Epidemiology of hepatitis D virus infection in Europe: Is it vanishing?

Co-infection with hepatitis delta virus (HDV) is a challenging health care problem worldwide, estimated to occur in approximately 5%-10% of patients with chronic hepatitis B virus (HBV) infection. While HBV prevalence is decreasing globally, the prevalence of HDV infection is rising in some parts mainly due to injection drug use, sexual transmission and immigration from high endemicity areas. Eastern Europe and the Mediterranean are among the regions with high rates of endemicity for HDV and the immigration from high endemicity areas to Central and Western Europe has changed the HDV epidemiology. We aimed to review the prevalence of HDV infection in Europe. A paucity of publication appears in many European countries. Prevalence studies from some countries are old dated and some other countries did not report any prevalence studies. The studies are accumulated in few countries. Anti-HDV prevalence is high in Greenland, Norway, Romania, Sweden and Italy. Belgium, France, Germany, Spain, Switzerland, Turkey and United Kingdom reported decreasing prevalences. Among cirrhotic HBV patients, Germany, Italy and Turkey reported higher rates of HDV. The studies including centres across the Europe reported that HIV-HBV coinfected individuals have higher prevalence of HDV infection. The immigrants contribute the HDV infection burden in Greece, Italy, and Spain in an increasing rate. Previous studies revealed extremely high rates of HDV infection in Germany, Greece, Italy and Sweden. The studies report a remarkably high prevalence of hepatitis delta among HIV/HBV-coinfected individuals, individuals who inject drugs, immigrants and severe HBV infected patients across Europe. The HDV infection burden still appears to be significant. In the lack of an effective HDV therapy, prevention strategies and active screening of HBV/HDV appear as the most critical interventions for reducing the burden of liver disease related to HDV infection in Europe.

The changing epidemiology of delta hepatitis in Türkiye over three decades: A systematic review.

Hepatitis D virus (HDV) infection represents the most serious form of chronic hepatitis. Turkey is among the countries with high HDV and intermediate hepatitis B virus prevalence. In Turkey, hepatitis B virus (HBV) vaccine series was included in the routine vaccination program in 1998. There have been regional differences in prevalence of HBV and HDV. Although a decline in HDV prevalence is estimated, there are uncertainties about the epidemic patterns of it. HDV prevalence was studied in varying groups and geographic regions. In this study, we aimed to analyse hepatitis D epidemiology in all groups and geographic regions in recent 35 years. During the study period of 35 years, 111 publications were noted. The analysis was done on the basis of three periods: 1999 and before (Period 1), 2000-2009 (Period 2), and 2010 and after (Period 3). The groups studied included inactive carrier state, chronic hepatitis B, all HBsAg-positive individuals and special groups. Among inactive HBV carriers, HDV prevalence did not change significantly over three decades. Among patients with chronic hepatitis, studies reported decreasing (from Period 1 to Period 2) and then increasing (from Period 2 to period 3) HDV prevalence. The studies including all HBsAg-positive patients reported decreasing (from Period 1 to Period 2) and then increasing (from Period 2 to period 3) HDV prevalence. Cumulative data of these 3 groups were taken to reveal HDV prevalence in HBV-infected patients, and it showed decreasing (from Period 1 to Period 2) and then increasing (from Period 2 to period 3) HDV prevalence. Cumulative data of these 3 groups analysed according to the geographic regions of the country showed that Eastern and Southeastern Anatolia regions still have a high burden of HDV. The study showed that although HDV prevalence decreased from 8.3% in Period 1 to 4.8% in Period 2, it tended to increase 5.5% in Period 3. HDV infection is still a healthcare problem in Turkey.

Influenza and COVID-19 coinfection: Report of six cases and review of the literature.

Coronavirus disease 2019 (COVID-19) pandemic caused infection in a season when influenza is still prevalent. Both viruses have similar transmission characteristics and common clinical manifestations. Influenza has been described to cause respiratory infection with some other respiratory pathogens. However, the information of COVID-19 and influenza coinfection is limited. In this study, we reported our coinfected cases and reviewed the literature. We included all COVID-19 diagnosed patients. All patients with a presumed diagnosis of COVID-19 were routinely screened for influenza. Their thorax radiology was reviewed for COVID-19-influenza differentiation. During the study period, 1103 patients have been diagnosed with COVID-19. Among them, six patients (0.54%) were diagnosed coinfected with influenza. There have been 28 more coinfected patients reported. Laboratory-based screening studies reported more patients. Thorax radiology findings were compatible with COVID-19 in five and with influenza in one of our patients. Our cases were mild to moderate in severity. The reported cases in the literature included patients died (n = 2) and those living ventilator dependent or under mechanical ventilation. COVID-19 and influenza coinfection is rare. Screening studies report more cases, suggesting that unless screening patients with COVID-19, the coinfection remains undiagnosed and underestimated. Increasing experience in thoracic radiology may contribute to diagnose the responsible virus(es) from the clinical illness. Influenza vaccine for larger population groups can be recommended to simplify clinicians' work.

