AIM: To assess whether Most Care is able to detect the cardiovascular alterations in response to physiological stress (posture). METHODS: Non invasive hemodynamic was assessed in 26 cirrhotic ...patients compared to healthy subjects, both in the supine and standing positions. RESULTS: In baseline conditions, when compared to healthy subjects, cirrhotic patients showed significantly lower values of dicrotic and diastolic pressures and systemic vascular resistance. While in the standing position, cirrhotic patients showed higher values of cardiac index, stroke volume index and cardiac cycle efficiency. When returning to the supine position, cirrhotic patients exhibited lower values of dicrotic and diastolic pressures and systemic vascular resistance in the presence of higher values of cardiac index, stroke volume index and cardiac cycle efficiency.
Uveitis in autoimmune hepatitis： A case report Romanelli, Roberto Giulio; La Villa, Giorgio; Almerigogna, Fabio ...
World journal of gastroenterology : WJG,
03/2006, Letnik:
12, Številka:
10
Journal Article
Odprti dostop
In this case report we describe for the first time an association between autoimmune hepatitis （AIH） and uveitis, without any doubts about other possible etiologies, such as HCV, since all the old ...reports describe the association of AIH with iridocyclitis before tests for HCV-related hepatitis could be available. A 38-year-old businessman with abnormal liver function tests and hyperemia of the bulbar conjunctiva was admitted to the hospital. Six years before admission, the patient presented with persistent fever, arthralgias, conjunctival hyperemia, leukocytosis and increased ESR, referred to acute rheumatic fever. The presence of systemic diseases, most commonly associated with uveitis, was investigated without results and the patient was then treated with topical corticosteroids. His symptoms resolved. A test for anti-nuclear antibodies was positive, at a titre of 1：320, with a speckled and nucleolar staining pattern. Liver ultrasound showed mild hepatomegaly with an increased echostructure of the liver. Percutaneous liver biopsy was performed under ultrasound assistance. Histological examination showed necroinflammation over the portal, periportal and Iobular areas, fibrotic portal tracts, with periportal fibrosis and occasional portal-to-portal bridgings, but intact hepatic architecture. Some hepatocytes showed barely discernible granules of hemosiderin in the Iobular area. Bile ductules had not any significant morphological alterations. METAVIR score was A2-F3, according to the modified HAI grading/fibrosis staging. The patient was diagnosed to have AIH with mild activity and fibrosis and was discharged on 25 mg prednisone, entering clinical and biochemical remission, further confirming diagnosis. After discharge the patient continued to have treatment with corticosteroids as an outpatient at a dose of 5 mg. On January 2002 the patient was readmitted to the hospital. A test for anti-nuclear antibodies was positive, at a titre of 1：320, with a speckled and nucleolar staining pattern. Anti-smooth muscle antibody test was also positive （1：160）, while anti-LKM antibodies were negative. Ophthalmologic examination revealed inflammatory cells and proteinaceous flare in the anterior chamber of the left eye, and a stromal lesion in the cornea. He was maintained on immunosuppressive therapy （5 mg prednisone plus topical antibiotic therapy for two weeks） and then discharged. A complete remission of the symptoms was registered on follow-up. At present （July 2005）, the patient is on prednisone （5 rag） and has no symptoms. Liver function tests are also within the normal range.
Limited data are available about the efficacy of antiviral treatment in hepatitis C virus (HCV)–associated mixed cryoglobulinemia (MC), especially concerning the long‐term effects of HCV eradication. ...The aim of this study was to evaluate the influence of MC on the virological response and the long‐term effects of viral eradication on MC. We prospectively enrolled 424 HCV+ patients belonging to the following groups: MC syndrome (MCS)‐HCV (121 patients with symptomatic MC), MC‐HCV (132 patients with asymptomatic MC), and HCV (158 patients without MC). Pegylated interferon plus ribavirin treatment was administered according to standard protocols. Posttreatment follow‐up ranged from 35 to 124 months (mean 92.5 months). A significant difference was observed in the rate of sustained virological response between the HCV group and both the MC‐HCV (P = 0.009) and MC‐HCV+MCS‐HCV (P = 0.014) groups. Multivariate logistic regression analysis identified cryoglobulinemia as an independent prognostic factor of nonresponse. The clinical–immunological response in MCS‐HCV correlated with the virological one. All patients with sustained virological response also experienced a sustained clinical response, either complete or partial. In the majority of sustained virological response patients all MCS symptoms persistently disappeared (36 patients, 57%); in only two (3%) did definite MCS persist. All virological nonresponders were also clinical nonresponders, in spite of a transient improvement in some cases. No evolution to lymphoma was observed. For the first time we have evaluated both the effects of interferon‐based therapy on HCV patients with and without MC and with and without symptoms, as well as the long‐term effects of viral eradication on MC. Conclusion: MC is a negative prognostic factor of virological response. Clearance of HCV led to persistent resolution or improvement of MCS, strongly suggesting the need for a next generation of highly effective antiviral drugs. (Hepatology 2015;61:1145‐1153)
Thrombocytopenia is a hallmark for patients with cirrhosis and it is perceived as a risk factor for bleeding events. However, the relationship between platelet count and bleeding is still unclear.
We ...investigated the relationship between platelet count and major or clinical relevant nonmajor bleedings during a follow-up of ∼4 years.
