Results from the interferon era have demonstrated reversibility of cirrhosis following viral eradication, but only for patients in the initial stage of cirrhosis. Although direct-acting antivirals ...(DAA) represent revolutionary treatment of hepatitis C, there are currently no studies showing histological effects of therapy on a large number of cirrhotic patients. However, studies involving transient elastography demonstrated a rapid decrease in liver stiffness after successful DAA therapy, probably due to resolution of inflammation, rather than fibrosis regression, as the latter requires a longer period of time. Reversal of fibrosis and cirrhosis upon viral eradication is a prerequisite for the reduction of portal pressure, but this effect has only been observed for the subclinical stage of portal hypertension (PH). On the other hand, the majority of patients with clinically significant PH remain at risk of decompensation and death, despite hepatitis C virus cure, as PH remains high in this setting. This calls for novel therapeutic approaches.
BACKGROUNDInfections are common in patients with liver cirrhosis and increase mortality. We explored the relationship between infection and liver dysfunction in their effects on mortality.
...METHODSSingle-center data on decompensated liver cirrhosis patients hospitalized between March 2014 and December 2017 (index period) were reviewed until death, liver transplantation or 31 December 2018. Infections were classified as community-acquired infection (CAi) or hospital/healthcare associated infection (HCAi). Child-Pugh, model for the end-stage liver disease (MELD) and chronic liver failure-organ failure (CLiF-OF) scores indicated liver (dys)function.
RESULTSWe enrolled 155 patients (85% alcoholic liver disease), 65 without infection at first hospitalization, 48 with CAi and 42 with HCAi. Multidrug resistant agents were confirmed in 2/48 (4.2%) CAi and 10/42 (23.8%) HCAi patients. At first hospitalization, infection was independently associated with worse liver dysfunction and vice versa, and with higher 30-day mortality odds ratio (OR) = 2.73, 95% confidence interval (CI) 1.07–6.94. The association was reduced with adjustment for MELD/CLiF-OF scores, but mediation analysis detected an indirect (via liver dysfunction) association. Twenty-eight patients were repeatedly hospitalized, 11 with new HCAi. HCAi was independently associated with twice higher risk of medium-term mortality and added an additional risk to any level of liver dysfunction, considering all or patients who survived the first 30 days. In those repeatedly hospitalized, HCAi appeared independently associated with a higher probability of infection and higher MELD scores at subsequent hospitalizations.
CONCLUSIONInfection (particularly HCAi) adds mortality risk to any level of liver dysfunction in decompensated liver cirrhosis patients. Mechanisms of long(er)-term effects (in acute episode survivors) seemingly include enhanced deterioration of liver function.
Liver stiffness measurement (LSM) is a tool used to screen for significant fibrosis and portal hypertension. The aim of this retrospective multicentre study was to develop an easy tool using LSM for ...clinical outcomes in advanced chronic liver disease (ACLD) patients.
This international multicentre cohort study included a derivation ACLD patient cohort with valid two-dimensional shear wave elastography (2D-SWE) results. Clinical and laboratory parameters at baseline and during follow-up were recorded. LSM by transient elastography (TE) was also recorded if available. The primary outcome was overall mortality. The secondary outcome was the development of first/further decompensation.
After screening 2148 patients (16 centres), 1827 patients (55 years, 62.4% men) were included in the 2D-SWE cohort, with median liver SWE (L-SWE) 11.8 kPa and a model for end stage liver disease (MELD) score of 8. Combination of MELD score and L-SWE predict independently of mortality (AUC 0.8). L-SWE cut-off at ≥20 kPa combined with MELD ≥10 could stratify the risk of mortality and first/further decompensation in ACLD patients. The 2-year mortality and decompensation rates were 36.9% and 61.8%, respectively, in the 305 (18.3%) high-risk patients (with L-SWE ≥20 kPa and MELD ≥10), while in the 944 (56.6%) low-risk patients, these were 1.1% and 3.5%, respectively. Importantly, this M10LS20 algorithm was validated by TE-based LSM and in an additional cohort of 119 patients with valid point shear SWE-LSM.
The M10LS20 algorithm allows risk stratification of patients with ACLD. Patients with L-SWE ≥20 kPa and MELD ≥10 should be followed closely and receive intensified care, while patients with low risk may be managed at longer intervals.
