Hepatitis C screening in Lithuania: first-year results and scenarios for achieving WHO elimination targets.

BACKGROUND: The World Health Organization (WHO) has outlined a set of targets to achieve eliminating hepatitis C by 2030. In May 2022, Lithuanian health authorities initiated a hepatitis C virus (HCV) screening program to start working towards elimination. In the program, bonus was given to general practitioners (GPs) to promote and conduct anti-HCV tests for two situations: (1) one time testing for individuals born in 1945-1994 and (2) annual HCV testing for persons who inject drugs or are living with human immunodeficiency virus (HIV) regardless of age. This study aimed to model the current viral hepatitis C epidemiological status in Lithuania and to outline the requirements for WHO elimination targets using the first-year HCV screening results. METHODS: Individuals were invited to participate in the anti-HCV screening by GPs during routine visits. Patients who tested positive were then referred to a gastroenterologist or infectious disease doctor for further confirmatory testing. If a patient received a positive RNA test and a fibrosis staging result of ≥ F2, the doctor prescribed direct-acting antivirals. Information on the patients screened, diagnosed, and treated was obtained from the National Health Insurance Fund. The Markov disease progression model, developed by the CDA Foundation, was used to evaluate the screening program results and HCV elimination progress in Lithuania. RESULTS: Between May 2022 and April 2023, 790,070 individuals underwent anti-HCV testing, with 11,943 individuals (1.5%) receiving positive results. Anti-HCV seroprevalence was found to be higher among males than females, 1.9% and 1.2%, respectively. Within the risk population tested, 2087 (31.1%) seropositive individuals were identified. When comparing the screening program results to WHO elimination targets through modelling, 2180 patients still need to be treated annually until 2030, along with expanding fibrosis restrictions. If an elimination approach was implemented, 1000 new infections would be prevented, while saving 150 lives and averting 90 decompensated cirrhosis cases and 110 hepatocellular carcinoma cases. CONCLUSIONS: During the first year of the Lithuanian screening program, GPs were able to screen 44% of the target population. However, the country will not meet elimination targets as it currently stands without increasing treatment levels and lifting fibrosis restrictions.

Menstrual cycle abnormalities in women with inflammatory bowel disease and effects of biological therapy on gynecological pathology.

Inflammatory bowel disease (IBD) is a chronic condition that affects young individuals in their reproductive years. It may have long-term implications on their reproductive, sexual, and mental health. IBD has been related to menstrual abnormalities. Furthermore, the administration of biological therapy can also result in gynecological issues in addition to the disease itself. The purpose of this review was to present potential menstrual cycle problems in patients with IBD, as well as the impact of adalimumab and other anti-tumor necrosis factor medications on gynecological pathology.

Gut microbiota contribution to hepatocellular carcinoma manifestation in non-alcoholic steatohepatitis.

Recently, the gut microbiota has been recognized as an obvious active player in addition to liver steatosis/steatohepatitis in the pathophysiological mechanisms of the development of hepatocellular carcinoma (HCC), even in the absence of cirrhosis. Evidence from clinical and experimental studies shows the association of specific changes in the gut microbiome and the direct contribution to maintaining liver inflammation and/or cancerogenesis in nonalcoholic fatty liver disease-induced HCC. The composition of the gut microbiota differs significantly in obese and lean individuals, especially in the abundance of pro-inflammatory lipopolysaccharide-producing phyla, and, after establishing steatohepatitis, it undergoes minor changes during the progression of the disease toward advanced fibrosis. Experimental studies proved that the microbiota of obese subjects can induce steatohepatitis in normally fed mice. On the contrary, the transplantation of healthy microbiota to obese mice relieves steatosis. However, further studies are needed to confirm these findings and the mechanisms involved. In this review, we have evaluated well-documented clinical and experimental research on the role of the gut microbiota in the manifestation and promotion of HCC in nonalcoholic steatohepatitis (NASH). Furthermore, a literature review of microbiota alterations and consequences of dysbiosis for the promotion of NASH-induced HCC was performed, and the advantages and limitations of the microbiota as an early marker of the diagnosis of HCC were discussed.

