Chronic hepatitis

Helicobacter hepaticus causes hepatitis in susceptible strains of mice. Previous studies indicated that A/JCr mice are susceptible and C57BL/6NCr mice are resistant to H. hepaticus -induced hepatitis. We used F1 hybrid mice derived from A/J and C57BL/6 matings to investigate their phenotype and determine their hepatic gene expression profile in response to H. hepaticus infection. F1 hybrid mice, as well as parental A/J and C57BL/6 mice, were divided equally into control and H. hepaticus -infected groups and euthanized at 18 months postinoculation. Hepatic lesions were evaluated histologically and the differential hepatic gene expression in F1 mice was determined by microarray-based global gene expression profiling analysis. H. hepaticus -infected parental strains including A/J and C57BL/6 mice, as well as F1 mice, developed significant hepatitis. Overall, hepatocellular carcinomas or dysplastic liver lesions were observed in 69% of H. hepaticus -infected F1 male mice and H. hepaticu...

This investigation delineates an exhaustive analysis of the clinical, immunological, and genomic landscapes of hepatitis B virus (HBV) infection across a cohort of 22 verified patients. The demographic analysis unveiled a pronounced male bias (77.27%), with patient ages spanning 20 to 85 years and durations of illness ranging from 10 days to 4 years. Predominant clinical manifestations included fever, fatigue, anorexia, abdominal discomfort, and arthralgia, alongside observed co-morbidities such as chronic renal disorders and hepatocellular carcinoma. Antigenic profiling of the HBV envelope proteins elucidated significant heterogeneity among the infected subjects, particularly highlighted by discordances in the detection capabilities of small and large HBsAg assays, suggesting antigenic diversity. Quantitative assessment of viral loads unveiled a broad spectrum, accompanied by atypical HBeAg reactivity patterns, challenging the reliability of existing serological markers. Correlative studies between viral burden and antigenicity of the envelope proteins unearthed phenomena indicative of diagnostic evasion. Notably, samples demonstrating robust viral replication were paradoxically undetectable by the large HBsAg ELISA kit, advocating for more sophisticated diagnostic methodologies. Genotypic examination of three HBV isolates classified them as genotype D (D2), with phylogenetic alignment to strains from various global origins. Mutational profiling identified pivotal mutations within the basic core promoter and preS2/S1 regions, associated with an augmented risk of hepatocellular carcinoma. Further, mutations discerned in the small HBsAg and RT/overlap regions were recognized as contributors to vaccine and/or diagnostic escape mechanisms. In summation, this scholarly discourse elucidates the intricate interplay of clinical presentations, antigenic diversity, and genomic attributes in HBV infection, accentuating the imperative for ongoing investigative endeavors to refine diagnostic and therapeutic modalities.

Background Patients with bleeding disorders are frequently infected with hepatitis C virus (HCV). There are few reports on the effect of standard interferon in these patients and no published report on pegylated interferon. The aim of this study was to compare pegylated interferon alpha-2a and standard interferon alpha with ribavirin in patients with bleeding disorders and chronic HCV infection. Materials and Methods Consecutive patients referring to a specialized clinic in Tehran were included in the study. The first 37 patients received pegylated interferon (PEGASYS, Hoffmann-La Roche Inc., Basel, Switzerland), 180 µg weekly and the next 38 patients received standard interferon, 3 million units 3 times a week. Both groups also received ribavirin 800 mg daily. Patients were treated for 48 weeks and were followed for 24 weeks. Liver biopsy was not performed due to the potential risks involved in patients with bleeding disorders. Results 34 patients in each group completed the study. The intention-to-treat sustained viral response was 34% and 62% in the standard interferon and pegylated interferon group, respectively (p=0.02). Conclusions Pegylated interferon alpha-2a and ribavirin is almost twice as effective as standard interferon and ribavirin in treating HCV infection in patients with bleeding disorders and is an acceptable treatment option even when histologic data is not available.

Objective: Hepatitis B is an important infectious disease, which can cause severe chronic cirrhosis and hepatocellular carcinoma in 1-5 % of adult patients. Whereas, Hepatitis D is a defective virus infection that develops in people with HBsAg (+). It has been known that Hepatitis D virus has a cytopathic effect but the immune mechanisms which play a role in the development of this disease are still under investigation. Therefore, in this study it was aimed to investigate whether lymphocytes numbers change in a variety of patients with chronic hepatitis. Methods: In this study, 22 patients (12 females and 10 males) with chronic liver diseases were examined. These patients were compared to the control group which consists of 20 healthy individuals (12 females, 8 males). A flow cytometry assay was conducted to examine T lymphocyte subgroups using CD3, CD4, CD8, CD25, CD56, CD161 and Vα24 monoclonal antibodies in peripheral blood samples of both patient and control groups.

