Impact of multiple primary cancers on overall survival of patients with hepatocellular carcinoma.

The increasing occurrence of multiple primary cancers (MPC) is a long-term trend, but the prevalence of MPC in patients with hepatocellular carcinoma (HCC) and its impact on overall survival (OS) remains unknown. We retrospectively analyzed 497 patients with HCC treated at two tertiary centers. The cohort was divided into two subgroups - liver transplant (LT, 324 patients) and non-liver transplant (non-LT, 173 patients). We analyzed MPC occurrence, its impact on survival, and identified variables predicting unfavorable outcomes. The MPC were detected in 88 patients (18%). The most common MPC were prostate (17%), skin (15.9%), kidney (12.5%), and lung (10.2%). The median OS of the whole cohort and the LT and non-LT subgroups were 70, 116, and 17 months, respectively (p<0.0001). The median OS in patients with HCC only and HCC with another cancer was 77 (95% CI, 67-96) and 50 months (95% CI, 37-62), respectively (p=0.25). The OS of LT patients was significantly better than that of those in whom LT had been contraindicated owing to concomitant MPC (116 vs. 35 months, p<0.0009). Autoimmune etiology, non-alcoholic steatohepatitis (NASH), HCC as the first diagnosed malignancy, and male sex were identified as factors significantly influencing the patients' outcomes (HR 0.43, 3.2326, 0.70, and 1.43, respectively). The MPC frequency was 18%. The impact of MPC on OS was not significant, except for individuals contraindicated for LT because of MPC. A better prognosis is associated with the autoimmune etiology of cirrhosis, and when HCC is diagnosed as the first malignancy. Male sex and NASH worsened the outcomes.

Efficacy of blood plasma spectroscopy for early liver cancer diagnostics in obese patients.

INTRODUCTION AND OBJECTIVES: Hepatocellular carcinoma (HCC) represents one of the most common cancers worldwide. A considerable proportion of HCC is caused by cirrhosis related to metabolic dysfunction-associated steatohepatitis (MASH). Due to the increasing prevalence of metabolic syndrome, it is estimated that MASH-related HCC will become the most prevalent etiology of HCC. Currently, HCC screening is based on liver ultrasonography; however, the sensitivity of ultrasonography for early HCC stages in obese patients only reaches 23 %. To date, no studied biomarker shows sufficient efficacy for screening purposes. Nevertheless, the usage of spectroscopic methods offers a new perspective, as its potential use would provide cheap, fast analysis of samples such as blood plasma. MATERIAL AND METHODS: We employed a combination of conventional and chiroptical spectroscopic methods to study differences between the blood plasma of obese cirrhotic patients with and without HCC. We included 20 subjects with HCC and 17 without evidence of liver cancer, all of them with body mass index ≥ 30. RESULTS: Sensitivities and specificities reached values as follows: 0.780 and 0.905 for infrared spectroscopy, 0.700 and 0.767 for Raman spectroscopy, 0.840 and 0.743 for electronic circular dichroism, and 0.805 and 0.923 for Raman optical activity. The final combined classification model based on all spectroscopic methods reached a sensitivity of 0.810 and a specificity of 0.857, with the highest area under the receiver operating characteristic curve among all models (0.961). CONCLUSIONS: We suggest that this approach can be used effectively as a diagnostic tool in patients who are not examinable by liver ultrasonography. CLINICAL TRIAL REGISTRATION: NCT04221347.

Vibrational and chiroptical analysis of blood plasma for hepatocellular carcinoma diagnostics.

More than one fifth of the world's population suffers from liver cirrhosis or other chronic liver diseases. Unfortunately, some of them will inevitably develop hepatocellular carcinoma (HCC), due to the vast majority of HCC cases arising against the background of liver cirrhosis. Despite this clearly identified high-risk group, the lack of early diagnostic options causes HCC mortality to approach its incidence. As opposed to many types of cancer, the incidence of HCC is expected to grow in the coming decades, which makes the search for an effective early diagnostic option a pressing necessity. This study presents evidence that blood plasma analysis employing a combination of chiroptical and vibrational spectroscopic methods might be the key to the improvement of the current status. One hundred samples of patients with HCC and controls with cirrhosis were classified using principal component analysis together with a random forest algorithm. Differentiation of the specific spectral patterns of the studied groups was successful in more than 80%, indicating the prospect of including spectroscopy in the screening of high-risk groups, such as patients with cirrhosis.

