Genotype Distribution and Characteristics of Chronic Hepatitis C Infection in Estonia, Latvia, Lithuania, and Ukraine: The RESPOND-C Study.

Background and objectives: Since 2013, highly effective direct-acting antiviral (DAA) treatment for chronic hepatitis C (CHC) has become available, with cure rates exceeding 95%. For the choice of optimal CHC treatment, an assessment of the hepatitis C virus (HCV) genotype (GT) and liver fibrosis stage is necessary. Information about the distribution of these parameters among CHC patients in Estonia, Latvia, and Lithuania (the Baltic states) and especially in Ukraine is scarce. This study was performed to obtain epidemiologic data regarding CHC GT and fibrosis stage distribution for better planning of resources and prioritization of patients for DAA drug treatment according to disease severity in high-income (the Baltic states) and lower-middle-income (Ukraine) countries. Materials and methods: The retrospective RESPOND-C study included 1451 CHC patients. Demographic and disease information was collected from medical charts for each patient. Results: The most common suspected mode of viral transmission was blood transfusions (17.8%), followed by intravenous substance use (15.7%); however, in 50.9% of patients, the exact mode of transmission was not clarified. In Ukraine (18.4%) and Estonia (26%), transmission by intravenous substance use was higher than in Lithuania (5%) and Latvia (5.3%). Distribution of HCV GT among patients with CHC was as follows: GT1-66.4%; GT3-28.1; and GT2-4.1%. The prevalence of GT1 was the highest in Latvia (84%) and the lowest in Ukraine (63%, p < 0.001). Liver fibrosis stages were distributed as follows: F0-12.2%, F1-26.3%, F2-23.5%, F3-17.1%, and F4-20.9%. Cirrhosis (F4) was more prevalent in Lithuanian patients (30.1%) than in Estonians (8.1%, p < 0.001). Conclusions: This study contributes to the knowledge of epidemiologic characteristics of HCV infection in the Baltic states and Ukraine. The data regarding the patterns of HCV GT and fibrosis stage distribution will be helpful for the development of national strategies to control HCV infection in the era of DAA therapy.

Hepatitis C Virus Epidemiology in Lithuania: Situation before Introduction of the National Screening Programme.

In 2022, the Lithuanian health authorities decided to pay general practitioners a fee for performing serological tests for hepatitis C virus (HCV) antibodies in the population born from 1945 to 1994 once per life and annual HCV testing for PWID and HIV infected patients. This study aimed to assess trends in HCV-related mortality in the country and the prevalence of HCV infection among patients with liver diseases and evaluate possibilities of screening for HCV infection at a primary health care center. Age-standardized mortality rates in 2010-2020 were calculated for deaths caused by chronic hepatitis C and some liver diseases. Data on HCV infection among patients with liver cirrhosis, cancer and transplant patients were collected from the tertiary care hospital Kauno Klinikos. The prevalence of anti-HCV and risk factors of HCV infection was assessed among patients registered with the health care center in Klaipeda, where a pilot study of screening was performed. No steady trend in mortality was observed. Analysis of medical documentation showed that 40.5% of patients with liver cirrhosis, 49.7% with cancers and 36.9% of transplant patients were HCV infected. Over the year, 4867 patients were screened in the primary health care center. Positive anti-HCV prevalence was 1.7% (2.1% in men and 1.3% in women). Blood transfusion and being a blood donor before 1993 also having tattoos were associated with higher odds of HCV infection. The study revealed the active participation of individuals in HCV screening.

SERPINA1 and HSD17B13 Gene Variants in Patients with Liver Fibrosis and Cirrhosis.