Background Hepatitis C virus (HCV) infection is still common in patients with chronic renal failure, even those on maintenance dialysis. A bidirectional association exists between HCV infection and chronic renal disease. Objective To assess the efficacy of sofosbuvir and velpatasvir combination in the treatment of chronic HCV in chronic kidney disease (CKD) patients. Methodology This descriptive, cross-sectional study was undertaken at the departments of Gastroenterology and Nephrology Lady Reading Hospital, Peshawar, from April 7, 2021, to October 7, 2021. Patients with chronic HCV and chronic renal disease at stage 4 or 5 were included while patients with decompensated cirrhosis liver, hepatoma, hepatitis B virus/HCV (HBV/HCV) coinfection, and post liver transplant patients were excluded. HCV infection was diagnosed based on detectable HCV ribonucleic acid (HCV RNA) by PCR (polymerase chain reaction). In contrast, CKD was diagnosed based on the Kidney Disease Improving Global Outcomes (KDIGO) criteria for CKD. Sofosbuvir 400 mg orally daily and velpatasvir 100 mg orally with meals were given daily for 12 weeks. Effectiveness was defined as negative HCV RNA by PCR 12 weeks after treatment completion called sustained virological response rate 12 weeks after treatment completion (SVR12). Results A total of 73 patients including 67 (91.78%) males and six (8.22%) females between the ages of 20 years and 70 years were included in this study. The mean age of the participants was 48.77±8.0 years. Twelve weeks after the treatment completion, 69 (94.52%) had negative HCV RNA, whereas four (5.48%) patients had detectable HCV RNA. Conclusion It can be concluded from our study that a fixed-dose combination of sofosbuvir 400 mg and velpatasvir 100 mg is quite effective and recommended for treating chronic hepatitis C infection in patients with chronic renal disease in our local setup.

Introduction: Adipocytokines are cytokines secreted primarily by adipose tissue and are soluble mediators derived from adipocytes (fat cells) that play an important role in the interaction between adipose tissue, inflammation, immunity, adipose tissue physiology and metabolism. Alterations in the adipocytokine pattern are involved in different obesity-related diseases and progression of hepatic fibrosis. This progression of hepatic fibrosis frequently happens in the chronic hepatitis B (CHB) and chronic hepatitis C (CHC) patients, apart from non-alcoholic steato hepatitis (NASH). Objectives: To study the prevalence of steatosis, adipocytokines levels, and its relationship with biochemical, metabolic, and histological parameters in patients with CHB and CHC. Patients and Methods: Well-characterized patients of CHB (n = 114) and CHC (n = 63) were included in the study. ELISA for adiponectin (n = 116), leptin (n = 132), resistin (n = 130), TNF-alpha (n = 153) and IL-6 (n = 101) was randomly performed in these patients. Results: Presence of steatosis and fibrosis scores was significantly higher in CHC than CHB patients. Majority of CHC patients (70%) were of genotype 3. In CHC patients, the fibrosis stage was higher with increased steatosis. Patients with CHC and CHB showed increased serum leptin (p = 0.029), TNF-alpha (p = 0.003) with higher HCV RNA and HBV DNA respectively. In CHC patients, there was a significant association between following parameters-higher serum resistin with raised steatosis > 10% (p = 0.01) and raised ALT (p = 0.002). Higher IL-6 with raised serum alkaline phosphates (SAP) (p = 0.001) and higher fibrosis (fib = 3-6) (p = 0.004). Higher serum adiponectin with raised triglycerides (TG) (p = 0.004). Higher serum leptin with higher fibrosis (fib = 3-6) (p = 0.005). In CHB patient's higher serum leptin have significant association with higher fibrosis (fib = 3-6) (p = 0.005). Conclusion: Steatosis is seen in CHB and CHC and it correlates with increased hepatic fibrosis. The altered adipocytokine levels influence progression of fibrosis in chronic hepatitis patients with viral etiology.

Hepatitis C virus (HCV) is an enveloped positive-strand RNA virus of the genus hepacivirus in the family of Flaviviridae. HCV causes chronic infection in more than 80% of cases. It is responsible for more than 50% of liver transplantation among adults in the developed countries. Approximately 200 million people are infected with HCV entire of the world. Africa and many parts of Asia are the major endemic areas for HCV infection. Although HCV is one of the most common cause of chronic liver disease in middle-east, its epidemiology remains unclear around the Lake Van region. Therefore, we assessed the prevalence of HCV infection in individuals who live in rural areas of eastern part of Turkey. We retrospectively analyzed 1062 (405 male, 657 female) patients who admitted to Gastroenterology clinic of Yuzuncu Yil University Faculty of Medicine between January -October in 2011. Patients with prior HCV infection and with acute HCV infection were excluded. Presence of HCV infection was ass...

Objective: The etiology of bronchopulmonary dysplasia (BPD) which is the most important unwanted consequence of premature delivery at long term has not been determined clearly yet.. Insulin-like growth factor-1 (IGF-1) is involved in both prenatal and postnatal lung growth. Our aim is to characterize postnatal changes in serum IGF-1 in relation to development of BPD in preterms. Method: Sixty-seven preterm newborns were evaluated prospectively in order to investigate independent risk factors associated with BPD and to determine the relation between serum IGF-1 levels and BPD. Infants included in the study were divided into two groups as those that developed (Group 1; n=12) and did not develop BPD (Group 2; n=55). Serum IGF-1 levels were measured from venous blood samples of each infant on days 1, 7, 14 and 28 after birth. Results: When the variables showing significant differences in the comparisons between the two groups were evaluated in different logistic regression models, according to the most significant model; presence of chorioamnionitis did not contribute significantly to the development of BPD. It was found that 1 week increase in gestational week reduced the risk of BPD formation by half, while the presence of RDS or sepsis increased the risk of development of BPD by 14.4, and 9.6 times, respectively. ROC analysis with serial measurements of IGF-1 showed that IGF-1 was not a determinant of BPD development. Conclusion: We could not find any relation between development of BPD and serum IGF-1 levels in our study and concluded that the smaller number of newborn who developed BPD could have limited the evaluation of this association.