Acute pancreatitis - predicting the severity of the disease.

RATIONALE: Acute pancreatitis (AP) is a serious acute abdominal disease. AP is often referred to as an unpredictable illness, which can take a mild to severe (fatal) course. AIMS OF THE STUDY: 1) To identify clinical parameters that are significantly related to the clinical course of acute pancreatitis. 2) To compile a scoring system enabling the severity of AP to be predicted when the patient is first admitted to hospital. METHODS: Analysis of available publications and clinical guidance, and retrospective analysis of data on patients hospitalised with AP at our clinic enable us to identify clinical details and laboratory results recorded at the time of patients' admission to hospital that are related to the subsequent severity of the disease. For the purposes of statistical analysis, the sample of patients was divided into two groups: group A (mild AP, without local or organ complications), group B (moderately severe and severe AP with local and/or organ complications). PATIENT GROUPS AND RESULTS: In total, between 01.01.2013 and 30.06.2022, 312 patients with acute pancreatitis were allocated to the retrospective-prospective study sample. 74 % (231/312) of these patients were allocated to group A and 26 % (81/312) were allocated to group B. Univariate analysis of the data collected on the patient sample identified 5 parameters that are statistically significantly associated with the severity of the clinical course of the disease. Presence of SIRS on admission (A vs B, Odds ratio 10.787, 95% CI 5.09-22.85, p < 0.0001), diabetes mellitus type 2 in case history (A vs B, Odds ratio 7.703, 95% CI 3.04-19.51, p 2 mmol/l (A vs B, Odds ratio 3.293, 95% CI 1.59-6.82, p = 0.0013).In order to develop a scoring system, each of these parameters was allocated a points value based on its Odds ratio (OR): presence of SIRS 3 points, hypocalcaemia 3 points, diabetes mellitus type 2 in case history 2 points, urea concentration > 8 mmol/l 1 point and lactate concentration > 2 mmol/l 1 point. The authors refer to their scoring system as The Acute Pancreatitis Admission Score (APAS). The accuracy of APAS was modelled for various cut off values. Across the whole sample, we ascertained that an APAS ≥ 4 points predicts moderately severe or severe AP with a sensitivity of 81 % (95% CI: 71 - 89 %) and specificity of 87 % (95 CI: 81 - 91 %). The positive predictive value (PPV) of APAS ≥ 4 is 0.68, while its negative predictive value (NPV) is 0.93 and accuracy 0.85 (95% CI 0.81 - 0.89). CONCLUSION: In this study we identify significant simple clinical and laboratory parameters that are commonly tested as part of an initial examination when admitting a patient with AP to hospital. Having identified these parameters we are able to establish a simple scoring system that is able to predict the severity of the course of AP at the moment of hospitalisation (Tab. 5, Fig. 2, Ref. 27).

Hepatocellular carcinoma, multiple primary neoplasia, and their association with diabetes type 2.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer and a frequent fatal complication of chronic liver diseases in the stage of liver cirrhosis. HCC develops at a higher rate in patients with type 2 diabetes mellitus (DM2). DM2 is associated with an increased risk of developing malignant tumors. The term multiple primary neoplasia (MPN) is used to describe the occurrence of multiple primary tumors of different organs in the same individual. To the best of the authors knowledge, the topic of the association between HCC and MPN and DM2 has not been addressed in the Czech literature. Here we present the outcomes of retrospective statistical analysis of a cohort of patients with HCC who were dispensed at the Internal Medicine Clinic of the 1st Faculty of Medicine of the Charles University in the period 2011-2021 and the impact of DM2 and MPN on overall survival (OS). MPNs are relatively common in patients with HCC. The occurrence of MPNs in our cohort was associated with DM2 in half of the cases. Median OS in HCC patients was not significantly affected by the coincidence of DM2 and/or MPNs.

