Hepatic complications of allogeneic hematopoietic cell transplantation

Hepatic complications of allogeneic hematopoietic cell transplantation contribute substantially to the overall success of the procedure and represent a major cause of morbidity and mortality. Early hepatic complications consist of the sinusoidal obstruction syndrome, drug toxicities, infections, and acute graft-versus-host disease, while late hepatic complications consist of chronic graft-versus host disease, chronic viral hepatitis, and iron overload states. Successful management of the hepatic complications of allogeneic hematopoietic cell transplantation is dependent on several factors. These include the recognition and elimination of any pre-transplant risk factors for these problems and the development of strategies to evaluate and prevent them in both the early and later post-transplant periods. The aims of the present review are 1) to identify the early and late hepatic complications of allogeneic hematopoietic cell transplantation, in the chronological order in which they occur, 2) to characterize the diagnostic procedures used to identify them, and finally 3) to present the current therapeutic approaches used to manage these problems

Real-world efficacy and safety of Ledipasvir + Sofosbuvir and Ombitasvir/Paritaprevir/Ritonavir ± Dasabuvir combination therapies for chronic hepatitis C: A Turkish experience

Background/Aims: This study aimed to evaluate the real-life efficacy and tolerability of direct-acting antiviral treatments for patients with chronic hepatitis C (CHC) with/without cirrhosis in the Turkish population. Material and Methods: A total of 4,352 patients with CHC from 36 different institutions in Turkey were enrolled. They received ledipasvir (LDV) and sofosbuvir (SOF)+/- ribavirin (RBV) ombitasvir/paritaprevir/ritonavir +/- dasabuvir (PrOD)+/- RBV for 12 or 24 weeks. Sustained virologic response (SVR) rates, factors affecting SVR, safety profile, and hepatocellular cancer (HCC) occurrence were analyzed. Results: SVR12 was achieved in 92.8% of the patients (4,040/4,352) according to intention-to-treat and in 98.3% of the patients (4,040/4,108) according to per-protocol analysis. The SVR12 rates were similar between the treatment regimens (97.2%-100%) and genotypes (95.6%-100%). Patients achieving SVR showed a significant decrease in the mean serum alanine transaminase (ALT) levels (50.90 +/- 54.60 U/L to 17.00 +/- 14.50 U/L) and model for end-stage liver disease (MELD) scores (7.51 +/- 4.54 to 7.32 +/- 3.40) (p<0.05). Of the patients, 2 were diagnosed with HCC during the treatment and 14 were diagnosed with HCC 37.0 +/- 16.0 weeks post-treatment. Higher initial MELD score (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.22-2.38; p=0.023]), higher hepatitis C virus (HCV) RNA levels (OR: 1.44, 95% CI: 1.31-2.28; p=0.038), and higher serum ALT levels (OR: 1.38, 95% CI: 1.21-1.83; p=0.042) were associated with poor SVR12. The most common adverse events were fatigue (12.6%), pruritis (7.3%), increased serum ALT (4.7%) and bilirubin (3.8%) levels, and anemia (3.1%). Conclusion: LDV/SOF or PrOD +/- RBV were effective and tolerable treatments for patients with CHC and with or without advanced liver disease before and after liver transplantation. Although HCV eradication improves the liver function, there is a risk of developing HCC.Turkish Association for the Study of The Liver (TASL)The present study was supported by The Turkish Association for the Study of The Liver (TASL)

Predictive performance of newer Asian hepatocellular carcinoma risk scores in treated Caucasians with chronic hepatitis B