Objective: Decreased serum insulin-like growth factor-1 (IGF-1) and insulin like growth factor binding protein-3 (IGFBP-3) levels have been found in patients with chronic liver disease of different etiologies, but these factors have not been studied extensively in patients with hepatitis B virus (HBV)-induced chronic liver disease.Methods: We have investigated serum IGF-1 and IGFBP-3 levels in 40 patients with chronic HBV and 40 patients with HBV-induced cirrhosis. According to Child-Pugh classification cirrhotic patients were divided into three groups. Forty age-and sex-matched healthy subjects served as controls. IGF-1 and IGFBP-3 levels were measured by immunochemiluminescence. The results were compared with those for serum albumin, total bilirubin, transaminase activity, and with prothrombin time.Results: IGF-1 and IGFBP-3 levels were significantly lower in patients with cirrhosis than in those with chronic HBV and in controls (p<0.001). In chronic HBV patients, IGFBP-3 level...

Background: Many noninvasive methods, including amino transaminase (AST)/amino transaminase (ALT) ratio (AAR), AST-to-platelet ratio index (APRI), Bonacini cirrhosis discriminant score (CDS), fibrosis-4 (FIB4) index, and age-platelet index (API), have been described to determine the stage of hepatic fibrosis. However, these methods are developed for patients with chronic hepatitis C (CHC) and produce conflicting results in the prediction of liver fibrosis in patients with chronic hepatitis B (CHB). Objectives: The aim of this study was to evaluate the relationship between 7 noninvasive models, including AAR, APRI, CDS, API, FIB-4, neutrophil-to-lymphocyte ratio (NLR), and red cell distribution width (RDW)-to-platelet ratio (RPR) in patients with CHB. Methods: The study population included all patients with CHB, undergoing liver biopsy to determine HBsAg and HBV DNA positivity in more than 6 months. Results: A total of 2520 treatment-naive CHB patients from 40 different centers were included in the study. In total, 62.6% of the patients were male, and the mean age was 40.60 ± 12.34 years (minimum, 18 years; maximum, 77 years). The Ishak fibrosis score was ≥ 3 in 29.8% of the patients, indicating significant fibrosis. The mean API, APRI, CDS, NLR, FIB4, and RPR scores in the noninvasive models were significantly different between the groups with significant and low fibrosis (P < 0.05). All the noninvasive models (API, APRI, AAR, CDS, NLR, RPR, and FIB4) were found to be significant in the discrimination of cirrhosis (P < 0.05). In the multiple logistic regression analysis, CDS, albumin, alkaline phosphatase (ALP), total bilirubin, neutrophil count, NLR, mean platelet volume (MPV), and FIB4 were independent indices for cirrhosis. Conclusions: In the present study, the role of noninvasive tests in the prediction of liver fibrosis stage and cirrhosis was evaluated in a large cohort of CHB patients. Overall, noninvasive models are gradually becoming more promising. Accordingly, the need for liver biopsy can be reduced with a combination of noninvasive methods in the future.

The infection of Viral Hepatitis D (HDV) is life-threatening due to the chronically infected hepatitis B virus carriers which lead to the sudden acute hepatitis or severe chronic active hepatitis. Thus, an active surveillance of these patients with HDV co-infection is an important step to reduce the risk of hepatitis clinical complications. At present, we aimed to update the Moroccan sero-prevalence for HDV in these individuals and determine the status of hepatitis in chronic HBV carriers. Methods: A one year follow-up was performed for 280 chronic HBV carriers and all patients were youngadults and adults. The anti-HDV antibodies (Total IgG and IgM Abs), while HBeAg and anti-HBe antibodies were additionally assessed by DiaSorin. The HBV-DNA levels were measured by Cobas Ampliprep Cobas TaqMan 48: KIT CAPA-G/CTM HBV V2.0 72 TESTS CE-IVC. The HDV-RNA detection and/or viral load quantification were performed in France in Avicenne laboratory of virology, as it has been described by Lunel-Fabiani. Results: Only 2 (0.8%) individuals among chronic HBV infected individuals had been in contact with hepatitis D virus and have anti-HDV antibodies and both were HDV-RNA negative while 278 (99.2%) had a negative serology anti-HDV antibodies. 98% of chronic HBV individuals were HBeAg-negative with very low DNA HBV levels and five patients had "isolated anti-HBc" profile carriers with low DNA HBV levels. Two patients with a positive HBeAg had elevated ALT with higher HBV DNA loads. Conclusion: A low prevalence of HDV in Moroccan chronic HBV carriers was demonstrated by this study, while 35% of patients with negative HBeAg were established as inactive carriers.

Background/Aims: Host factors that may influence progression of hepatitis C infection to chronic hepatitis include T-cell responses and iron accumulation. We evaluated the hepatic expression of immunological markers relevant for a cytotoxic response in relation to viral and HFE genotype. Methods: Frozen liver biopsies were obtained at diagnosis from 28 HFE genotyped patients. Sections stained for CD8, MHC-I, b 2 m, HFE and CD68 were analyzed blind by morphometry. Response to therapy was available in 12 cases. Results: A negative correlation was found between the number of CD8 1 cells and fibrosis. CD8 1 cells localized as clusters in portal tracts and sinusoids and were seen interacting with MHC-I positive lining cells. MHC-I and b 2 m were expressed mainly in the endothelial and Kupffer cells. HFE was expressed in most, but not all, round and dendritic CD68 1 cells. Patients with virus genotype 3a had higher hepatic MHC-I and HFE expression, and a better-sustained response to IFN therapy than other patients. Conclusions: In chronic hepatitis C virus infection MHC-I expression in the liver seems to relate to viral-genotype. In addition, the expression of MHC-I molecules by Kupffer cells places them as probable important players in the host response to HCV.