Etiopathogenetic Factors of Hepatocellular Carcinoma, Overall Survival, and Their Evolution over Time-Czech Tertiary Center Overview.

Background and Objectives: Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer with a highly unfavorable prognosis. Aims: Retrospective statistical analysis of patients with HCC in the field of liver cirrhosis treated at our center from the perspective of demography, and the effects of key changes in diagnostic and therapeutic procedures in the last 10 years on overall survival (OS) and earlier diagnosis. Materials and Methods: This study included 170 cirrhotic patients with HCC (136 men, 80%). Demographic and etiological factors and OS were analyzed based on distribution into three groups according to the period and key changes in diagnostic and therapeutic approaches (BCLC classification staging; standardization of protocol for transarterial chemoembolization (TACE) and the introduction of direct-acting antivirals (DAA) for the treatment of chronic viral hepatitis C (HCV); expansion of systemic oncological therapy). Results: The mean age at the time of diagnosis was 69.3 years (SD = 8.1), and etiology was as follows: non-alcoholic steatohepatitis (NASH) 39%, alcoholic liver disease (ALD) 36%, HCV 18%, cryptogenic liver cirrhosis 3%, chronic hepatitis B infection (HBV) 2%, and other etiology 2%. Distribution of stages according to the BCLC: 0 + A 36%, B 31%, C 22%, and D 11%. However, the distribution in the first studied period was as follows: 0 + A 15%, B 34%, C 36%, and D 15%; and in the last period: 0 + A 45%, B 27%, C 17%, and D 11%, and difference was statistically significant (p < 0.05). The median OS for stages 0 + A, B, C, and D was 58, 19, 6, and 2 months, respectively. During the monitored period, there was a visible increase in the etiology of ALD from 30% to 47% and a decrease in HCV from 22% to 11%. In patients treated with TACE (stage B), the median OS grew from 10 to 24 months (p < 0.0001) between the marginal monitored periods. Conclusions: We described a decreasing number of patients with HCV-related HCC during follow-up possibly linked with the introduction of DAA. In our cohort, an improvement in early-stage diagnosis was found, which we mainly concluded as a result of proper ultrasound surveillance, the institution of a HCV treatment center, and increased experience of our sonographers with an examination of cirrhotic patients. Lastly, we described significantly improved overall survival in patients with intermediate HCC treated by TACE, due to the increased experience of interventional radiologists with the method at our facility and an earlier switch to systemic therapy in case of non-response to TACE.

The role of endoscopic ultrasound in patients with acute pancreatitis.

OBJECTIVES: Acute biliary pancreatitis is the most common form of acute pancreatitis worldwide. Endoscopic ultrasound (EUS) may be helpful in detecting common bile duct stones and in indicating more invasive endoscopic retrograde cholangiopancreatography (ERCP) examinations or determining rarer aetiologies of acute pancreatitis. METHODS: Over a period of six years, we prospectively collected 131 patients with acute biliary pancreatitis and observed the need for endoscopic examination alongside with a decrease in the number of necessary ERCP examinations as a result of negative EUS results (no bile duct stones detected). We compared groups of patients given different endoscopic treatments in relation to their hospital mortality relative to the incidence of severe acute pancreatitis. RESULTS: As many as 68 % of primarily indicated EUS examinations had a negative result (no common bile duct stones detected) and this result saved the patients from needing to undergo an invasive ERCP procedure. Both the incidence of the severe form of acute pancreatitis and the hospital mortality rate were lower among patients who underwent only EUS or ERCP after EUS as compared to patients who underwent ERCP straight away. CONCLUSION: The use of EUS in patients with acute pancreatitis is very helpful in determining the treatment strategy (ERCP indication) and may reduce hospital mortality (Tab. 2, Ref. 14).

Glecaprevir/pibrentasvir for 8 weeks in treatment-naïve patients with chronic HCV genotypes 1-6 and compensated cirrhosis: The EXPEDITION-8 trial.

