It is unclear whether the current antiviral treatment for chronic hepatitis C virus (HCV) infection results in complete elimination of the virus, or whether small quantities of virus persist. Our study group comprised 17 patients with chronic HCV who had sustained virological response (SVR) after interferon/ribavirin treatment. Serum and peripheral blood mononuclear cells were collected 2 to 3 times at 3-to 6-month intervals starting 40 to 109 months (mean, 64.2 ؎ 18.5 months) after the end of therapy. In addition, lymphocyte and macrophage cultures were established at each point. In 11 patients, frozen liver tissue samples were available from follow-up biopsies performed 41 to 98 months (mean, 63.6 ؎ 16.7 months) after therapy. Presence of HCV RNA was determined by sensitive reversetranscriptase polymerase chain reaction, and concentration of positive and negative strands was determined by a novel quantitative real-time reverse transcriptase polymerase chain reaction. Only 2 of 17 patients remained consistently HCV RNA negative in all analyzed compartments. HCV RNA was detected in macrophages from 11 patients (65%) and in lymphocytes from 7 patients (41%). Viral sequences were also detected in 3 of 11 livers and in sera from 4 patients. Viral replicative forms were found in lymphocytes from 2 and in macrophages from 4 patients. In conclusion, our results suggest that in patients with SVR after therapy, small quantities of HCV RNA may persist in liver or macrophages and lymphocytes for up to 9 years. This continuous viral presence could result in persistence of humoral and cellular immunity for many years after therapy and could present a potential risk for infection reactivation. (HEPATOLOGY 2005;41:106 -114.)

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It is unclear whether patients who test positive for anti-hepatitis C virus (HCV) antibodies and have normal alanine aminotransferase (ALT) levels remain infected with the virus. Eleven patients who tested positive for anti-HCV antibodies, had persistently normal ALT levels, and tested negative for HCV RNA by commercial test were studied. Serum and peripheral blood mononuclear cells (PBMCs) were collected 2-3 times at 3-6-month intervals, and PBMCs were cultured with phytohemagglutinin and pokeweed mitogen. HCV RNA was detected in serum samples from 6 (55%) and in PBMCs from 11 (100%) patients. Our results suggest that, in asymptomatic patients who test positive for anti-HCV antibodies, small quantities of HCV RNA commonly persist, even in patients who test negative for HCV RNA in serum by commercial tests.

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BackgroundAlthough hepatitis C virus (HCV) is primarily hepatotropic, markers of HCV replication were detected in peripheral blood mononuclear cells (PBMC) as well as in ex vivo collected tissues and organs. Specific strains of HCV were found to be capable to infect cells of the immune system: T and B cells and monocytes/macrophages as well as cell lines in vitro. The direct invasion of cells of the immune system by the virus may be responsible for extrahepatic consequences of HCV infection: cryoglobulinemia and non-Hodgkin’s lymphoma.The aim of the present study was to determine the prevalence of markers of HCV infection: negative strand HCV RNA and non-structural NS3 protein in PBMC subpopulations: CD3+, CD14+ and CD19+. The presence of virus and the proportion of affected cells within a particular PBMC fraction could indicate a principal target cell susceptible for HCV.MethodsPBMC samples were collected from 26 treatment-free patients chronically infected with HCV. PBMC subpopulations: CD3+, CD14+, CD19+ were obtained using positive magnetic separation. The presence of negative strand RNA HCV and viral NS3 protein were analyzed by strand-specific RT-PCR and NS3 immunocytochemistry staining.ResultsNegative strand HCV RNA was detectable in 7/26 (27%), whereas NS3 protein in 15/26 (57.6%) of PBMC samples. At least one replication marker was found in 13/26 (50%) of CD3+ cells then in 8/26 (30.8%) of CD14+ and CD19+ cells. The highest percentage of cells harboring viral markers in single specimen was also observed in CD3+ (2.4%), then in CD19+ (1.2%), and much lower in CD14+ (0.4%) cells.ConclusionsOur results indicate that CD3+ cells are a dominant site for extrahepatic HCV replication, although other PBMC subpopulations may also support virus replication.