Genome-wide Association Study Identifies Genetic Variants Associated With Early and Sustained Response to (Pegylated) Interferon in Chronic Hepatitis B Patients: The GIANT-B Study.

BACKGROUND: (Pegylated) Interferon ([Peg]IFN) therapy leads to response in a minority of chronic hepatitis B (CHB) patients. Host genetic determinants of response are therefore in demand. METHODS: In this genome-wide association study (GWAS), CHB patients, treated with (Peg)IFN for at least 12 weeks ± nucleos(t)ide analogues within randomized trials or as standard of care, were recruited at 21 centers from Europe, Asia, and North America. Response at 24 weeks after (Peg)IFN treatment was defined as combined hepatitis B e antigen (HBeAg) loss with hepatitis B virus (HBV) DNA <2000 IU/mL, or an HBV DNA <2000 IU/mL for HBeAg-negative patients. RESULTS: Of 1144 patients, 1058 (92%) patients were included in the GWAS analysis. In total, 282 (31%) patients achieved the response and 4% hepatitis B surface antigen (HBsAg) loss. GWAS analysis stratified by HBeAg status, adjusted for age, sex, and the 4 ancestry components identified PRELID2 rs371991 (B= -0.74, standard error [SE] = 0.16, P = 3.44 ×10-6) for HBeAg-positive patients. Importantly, PRELID2 was cross-validated for long-term response in HBeAg-negative patients. G3BP2 rs3821977 (B = 1.13, SE = 0.24, P = 2.46 × 10-6) was associated with response in HBeAg-negative patients. G3BP2 has a role in the interferon pathway and was further examined in peripheral blood mononuclear cells of healthy controls stimulated with IFNα and TLR8. After stimulation, less production of IP-10 and interleukin (IL)-10 proteins and more production of IL-8 were observed with the G3BP2 G-allele. CONCLUSIONS: Although no genome-wide significant hits were found, the current GWAS identified genetic variants associated with (Peg)IFN response in CHB. The current findings could pave the way for gene polymorphism-guided clinical counseling, both in the setting of (Peg)IFN and the natural history, and possibly for new immune-modulating therapies. CLINICAL TRIALS REGISTATION: NCT01401400.

Hepatitis E virus infection in Turkey: a systematic review.

Hepatitis E virus (HEV), a non-enveloped single stranded RNA virus causes sporadic cases of hepatitis or outbreaks. The disease is generally self-limited although it may cause fulminant hepatitis in pregnant women, elderly, those with underlying chronic hepatitis, immunosuppressed, and transplant recipients. It is transmitted through fecal-oral route and zoonotic transmission. Hepatitis is a main health care problem in Turkey; HBV and HCV prevalences are 4 and 1% respectively. Hepatitis D represents another considerable hepatitis etiology with a prevalence of 5-27%. The information about HEV is not clear. In this systematic review, we aimed to analyze HEV studies reported from Turkey, to determine the current situation of the disease in the country, to delineate the limits of the studies and to determine the future study areas. The prevalence of HEV ranged from 0 to 12.4%. Children had lower prevalence than the adults. The prevalence was determined as 7-8% in pregnant women, 13% in chronic HBV patients, 54% in chronic HCV patients, 13.9-20.6% in patients with chronic renal failure, and ≈ 35% in agriculture workers. Among individuals immigrating form Turkey to Europe, HEV seroprevalence was found 10.3% in Italy and 33.4% in the Netherlands. HEV prevalence seems high in certain risk groups. Although previous studies suggest that Turkey is among the endemic countries of HEV, there are some pitfalls for the analysis of data: the studies are not powered enough to represent the whole population; they did not include immunosuppressed patients and solid organ recipients; and the prevalence of non-A non-B hepatitis was not determined.

Daclatasvir plus asunaprevir dual therapy for chronic HCV genotype 1b infection: results of Turkish early access program.