BACKGROUND & AIMS: Eight-week glecaprevir/pibrentasvir leads to high rates of sustained virological response at post-treatment week 12 (SVR12) across HCV genotypes (GT) 1-6 in treatment-naïve patients without cirrhosis. We evaluated glecaprevir/pibrentasvir once daily for 8 weeks in treatment-naïve patients with compensated cirrhosis. METHODS: EXPEDITION-8 was a single-arm, multicenter, phase IIIb trial. The primary and key secondary efficacy analyses were to compare the lower bound of the 95% CI of the SVR12 rate in i) patients with GT1,2,4-6 in the per protocol (PP) population, ii) patients with GT1,2,4-6 in the intention-to-treat (ITT) population, iii) patients with GT1-6 in the PP population, and iv) patients with GT1-6 in the ITT population, to pre-defined efficacy thresholds based on historical SVR12 rates for 12 weeks of glecaprevir/pibrentasvir in the same populations. Safety was also assessed. RESULTS: A total of 343 patients were enrolled. Most patients were male (63%), white (83%), and had GT1 (67%). The SVR12 rate in patients with GT1-6 was 99.7% (n/N = 334/335; 95%CI 98.3-99.9) in the PP population and 97.7% (n/N = 335/343; 95% CI 96.1-99.3) in the ITT population. All primary and key secondary efficacy analyses were achieved. One patient (GT3a) experienced relapse (0.3%) at post-treatment week 4. Common adverse events (≥5%) were fatigue (9%), pruritus (8%), headache (8%), and nausea (6%). Serious adverse events (none related) occurred in 2% of patients. No adverse event led to study drug discontinuation. Clinically significant laboratory abnormalities were infrequent. CONCLUSIONS: Eight-week glecaprevir/pibrentasvir was well tolerated and led to a similarly high SVR12 rate as the 12-week regimen in treatment-naïve patients with chronic HCV GT1-6 infection and compensated cirrhosis. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03089944. LAY SUMMARY: This study was the first to evaluate an 8-week direct-acting antiviral (DAA) regimen active against all major types of hepatitis C virus (HCV) in untreated patients with compensated cirrhosis. High virological cure rates were achieved with glecaprevir/pibrentasvir across HCV genotypes 1-6, and these high cure rates did not depend on any patient or viral characteristics present before treatment. This may simplify care and allow non-specialist healthcare professionals to treat these patients, contributing to global efforts to eliminate HCV.

Chronic hepatitis C in the Czech Republic: Forecasting the disease burden.

OBJECTIVE: Chronic HCV infection is associated with cirrhosis of the liver, hepatocellular carcinoma (HCC), and liver transplantation. HCV disease burden and the impact of new potent direct acting antivirals (DAAs) in the Czech Republic are unknown. METHODS: Using a modelling framework, HCV disease progression in the Czech Republic was predicted to 2030 under the current standard of care treatment structure. In addition, two strategies to reduce the future burden of HCV infection were modelled: an incremental increase in treatment annually and WHO targets. RESULTS: The number of viremic infected individuals in the Czech Republic is estimated to peak in 2026 (n = 55,130) and to decline by 0.5% by 2030 (n = 54,840). The number of individuals with compensated cirrhosis (n = 1,400), decompensated cirrhosis (n = 80), HCC (n = 70), and liver-related deaths (n = 60) is estimated to more than double by 2030. Through aggressive increases in diagnosis and treatment, HCV related mortality may decrease by 70% by 2030. CONCLUSIONS: Disease burden associated with chronic HCV infection is projected to peak in the Czech Republic in 30-40 years. Assuming that the current portion of DAAs used remains constant, a significant reduction in HCV disease burden is possible through increased diagnosis and treatment through 2030. This analysis provides evidence in order to facilitate the development of national strategies for HCV care and management in the Czech Republic.

Pangenotypic treatment regimens for chronic hepatitis C.