BACKGROUND AND AIMS: Two single nucleotide polymorphisms (SNPs) in SERPINA1 (Pi*Z rs28929474 and Pi*S rs17580) are risk factors for developing liver cirrhosis. A recent study identified a common SNP in HSD17B13 (rs72613567) that conferred protection from chronic liver disease. The aim of the present study was to test these associations in a cohort of Lithuanian patients with liver fibrosis or cirrhosis. METHODS: The study included 302 patients with cirrhosis, 127 patients with liver fibrosis (METAVIR stages I-III) and 548 controls, all from Lithuania. SNPs were genotyped by quantitative PCR, using TaqMan allelic discrimination assays. Adjusted p value of ≤ 0.016 was considered significant. RESULTS: Genotype distributions of SERPINA1 and HSD17B13 SNPs were in Hardy-Weinberg equilibrium. SERPINA1 Pi*Z was not associated with liver fibrosis or cirrhosis. HSD17B13 rs10433937 (in high linkage disequilibrium with rs72613567; r 2 =0.96) also showed no overall association with liver disease, but the GG- genotype was associated with reduced risk of liver fibrosis (aOR 0.37, p=0.03). SERPINA1 Pi*S was associated with higher risk of developing hepatic fibrosis (aOR 3.42, p=0.001) and cirrhosis (aOR 2.59, p=0.02). CONCLUSIONS: We found that SERPINA1 Pi*S variant conferred an increased risk of developing liver fibrosis, while SERPINA1 Pi*Z and HSD17B13 rs10433937 were not associated with liver fibrosis or cirrhosis of different aetiology.

TM6SF2 and MBOAT7 Gene Variants in Liver Fibrosis and Cirrhosis.

Previous large-scale genetic studies identified single nucleotide polymorphisms (SNPs) of the TM6SF2 and MBOAT7 genes as risk factors for alcoholic liver cirrhosis and non-alcoholic fatty liver disease. In this study, we tried to evaluate the association between TM6SF2 variant rs58542926 and MBOAT7 variant rs641738 and the risk of hepatic fibrosis or liver cirrhosis of different etiology. In parallel, we also aimed to evaluate whether these two SNPs modify the effects of the PNPLA3 rs738409 risk variant for the development of hepatic fibrosis and liver cirrhosis. The study was conducted at the Department of Gastroenterology, Lithuanian University of Health Sciences Hospital, and included 334 patients with liver cirrhosis, 128 patients with liver fibrosis, and 550 controls. SNPs were genotyped by quantitative PCR, using TaqMan allelic discrimination assays. Overall, TM6SF2 rs58542926 as well as MBOAT7 rs641738 were not linked to hepatic fibrosis, alcohol or hepatitis C virus induced liver cirrhosis in an Eastern European population. These genetic variations also did not mediate the effect of PNPLA3 rs738409 SNP for liver developing liver fibrosis or liver cirrhosis.

PNPLA3 and RNF7 Gene Variants are Associated with the Risk of Developing Liver Fibrosis and Cirrhosis in an Eastern European Population.

BACKGROUND AND AIMS: Genome-wide association studies have revealed an association between the risk of developing liver fibrosis or cirrhosis and the single nucleotide polymorphisms (SNPs) of the PNPLA3, RNF7, MERTK and PCSK7 genes. We aimed to validate these results in an Eastern European population. METHODS: We evaluated the associations between the PNPLA3 (rs738409), RNF7 (rs16851720), MERTK (rs4374383) and PCSK7 (rs236918) variants and liver fibrosis and cirrhosis in a series of consecutive patients recruited at the Department of Gastroenterology, Lithuanian University of Health Sciences Hospital, during the period 2012-2015. The study included 317 individuals with liver cirrhosis, 154 individuals with liver fibrosis, and 498 controls. The studied SNPs were determined using RT-PCR TaqMan assays. RESULTS: MERTK and PCSK7 SNPs were not associated with liver fibrosis or cirrhosis. The PNPLA3 SNP rs738409 was associated with a higher risk of developing liver fibrosis (aOR: 1.65, P=0.001) and cirrhosis (aOR: 1.92, P=5.57*10-7). PNPLA3 genotypes were also associated with higher risk of developing liver fibrosis and cirrhosis in dominant (aOR: 1.98, P=2.20*10-5; aOR: 1.67, P=0.008, respectively) and recessive (aOR: 3.94, P=5.16*10-5; aOR: 3.02, P=0.003, respectively) models. RNF7 rs16851720 was associated with liver cirrhosis comparing CC vs. AA + CA genotypes (aOR: 0.26, P=0.020). CONCLUSION: Our study showed that PNPLA3 rs738409 and RNF7 rs16851720 confer an increased risk of developing liver fibrosis and cirrhosis in this Eastern European population, while the MERTK and PCSK7 SNPs are not associated with these conditions.

Association of HFE gene C282Y and H63D mutations with liver cirrhosis in the Lithuanian population.