There is a paucity of information on Chronic Hepatitis C (CHC) patients treated with direct antiviral agents (DAA) in Asia. We invited Asia-Pacific physicians to collate databases of patients enrolled for CHC treatment, recording baseline clinical, virological and biochemical characteristics, sustained virological response at week 12 (SVR12), and virologic failure. SVR12 outcome was based on intention-to-treat (ITT). Multivariate analysis was used to assess independent risk factors for SVR12 using SPSS version 20. 2171 patients from India (n=977), Myanmar (n=552), Pakistan (n=406), Thailand (n=139), Singapore (n=72) and Malaysia (n=25) were collected. At baseline, mean age was 49years, 50.2% were males and 41.8% had cirrhosis. Overall SVR12 was 89.5% and by genotype (GT) based on ITT and treatment completion respectively, was 91% and 92% for GT1, 100% and 100% GT2, 91% and 97% GT3, 64% and 95% GT4, 87% and 87% GT6, and 79% and 91% in GT untested. Patients with cirrhosis had SVR12 of...

The aim of this study was to investigate the factors contributing to health-related quality of life (HRQOL) among patients with chronic hepatitis B (CHB). Methods: A cross-sectional, descriptive design was used. The sample included 114 patients in a gastroenterology outpatient department at one hospital located in G city. Data were collected using a structured questionnaire from June to December 2009. The collected data were analyzed using SPSS/WIN 15.0. Results: Health-related quality of life was most strongly related to age, sex, income, occupation, and the care provider. Old age, female gender, lower income, not having an occupation and having a non-medical person were associated with lower HRQOL (R 2 =.03~.22, p=.041~<.001). Conclusion: CHB infection had a negative impact on HRQOL among the older, female gender, low socioeconomic status and not having medically knowledgeable care givers. Interventions beyond nursing care may be needed to improve the quality of health for patients with Chronic Hepatitis B.

Background: Loss of hepatitis B surface antigen (HBsAg) in chronic hepatitis B (CHB) infection is a favorable outcome. Type I interferon (IFNI) has an essential role to fight virus infections when they bind to the IFN-α/β receptor (IFNAR). Free-circulating IFNARs, known as IFNAR2, perform as carrier proteins to keep the ligands from proteolysis as well as antagonists for ligand binding. Objectives: In this study, we evaluated the HBsAg titer and IFNAR2 in serum baseline of a subcohort of Iranian HBeAg-negative patients with chronic hepatitis B. Methods: Sixty-four patients who spontaneously cleared HBsAg and 100 chronic hepatitis B patients enrolled in this study for assessment of the serum levels of HBsAg and IFNAR2. Results: Serum levels of HBsAg and IFNAR2 were both powerfully associated with loss of HBsAg. The baseline HBsAg titer was significantly lower (333.72 ± 1300 IU/mL vs 3811 ± 6779 IU/mL, P = 0.00) and the IFNAR2 serum level was significantly higher (1.64 ± 0.6 vs 0.87 ± 0.5 ng/mL, P = 0.00) in those who cleared HBsAg compared to the CHB patients. Conclusions: These findings indicated the association of the HBsAg titer and serum IFNAR2 in HBsAg clearance in hepatitis B virusinfected patients. In consequence, immune mechanisms related to IFN-α/β signaling might be responsible in CHB outcome.

Objectives: If not treated early, morbidity and mortality will remain high in hepatitis B virus infection. In this study, it was aimed to analyze the liver biopsy results of patients with chronic hepatitis B with normal alanine aminotransferase (ALT) levels. Materials and Methods: The study was conducted retrospectively. The patients who were admitted in the infectious diseases and clinical microbiology outpatient clinic, had liver biopsy and received treatment between 01.09.2019 and 01.12.2019, were included. Results: A total of 169 patients were included in the study. Of the individuals, 95 (56.2%) were female, with a mean age of 42.4±11.15 years. The rates of having an histological activity index (HAI) score of 6/18 and above and a fibrosis stage of 2/6 or more (90%, 100%, respectively) in patients with ALT level above upper limit of normal (ULN) were higher than in patients with ALT level belowULN (63.6% and 79.1%, respectively) (p=0.001 and p=0.002, respectively). When 129 patients with ALT level below ULN were evaluated in subgroup analyses. HAI score was 6 or higher in 59 (58.4%) of the hepatitis B e antigen (HBeAg) negative patients, and fibrosis stage was 2 or higher in 76 (75.2%) patients. In patients with ALT below ULN and HBeAg positivity, the rates of HAI score of 6 and above and fibrosis stage of 2 and above were found to be statistically significantly higher than in HBeAg negative patients. Conclusion: Liver fibrosis and necroinflammation may develop in patients with normal ALT levels. In making the biopsy decision, ALT level should be considered together with other factors that may affect liver damage.