The treatment of chronic hepatitis C is currently based exclusively on the use of drugs from the direct-acting anti-viral class. They are substances that inhibit one of the 3 most important enzymes of the virus replication cycle. Anti-viral drugs are divided according to the target structure into 3 basic classes, further division is mainly based on the chemical structure of individual antivirals. A common feature of all the regimens is high efficiency and safety. Pangenotypic efficacy regimens are those that utilize a combination of 2 or 3 antiviral agents of different classes, and are effective for all HCV genotypes. Currently there are 3 such regimens available. Pangenotypic regimens probably represent the latest stage of development of treatment for chronic hepatitis C. The review discusses in detail the efficiency of different pangenotypic regimens in individual subgroups of patients with HCV infection. Atten-tion is primarily paid to the data bases for their use.

[Diagnosis and therapy of hepatitis B virus infection: Czech national guidelines].

The new recommendations reflect the increase in knowledge that has been reported since the release of previous Czech guidelines in September 2014. The basis for these guidelines were the European Association for the Study of the Liver guidelines from April 2017. According to qualified estimates, there are 240 million people with chronic hepatitis B (HBV) infection worldwide. The Czech Republic is among the countries with a low prevalence of HBV infection. According to the latest seroprevalence study, 0.56 % of the Czech citizens were chronically infected with HBV in 2001. A similar study conducted in only two regions of the Czech Republic in 2013 showed a prevalence of only 0.064 %. HBV infection can lead to serious life-threatening liver damage - fulminant hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). The main goals of treatment are to prolong the length of life and improve its quality by preventing the progression of chronic hepatitis to cirrhosis, cirrhosis decompensation and development of HCC. The goals may be achieved if HBV replication is suppressed in a sustained manner. Additional goals are prevention of vertical transmission from mother to newborn, inhibition of HBV reactivation and therapy of HBV-related extrahepatic manifestations. Generally, there are two different strategies of chronic hepatitis B therapy available - treatment with nucleoside or nucleotide inhibitors (NIs) or with pegylated interferon alfa. Currently, the vast majority of Czech and European patients are treated with NIs. The NIs that have been approved for HBV treatment in the European Union include lamivudine, adefovir dipivoxil, entecavir (ETV), telbivudin (TBV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF). TAF and TBV have not yet been marketed in the Czech Republic. The main advantages of treatment with potent NIs with a high barrier to resistance (ETV, TDF, TAF) are their predictable high long-term antiviral efficacy leading to undetectable HBV DNA levels in the vast majority of compliant patients as well as their favorable safety profiles. These drugs can be used in any HBV infected patient and represent the only treatment option for patients with decompensated liver cirrhosis, liver transplants, extrahepatic HBV-related manifestations, severe acute hepatitis B or chronic HBV reactivation.

Efficacy and safety of elbasvir/grazoprevir and sofosbuvir/pegylated interferon/ribavirin: A phase III randomized controlled trial.