 Background. Daclatasvir and asunaprevir dual therapy is approved for the treatment of HCV genotype 1b infection in several countries. AIM: To evaluate the efficacy and safety of daclatasvir and asunaprevir dual therapy in Turkish patients. MATERIAL AND METHODS: Sixty-one patients with HCV genotype 1b were enrolled in the Turkish early access program. Most of the patients were in difficult-to-treat category. Patients were visited at each 4 week throughout the follow-up period. Laboratory findings and adverse events were recorded at each visit. RESULTS: Fifty-seven of 61 enrolled patients completed 24 weeks of treatment. Two patients died as a result of underlying diseases at 12-14th weeks of treatment. Two patients stopped the treatment early as a consequence of virological breakthrough, and 2 patients had viral relapse at the post-treatment follow-up. Overall SVR12 rates were 90% (55/61) and 93.2% (55/59) according to intention-to-treat (ITT) and per protocol (PP) analysis respectively. In ITT analysis, SVR12 was achieved by 93% (13/14) in relapsers, 80% (12/15) in interferon-ineligible patients and 91% (20/22) in previous nonresponder patients. SVR12 rates were 86.5% and 91.4% in patients with cirrhosis according to ITT and PP analysis respectively. SVR12 was 95.8% in non-cirrhosis group in both analysis. Patients with previous protease inhibitor experience had an SVR12 of 87.5%. Common adverse events developed in 28.8% of patients. There were no treatment related severe adverse event or grade-4 laboratory abnormality. CONCLUSIONS: Daclatasvir and asunaprevir dual therapy is found to be effective and safe in difficult-to-treat Turkish patients with HCV genotype 1b infection.

Recommendations for intra-abdominal infections consensus report.

Guidelines include the recommendations of experts from various specialties within a topic in consideration of data specific to each country. However, to date there has not been a guideline standardizing the nomenclature and offering recommendations for intra-abdominal infections (IAIs) in Turkey. This is mainly due to the paucity of laboratory studies regarding the clinical diagnosis and treatment of IAIs or the sensitivity of microorganisms isolated from patients with IAIs. However, due to the diversification of host characteristics and advancements in technological treatment methods, it has become imperative to 'speak a common language'. For this purpose May 2015, a group of 15 experts in intra-abdominal infections, under the leadership of the Infectious Diseases and Clinical Microbiology Specialty Society of Turkey (EKMUD) and with representatives from the Turkish Surgical Association, Turkish Society of Colon and Rectal Surgery, Hernia Society, Turkish Society of Hepato-pancreato-biliary Surgery, and the Turkish Society of Hospital Infections and Control, was formed to analyze relevant studies in the literature. Ultimately, the suggestions for adults found in this consensus report were developed using available data from Turkey, referring predominantly to the 2010 guidelines for diagnosing and managing complicated IAIs in adults and children by the Infectious Diseases Society of America (IDSA) and the Surgical Infection Society. The recommendations are presented in two sections, from the initial diagnostic evaluation of patients to the treatment approach for IAI. This Consensus Report was presented at the EKMUD 2016 Congress in Antalya and was subsequently opened for suggestions on the official websites of the Infectious Diseases and Clinical Microbiology Specialty Society of Turkey and Turkish Surgical Association for one month. The manuscript was revised according to the feedback received.

Corticosteroid treatment in the management of idiopathic granulomatous mastitis to avoid unnecessary surgery.

PURPOSE: Idiopathic granulomatous mastitis (IGM) is a rare benign inflammatory disease of the breast. It can mimic breast carcinoma clinically and radiologically, and usually affects females of childbearing age. There is no commonly accepted optimal treatment for IGM. In this study, we present the clinical and histopathological features and outcomes of the therapeutic management of IGM, as well as the clinical course of the disease when patients were treated with oral corticosteroids. METHODS: This retrospective study included 49 of 87 patients who met the required histological criteria for IGM who were followed up between January 2009 and December 2011. All patients had a disease-free follow-up period of at least 6 months. The data regarding the clinical features at presentation, laboratory values and the treatment modalities were obtained from the medical records of the patients. RESULTS: The mean age of the patients was 34.3 ± 4.37 years. Forty patients were treated with prednisolone, five were started on antituberculosis treatment, two received non-steroidal anti-inflammatory drugs, one received antibiotics and one underwent wide excision. All patients who received steroids responded well to the therapy. CONCLUSION: Systemic therapy with corticosteroids is an effective and appropriate treatment option for IGM. It can provide complete disease resolution and prevent recurrence in the long term. A multidisciplinary approach including specialists in the fields of both general surgery and infectious diseases is essential for the diagnosis, treatment and follow-up of IGM.

Comparison of cellular immunity in patients with chronic hepatitis B, inactive hepatitis B surface antigen carriers and spontaneously recovered individuals.