Management of Flood syndrome: What can we do better?

Approximately 20% of cirrhotic patients with ascites develop umbilical herniation. These patients usually suffer from multisystemic complications of cirrhosis, have a significantly higher risk of infection, and require accurate surveillance- especially in the context of the coronavirus disease 2019 pandemic. The rupture of an umbilical hernia, is an uncommon, life-threatening complication of large-volume ascites and end-stage liver disease resulting in spontaneous paracentesis, also known as Flood syndrome. Flood syndrome remains a challenging condition for clinicians, as recommendations for its management are lacking, and the available evidence for the best treatment approach remains controversial. In this paper, four key questions are addressed regarding the management and prevention of Flood syndrome: (1) Which is the best treatment approach-conservative treatment or urgent surgery? (2) How can we establish the individual risk for herniation and possible hernia rupture in cirrhotic patients? (3) How can we prevent umbilical hernia ruptures? And (4) How can we manage these patients in the conditions created by the coronavirus disease 2019 pandemic?

Complicated course of biliary inflammatory myofibroblastic tumor mimicking hilar cholangiocarcinoma: A case report and literature review.

BACKGROUND: The inflammatory myofibroblastic tumor (IMT) is a rare, idiopathic, usually benign, mass-forming disease with myofibroblastic proliferation and a varying amount of inflammatory cells. Although it can affect various organs, the biliary tract is a rare localization of primary IMT, clinically, endoscopically and radiologically imitating cholangiocarcinoma. The treatment options are based only on clinical practice experience. CASE SUMMARY: A 70-year-old woman was referred to our center due to progressive fatigue, weight loss, abdominal pain, night sweats, and elevated liver enzymes. Magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography (ERCP) revealed proximal common hepatic duct and hilar biliary strictures extending bilaterally to lobular bile ducts. Although initial clinical, endoscopic and radiological signs were typical for hilar cholangiocarcinoma, histological examination showed no signs of malignancy. In total, 8 biopsies using different approaches were performed (several biopsies from dominant stricture during ERCP and direct cholangioscopy; ultrasound-guided liver biopsy; diagnostic laparoscopy with liver and lymph node biopsies). Histological examination revealed signs of IMT, and the final diagnosis of biliary IMT was stated. Although IMT is usually a benign disease, in our case, it was complicated. All pharmacological treatment measures were ineffective. The patient still needs permanent stenting, suffers from recurrent infections and mechanical jaundice. Despite that, the patient already survived 24 mo. CONCLUSION: IMT presenting with hilar biliary strictures is a unique diagnostic and clinical challenge as it is indistinguishable from cholangiocarcinoma, and there are no evidence-based treatment options. Our goal is to increase the understanding of this rare disease and its possible course.

Paraneoplastic Phenomena of Disseminated Intravascular Coagulopathy in Hepatic Angiosarcoma - Rare, Challenging and Fatal. Case Report and Literature Review.

Background: Hepatic angiosarcoma is an uncommon, malignant, primary liver tumor, comprising 2% of liver cancers and accounting for < 1% of all sarcomas. Patients usually present with nonspecific symptoms, such as fatigue, weight loss, right upper quadrant pain, anemia, which leads to late diagnosis of an advanced stage tumor. The median life expectancy after the diagnosis of hepatic angiosarcoma is about 6 months, with only 3% of patients surviving more than 2 years. Liver failure and hemoperitoneum are the leading causes of death in patients with liver angiosarcoma. In rarer cases, it might cause paraneoplastic syndromes such as disseminated intravascular coagulopathy. The treatment of angiosarcomas is complicated as there are no established and effective treatment guidelines due to the tumor's low frequency and aggressive nature. Case summary: We present the case of a 68-year old woman who was admitted to the hospital due to fatigue and severe anemia (hemoglobin 65 g/l). Laboratory results also revealed high-grade thrombocytopenia (8 × 109/l). The abdominal ultrasound and computed tomography scan showed multiple lesions throughout the liver, spleen and kidneys. After the histological examination of the liver biopsy, the patient was diagnosed with hepatic angiosarcoma. The treatment with first-line chemotherapy (doxorubicin) was initiated despite ongoing paraneoplastic syndrome - disseminative intravascular coagulopathy. However, the disease was terminal, and the patient died 2 months since diagnosed. Conclusions: Hepatic angiosarcoma is a rare and terminal tumor. Therefore, knowledge about its manifestations and effective treatment methods is lacking. Disseminative intravascular coagulopathy is a unique clinical characteristic of angiosarcoma seen in a subset of patients.