BACKGROUND AND OBJECTIVE: Liver cirrhosis is the end-stage disease of chronic liver injury. Due to differences in the natural course of chronic liver diseases, identification of genetic factors that influence individual outcomes is warranted. HFE-linked hereditary hemochromatosis (HH) predisposes disease progression to cirrhosis; however, the role of heterozygous C282Y or H63D mutations in the development of cirrhosis in the presence of other etiological factors is still debated. The aim of this study was to determine the association between heterozygous C282Y and H63D mutations and non-HH liver cirrhosis in Lithuanian population. MATERIALS AND METHODS: The patient cohort consisted of 209 individuals. Diagnosis of cirrhosis was confirmed by clinical, laboratory parameters, liver biopsy, and radiological imaging. Control samples were obtained from 1005 randomly selected unrelated healthy individuals. HFE gene mutations were determined using the PCR-RFLP method. RESULTS: The most common causes of cirrhosis were hepatitis C (33.9%), hepatitis B (13.6%), and alcohol (25.8%). C282Y allele was associated with the presence of cirrhosis (OR=2.07; P=0.005); this was also observed under recessive model for C282Y (OR=2.06, P=0.008). The prevalence of C282Y allele was higher in cirrhotic men than in controls (7.0% vs. 2.8%, P=0.002). The carriage of H63D risk allele (OR=1.54; P=0.02), heterozygous C282Y/wt and homozygous H63D/H63D genotypes were associated with liver cirrhosis in males (OR=2.48, P=0.008, and OR=4.13, P=0.005, respectively). CONCLUSIONS: Heterozygous C282Y mutation of the HFE gene was associated with liver cirrhosis in the Lithuanian population. In gender-related analysis, heterozygous C282Y and homozygous H63D mutations were linked to liver cirrhosis in men, not in women.

Aorto-duodenal fistula: a rare but serious complication of gastrointestinal hemorrhage. A case report.

A primary aortoduodenal fistula (PADF) is a rare cause of gastrointestinal bleeding that is difficult to diagnose (and sometimes not diagnosed until a laparotomy.) A PADF is associated with high mortality if undiagnosed and untreated (the mortality rate of nearly 100% in the absence of a surgical intervention). While this condition is extremely rare with an incidence rate at autopsy of 0.04% to 0.07%, a secondary ADF occurs much more commonly (the post-operative incidence of 0.5% to 2.3%) and is due to prior aortic surgery and/or the placement of a synthetic aortic graft. It should be considered in any elderly patient who presents with upper gastrointestinal bleeding in the context of a known abdominal aortic aneurysm or without it when no identifiable source of bleeding is found. We present an autopsy case of a 59-year-old man with no history of an abdominal aortic aneurysm who presented with intermittent massive gastrointestinal bleeding. The autopsy revealed a pinhole fistula. It was identified between an atherosclerotic abdominal aortic aneurysm and the lower horizontal part of the duodenum. Our case indicates that the aortoenteric fistula can result in fatal gastrointestinal bleeding. This case is unique in that the fistula formed as a result of a complex atherosclerotic abdominal aorta and a localized necrotizing granulomatous aortitis the etiology of which was not clear.

Health-related quality of life measurement in chronic liver disease patients.

BACKGROUND AND OBJECTIVE: Health-related quality of life (HRQOL) is an important health indicator in medical outcome research and clinical practice. This issue tends to attract even more attention with the recent improvements of patient survival after liver transplantation. This review article aims at providing a deeper insight into practices used for evaluating HRQOL in chronic liver diseases (CLDs) and especially cirrhosis patients during different stages of the disease including liver transplantation. MATERIALS AND METHODS: A systematic review of the MEDLINE database and Cochrane library was conducted. A search using the Medical Subject Headings (MeSH) major terms "liver disease" AND "quality of life" was applied for the period from 1966 to 2012. RESULTS: Our review identified 1483 publications. The searched showed that significant increase of publications (from 362 to 1018) was observed during last decade (period 2003-2012) in comparison with previous. The majority of publications were in English (n=1179). The literature search and analysis provided information on the most common generic and disease-specific HRQOL instruments, which are used in CLD patients: Medical Outcomes Study Short Form-36, the National Institute of Diabetes and Digestive and Kidney Diseases Quality of Life questionnaire, the Chronic Liver Disease questionnaire, the Liver Disease Quality of Life questionnaire, and other. CONCLUSIONS: Quality of life instruments are potentially powerful tools for evaluating the functional status, presenting gains of treatment and reflecting patients' ability to return to a normal lifestyle in CLD patients. More attention should be paid by clinicians for integrated use of clinical tests together with HRQOL instruments in liver transplantation for establishing the reference levels of mental, physical, and role-social functioning.