Anemia associated with ribavirin (RBV) and interferon therapy in patients with chronic viral hepatitis C is a hemolytic, multifactorial adverse effect, in direct correlation with the RBV dose. Additionally, the anemic syndrome is worsened by the interferon-induced bone marrow suppression of erythroid precursors. The resulting anemia is associated with low production of erythropoietin, similar to anemia seen in HIV-infected patients or in those with cancer. Our study was performed on a group of 28 patients with viral hepatitis C treated with 3 MU interferon alfa 3 times a week and RBV 1000-1200 mg/day for 12 months. A normochromic normocytic anemia was observed, requiring a reduction of the RBV dose to 600 mg/day if the hemoglobin was below 10 g/dL and interrupted if the hemoglobin level was below 8.5 g/dL. In this case, reversibility can occur within a time interval of 4-8 weeks after discontinuation of treatment.

Background: The potential benefit of pre-transplant treatment of chronic hepatitis C on long-term evolution after renal transplantation is not clear. Methods: Fifty successive renal transplant candidates had their sera positive for HCV RNA and a biopsy-proven chronic hepatitis. Out of these, 18 patients received a standard course of interferon-α2b (IFN; 3 MU three times weekly after hemodialysis sessions for 6 months). Results: IFN was discontinued in 2 patients (11%) due to persistent leukopenia. HCV RNA turned negative in 10 patients of the treatment group and in none of the control group. Two patients of the IFN group had a virological relapse post-transplantation. Post-transplant follow-up periods were 41.5 ± 15 and 50 ± 16 months for the treated and control groups respectively. Transaminases remained normal in all patients of the IFN group after transplantation. In contrast, biochemical evidence of acute and chronic hepatitis was observed in 5 (p = 0.03) and 13 (p = 0.002) pati...

Hepatitis C virus (HCV) infection is associated with hepatic and extrahepatic manifestations, including immunological disorders. Chronic Hepatitis C (CHC) is often characterized by cholesterol and lipid metabolism alterations, leading to hepatic steatosis. Cholesterol metabolism, in fact, is crucial for the viral life cycle. Recent works described that a higher dietary cholesterol intake is associated with the progression of HCV-related liver disease. CHC patients have increased levels of T helper 17 (Th17)-cells, a lymphocytic population involved in the pathogenesis of liver inflammation and autoimmune hepatitis. The balance between Th17 and regulatory T (Treg) cells is crucial for chronic inflammation and autoimmunity. Th17cell differentiation is deeply influenced by the activation LXRs, nuclear receptors modulating cholesterol homeostasis. Moreover, HCV may affect these nuclear receptors, and cholesterol metabolism, through both direct and indirect mechanisms. On these bases, we hypothesized that modulation of cholesterol levels through Normocaloric Low Cholesterol Diet (NLCD) may represent an innovative strategy to reduce the progression of HCV infection, through the modulation of peripheral Th17/Treg balance. To this end, we performed a pilot study to investigate whether a Normocaloric Low Cholesterol Diet may be able to modulate Th17/Treg balance in patients affected by chronic HCV infection. After 30 days of NLCD CHC patients showed a significant reduction in Th17 cells frequency, which correlated with strong reduction of IL-17 and IL-22 serum levels. At the same time, we appreciated an increase in the percentage of Treg cells, thus improving Treg/Th17balance. Moreover, we observed an increased expression of LXRs and their target genes: SREBP-1c and ABCA-1. In conclusion, NLCD finely regulates

Background:

This study aimed to evaluate the effectiveness and safety of direct-acting antivirals (DAAs) for hepatitis C treatment by measuring sustained virologic response (SVR) and serious adverse events to help design effective interventions for reducing disease prevalence.
Methods:

This was a retrospective, observational, real-life study of patients with chronic hepatitis C receiving DAA treatment in the state of Ceará, Brazil. Data were collected in REDCap and analyzed using R® software by the Student's t, chi-square, and Fisher’s exact tests, with a significance level of 5%.
Results:

In this study, 1075 patients who were diagnosed with hepatitis C infection between October 2015 and October 2023 were included. The mean age of the participants was 56.6 ± 11 years and 60.2% were men. The sample included 51 HIV-infected patients (6.6%), 166 (15,4%) liver transplant recipients, 34 (3,1%) kidney transplant recipients, and 446 patients with cirrhosis (41.4%). The overall SVR rate was 96.4%. The sofosbuvir/daclatasvir/ribavirin regimen used in 354 (32.9%) patients achieved an SVR of 96%. The cure rate was 96.5%, with a lower SVR in patients with cirrhosis (93.4%) than in those with less severe fibrosis (97.9%) (p=0.0015). Serious adverse events associated with ribavirin use occurred in 3.5% of patients.
Conclusions:

DAA treatment for hepatitis C achieved SVR in real life in all patient profiles, including transplant recipients, HIV carriers, and patients with cirrhosis. Although these drugs are safe, a few decompensated patients with cirrhosis died during treatment.