A total of 280 cirrhotic patients with different degrees of liver disease (67% males; age 64±37 years; 47% Child-Pugh B and C) were followed up for a median of 1,129 (interquartile range: 800-1,498) days yielding 953.12 patient-year of observation. The annual rate of any significant bleeding was 5.45%/year (3.57%/year and 1.89%/year for major and minor bleeding, respectively). Fifty-two (18.6%) patients experienced a major (n=34) or minor (n=18) bleeding event, predominantly from gastrointestinal origin. Platelet counts progressively decreased with the worsening of liver disease and were similar in patients with or without major or minor bleeding: a platelet count ≤50 × 10
/μl was detected in 3 (6%) patients with and in 20 (9%) patients without any bleeding event. Conversely, prothrombin time-international normalized ratio was slightly higher in patients with overall or major bleeding. On Cox proportional hazard analysis, only a previous gastrointestinal bleeding (hazard ratio (HR): 1.96; 95% confidence interval: 1.11-3.47; P=0.020) and encephalopathy (HR: 2.05; 95% confidence interval: 1.16-3.62; P=0.013) independently predicted overall bleeding events.
Platelet count does not predict unprovoked major or minor bleeding in cirrhotic patients.
In chronic hepatitis B (CHB) patients, fibrosis assessment during antiviral treatment is a key step in the clinical management. Aim of this study was to evaluate the performance of elastography in ...assessing fibrosis stage in CHB before and after two years of nucleoside/nucleotide analogues (NUC) treatment in comparison with indirect serum markers. CHB diagnosis was made according to standard criteria. A clinical and virological evaluation was performed at baseline and again at 3, 6, 9, 12 18, and 24 months during treatment. Fibrosis was evaluated by liver biopsy, elastography and indirect serum markers. Of 75 patients, 50 had CHB, HBeAg negative and were deemed eligible for this study. Of these, 22 underwent liver biopsy. Mean histo-morphometric values of fibrotic tissue differed significantly in the stage < S3 vs. stage ≥S3: 2.01±2.62% vs. 12.85±7.31% (p=0.03), respectively. At 18 and 24 months, stiffness values were statistically reduced from those previously observed (P=0.03 and P<0.001). At 24 months the values of APRI, FIB-4 and LOK were not different from baseline values, while the value of FORNS score at 24 months was the only one statistically reduced. In two patients with fibrosis stage S3 and S6, respectively, fibrosis regressed to stage S2 and S5. In conclusion, the results of the present study show that liver histology, stiffness and FORNS score improve significantly during a long-term follow-up of HBV patients successfully treated with NUC. These results strongly suggest that the non-invasive evaluation of liver fibrosis represents a key step in the management and treatment of chronic HBV hepatitis.
Thrombopoietin (TPO), a cytokine that participates in the differentiation and maturation of megakaryocytes, is produced in the liver, but only limited information is available on the biological ...response of liver-derived cells to TPO. In this study, we investigated whether HepG2 cells express c-Mpl, the receptor for TPO, and whether TPO elicits biological responses and intracellular signaling in this cell type. Specific transcripts for c-Mpl were detected in HepG2 cells by RT-PCR, and expression of the protein was demonstrated by Western blot analysis and immunofluorescence. Exposure of HepG2 cells to TPO was associated with a dose-dependent increase in cell migration and chemoinvasion through Matrigel-coated filters. A checkerboard analysis showed that the effects of TPO on cell migration were dependent on both chemotaxis and chemokinesis. Exposure of HepG2 cells to TPO resulted in the activation of different members of the MAPK family, including ERK and JNK, as assessed using phosphorylation-specific antibodies and immune complex kinase assays. TPO also activated phosphatidylinositol 3-kinase (PI3K) and the downstream kinase Akt in a time-dependent manner. Finally, activation of c-Mpl was associated with increased activation of nuclear factor-kappaB. With the use of specific inhibitors, tyrosine phosphorylation and activation of PI3K were found to be required for the induction of migration in response to TPO. We conclude that TPO exerts biological actions on cultured hepatoblastoma cells via activation of c-Mpl and its downstream signaling.
Hepatitis C virus (HCV) infection is a global health problem, being the second most common chronic viral infection in the world with a global prevalence of about 3% (about 180 million people). HCV is ...both an hepatotropic and a lymphotropic virus; and chronic infection could cause, on one hand, chronic hepatitis, cirrhosis and hepatocellular carcinoma and on the other hand several extrahepatic diseases including, first, mixed cryoglobulinemia and lymphoma.
The association between hepatic (hepatocellular carcinoma) and extrahepatic (lymphoma, thyroid cancer) malignancies has justified the inclusion of HCV among human cancer viruses.
The pathogenesis of HCV-related sequelae (hepatic or extrahepatic) is not fully understood representing a challenge of prime importance in light of the optimization of clinico-therapeutic management of these patients. Combined treatment with pegylated interferon plus ribavirin is presently the first-line, gold standard treatment of most HCV-related diseases. However, mainly in the case of extrahepatic manifestations, a cautious approach to the patient, with a case to case accurate tailoring of therapy is frequently requested.
The present review will outline the principal aspects of such HCV-induced systemic disease focusing on extrahepatic manifestations.
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