BACKGROUND & AIMS: Direct-acting antiviral agents have improved treatment outcomes for patients with hepatitis C virus (HCV) infection; however, head-to-head comparisons are limited. The C-EDGE Head-2-Head Study compared the safety and efficacy of elbasvir/grazoprevir (EBR/GZR) with sofosbuvir plus pegylated interferon/ribavirin (SOF/PR) in patients with HCV infection. METHODS: This was a randomized, open-label, phase III trial. Two hundred fifty-seven patients with HCV genotype (GT)1 or 4 infection and baseline viral load >10,000IU/ml were randomized to receive 12weeks of EBR/GZR 50mg/100mg once daily (n=129) or sofosbuvir (400mg once daily) plus PR (n=128). Primary efficacy objective was sustained virologic response 12weeks after the end of therapy (SVR12, HCV RNA <15IU/ml). The primary safety objective was the proportion of patients experiencing a tier 1 safety event. RESULTS: The majority of patients were non-cirrhotic (83.1%), treatment-naïve (74.9%) and had HCV GT1b infection (82.0%). SVR12 rates were 99.2% (128/129) and 90.5% (114/126) in the EBR/GZR and SOF/PR groups, respectively. The estimated adjusted difference in SVR12 was 8.8% (95% confidence interval [CI], 3.6-15.3%). Because the lower bound of the 1-sided 1-sample exact test was greater than -10% and greater than zero, both non-inferiority and superiority of EBR/GZR vs. SOF/PR were established. The frequency of tier 1 safety events was lower among patients receiving EBR/GZR than SOF/PR (0.8% vs. 27.8%, between group difference, 27.0% [95% CI, -35.5% to -19.6%; p<0.001]). CONCLUSIONS: EBR/GZR has a superior efficacy and safety profile in patients with HCV GT1 or 4 infection compared with SOF/PR. LAY SUMMARY: The combination of elbasvir/grazoprevir for 12weeks was highly effective in treating patients with chronic hepatitis C, genotypes 1 or 4 infection. This regimen was more effective than sofosbuvir/pegylated interferon/ribavirin for 12weeks, and was notably superior in patients regarded as difficult to treat, including those with previous treatment failure, cirrhosis, or a high baseline viral load. The combination of elbasvir/grazoprevir also demonstrated a superior safety and tolerability profile based on fewer serious adverse events, no serious drug-related adverse events, and no treatment discontinuations. CLINICAL TRIAL REGISTRATION: Clinical trials.gov Identifier: NCT02358044.

Predictive role BLVRA mRNA expression in hepatocellular cancer.

 Introduction and aim. Hepatocellular carcinoma (HCC) is the most common primary malignant liver tumor. It is primarily caused by hepatic cirrhosis or chronic viral hepatitis. Hepatic carcinogenesis is associated with increased oxidative stress. Thus, the aim of our study was to assess expression of the genes involved in the homeostasis of oxidative stress in patients with HCC. MATERIAL AND METHODS: The study was performed on 32 patients with primary HCC (verified by liver histology in 29 patients) and 27 control subjects (in 11 subjects, liver histology was available either with no or minimal changes in the liver tissue). Gene expressions of heme oxygenase 1 (HMOX1), biliverdin reductase A/B (BLVRA/B), NADPH oxidase 2 (NOX2) and p22phox were analyzed in the liver and peripheral blood leukocytes (PBL) in the subjects. RESULTS: Compared to controls, almost a 3 times higher mRNA level of BLVRA was detected in livers of HCC patients (p = 0.002); while those of BLVRB as well as HMOX1 were unchanged (p > 0.05). In accord with these results in the liver tissue, BLVRA mRNA levels in PBL were also significantly increased in HCC patients (p = 0.012). mRNA levels of NOX2 and p22phox in the liver tissue, although higher in HCC patients, did not differ significantly compared to control subjects (p > 0.05). Nevertheless, NOX2 mRNA level in PBL was significantly higher in HCC patients (p = 0.003). CONCLUSIONS: BLVRA mRNA levels in the liver as well as in PBL are significantly higher in HCC patients most likely as a feedback mechanism to control increased oxidative stress associated with HCC progression.

[ART score prognostic significance in patients with intermediate hepatocellular carcinoma]. / Prognostický význam ART skóre u pacientu s intermediárním hepatocelulárním karcinomem.

Palliative transarterial chemoembolization is indicated for patients with stage B hepatocellular carcinoma (HCC) based on the Barcelona Clinic Liver Cancer classification (BCLC). As this is a very wide and heterogenous group of patients, the ART score was designed to better differentiate these patients and to guide the decision for a second transarterial chemoembolization cycle.The goal of the study is to prove that the ART score is appropriate to define subgroups within the stage BCLC-B HCC group with significantly better or worse overall survival (OS) after repeated transarterial chemoembolization. A combined retrospective and prospective study was performed of the OS of patients with stage BCLC-B HCC that were monitored and treated at the Internal Medicine Clinic of the First Faculty of Medicine, Charles University in Prague and the Central Military Hospital Prague. An analysis of the survival curve using the Kaplan-Meier method was performed using the R software package.The median OS of the entire patient group was 18 months (95% CI 12-33). The median OS of patients with a favorable ART score was 33 months (95% CI 12-33) compared to 12 months (95% CI 6-18) for patients with an unfavorable ART score. The difference in OS in the subgroups differentiated by ART score was statistically significant (p < 0.01). Due to the significant difference in OS of patients differentiated by ART score, the currently recommended guidelines for the treatment of patients with stage BCLC-B hepatocellular carcinoma should be revised.