Keywords:
Chronic Hepatitis C; Antiviral Drugs; Sustained Virologic Response; Epidemiology

OBJECTIVE: Although possible implications of nitric oxide in the pathophysiology of liver cirrhosis have been extensively studied, until now few articles have addressed the assessment of nitric oxide production in primary biliary cirrhosis. This study was directed to evaluate circulating nitrosyl-hemoglobin levels as well as neutrophil elastase and soluble adhesion molecule concentrations in this condition, by assuming these parameters as possible markers of either inflammatory response or neutrophil activation. METHODS: Laboratory investigations were performed in 30 patients with primary biliary cirrhosis, in 13 patients with postviral and/or alcoholic cirrhosis, and in a group of eight subjects with chronic hepatitis. RESULTS: Although no difference was detected with respect to chronic hepatitis subjects, higher levels of nitrosyl-hemoglobin adducts were found in primary biliary cirrhosis patients than in postviral or alcoholic cirrhotics and in normal subjects (3.55 Ϯ 1.75 arbitrary units vs 1.95 Ϯ 0.57 and 0.84 Ϯ 0.34, p ϭ 0.0004 and p Ͻ 0.0001, respectively). Similarly, more elevated concentrations of neutrophil elastase (213.7 Ϯ 192.0 g/L vs 51.1 Ϯ 34.3 and 38.0 Ϯ 11.5, p Ͻ 0.0001 and p Ͻ 0.0001, respectively) as well as of soluble forms of intercellular adhesion molecule 1 and endothelial-leukocyte adhesion molecule 1 were shown in primary biliary cirrhosis patients than in subjects with cirrhosis of other etiologies and in controls. CONCLUSIONS: Highly enhanced nitric oxide production in primary biliary cirrhosis could be related to the development of strong inflammation and at least partially to neutrophil activation, thus suggesting a putative role of these cellular mediators in the development of liver damage owing to their ability to synthesize and release a wide variety of important factors, including elastase and nitric oxide.

See Editorial, pages 471±473 Background/Aims: In approximately 5% of chronic liver disease cases, no aetiology can be identi®ed. We selected sera from 50 patients with chronic hepatitis of unknown aetiology who were enrolled in this follow-up study whose aim is to gain insight into the possible role of viruses and to de®ne potential clinical outcomes. Methods: Patients' sera were screened with highly sensitive polymerase chain reaction assays for hepatitis B (HBV), C, D, and G viruses and TT virus. Sera were also retested for antibodies against the core antigen of HBV. Results: Surprisingly, HBV DNA was detected in both serum and liver in 15/50 (30%) patients. Immunostaining for HBV antigens on biopsies from patients positive for HBV DNA showed HBcAg and/or HBsAg expression at low levels in 9/15 samples. Eleven of the ®fteen patients were anti-HBc positive. With one exception, all patients carried HBV genomes at low levels (10 4 copies/ml or less). Histological signs of chronic liver disease were observed in all patients. Conclusion: Unrecognised HBV infections may account for a high proportion of chronic hepatitis cases of unknown aetiology. Improved HBV detection tests, which appear mandatory for the diagnosis and management of non-A nonE hepatitis as well as for improved safety of transfusions and transplantations are needed.

Background: Therapy for the hepatitis C virus (HCV) has undergone a revolution with the introduction of direct-acting antivirals (DAA). DAAs achieve sustained virological response (SVR) in 90-95% of treated patients, compared to 50-70% of those receiving dual pegylated interferon and ribavirin therapy. Although they are already available, there are few studies on DAAs efficacy in the Brazilian population. Objective: To evaluate the efficacy of DAAs in individuals with hepatitis C at the Liver Study Center (LSC) in Hospital Universitário Onofre Lopes (HUOL). Methods: Medical records of chronic HCV patients treated with DAAs from LSC were analyzed. Only those patients with a follow-up of at least 12 weeks after the end of treatment were included. Results: A total of 50 patients underwent treatment with DAAs at LSC. Of these, genotype 1 was present in 39 patients (81.2%, 1a8.3%, 1b68.7%), genotype 2, in 2 patients (4.2%) and genotype 3, in 6 patients (14.5%, 3a 2%). Thirty-two were cirrhotic (64%), and 20 were treatment-experienced (40%). The therapeutic regimens used were mainly sofosbuvir (SOF) + simeprevir (SMV) in 23 patients (46%) and SOF + daclatasvir (DCV), in 22 (44%). SVR-12 was achieved in 92% of patients. Four patients had virological failure: three of them were cirrhotic and treatment experienced. The other one had advanced liver fibrosis (F3) with no previous treatment for HCV infection. No adverse events were reported during DAA treatment. Conclusion: The experience of the LSC with DAAs showed a high rate of SVR and excellent tolerability.

Liver plays an important role in lipid metabolism and any acute or chronic malfunction of theliver due to viral hepatitis or liver cirrhosis may induce lipid derangements Objective: To determine thepatterns of deranged lipid profiles in patients of chronic hepatitis C Methods: It is a prospective,observational study, conducted at Medicine Department, Mayo Hospital Lahore for 6 months i.e.1stJanuary to 30th June 2018. After the ethical approval, 160 diagnosed cases of chronic hepatitis C of ages18-70 years of either gender were selected by non-probability purposive sampling. Informed writtenconsent was taken. Demographic information such as name, age and gender were recorded. Venous bloodsamples from patients after 10 to 14 hours of fasting were drawn for lipid profiles and sent to pathologylaboratory. All results were expressed as mg/dl. Data were analyzed in SPSS version 22 Results: Out of160 patients in this study, there were 94 males and 66 females. Total cholesterol was lower in...

S arcoidosis is a chronic multisystemic disease of unknown origin; it is characterized by an accumulation of noncaseating epithelioid granulomas. This pathology affects most commonly the lung, skin, lymph nodes, eyes, and rarely the nervous system. [1] The relationship between the occurrence of sarcoidosis and interferon alfa (IFN-α) therapy in viral hepatitis C was suggested in earlier reports. [1-4] This was also supported by the spontaneous resolution of sarcoidosis after cessation of IFN-α treatment for hepatitis C. Reported clinical manifestations include cutaneous sarcoidotic lesions, pulmonary nodules, and peripheral neuropathy. [1,4] In this paper, we report the second case in the literature of fatal central nervous system sarcoidosis secondary to IFN-α and ribavirin treatment. [5] We aim to underline the importance of screening for sarcoidosis before and during the follow-up of hepatitis C virus (HCV) patients undergoing antiviral therapy.