Objectives Ascites and spontaneous bacterial peritonitis (SBP) are among the most important complications of decompensated liver cirrhosis. In clinical practice, new inflammation biomarkers are needed for the early diagnosis of SBP, as well-known biomarkers, such as C-reactive protein (CRP), procalcitonin (PCT), or peripheral blood white blood cell (WBC) count, lack the required specificity and sensitivity. The aim of the study was to evaluate the significance of heparin-binding protein (HBP) in comparison to CRP, PCT, WBC, and D-dimers in the diagnosis of SBP. Design Cross-sectional descriptive single-center study. Setting Department of Infectious and Tropical Diseases and Hepatology, Medical University of Warsaw, Poland. Patients All patients admitted to the aforementioned department with decompensated liver cirrhosis and ascites between February 1, 2016, and June 30, 2017. Intervention Several markers (HBP, CRP, PCT, WBC, and D-dimers) were analysed in blood serum in regard to their potential use in the diagnosis of SBP in patients with decompensated liver cirrhosis and ascites. We correlated the levels of the aforementioned markers with an ascitic fluid polymorphonuclear count using simple linear regression and multiple linear regression. Sensitivities, specificities, and positive and negative predictive values for SBP were calculated for the aforementioned makers of inflammation. Measurements and Main Results A total of 63 patients with decompensated liver cirrhosis and ascites participated in the study. The etiology of liver cirrhosis was varied (HCV: n = 40, HBV: n = 13, HCV/HBV: n = 4, AIH: n = 3, PBC: n = 2, and haemochromatosis: n = 1). After the peritoneal tap, 31 patients were determined to have SBP (defined as an ascitic fluid polymorphonuclear count > 250 cells/μL) and 32 patients had no evidence of SBP on peritoneal tap. A very weak, but statistically significant, correlation of HBP, WBC, and D-dimer levels with the peritoneal fluid polymorphonuclear (PMN) count was observed in the simple regression model, but multivariable analysis using the multiple regression model showed that only D-dimers correlated with peritoneal fluid PMNs independently from other inflammation biomarkers. A D-dimer cutoff value of 1500 ng/mL was determined optimal for ruling out SBP due to high sensitivity (96.8%) and a high negative predictive value (92.9%), although predictably, this marker was not useful for confirming SBP due to low specificity (40.6%) and a low positive predictive value (61.2%). The usefulness of D-dimers was limited by the fact that only 22.2% of the studied patients had D-dimer levels below 1500 ng/mL. HBP and WBC showed little to no predictive value in this study. Conclusions D-dimers < 1500 ng/mL make the diagnosis of SBP unlikely, although the peritoneal tap is still the reference method in such situations. In the studied group, the determination of HBP was of no diagnostic benefit in the diagnosis of SBP.

IntroductionLiver biopsy is a well-known method for the diagnosis and evaluation of chronic diffuse liver diseases, especially among patients with “hepatopathy of unknown origin”.Material and methodsIn the years 2014–2015 we performed 259 liver biopsies in 28 patients (22 females, 6 males, aged 18–65 years, mean: 45 years) with an initial diagnosis of “hepatopathy of unknown origin”. The liver biopsies of these 28 patients were revised by two independent pathologists.ResultsHistopathological features of autoimmune conditions were found in 11 cases, steatohepatitis with/without Mallory bodies in 7, simple steatosis without inflammation in 2 cases. In the other 8 cases the histopathological features were non-specific but pointed to vanishing bile duct syndrome, hemochromatosis, acute inflammation or fibrosis without inflammation. Surprisingly, only mild fibrosis without inflammatory infiltrates was present in one patient with a high titer of antinuclear antibodies (ANA > 1 : 3200). Mild cholestasis with bilirubinostasis was found in 4 cases. One patient had prominent lobular iron deposits and is now under observation for hemochromatosis. Vanishing bile duct syndrome as ductopenia without any signs of inflammation was found in one patient with suspicion of primary biliary cirrhosis. In one liver biopsy specimen we found normal liver architecture without inflammation or steatosis in a patient with elevated ALT and GGT, negative for viral antibodies and autoantibodies.ConclusionsLiver biopsy – despite the increasing access to new, non-invasive methods – remains a useful method in the differential diagnosis of liver diseases.