[Dangerous cucumbers - Leylls syndrome]. / Nebezpecné okurky - Leylluv syndrom.

Leylls syndrome (syndrome of toxic epidermal necrolysis) is a rare disease, firstly described by Scottish doctor of medicine Allan Lyell in 1956. It is characterized by huge skin and mucosa necrolysis, which affects at least 30 % of body surface, and systemic symptoms. According to the frequency of the occurrence it is an extremely rare condition, with an incidence of 0.5-2 cases per million residents per year. Leylls syndrome is considered as a toxoallergic reaction, triggered mostly by some medication and it is associated with a very high mortality rate (in the literature reported between 30 to 90 %). Adequate and timely local and systemic treatment at the Intensive Care Unit or at the specialized clinic can improve the overall poor prognosis of the patients. In our case report we describe a very rare case of the Lyells syndrome after exposure to the antifungal organosulfur compound, which is widely used by the homegardners and farmers.

Sustained virological response with telaprevir in 1,078 patients with advanced hepatitis C: the international telaprevir access program.

BACKGROUND & AIMS: There is little information regarding the extent to which difficult to cure patients with advanced liver fibrosis, due to hepatitis C virus genotype-1 (HCV-1) can successfully and safely be treated with triple therapy with telaprevir (TVR), pegylated interferon alpha (P) and ribavirin (R). In the TVR early access program HEP3002 we aimed to explore treatment safety and efficacy, and identify predictors of sustained virological response at week 24 (SVR24). METHODS: 1078 patients with bridging fibrosis (n=552) or cirrhosis (n=526) diagnosed by either liver biopsy or non-invasive markers, with compensated bone marrow (neutrophils >1500/mm(3), Hb >12/13 g/dl) and liver function (Albumin >3.3g/dl, Platelets >90,000/ml) received TVR PR for 12 weeks, followed by a PR tail according to label. RESULTS: Overall, 614 (57%) achieved SVR24 by intention-to-treat analysis. The SVR24 rate was 68% in 221 treatment naïve patients (62.8% F4), 72% in 356 prior relapsers (64.4% F4), 55% in 139 partial responders (53.2% F4), and 34% in 294 null responders (28.6% F4). The SVR24 rate to response-guided therapy (24 weeks treatment duration if undetectable viremia at weeks 4 and 12) was 84% in 222 naïve/relapser F3 patients. Independent predictors of response were: (A) F3 (odds ratio (OR)=1.51, 95% CI 1.31-2.00, p=0.005), (B) subtype 1b (OR=1.63, 95% CI 1.18-2.24, p=0.0029), (C) alpha-fetoprotein <10 ng/ml (OR=2.50, 95% CI 1.87-3.36, p<0.0001) and (D) any prior response other than null (OR=3.29, 95% CI 2.40-4.52, p<0.0001). SVR24 rose for patients who had more of these predictive factors: 6/32 (19%) for none, 38/139 (27%) for 1, 129/260 (50%) for 2, 202/329 (61%) for 3, and 194/235 (83%) for 4 factors. Grade 2-4 treatment-related adverse events (AE) were experienced by 719 (67%) patients; 169 (16%) discontinued therapy for AE and 7 (0.6%) died during the PR tail. CONCLUSIONS: Naïve and experienced patients with advanced fibrosis or cirrhosis due to HCV-1 who have compensated bone marrow and liver function, can effectively and safely be treated by TVR triple therapy. Baseline predictors of outcome have been identified to optimize pre-treatment counselling.

[Diagnosis and therapy of chronic hepatitis B: Czech national guidelines]. / Doporucený postup diagnostiky a lécby chronické hepatitidy B: Datum vydání doporucení: zárí 2014.