Different clinical outcomes of acute HBV infection have been partially explained by individual differences in immune response. In this study we investigated interferon gamma (IFN-γ) secretion of peripheral blood mononuclear cells (PBMC) in vitro against specific (Hepatitis B core antigen; recombinant HB-cAg) and non-specific (CMV, EBV, Influenza peptide pool; CTL CEF peptide pool "plus") antigens using enzyme linked immunospot (ELISPOT) assay in 7 patients with chronic hepatitis B (CHB group), 8 inactive carriers Of HBV (carrier group) and 8 subjects who spontaneously recovered from acute HBV infection as detected by anti-HBs positivity (immune group). Phytohemaglutinin served as the positive test control. Response against recombinant HBcAg was 88±135, 50±110, 105±150 spot forming cell (SFC)/10(5) PBMC, in CHB, carrier and immune groups, respectively. HBcAg-specific T-cell response was slightly higher in the immune group; however, statistically there was no significant difference between the groups. Assessment of cellular immunity by IFN-γ ELISPOT was not sufficient to explain the various outcomes of HBV infection such as resolution, chronicity and carriership.

Port-related Delftia tsuruhatensis bacteremia in a patient with breast cancer.

Delftia tsuruhatensis is a non-glucose fermenting, oxidase positive, motile, gram-negative bacillus first isolated from activated sludge collected from a domestic wastewater treatment plant in Japan. To the best of our knowledge only one case of infection with Delftia tsuruhatensis exists in the medical literature. This is the second case report of human infection having Delftia tsuruhatensis as a causative agent.

Ecthyma Gangrenosum-like Lesions in a Febrile Neutropenic Patient with Simultaneous Pseudomonas Sepsis and Disseminated Fusariosis.

UNLABELLED: Fusarium spp. is an opportunistic mold that causes disseminated infections in immunocompromised patients. It is important to make a definite diagnosis because of high mortality rates. We present the case of a 27-year-old pregnant woman diagnosed with acute myeloid leukemia with a prolonged febrile neutropenic period. She developed ecthyma gangrenosum-like lesions and simultaneously had Pseudomonas bacteremia and disseminated fusariosis. Histopathological and microbiological features of skin lesions had a critical role in differential diagnosis. Ecthyma gangrenosum-like lesions due to disseminated fusariosis might be easily misdiagnosed as lesions associated with Pseudomonas unless tissue cultures and histopathological examinations are performed. CONFLICT OF INTEREST: None declared.

Discontinuation of Nucleos(t)ide Analog treatment in HBeAg-Negative Non-Cirrhotic Chronic Hepatitis B Patients: Real-Life Data of 20 Years.

BACKGROUND/AIMS: Discontinuation of nucleos(t)ide analog is controversial in HBeAg-negative chronic hepatitis B patients not achieved HBsAg loss. We aimed to evaluate re-treatment rates and risk factors in non-cirrhotic HbeAg-negative chronic hepatitis B patients for whom nucleosi(t)ides analogs were discontinued. MATERIALS AND METHODS: Demographic, clinical, and laboratory data before and at the end after discontinuation of nucleos(t)ide analogs were collected retrospectively. RESULTS: Seventy-two patients followed up between January 2000 and December 2019 were included; 43 were male, with a mean age of 46.3 (±10.8). Baseline median alanine aminotransferase (ALT) and hepatitis B virus DNA levels were 55.5 IU/L and 465 925 IU/mL, respectively. The median histologic activity index was 5.5 and the fibrosis score was 2. The median duration of treatment and consolidation therapy were 59 and 56 months, respectively. The median follow-up time after discontinuation of treatment was 55 months. Among 56 patients eligible for evaluation according to proposed re-treatment criteria, 29 (51.7%) patients were re-treated. The median time for relapse was 11 months. Re-treatment was significantly common in males (P = .034) and patients treated with tenofovir/entecavir (P = .04). Baseline hepatitis B virus DNA and levels of ALT, aspartate aminotransferase (AST) at the third and sixth months of treatment and at the end of treatment were statistically significantly higher in re-treated patients. A cutoff value of ≥405 000 IU/L for hepatitis B virus DNA discriminated patients for re-treatment. HBsAg was lost permanently in 2 non-re-treated patients. CONCLUSION: In resource-limited areas where follow-up of HBsAg or other markers is not possible, nucleos(t)ide analog discontinuation can be considered in patients in the early stage, with low baseline hepatitis B virus DNA and ALT levels, after a long consolidation therapy.