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.

Human Papillomavirus Infection and Oropharyngeal and Gastrointestinal Cancers: A Causal Relationship?

The human papillomavirus (HPV) is one of the most common sexually transmitted infections worldwide. The risk of being infected at least once in a lifetime among both men and women is estimated to be 50%. Although the majority of HPV infections are asymptomatic and improve within 2 years, approximately 10% of individuals develop a persistent infection and have an increased risk of developing carcinomas. The association of HPV and genital cancer is well established. However, there is evidence that HPV may also be associated with other cancers, including those of the gastrointestinal system. The aim of this review is to organize the current evidence of associations between HPV infections and oropharyngeal and gastrointestinal cancers, including the following: oropharyngeal, esophageal, gastric, colorectal, and anal cancers. A comprehensive review of the most up-to-date medical literature concluded that an HPV infection might have a role in the oncogenesis of gastrointestinal tract cancers. HPV may have a causal relationship with oropharyngeal and esophageal squamous cell cancers. However, the association between HPV and gastric and colorectal cancers is weaker. The development of cancer in the oropharyngeal and gastrointestinal tract is usually multifactorial, with HPV having a role in at least a subset of these cancers. HPV infections pose a big challenge due to their burden of infection and their oncogenic potential.

Therapeutic Effects of Prebiotics on Constipation: A Schematic Review.

Constipation is a highly prevalent functional gastrointestinal disorder that may significantly affect the quality of life and health care costs. Treatment for constipation has been broadly reviewed by cognitive therapies, medications, and surgical interventions. Gut microbiota such as Bifidobacterium, Clostridium, Bacteroidetes, and Lactobacilli have been demonstrated in functional gastrointestinal disorders and prebiotics to play a role in augmenting their presence. Prebiotics are ingredients in foods that remain undigested, stimulating the bacteria. There are a variety of prebiotics; however, there exists only a handful of studies that describe their efficacy for chronic constipation. The purpose of this study is to review the available literature on the utility of different commercially available prebiotics in patients with functional and chronic idiopathic constipation. To fulfil the objectives of the study, published articles in the English language on databases such as Pubmed, Ovid Medline, and EMBASE were searched. The terms prebiotics, constipation, chronic constipation, functional constipation were used. We reviewed and included 21 randomized controlled trials exploring the role of prebiotics in constipated adults. Prebiotics are effective treatments for chronic idiopathic constipation and showed improvement in the stool consistency, number of bowel moments and bloating. Although which prebiotic formulary would promote improved symptoms of constipation is still not clear.

Correction: An Unusual Finding of a Ladybug on Screening Colonoscopy.

[This corrects the article DOI: 10.14309/crj.0000000000000174.].

Clostridium Difficile Infection in Inflammatory Bowel Disease Patients.

BACKGROUND: The rising incidence of Clostridium difficile infection (CDI) in the general population has been recognized by health care organizations worldwide. The emergence of hypervirulent strains has made CDI more challenging to understand and treat. Inflammatory bowel disease (IBD) patients are at higher risk of infection, including CDI. OBJECTIVE: A diagnostic approach for recurrent CDI has yet to be validated, particularly for IBD patients. Enzyme immunoassay (EIA) for toxins A and B, as well as glutamate dehydrogenase EIA, are both rapid testing options for the identification of CDI. Without a high index of suspicion, it is challenging to initially differentiate CDI from an IBD flare based on clinical evaluation alone. METHODS: Here, we provide an up-to-date review on CDI in IBD patients. When caring for an IBD patient with suspected CDI, it is appropriate to empirically treat the presumed infection while awaiting further test results. RESULTS: Treatment with vancomycin or fidaxomicin, but not oral metronidazole, has been advocated by an expert review from the clinical practice update committee of the American Gastroenterology Association. Recurrent CDI is more common in IBD patients compared to non-IBD patients (32% versus 24%), thus more aggressive treatment is recommended for IBD patients along with early consideration of fecal microbiota transplant. CONCLUSION: Although the use of infliximab during CDI has been debated, clinical experience exists supporting its use in an IBD flare, even with active CDI when needed.

N-acetylcysteine expresses powerful anti-inflammatory and antioxidant activities resulting in complete improvement of acetic acid-induced colitis in rats.

