42 to 2.15; p = 0.015). After DAAs, the HBsAg returned to pre-treatment levels in CHB, but not in ENI (six cleared HBsAg). Female gender and SOF were associated with a greater HBsAg decline. In conclusion, HBV reactivations during DAAs in HCV co-infected ENI caused moderate increases of HBV-DNA without ALT elevations. The concomitant HBsAg decline, although significant, did not modify individual pre-treatment profiles.
Pretreatment predictors of finite nucleo(s)tide analogue (NUC) therapy remain elusive. We studied the association between pretreatment HBV DNA levels and outcomes after therapy cessation.
Patients ...with chronic hepatitis B who were HBeAg negative at the start of NUC treatment were enrolled from sites in Asia and Europe. We studied the association between pretreatment HBV DNA levels and (1) clinical relapse (defined as HBV DNA >2,000 IU/ml + alanine aminotransferase >2 × the upper limit of normal or retreatment) and (2) HBsAg loss after NUC withdrawal.
We enrolled 757 patients, 88% Asian, 57% treated with entecavir, with a median duration of treatment of 159 (IQR 156–262) weeks. Mean pretreatment HBV DNA levels were 5.70 (SD 1.5) log IU/ml and were low (<20,000 IU/ml) in 150 (20%) and high (>20,000 IU/ml) in 607 (80%). The cumulative risk of clinical relapse at 144 weeks after therapy cessation was 22% among patients with pretreatment HBV DNA levels <20,000 IU/ml vs. 60% among patients with pretreatment HBV DNA levels >20,000 IU/ml, whereas the cumulative probabilities of HBsAg loss were 17.5% vs. 5% (p <0.001). In multivariable analysis, pretreatment HBV DNA levels <20,000 IU/ml were independently associated with a reduced likelihood of clinical relapse (adjusted hazard ratio 0.379, p <0.001) and with an increased chance of HBsAg loss (adjusted hazard ratio 2.872, p <0.001).
Lower pretreatment HBV DNA levels are associated with a lower risk of clinical relapse and a higher chance of HBsAg loss after cessation of NUC therapy, independent of end-of-treatment viral antigen levels. Further studies are needed to confirm these findings in non-Asian populations.
A subgroup of patients with chronic hepatitis B may not require retreatment after stopping antiviral therapy. In this study, comprising 757 patients with chronic hepatitis B from Europe and Asia, we found that higher viral load before initiation of treatment was a risk factor for relapse after stopping treatment. Patients with a low HBV DNA level before starting antiviral therapy had the lowest risk of relapse, and a high chance of HBsAg loss, after stopping treatment. These findings can help select patients for treatment withdrawal and guide intensity of off-treatment monitoring.
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•A subset of patients may achieve sustained remission and even HBsAg loss after cessation of nucleo(s)tide analogue therapy.•Higher pretreatment HBV DNA levels were associated with a higher risk of clinical relapse, and a lower chance of HBsAg loss, after cessation of treatment.•A pretreatment HBV DNA level <20,000 IU/ml was associated with favourable outcomes after cessation of antiviral therapy.•The association between pretreatment HBV DNA levels and off-treatment outcomes was independent of other established predictors, including end-of-treatment HBsAg and HBcrAg levels.
The simulation of the dynamics of viral infections by mathematical equations has been applied successfully to the study of viral infections during antiviral therapy. Standard models applied to viral ...hepatitis describe the viral load decline in the first 2-4 wk of antiviral therapy, but do not adequately simulate the dynamics of viral infection for the following period. The hypothesis of a constant clearance rate of the infected cells provides an unrealistic estimation of the time necessary to reach the control or the clearance of hepatitis B virus （HBV）/ hepatitis C virus （HCV） infection. To overcome the problem, we have developed a new multiphasic model in which the immune system activity is modulated by a negative feedback caused by the infected cells reduction, and alanine aminotransferase kinetics serve as a surrogate marker of infected-cell clearance. By this approach, we can compute the dynamics of infected cells during the whole treatment course, and find a good correlation between the number of infected cells at the end of therapy and the long-term virological response in patients with chronic hepatitis C. The new model successfully describes the HBV infection dynamics far beyond the third month of antiviral therapy under the assumption that the sum of infected and non-infected cells remains roughly constant during therapy, and both target and infected cells concur in the hepatocyte turnover. In clinical practice, these new models will allow the development of simulators of treatment response that will be used as an ＂automatic pilot＂ for tailoring antiviral therapy in chronic hepatitis B as well as chronic hepatitis C patients.