The phosphodiesterase-5-inhibitor udenafil lowers portal pressure in compensated preascitic liver cirrhosis. A dose-finding phase-II-study.

BACKGROUND: Phosphodiesterase-5-inhibitors may lower portal pressure. AIMS: To investigate the effect of the phosphodiesterase-5-inhibitor udenafil on hepatic and systemic haemodynamics in liver cirrhosis. METHODS: In an open-label phase-II-study, patients with liver cirrhosis Child A/B and hepatic venous pressure-gradient ≥ 12 mmHg received 12.5mg/day, 25mg/day, 50mg/day, 75 mg/day (n = 5, each), or 100mg/day (n = 10) udenafil p.o. for one week. On days 0 and 6, hepatic venous pressure-gradient was measured prior to and one hour after drug ingestion. Endpoints were reduction of hepatic venous pressure-gradient from day 0 pre to day 6 post intake and reduction in the acute setting. Pharmacokinetics were measured in the two lowest dosage groups. RESULTS: Combining the 75 and 100mg/day groups hepatic venous pressure-gradient reduction after drug intake was 19.9% (p = 0.0006) on day 0. From day 0 pre-dose to day 6 post-dose hepatic venous pressure-gradient decreased by 15.7% (p = 0.040) and in 5/15 patients by ≥ 20% or to <12 mmHg. In the 100mg/day group, mean arterial pressure decreased from 98.9 mmHg by 6.2 mmHg (p = 0.037) from day 0 pre-dose to day 6 post-dose. Heart rates or electrocardiograms were unchanged. Udenafil was eliminated with t1/2 = 25 h. CONCLUSIONS: Oral application of 75-100mg of the phosphodiesterase-5-inhibitor udenafil lowers portal pressure in the acute setting by about 20% without relevant systemic cardiovascular side effects.

An unusual case of bleeding from stomach due to a giant diospyrobezoar.

Gastric bezoars may be formed in the stomach as a result of foreign body accumulation with inability to pass through the pylorus. Usually bezoars are found in patients with a history of previous gastric surgery. Phytobezoars are the most common type of bezoars. Major complications of bezoars include intestinal obstruction, gastric ulcer, gastric perforation, and bleeding. We present the case of a 51-year-old woman with the features of gastrointestinal bleeding due to a giant diospyrobezoar in the stomach. During endoscopy besides the bezoar, a giant acute ulcer was found. Histological examination of biopsy specimens from ulcer area revealed changes typical of superficial ischemic damage due to prolonged bezoar compression. The patient had undergone a vagotomy and pyloroplasty 13 years ago, and she used to eat two or three persimmons per week during the last six months. The bezoar was fragmented during two endoscopies, and the fragments drifted away through the intestine. We conclude that delayed gastric emptying due to previous gastric surgery and regular eating of persimmons caused the formation of a giant bezoar with ischemic ulcer of gastric mucosa and bleeding. Such pathology potentially could be prevented by dietary advice.

Quality of life and voice in patients treated for early laryngeal cancer.

OBJECTIVES: To evaluate quality of life and voice in patients previously treated for early laryngeal cancer versus healthy controls and to assess correlations between demographic and cancer characteristics and posttreatment quality of life and voice. MATERIAL AND METHODS: A total of 49 patients diagnosed with early (Tis-T2N0) laryngeal carcinoma, treated by radiotherapy or endoscopic surgery at least 6 months before, who were alive and free of recurrence formed study group. Postservice with questionnaires was accomplished. Quality of life was evaluated using Medical Outcomes Study 36-Item Health Survey (SF-36), Hospital Anxiety and Depression (HAD) Scale, voice quality--by Voice Handicap Index (VHI). Normative data were obtained from database or concurrently assessed healthy adult subjects. RESULTS: Hoarseness was the most frequent complain. Majority of patients consider their health as fair (69.4%), one third--good or excellent. The means of summary of SF-36 scores for physical and mental health differ significantly from normative age-matched population (P<0.001). Emotional distress on HAD scale was found in 40.8% of patients vs. 17.0% of healthy controls. Majority (87.8%) of patients rated their voice abnormal; vast majority of them had slight to moderate dysfunction. Mean VHI scores were slight elevated for patients and differed significantly from healthy ones. Correlation analysis revealed a significant relationship between patients' physical health and some demographic-clinic factors. CONCLUSIONS: Quality of life in patients previously treated for early laryngeal cancer was worse than healthy subjects. Psychiatric morbidity was indicated in around of one-third of the patients. Voice changes were reported in most patients with low handicap level. Physical health perception was better for patients with higher grade of cancer differentiation, not using alcohol, and treated first.