Introduction: The presence of background HCV infection cannot be overestimated in view of the prevalence of chronic hepatitis C and the risk of adverse outcomes of this disease. Purpose of this study was to evaluate the effectiveness of the combined use of antiviral therapy (Roferon + Vero-Ribavirin) and resort factors in patients with chronic hepatitis C in the phase of replication. Material and methods: We observed 48 patients with chronic hepatitis C; the minimum level of activity of the process defined the phase of replication. Markers of HCV infection were determined by enzyme linked immunosorbent assay (ELISA) (a-HCV and HCV-Ig M). HCV RNA was determined twice by the polymerase chain reaction (PCR). Genotyping of hepatitis C virus was performed. Biochemical blood analysis and the study of HCV infection markers were carried out four times. Results of therapy were assessed immediately after the end of the resort (spa) treatment, then at 3, 6 and 12 months after starting treatmen...

The envelope glycoprotein E2 of hepatitis C virus (HCV) is the target of neutralizing antibodies and is presently being evaluated as an HCV vaccine candidate. HCV binds to human cells through the interaction of E2 with the tetraspanin CD81, a putative viral receptor component. We have analyzed four different E2 proteins from 1a and 1b viral isolates for their ability to bind to recombinant CD81 in vitro and to the native receptor displayed on the surface of Molt-4 cells. A substantial difference in binding efficiency between these E2 variants was observed, with proteins derived from 1b subtypes showing significantly lower binding than the 1a protein. To elucidate the mechanism of E2-CD81 interaction and to identify critical regions responsible for the different binding efficiencies of the E2 variants, several mutants were generated in E2 protein regions predicted by computer modeling to be exposed on the protein surface. Functional analysis of these E2 derivatives revealed that at l...

Our data revealed that HLA-A2 may be regarded as an immunologic risk factor for the development of antithyroid autoantibodies in patients with chronic HCV infection and these autoantibodies should be evaluated prior to initiating IFN-α therapy.

Neuropsychiatric Interview. The severity of depression, anxiety, and cognitive impairment was assessed at baseline and after 12 weeks using the Hamilton Depression Rating Scale, the Hamilton Anxiety Rating Scale, and the Mini Mental State Examination scale. None of the patients received psychiatric treatment during the study. Sustained virological response was defined as a failure to detect HCV by PCR 24 weeks after therapy. Six patients developed major depressive disorder and two patients developed anxiety disorders after 12 weeks of antiviral therapy. Baseline depressive and anxiety symptom scores were found to predict the depressive and anxiety symptoms, respectively, after 12 weeks. No significant association was found between depression and response to antiviral therapy. Greater collaboration between psychiatrists and hepatologists would promote IFN treatment compliance and improve patients' quality of life.

transfused during open-heart surgery in Stockholm, Sweden, were studied prospectively for the development of posttransfusion non-A, non-B (NANB) hepatitis, seroconversion to hepatitis C virus antibodies (anti-HCV) (C-100), time lag to seroconversion to anti-HCV and outcome of posttransfusion NANB/C hepatitis. Anti-HCV was tested up to six months after transfusions in patients from 1978 and up to one year after transfusions in patients from 1986. Fifty-four percent of the patients who developed posttransfusion NANB hepatitis seroconverted to anti-HCV, 7/15 (47%) in 1978 and 8/13 (62%) in 1986. Four (27%) of the 15 patients who seroconverted to anti-HCV were anti-HCV reactive within one week, 12 (80%) within eight weeks and all within 18 weeks after the onset of hepatitis. The ELISA optical density/cut-off (OD/CO) ratio was above 4.0 in all patients with hepatitis C who seroconverted. One transfused patient with normal serum aminotransferase levels throughout follow-up seroconverted after six months. He had a temporary positive anti-HCV reactivity with a maximal ELISA OD/CO ratio for anti-HCV of only 1.2, which became negative three years later. Development of chronic hepatitis was noticed in 9/15 (60%) patients who seroconverted to anti-HCV and in 5/13 (38%) patients with posttransfusion NANB hepatitis who did not seroconvert. Non-A, Non-B-Hepatitis nach Transfusion in Schweden. 74 Patienten, die 1978, und 316 Patienten, die, 1986 w/~hrend oftener Herzchirurgie in Stockholm, Schweden, Transfusionen erhielten, wurden in eine prospektive Studie aufgenommen und im Hinblick auf das Auftreten einer Non-A, Non-B-Posttransfusionshepatitis, Serokonversion f/Jr Hepatitis C Virus-Antik6rper (anti-HCV, C-100), Zeitspanne bis zur Serokonversion ffir anti-HCV und Verlauf der NANB/C-Posttransfusionshepatitis untersucht. Bei Patienten, die 1978 transfundiert worden waren, wurden Untersuchungen auf anti-HCV bis zu sechs Monate nach der Transfusion und bei 1986 Transfundierten bis zu einem Jahr nach Transfusion durchgeffihrt. Eine Serokonversion zu anti-HCV trat bei 54% der Patienten mit NANB-Posttransfusionshepatitis ein, 7/15 (47%) der Patienten aus dem Jahr 1978 und 8/13 (62%) aus dem Jahr 1986. Die Serokonversion zu anti-HCV trat bei vier der 15 Patienten (27%) schon innerhalb einer Woche ein, bei 12 (80%) innerhalb acht Wochen und bei allen innerhalb 18 Wochen nach Beginn der Hepatitis. Bei den Patienten mit Hepatitis C, die eine Serokonversion entwickelten, lag der Quotient von ELISA MeBwert zu Grenzwert (Optical density/Cut-off, OD/CO) in allen Fallen fiber 4,0. Ein Patient, bei dem nach der Transfusion stets normale Serum-Aminotransferase-Spiegel vorlagen, zeigte nach sechs Monaten eine Serokonversion. Er war voriibergehend anti-HCV positiv, der ELISA OD/CO-Quotient ffir anti-HCV betrug maximal 1,2; nach drei Jahren war er seronegativ. Bet neun der 15 Patienten (60%) war eine chronische Hepatitis nach Serokonversion for anti-HCV zu beobachten. Unter den 13 Patienten mit NANB-Posttransfusionshepatitis, die keine Serokonversion zeigten, entwickelten ffinf eine chronische Hepatitis (38%).