High free radical production, low antioxidant capacity and excessive inflammation are well known features in the pathogenesis of inflammatory bowel disease. N-acetylcysteine (NAC) is a powerful antioxidant and a scavenger of hydroxyl radicals. Recently, NAC has also been shown to have anti-inflammatory activities in tissues. Our study objective was to investigate the effects of NAC on tissue inflammatory activities using an ulcerative colitis model induced by acetic acid (AA) in rats. Wistar rats (n = 32) were divided into four groups. AA-induced colitis was performed in two of the groups while the other two groups were injected with saline intrarectally. One of the AA-induced colitis groups and one of the control groups were administered NAC (500 mg/kg/day) intrarectally, and the other control groups were given saline. After 4 days, colonic changes were evaluated biochemically by measuring proinflammatory cytokines [tumor necrosis factor (TNF)-α, interleukin (IL)-1ß and IL-6], myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) levels in tissue homogenates and by histopathological examination. AA caused colonic mucosal injury, whereas NAC administration suppressed these changes in the AA-induced colitis group (p < 0.001). AA-administration resulted in increased TNF-α, IL-1ß, IL-6, MPO and MDA levels, and decreased GSH and SOD levels, whereas NAC reversed these effects (all p < 0.001). In conclusion, the present study proposes that intrarectal NAC therapy has a dual action as an effective anti-inflammatory and an antioxidant, and may be a promising therapeutic option for ulcerative colitis.

Xanthomatous hyperplastic polyps of the stomach: clinicopathologic study of 5 patients with polypoid gastric lesions showing combined features of gastric xanthelasma and hyperplastic polyp.

Gastric xanthelasmas are uncommon benign lesions that are macroscopically well-demarcated yellow or yellow-white plaques and are microscopically formed by collections of foamy macrophages. Because gastric hyperplastic polyps may rarely be associated with xanthelasma, we aimed to report 5 cases of combined lesions showing features of gastric xanthelasma and hyperplastic polyps observed over the past 3 years at our institution among 4497 patients who underwent gastric endoscopy. The patients were 3 men and 2 women aged 45 to 78 years. The lesions were located in oxyntic mucosa, except one in the antrum, and measured 2 to 6 mm. Three patients showed associated chronic gastritis; none showed evidence of Helicobacter pylori infection. Combined lesions of hyperplastic polyp with xanthelasma appear to have an association with chronic gastritis, and the lipid accumulation may be the cause of hyperplasia in the overlying mucosa.

CDX2, COX2 and MUC2 expressions in Barrett's esophagus: can they be useful in determination of the dysplasia?

OBJECTIVE: The description of Barrett's esophagus which is a risk factor for esophageal adenocarcinoma has differences, and the need of goblet cells for diagnosis is controversial. However, the pathophysiology in the metaplasia seen in Barrett's esophagus is not totally understood and new methods are searched for the assessment of progression to dysplasia. We aimed to search the immunohistochemical expression of CDX2, COX2 and MUC2 in Barrett's esophagus to detect any early evidence of intestinal metaplasia or dysplasia. MATERIAL AND METHOD: The staining properties were examined in the intestinal metaplastic (goblet cell-containing columnar epithelium), columnar (non-goblet columnar epithelium), distant columnar (non-goblet columnar epithelium distant from intestinal metaplastic epithelium) and squamous epithelium in 59 pathologically diagnosed Barrett's esophagus, 22 of which having dysplasia. The results were compared statistically with Pearson and Fisher exact tests. RESULTS: The distribution of the staining of intestinal metaplastic, non-goblet columnar distant columnar, and squamous epithelium, respectively were as follows: for CDX2 76.3%, 23.7%, 1.7%, 0%; for COX-2 93.2%, 47.5%, 8%, 62.9%; for MUC2 93.2%, 11.9%, 4% and 0%. The expression of CDX2, COX2 and MUC2 in the intestinal metaplastic epithelium was higher than the expression in distant and non-goblet columnar epithelium. The expression of CDX2, COX2 and MUC2 in the foci of dysplasia decreased significantly (18.2%, 27.3%, 31.9%, and p=0.039, 0.0001, 0.0001, respectively). COX2 expression in squamous epithelium was also lower when the adjacent mucosa has dysplasia (p=0.014). CONCLUSION: The CDX2, COX2 and MUC2 expressions were seen in the intestinal epithelium having goblet cells. The use of the markers in the diagnosis is controversial but the difference in the Barrett esophagus-dysplasia sequence seems to be meaningful.