Multi-organ IgG4-related disease continues to mislead clinicians: A case report and literature review.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is a multisystemic mass forming immune-mediated disease that affects almost every organ and is a diagnostic challenge for every clinician. There is a lack of adequate epidemiological data worldwide, and evidence-based treatment recommendations are not yet established. We report the first case of IgG4-RD from Lithuania and the Baltic Sea region presented with thyroiditis, orbital myositis, orbitopathy, uveitis, scleritis, sialadenitis, autoimmune pancreatitis and prostatitis. CASE SUMMARY: A 54-year-old Caucasian male was admitted to our tertiary Centre complaining of severe weight loss, diarrhoea, abdominal pain, salivary gland swelling, sicca symptoms and diplopia. On examination, bilateral palpable masses in the projection of major salivary glands, severe protrusion of the left eyeball and cachexia were noted. The patient was previously diagnosed with autoimmune thyroiditis and endocrine ophthalmopathy. The magnetic resonance imaging (MRI) of the head revealed enlarged extraocular muscles indicating orbital myositis. The biopsy from the salivary gland mass indicated sialadenitis. Abdominal MRI showed signs of autoimmune pancreatitis, and a serological test revealed the elevated serum IgG4 concentration. The patient was then diagnosed with IgG4-RD and successfully treated with prednisolone. There was a significant clinical, serological and radiological improvement after one month of treatment and no signs of relapse within twenty months. However, it took almost 18 years and the efforts of eight different medical specialists to establish the correct diagnosis. CONCLUSION: A comprehensive approach to the patient is essential to improving the recognition of rare immune system conditions, such as IgG4-RD.

Mucosa-associated lymphoid tissue lymphoma simulating Crohn's disease: A case report.

BACKGROUND: Differential diagnosis between extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue and inflammatory bowel disease is mainly based on histopathologic evaluation of intestinal biopsies, although there is no single definitive diagnostic investigation and that circumstance can lead to misdiagnosis in particular cases. Herein we present a rare, ulcerative form of marginal zone lymphoma which mimics the Crohn's disease (CD) of upper digestive tract. CASE SUMMARY: A 50-year-old man was presented with recurrent episodes of malaise and melena also weight loss. Enteroscopy of the small bowel demonstrated an ulcer in the jejunum. Microscopically, biopsies showed lymphoplasmacytic infiltrate. Diagnosis of CD was made. Primary treatment consisted of prednisone and azathioprine and was followed by azathioprine 100 mg per day with good clinical response in the following 2 years until relapse. At this time the results of endoscopic biopsies derived from proximal wall of stomach revealed Helicobacter pylori-negative marginal zone lymphoma of the gastric fundus. Immunophenotyping confirmed atypical CD20-positive cell population. Based on these biopsies, marginal zone lymphoma of mucosa-associated lymphoid tissue was diagnosed. Unfortunately, the contact with the patient was lost until one year later he was hospitalized with nausea, vomiting and severe pain because of gastrointestinal perforation. Four months later after laparotomy, the patient was treated with a course of chemotherapy. Complete remission was observed following 6 cycles of treatment. CONCLUSION: This case report highlights the clinical relevance of knowledge and awareness of marginal zone lymphoma simulating CD.

Impact of the Uridine⁻Cytidine Kinase Like-1 Protein and IL28B rs12979860 and rs8099917 SNPs on the Development of Hepatocellular Carcinoma in Cirrhotic Chronic Hepatitis C Patients-A Pilot Study.