Dendritic cells (DCs) play a key role in immune responses through antigen presentation and cytokine secretion. Hepatitis C virus (HCV) is able to escape elimination by the immune system and often ...establishes a chronic infection. To investigate whether DC dysfunction is involved in this process, we have studied monoycte-derived DCs (Mo-DCs) and plasmacytoid DCs (pDCs), which produce large amounts of IFN-α, from chronic HCV patients and healthy donors.
We have assessed TNF-α and IFN-α production by pDCs using intracellular staining after total PBMCs stimulation with unmethylated CG dinucleotides (CpGs). The induction of allogeneic T cell proliferation by immature Mo-DCs was measured using the MLR assay. The up-regulation of maturation markers and the production of TNF-α in response to LPS were analyzed using flow cytometry and ELISA, respectively.
We have detected comparable frequencies of pDCs producing TNF-α and IFN-α in both chronic HCV patients and healthy donors and we have found that immature Mo-DCs from both patients and donors similarly induce allogeneic T cell proliferation and mature and secrete TNF-α in response to LPS.
Our results demonstrate that both pDC and Mo-DCs are not impaired in HCV infected patients.
Background & Aims The accurate identification of inactive (serum HBV-DNA persistently ≤2000 IU/mL) hepatitis B virus (HBV) carriers (IC) is difficult because of wide and frequent HBV-DNA ...fluctuations. We studied whether hepatitis B surface antigen (HBsAg) serum levels (HBsAgsl) quantification may contribute to diagnosis of HBV phases in untreated hepatitis B e antigen-negative genotype D asymptomatic carriers. Methods HBsAgsl were measured at baseline and end of follow-up and correlated with virologic and biochemical profiles of 209 consecutive carriers followed-up prospectively (median, 29; range, 12–110 months). HBV phases were defined after 1-year monthly monitoring of HBV-DNA and transaminases. Results HBsAgsl were significantly lower in 56 inactive carriers (IC) than 153 active carriers (AC): median, 62.12 (range, 0.1–4068) vs median, 3029 (range, 0.5–82,480) IU/mL; P < .001. Among AC, HBsAgsl were lower in 31 AC whose viremia remained persistently <20,000 IU/mL (AC1) than in 122 AC with fluctuations ≥20,000 IU/mL (AC2): 883 (0.5–7838) vs 4233 (164–82,480) IU/mL, P = .002. HBV infection was less productive in IC and AC1 than AC2 (log10 HBV-DNA/HBsAgsl ratios 0.25 and 0.49 vs 2.06, respectively, P < .001) and in chronic hepatitis than cirrhosis (1.97 vs 2.34, respectively; P = .023). The combined single point quantification of HBsAg (<1000 IU/mL) and HBV-DNA (≤2000 IU/mL) identified IC with 94.3% diagnostic accuracy, 91.1% sensitivity, 95.4% specificity, 87.9% positive predictive value, 96.7% negative predictive value. During follow-up, HBsAgsl were stable in AC but declined in IC (yearly median decline, −0.0120 vs −0.0768 log10 IU/mL, respectively, P < .001), 10 of whom cleared HBsAg. Conclusions HBsAgsl vary during chronic hepatitis B e antigen-negative genotype D infection and are significantly lower in IC. Single-point combined HBsAg and HBV-DNA quantification provides the most accurate identification of IC, comparable with that of long-term tight monitoring.
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