Background-Cardiac amyloidosis is characterized by amyloid infiltration resulting in extracellular matrix disruption. Amyloid cardiomyopathy due to immunoglobulin light chain protein (AL-CMP) deposition has an accelerated clinical course and a worse prognosis compared with non-light chain cardiac amyloidoses (ie, forms associated with wild-type or mutated transthyretin [TTR]). We therefore tested the hypothesis that determinants of proteolytic activity of the extracellular matrix, the matrix metalloproteinases (MMPs), and their tissue inhibitors (TIMPs) would have distinct patterns and contribute to the pathogenesis of AL-CMP versus TTR-related amyloidosis. Methods and Results-We studied 40 patients with systemic amyloidosis: 10 AL-CMP patients, 20 patients with TTR-associated forms of cardiac amyloidosis, ie, senile systemic amyloidois (involving wild-type TTR) or mutant TTR, and 10 patients with AL amyloidosis without cardiac involvement. Serum MMP-2 and -9, TIMP-1, -2, and -4, brain natriuretic peptide values, and echocardiography were determined. AL-CMP and TTR-related amyloidosis groups had similar degrees of increased left ventricular wall thickness. However, brain natriuretic peptide, MMP-9, and TIMP-1 levels were distinctly elevated accompanied by marked diastolic dysfunction in the AL-CMP group versus no or minimal increases in the TTR-related amyloidosis group. Brain natriuretic peptide, MMPs, and TIMPs were not correlated with the degree of left ventricular wall thickness but were correlated to each other and to measures of diastolic dysfunction. Immunostaining of human endomyocardial biopsies showed diffuse expression of MMP-9 and TIMP-1 in AL-CMP and limited expression in TTR-related amyloidosis hearts. comparable left ventricular wall thickness with TTR-related cardiac amyloidosis, AL-CMP patients have higher brain natriuretic peptide, MMPs, and TIMPs, which correlated with diastolic dysfunction. These findings suggest a relationship between light chains and extracellular matrix proteolytic activation that may play an important role in the functional and clinical manifestations of AL-CMP, distinct from the other non-light chain cardiac amyloidoses. (Circ Heart Fail. 2008;1:249-257.) Key Words: amyloid Ⅲ cardiomyopathy Ⅲ metalloproteinases Ⅲ remodeling Ⅲ immunoglobulin light chains C ardiac amyloidosis, a rare disorder, is characterized by amyloid fibril deposition in the heart, resulting in a restrictive cardiomyopathy that manifests late with heart failure (HF) and conduction abnormalities. 1-3 Amyloid infiltration leads to extracellular matrix (ECM) disruption resulting in diastolic dysfunction from progressive thickening and stiffening of the myocardium. There are several types of cardiac amyloidoses, which are classified according to the biochemical nature of the amyloid deposit. In "primary" or immunoglobulin light chain amyloidosis (AL), fibrils are formed from aggregated subunits (or fragments thereof) of an amyloidogenic monoclonal light chain protein. Transthyretin Clinical Perspective see p 257 (TTR), normally a plasma-circulating protein, can also form amyloid deposits in myocardial tissue. Wild-type TTR is responsible for the cardiomyopathy in age-related senile systemic amyloidosis (SSA). Heritable mutations in TTR (ATTR) can result in cardiac or neuronal deposition of amyloid protein. Of these disease types, AL-cardiac amy-

About a quarter of familial Mediterranean fever (FMF) patients have recurrent painful attacks of polyserositis despite regular colchicine treatment. There is no known alternative drug for colchicine-resistant cases. We had previously observed a patient with FMF whose painful attacks disappeared during the 6 month period of interferon alpha (IFN) treatment for his chronic hepatitis B. The objective of the present study was to investigate the possible beneficial effect of IFN on these episodes. Twenty-one consecutive attacks in seven adult patients with FMF were treated at early onset with IFN, the dosage being 3-10 million IU s.c. Eighteen of the 21 attacks could be halted in a mean time of 3.05 h, while the intensity of abdominal pain remained very low. Observed side-effects were generally mild and acceptable. IFN may be a useful adjunct for the treatment of colchicine-resistant attacks in FMF patients.