Background and objectives: The hepatitis C virus (HCV) is the major causative agent of hepatocellular carcinoma (HCC) in the western world. The efficacy of surveillance programs for early detection of HCC is not satisfactory: many tumors are diagnosed at the late, incurable stages. Therefore, there is a need in reliable prognostic markers for the proper follow-up of HCV-positive patients. The aim of the present study was to assess the prognostic value of the uridine⁻cytidine kinase-like protein 1 (UCKL-1), a putative oncoprotein, together with genetically determined polymorphisms in the interleukin 28B (IL28B) gene (rs12979860, rs8099917) in the development of HCC in HCV-positive cirrhotic patients. Materials and Methods: We included 32 HCV cirrhotic patients, 21 (65.6%) of whom had HCC. The expression of UCKL-1 was assessed in liver tissue sections, using immunohistochemistry. For IL28B rs12979860 and rs8099917 genotype analysis, the corresponding genomic regions were amplified by polymerase chain reaction (PCR) with appropriate primers. Results: We have found that UCKL-1 expression was significantly increased in HCC (p = 0.003). The presence of rs8099917 TT single-nucleotide polymorphism (SNP) elevated the chances of HCC manifestation more than sevenfold (OR = 7.3, p = 0.0273). The presence of rs12979860 CC SNP also heightened HCC chances more than sevenfold (OR = 7.5, p = 0.0765). Moreover, in the HCC group, a combination of IL28B rs12979860 non-TT and rs8099917 TT genotypes was observed more often, compared with the non-HCC group. Other combinations of IL28B rs12979860 and rs8099917 SNIPs were associated with a reduced risk of HCC development, approximately at the same extent. Conclusions: The presence of IL28B rs8099917 TT and rs12979860 CC SNPs, but not the intensity of UCKL-1 expression, is strongly associated with increased chances of HCC development in HCV-positive cirrhotic patients.

Metabolic changes one year after laparoscopic adjustable gastric banding operation in morbidly obese subjects.

INTRODUCTION: Laparoscopic adjustable gastric banding (LAGB) is effective for weight reduction in severely obese patients. However, the data about its effect on metabolic syndrome (MS) are limited. AIM: To assess weight loss and changes of metabolic parameters 1 year after LAGB in a prospective, nonrandomized single center cohort study in morbidly obese subjects. MATERIAL AND METHODS: Physical examination, body weight (BW) parameters and metabolic profile were assessed at baseline and 1 year after LAGB in morbidly obese subjects. The incidence of MS was evaluated according to National Cholesterol Education Program Adult Treatment Panel III criteria. RESULTS: One year after the operation data from 90 patients out of 103 were available. Mean excess weight (EW) loss of 33.1% was associated with a significant improvement in all metabolic parameters: decrease of hypertension by 15.8%, hypertriglyceridemia by 42.6%, and hyperglycemia by 46.3%; and increase in high density lipoprotein cholesterol by 48.3%. This resulted in the resolution of MS in 44.2% of subjects. The significant change in the distribution of MS components was observed with the highest frequency of 4 components before and 2 components after surgery. Patients with MS at baseline lost 29.9% of EW compared to 44.3% in those without MS (p = 0.009). CONCLUSIONS: The LAGB resulted in effective reduction of BW parameters in morbidly obese subjects 1 year after the operation. Along with the weight loss, resolution of MS and a significant shift towards decrease in the number of MS components was observed. Patients with MS were more resistant to the weight loss.

Expression of cytokeratin 7 as a histological marker of cholestasis and stages of primary biliary cirrhosis.