The new recommendations reflect the increase in knowledge that has been reported since the release of previous Czech guidelines in April 2009. According to qualified estimates, there are 350-400 million people with chronic hepatitis B (HBV) infection worldwide. The Czech Republic is among the countries with a low prevalence of HBV infection. According to the latest seroprevalent study, 0.56 % of the Czech citizens were chronically infected with HBV in 2001. HBV infection can lead to serious life-threatening liver damage - fulminant hepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). The goals of treatment are to prolong the length of life and improve its quality by preventing the progression of chronic hepatitis to cirrhosis, cirrhosis decompensation and development of HCC. The goals can be achieved if HBV replication is suppressed in a sustained manner. Then, the accompanying reduction in histological activity lowers the risk of cirrhosis and HCC, particularly in non-cirrhotic patients. Currently, two different strategies for treating chronic hepatitis B are available. Treatment of finite duration is with pegylated interferon (PEG-IFN), entecavir (ETV), or tenofovir (TDV). A 48-week course of PEG-IFN is mainly recommended for HBeAg-positive patients with the best chance of anti-HBe seroconversion. Finite-duration of ETV or TDV treatment is available for HBeAg-positive patients who seroconvert to anti-HBe on treatment. However, treatment duration is unpredictable prior to the therapy as it depends on the timing of anti-HBe seroconversion and the treatment continuation following anti-HBe seroconversion (therapy should be prolonged for additional 12 months after anti-HBe seroconversion). Long-term ETV or TDV therapy is necessary for HBeAg-positive patients who do not develop anti-HBe seroconversion and for HBeAg-negative patients. This strategy is also recommended for patients with cirrhosis irrespective of the initial HBeAg status or anti-HBe seroconversion on treatment. The advantage of ETV and TDV is based on their high potency and optimal resistance profile.

Untargeted metabolomics of blood plasma samples of patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths in the world. HCC is often diagnosed late because patients with early-stage cancer have no apparent symptoms. Therefore, it is desirable to find a reliable method for an early diagnosis based on the detection of metabolites - biomarkers, that can be detected in the early stages of the disease. Untargeted metabolomics is often used as a tool to find a suitable biomarker for several diseases. In this work, untargeted metabolomics was performed on blood plasma samples of HCC patients and compared with healthy individuals and patients with liver cirrhosis. A combination of liquid chromatography and high-resolution mass spectrometry was used as an analytical method. More than a thousand peaks were detected in the blood plasma samples, from which mainly amino acids, carboxylic acids, lipids, and their derivatives were evaluated as potential biomarkers. The data obtained were statistically processed using the analysis of variance, correlation analysis, and principal component analysis.

Exploring the Role of GDF-15 in Inflammatory Bowel Disease: A Case-Controlled Study Comparing Crohn's Disease and Ulcerative Colitis with Non-Inflammatory Controls.

Inflammatory bowel disease, encompassing Crohn's disease and ulcerative colitis, is a persistent immune-mediated inflammatory gastrointestinal disease. This study investigates the role of growth differentiation factor 15 in severe IBD cases, aiming to identify a reliable parameter to assess disease severity and monitor activity. We analyzed plasma samples from 100 patients undergoing biologic therapy for severe IBD and 50 control subjects. Our analysis included evaluations of GDF-15 levels, inflammatory markers, and clinical features. We employed statistical methods such as the Mann-Whitney U test, ANOVA, and Spearman's correlation for an in-depth analysis. Our results demonstrated consistently higher GDF-15 levels in patients with both Crohn's disease and ulcerative colitis compared to the control group, irrespective of the biologic treatment received. The correlation analysis indicated significant relationships between GDF-15 levels, patient age, fibrinogen, and IL-6 levels. This study positions GDF-15 as a promising biomarker for severe IBD, with notable correlations with age and inflammatory markers. These findings underscore GDF-15's potential in enhancing disease monitoring and management strategies in an IBD context and encourage further research to clarify GDF-15's role in the IBD pathophysiology.