General evaluation of hepatectomy and hepatocellular carcinoma cases.

OBJECTIVE: Although the clinical and histopathological findings of hepatocellular carcinoma are well described, there are few national studies. In this study, we aimed to investigate the relationship between these findings in total or partial hepatectomy specimens in our series. MATERIAL AND METHOD: We first collected 190 cases of total or partial hepatectomies performed because of hepatocellular carcinoma, cirrhosis or other disorders from the archives of Pathology. After re-examining the histopathological and clinical features such as age, gender and etiology, the relationship between them and serology results were statistically analyzed using the chi square and Multiple Comparison Tests. RESULTS: Among 190 cases, there were 168 (88.5%) total and 18 (9.5%) partial hepatectomies and 4 (2%) tumorectomy or metastasectomy cases. After gross and microscopic examination, 170 (89.5%) cases had a diagnosis of cirrhosis, 85 (44.7%) hepatocellular carcinoma, 3 parasitic cyst, 7 metastasis, 1 hepatoblastoma, 1 hepatocellular adenoma, 2 cholangiocarcinoma, 2 Budd Chiari Syndrome, 1 focal nodular hyperplasia, 1 cavernous hemangioma, and 2 acute fulminant hepatitis. Among the hepatocellular carcinoma cases, 53 had Hepatitis B virus, 15 Hepatitis C virus , 3 Hepatitis B virus and Hepatitis C virus, and 3 Hepatitis B virus and Hepatitis delta virus etiology, while 6 were alcoholic and 4 were due to other causes. Among cirrhosis patients, 84 (49.4%) had hepatocellular carcinoma. The male to female ratio of hepatocellular carcinoma cases was 74/11. The mean age was 55 and the median age 56.7. CONCLUSION: The results of this study demonstrated that the most common hepatic disorder was cirrhosis due to Hepatitis B virus in the hepatectomy specimens of our series that mostly consisted of total hepatectomies performed for transplantation where 50% had hepatocellular carcinoma.

Is HCV genotyping cost-effective even when the prevalences of genotypes 2 and 3 are low?

BACKGROUND/AIMS: The management of chronic hepatitis C virus (HCV) infection is costly. Genotyping determines the indication, probability of response, and duration of treatment and the dose of ribavirin. Although genotyping is accepted cost-effective, the cost of genotyping in all of the patients to find out a minority may offset the gain. The present study aimed; (1) to determine the frequency rate of HCV genotypes and (2) to compare the cost of HCV treatment tailored according to the genotype versus that planned supposing it to be genotype 1. METHODOLOGY: Six centers were included into the study. Name, age, genotype, and serotype of each patient were entered. For genotyping, HCV-RNA was extracted by acid-guanidium-phenol-chloroform method. Cost of genotyping, HCV-RNA studies and the treatment with pegylated interferon and ribavirin was estimated. The cost was determined according to two scenarios: (A) To manage patients as if all had genotypes other than 2-3. (B) To manage them after determining the geno type. The management was assumed to be made by current guidelines. RESULTS: The data of 834 patients were analyzed: Genotypel was predominant: 730 (87.5%). The rest was composed of G2:26 (3.1%), G3:26 (3.1%), G4:14 (1.7%), mixed: 13 (1.6%), undetermined: 25(3%). The cost of approach A (for 100 patients) was 1,718,200 USD; that of approach B (for 100 patients) was 1,671,900 USD. With genotype targeted therapy, every 100 patient would save 46,300 USD. CONCLUSIONS: The prevalent genotype in our country is genotypel. The sum of genotypes 2 and 3 corresponds to 6%. Genotyping HCV and tailoring the treatment thereafter are cost-effective even in the countries where prevalence of these genotypes is low.

Hepatic arterial mapping by multidetector computed tomographic angiography in living donor liver transplantation.