Disease-specific health-related quality of life and its determinants in liver cirrhosis patients in Lithuania.

AIM: To evaluate disease-specific quality of life (QOL) in liver cirrhosis patients and to compare it with those of a healthy population. Also an important objective was to assess whether QOL in liver cirrhosis patients differs by age and gender, by type and severity of disease. METHODS: The case group of 131 liver cirrhosis patients was selected. The control group of 262 was enrolled from a healthy population according to the scheme of case-control study. Clinical, demographic, laboratory data were collected. QOL was measured with a specific chronic liver disease questionnaire (CLDQ), which was translated and validated in Lithuanian. QOL scores were compared between groups by age, gender, type and severity of disease. Cronbach's alpha statistics calculation was used for evaluation of internal consistency reliability. Student's t test or ANOVA were used for evaluation hypothesis about probability equation. RESULTS: QOL was significantly lower in liver cirrhosis patients than in healthy population (59.5 +/- 18.3 vs 85.3 +/- 12.3, P < 0.001). The significant QOL differences between case and control groups were observed in domains of worry and abdominal symptoms, the smaller differences-in emotional functions and systematic symptom domains. Significantly worse QOL was in observed patients with increased clinical severity of the disease measured by Child-Pugh class. Age, gender and etiology of disease had an insignificant effect on QOL in cirrhotic patients. CONCLUSION: QOL was significantly impaired in all CLDQ domains in liver cirrhosis patients. Increase in severity of disease was the major factor associated with poorer QOL.

Prognostic factors for short and long-term survival in patients selected for liver transplantation.

UNLABELLED: Indices for predicting of survival are essential tools for assessing prognosis and establishing priority for liver transplantation. Our aim was to investigate the survival and prognostic significance of Child-Turcotte-Pugh (CTP) score and model for end-stage liver disease (MELD) scale for short and long-term survival prognosis in waitlist of patients selected for liver transplantation. MATERIAL AND METHODS: The group of 236 patients with diagnosis of different chronic liver disease was investigated in period of 4.5 years. Persons with CTP scoring > or =10 were included into the waitlist for liver transplantation. Other inclusion criteria were based on CTP scoring > or =7 plus one or more liver cirrhosis complications. The cumulative and mean survivals were evaluated according to the Kaplan-Meier statistical analysis. The distribution and the survival data for the patients were based on biochemical variables. The clinical status of waitlist patients was evaluated by applying the CTP and MELD scales. The short and long-term survival prognosis was assessed. The odds ratios with 95% confidence interval univariate analysis were evaluated. RESULTS: During the period of 4.5 years 45 persons were selected for waitlist group. Mortality rate was 51.1%, average survival--17.9 months. The significant trends towards higher cumulative proportion of survival were observed for the patients with low serum bilirubin, creatinine and low blood urea. The highest mortality rate was in the group with CTP scores > or =12. The highest mortality and the shortest average of survival were in the group of cases with the highest scores. It was established the significant difference for short-term survival (less than 3 months) prognosis in MELD scale. CTP scores had no predictive influence for survival during 3 months. Also both scoring had high prognostic value for prediction of the long-term survival (more than 3 months). Deterioration of cumulative survival and overall survival were affected by increase of serum bilirubin, blood urea and creatinine. Increase of scores in CTP and MELD scale had the direct positive correlation with increased mortality. MELD scale has higher capability to predict short-term mortality risk in patients with end-stage liver disease. CTP and MELD scales have proven good prognostic capabilities both for short and long-term survival in patients with chronic liver disease.