UNLABELLED: The aim of this study was to estimate cytokeratin 7 (CK-7) expression in biopsy specimens of patients with different stages of primary biliary cirrhosis and clinicopathological patterns (cholestatic and hepatitic) and its correlation with some biochemical and pathological parameters and to examine a diagnostic value of CK-7 expression. MATERIAL AND METHODS: A total of 82 biopsy specimens of patients with primary biliary cirrhosis were analyzed. CK-7 expression was graded by 4 grades depending on the extent into parenchymal areas and bile duct epithelium. The correlations of CK-7 expression grade with copper deposition, bile duct/portal tract ratio, bilirubin concentration, and activity of alkaline phosphatase and gamma-glutamyl transpeptidase were studied. CK-7 expression was evaluated as a marker of cholestasis (cholestatic pattern) and inflammation (hepatitic pattern). RESULTS: A positive correlation of CK-7 expression grade with copper-binding protein grade (r=0.698, P<0.0001; OR=6.199, P<0.0001), serum bilirubin level (r=0.375, P=0.001), and alkaline phosphatase activity (r=0.276, p=0.014) was found. CK-7 expression grades correlated positively with histological stages of primary biliary cirrhosis (r=0.639, P<0.000) and negatively with granulomas (r=-0.432, P<0.0001; OR=0.173, P=0.0011). CONCLUSIONS: CK-7 expression is a sensitive marker of bile duct injury, which correlated well with histological stages of primary biliary cirrhosis, copper deposits, and biochemical markers of cholestasis: serum bilirubin level and alkaline phosphatase activity. Evaluation of CK-7 expression may improve the diagnosis of this serious and progressive disease. It is recommended to evaluate copper staining together with cytokeratin 7 expression in liver biopsy specimens for more precise diagnostic evaluation of asymptomatic primary biliary cirrhosis.

Changes in hepatitis C virus infection routes and genotype distribution in a Lithuanian cohort with chronic hepatitis C.

BACKGROUND: We evaluated the distribution of hepatitis C virus genotypes and determined their association with routes of infection according to the sex and age of the study subjects. MATERIAL/METHODS: We studied 1158 patients with chronic hepatitis C. Hepatitis C virus antibodies were detected with a microparticle enzyme immunoassay, hepatitis C virus ribonucleic acid was identified via polymerase chain reaction, and hepatitis C virus genotypes were determined with a line probe assay. An anonymous questionnaire completed by all subjects included the date of chronic hepatitis C diagnosis, the age and sex of the patient, the hepatitis C virus genotype and subtype, and possible routes of infection. RESULTS: Of the patients studied, 50.9% had more than 1 possible route of infection, 41.2% had a single route of infection, and 7.9% had an unknown route of infection. The most common hepatitis C transmission routes were intravenous drug use and tattoos in younger patients and surgery or long or multiple hospitalizations in older patients. The genotype distribution was as follows: genotype 1, 65.0% of patients; genotype 2, 26.3%; and genotype 3, 8.7%. The transmission of genotype 1 was associated primarily with surgery and that of genotype 3 was linked with intravenous drug use. CONCLUSIONS: Today, the main routes of hepatitis C virus transmission are intravenous drug use and tattoos. Some hepatitis C infections are associated with surgery or are acquired from a family member. The shift in transmission pathways predetermined the shift in hepatitis C virus genotypes from 1 to 3.

Prevalence of cryoglobulinemia in patients with chronic HCV infection.

BACKGROUND: The purpose of our research was to determine the prevalence of cryoglobulins in patients with chronic hepatitis C (CHC) at different levels of activity and stage of fibrosis and to identify their association with the extrahepatic clinical manifestations. MATERIAL/METHODS: 87 patients with CHC were investigated for the presence of cryoglobulins. Cryocrit was measured by the Weiner method. AntiHCV, HCV RNR, conventional biochemical tests and liver biopsy were also performed. RESULTS: Cryoglobulins were found in a total of 44 patients: 16 from Group I, 11 from Group II, and 17 from Group III. A low level of cryoglobulinemia (Cg) (cryocritL2%) was detected in 16 patients: 9 from Group I, 3 from Group II, and 4 from Group III. Moreover, a high Cg (cryocrit >5-10%) or very high Cg (cryocrit >10%) was found in a total of 13 patients: 1 patient from Group I, 3 from Group II, and 9 from Group III. Cryo positivity was found in 5 patients with F 1-2, in 13 with F 2-3, in 4 with F 3-4, and in 17 with F 4. CONCLUSIONS: Our findings confirmed the high prevalence of Cg in CHC patients in Lithuania, a clear association between Cg and the stage of fibrosis, the higher prevalence of Cg in cirrhotic patients, and the occurrence of several typical extrahepatic manifestations. The impact of Cg on the course of chronic hepatitis C is not clearly understood; therefore, further studies are needed to clarify this issue.