Severe alcoholic hepatitis (AH) is a distinct entity in the spectrum of alcohol-related liver disease, with limited treatment options and high mortality. Supportive medical care with corticosteroids ...in selected patients is the only currently available treatment option, often with poor outcomes. Based on the insights into the pathogenetic mechanisms of AH, which are mostly obtained from animal studies, several new treatment options are being explored. Studies have implicated impaired and deranged liver regeneration processes as one of the culprit mechanisms and a potential therapeutic target. Acknowledging evidence for the beneficial effects of granulocyte colony-stimulating factor (G-CSF) on liver regeneration and immunomodulation in animal models, several human studies investigated its role in the treatment of advanced alcohol-related liver disease and AH. Contrary to the previously published studies suggesting benefits of G-CSF in the outcomes of patients with severe AH, these effects were not confirmed by a recently published multicenter randomized trial, suggesting that other options should rather be pursued. Stem cell transplantation represents another option for improving liver regeneration, but evidence for its efficacy in patients with severe AH and advanced alcohol-related liver disease is still very scarce and unconvincing, with established lack of efficacy in patients with compensated cirrhosis. In this review, we summarize the current knowledge on the pathogenesis and experimental therapies targeting liver regeneration. The lack of high-quality studies and evidence is a major obstacle in further treatment development. New insights into the pathogenesis of not only liver injury, but also liver regeneration processes are mandatory for the development of new treatment options. A reliable experimental model of the pathogenesis of AH and processes involved in liver recovery is still missing, and data obtained from animal studies are essential for future research.
Liver cirrhosis is a major cause of death worldwide. Cirrhosis develops after a long asymptomatic period of fibrosis progression, with the diagnosis frequently occurring late, when major ...complications or cancer develop. Few reliable tools exist for timely identification of individuals at risk of cirrhosis to allow for early intervention. We aimed to develop a novel score to identify individuals at risk for future liver-related outcomes.
We derived the LiverRisk score from an international prospective cohort of individuals from six countries without known liver disease from the general population, who underwent liver fibrosis assessment by transient elastography. The score included age, sex, and six standard laboratory variables. We created four groups: minimal risk, low risk, medium risk, and high risk according to selected cutoff values of the LiverRisk score (6, 10, and 15). The model's discriminatory accuracy and calibration were externally validated in two prospective cohorts from the general population. Moreover, we ascertained the prognostic value of the score in the prediction of liver-related outcomes in participants without known liver disease with median follow-up of 12 years (UK Biobank cohort).
We included 14 726 participants: 6357 (43·2%) in the derivation cohort, 4370 (29·7%) in the first external validation cohort, and 3999 (27·2%) in the second external validation cohort. The score accurately predicted liver stiffness in the development and external validation cohorts, and was superior to conventional serum biomarkers of fibrosis, as measured by area under the receiver-operating characteristics curve (AUC; 0·83 95% CI 0·78–0·89) versus the fibrosis-4 index (FIB-4; 0·68 0·61–0·75 at 10 kPa). The score was effective in identifying individuals at risk of liver-related mortality, liver-related hospitalisation, and liver cancer, thereby allowing stratification to different risk groups for liver-related outcomes. The hazard ratio for liver-related mortality in the high-risk group was 471 (95% CI 347–641) compared with the minimal risk group, and the overall AUC of the score in predicting 10-year liver-related mortality was 0·90 (0·88–0·91) versus 0.84 (0·82–0·86) for FIB-4.
The LiverRisk score, based on simple parameters, predicted liver fibrosis and future development of liver-related outcomes in the general population. The score might allow for stratification of individuals according to liver risk and thus guide preventive care.
European Commission under the H20/20 programme; Fondo de Investigación Sanitaria de Salud; Instituto de Salud Carlos III; Spanish Ministry of Economy, Industry, and Competitiveness; the European Regional Development Fund; and the German Ministry of Education and Research (BMBF).
Some 25 years ago endoscopic ultrasound (EUS) was introduced in clinical practice for better visualization of pancreas. At the time of introduction EUS was superior to other methods in detection of ...pancreatic masses allowing tissue diagnosis by later introduced EUS-guided fine needle aspiration (FNA). During the time EUS was improved, electronic probes replaced mechanical probes adding ability of color Doppler, power Doppler, contrast enhanced endosonography as well as EUS elastography analysis. Meanwhile, CT technology has also experienced significant improvements raising the question whether EUS has lost ground in diagnostics of solid pancreatic masses. The aim of this review was to discuss the current evidence of clinical impact of EUS and EUS-FNA in evaluation of solid pancreatic masses with special emphasis on differentiation between benign and malignant pancreatic lesions. According to the literature, the detection of small pancreatic tumors, preoperative localization of pancreatic endocrine tumors and tissue sampling by fine-needle aspiration of pancreatic masses in cases with therapeutic consequences are considered firm indications for EUS. Cytological tissue analysis remains undisputed in differentiation benign from malignant lesions, but the question when FNA is needed is discussed. Color Doppler, power Doppler, contrast enhanced endosonography and especially elastography are also discussed as tools that are bringing additional information in evaluation of pancreatic masses, however insufficient for definitive judgment of the lesion's nature. Pancreatic cancer staging as indication for EUS is discussed controversially, inconsistent results and conflicting evidence in literature making adequate conclusion impossible. However, this indicates that at least the role of EUS is no longer undisputed in this matter. Resuming the role of EUS we can state that despite some controversies EUS is very valuable method in evaluation of solid pancreatic masses and with EUS guided FNA is nowadays by far the best method for obtaining tissue diagnosis.