PURPOSE: Our aims were to present the hepatic arterial variations that were detected with computed tomographic angiography (CTA) and confirmed by operation in living liver donors and to emphasize the usefulness of CTA in the assessment of hepatic arterial anatomy. MATERIALS AND METHODS: The donors of 100 patients (46 women and 54 men) who had undergone a living donor liver transplantation in a (blinded) hospital between July 2004 and June 2007 were evaluated. The age of the donors ranged from 18 to 63 years (mean, 39 years). The CTA images obtained by a 16-slice multidetector CT before the transplantation procedure were retrospectively evaluated for arterial variations, and the results were compared with the results of the operation. RESULTS: In 59 donors (59%), classic hepatic arterial anatomy was observed. In the remaining 41 donors (41%), various arterial variations were determined. In 11 of the donors (11%), variations were not compatible with the description of Michel's classification. In all of our patients, CTA findings were confirmed with operational findings. Our complication rate was 1%. Only 1 of the patients who had undergone the transplantation developed hepatic arterial thrombus, and the remaining 99 patients had no arterial complications. CONCLUSIONS: The course of the vascular structures before live donor liver transplantation is essential for planning and success of the operation. Our study showed that multidetector CTA can be used successfully in hepatic artery imaging of liver transplantation donors as a noninvasive method.

Midgut volvulus: value of multidetector computed tomography in diagnosis.

Midgut volvulus is a rare complication of intestinal malrotation in adults. We present a case of intestinal malrotation with surgically proven midgut volvulus. Multidetector computed tomography with postprocessing of imaging data using three-dimensional reconstruction techniques provided better demonstration of the abdomen than other imaging modalities. To our knowledge, this is the first presentation of midgut volvulus on multidetector computed tomography in adults. The literature on midgut volvulus is also reviewed and imaging findings of this disease are discussed.

Donor safety and remnant liver volume in living donor liver transplantation.

Living donor liver transplantation is now a common practice in countries in which the availability of cadaveric organs is limited. The preoperative preparation, intraoperative surgical technique, and postoperative care of donors and recipients have evolved in recent years. We retrospectively compared 67 donors with a remnant liver volume equal to or more than 30% (group 1) with 14 donors who had less than 30% remnant liver volume (group 2) for donor outcomes. All the complications in donors were systematically classified. Donors with less than 30% remnant liver volume showed significantly higher peak aspartate aminotransferase, alanine aminotransferase, international normalized ratio, and bilirubin levels. There were 6 complications in group 1 and 4 complications in group 2. The difference between the 2 groups in terms of donor complications did reach statistical significance (P = 0.043); donors with a remnant liver volume < 30% had a 4 times greater relative risk of morbidity. In conclusion, the use of donors with less than 30% remnant liver volume is highly debatable as donor safety should be of utmost importance in living donor liver transplantation.

Role of ursodeoxycholic acid in prevention of methotrexate-induced liver toxicity.

AIM: Methotrexate (MTX)-induced hepatotoxicity restricts the clinical use of this immunosuppressive drug. In this study, our aim was to research the role of oxidative stress in the hepatic toxicity of MTX and the protective effect of ursodeoxycholic acid (UDCA) in this setting. METHODS: Wistar type rats (n = 32) were divided into four groups; group-1 as the MTX + UDCA, group-2 as the MTX, group-3 as the UDCA, group-4 as the saline-receiving groups. The MTX + UDCA and MTX groups of rats received 50 mg/kg of UDCA administered orally; whilst physiological saline was administered orally to the MTX and saline groups and continued for the next 6 days. On the second day of the study, the MTX + UDCA and MTX groups had a single intraperitoneal dose of MTX of 20 mg/kg. The UDCA and saline groups also received similar volumes of physiological saline intraperitoneally. On the sixth day, serum samples were collected and analyzed for ALT, alkaline phosphatase (ALP) and gamma glutamyl transpeptidase (GGT) and homogenated liver tissues were examined for reactive oxygen metabolites (ROM); luminol, lucigenin, lipid peroxygenation product malondialdehyde (MDA) and glutathione (GSH) levels. RESULTS: In the MTX group, serum ALT, ALP, GGT and tissue ROM levels were higher and GSH level was lower. On the histopathological examination, hepatocellular necrosis was clearly more evident in the MTX group than the MTX + UDCA group. CONCLUSIONS: UDCA treatment protects against MTX-induced liver toxicity. Histopathologically hepatocyte necrosis can be prevented by UDCA treatment, indicating clearly the hepatoprotective effect of this agent on MTX-induced liver injury.