Aim To explore the prognostic value of modified Discriminant Function (mDF), Glasgow Alcoholic Hepatitis Score (GAHS), Model of End Stage Liver Disease (MELD), Age-Bilirubin-International Normalized ...Ratio-Creatinine score (ABIC), and the Lille Model for the 28- and 90-day mortality in patients with alcoholic hepatitis. Methods This retrospective study enrolled patients treated for alcoholic hepatitis in Dubrava University Hospital between January 2014 and May 2018. The diagnosis was established based on histology findings or the combination of patient's history of ongoing alcohol consumption before hospitalization, serum bilirubin above 50 mmol/L, and aspartate transaminase to alanine transaminase ratio greater than 1.5. We calculated mDF, MELD, GAHS, and ABIC on the first and seventh day of hospitalization (including the Lille model). Results In total, 70 patients were enrolled. ABIC at admission most accurately predicted the 28-day mortality, with a cut-off of 9.92 (AUC 0.727; 95% CI 0.608-0.827, P = 0.0119), while GAHS most accurately predicted the 90-day mortality, calculated both at admission (cut off >7, AUC 0.765, 95% CI 0.639-0.864, P< 0.000') and after seven days of hospitalization (cut-off >8, AUC 0.835 95% CI 0.716-0.918, P < 0.000'). Modified DF was able to predict the 28- and 90-day mortality only when calculated after seven days of hospitalization. Conclusion There is a need for better prognostic indicators for patients with AH.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Aim To explore the prognostic value of modified Discriminant Function (mDF), Glasgow Alcoholic Hepatitis Score (GAHS), Model of End Stage Liver Disease (MELD), Age-Bilirubin-International Normalized ...Ratio-Creatinine score (ABIC), and the Lille Model for the 28- and 90-day mortality in patients with alcoholic hepatitis. Methods This retrospective study enrolled patients treated for alcoholic hepatitis in Dubrava University Hospital between January 2014 and May 2018. The diagnosis was established based on histology findings or the combination of patient's history of ongoing alcohol consumption before hospitalization, serum bilirubin above 50 mmol/L, and aspartate transaminase to alanine transaminase ratio greater than 1.5. We calculated mDF, MELD, GAHS, and ABIC on the first and seventh day of hospitalization (including the Lille model). Results In total, 70 patients were enrolled. ABIC at admission most accurately predicted the 28-day mortality, with a cut-off of 9.92 (AUC 0.727; 95% CI 0.608-0.827, P = 0.0119), while GAHS most accurately predicted the 90-day mortality, calculated both at admission (cut off >7, AUC 0.765, 95% CI 0.639-0.864, P< 0.000') and after seven days of hospitalization (cut-off >8, AUC 0.835 95% CI 0.716-0.918, P < 0.000'). Modified DF was able to predict the 28- and 90-day mortality only when calculated after seven days of hospitalization. Conclusion There is a need for better prognostic indicators for patients with AH.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Data on the efficacy of particular therapeutic protocols of interferon-alpha (IFN-alpha) treatment for chronic hepatitis C in patients on hemodialysis (HD) vary.
To compare the efficacy of two ...different therapeutic protocols for HD patients.
15 hepatitis C virus (HCV)-positive patients on chronic HD at two dialysis centers: 8 patients treated with IFN-alpha 3 x 3 MU/week s.c. for 6 months (group A), and 7 patients treated with IFN-alpha 3 x 5 MU/week for 3 months, then 1 x 5 MU/week for another 3 months (group B). End of treatment response (ETR) and sustained virologic response (SVR) were evaluated by HCV-RNA determination. There was no statistically significant difference between the two patient groups according to age, sex, duration of HD and HCV infection.
ETR was 87.5% (7/8) in group A and 28.5% (2/7) in group B, being statistically significant (p < 0.05). Although better SVR 50% (4/8) vs. 28.5% (2/7) and lower drop-out rate 0% (0/8) vs. 28.5% (2/7) were achieved in group A compared to group B, these differences did not reach statistical significance (p > 0.05).
Therapy with IFN-alpha 3 x 3 MU/week s.c. for 6 months seems to be more appropriate for treatment of hepatitis C in HD patients, mostly due to better tolerability, i.e. lower drop-out rate. These differences could be attributed to different pharmacokinetic properties of the particular therapy protocol.
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