Cirrosi; Tenofovir; PrediccióCirrosis; Tenofovir; PredicciónCirrhosis; Tenofovir; PredictionBackground & Aims Recently, several risk scores for prediction of hepatocellular carcinoma (HCC) were developed in cohorts of treated Asian patients with chronic hepatitis B (CHB), but they have not been assessed in non-Asian patients. We evaluated the predictability and comparative utility of our PAGE-B and recent Asian HCC risk scores in nucleos(t)ide analogue (NA)-treated adult Caucasian patients with CHB, with or without well-documented compensated cirrhosis but not previous diagnosis of HCC. Methods We included 1,951 patients treated with entecavir/tenofovir and followed up for a median of 7.6 years. The c-statistic was used to estimate the predictability of PAGE-B, HCC-Rescue, CAMD, mPAGE-B, and AASL score for HCC development within 5 or 10 years. The low- and high-risk group cut-offs were used for estimation of negative (NPV) and positive predictive values (PPV), respectively. Results HCC developed in 103/1,951 (5.3%) patients during the first 5 years and in another 39/1,428 (2.7%) patients between years 5 and 10. The 3-, 5-, and 10-year cumulative HCC rates were 3.3%, 5.9%, and 9.6%, respectively. All scores offered good 5- and 10-year HCC prediction (c-statistic: 0.78–0.82). NPVs were always >99% (99.3–100%), whereas PPV ranged between 13% and 24%. Conclusions In NA-treated Caucasian patients with CHB including compensated cirrhosis, HCC risk scores developed in NA-treated Asian patients offer good 5- and 10-year HCC predictability, similar to that of PAGE-B. PAGE-B and mPAGE-B scores are simpler in clinical practice, as they do not require an accurate diagnosis of cirrhosis, but the addition of albumin in mPAGE-B score does not seem to offer an advantage in patients with well compensated liver disease. Lay summary Several risk scores for prediction of hepatocellular carcinoma (HCC) were recently developed in cohorts of treated Asian patients with chronic hepatitis B (CHB). In Caucasian patients with CHB treated with oral antivirals, newer Asian HCC risk scores offer good 5- and 10-year HCC predictability, similar to that of PAGE-B. For clinical practice, PAGE-B and mPAGE-B scores are simpler, as they do not require an accurate diagnosis of cirrhosis

The cost-effectiveness of treating chronic hepatitis B patients in a median endemic and middle income country

BACKGROUND/AIMS: Chronic hepatitis B (CHB) infection is a serious public health problem due to its potential liver disease sequelae and highly expensive medical costs such as the need for liver transplantation. The aim of this study was to quantify the burden of active CHB in terms of mortality and morbidity, the eligibility of antiviral treatment and to assess various treatment scenarios and possible salvage combinations for cost-effectiveness.METHODS: A population cohort from a large data base of chronic hepatitis B patients was constructed and stratified according to 10-year age groups, the prevalence of HBsAg, HBV DNA level, ALT level, HBeAg status and the presence of cirrhosis. An age-specific Markov model for disease progression and cost-effectiveness analysis was constructed and calibrated for the specific population setting.RESULTS: Of about 3.2 million estimated HBsAg carriers, 25% are eligible for treatment. If the active cohort remains untreated, 31% will die due to liver related complications. Within a 20-year period, 11% will have developed decompensated cirrhosis, 12% liver cancer and 6% will need liver transplantation. Quality adjusted life years (QALYs) for the no treatment scenario ranged from 9.3 to 14.0. For scenarios with antiviral treatment, QALYs ranged from 9.9 to 14.5 for lamivudine, 13.0-17.5 for salvage therapy, and 16.6-19.0 for the third generation drugs entecavir and tenofovir.CONCLUSION: In a country with considerable amount of active CHB patients, monotherapy with a highly potent third generation drug has the most health-gain, and is cost-effective in both HBeAg-positive and negative in all stages of liver disease.</p

A micro-elimination approach to addressing hepatitis C in Turkey

Background: In 2016, WHO passed the Global Health Sector Strategy on Viral Hepatitis (GHSS), calling for its elimination by 2030. Two years later, Turkey approved a strategy to reach the WHO targets. This study reports new national prevalence data, breaks it down by subpopulation, and models scenarios to reach HCV elimination. Methods: Literature was reviewed for estimates of HCV disease burden in Turkey. They were discussed with stakeholders and used as inputs to develop a disease burden model. The infected population was estimated by sequelae for the years 2015–2030. Three scenarios were developed to evaluate the disease burden in Turkey: a Base 2017 scenario, representing the current standard of care in Turkey; an increased treatment scenario, representing the impact of improved access to DAAs; and a WHO targets scenario, which meet the WHO GHSS viral hepatitis targets of a 65% reduction in mortality and 90% diagnosis rate of the infected population by 2030. Results: At the beginning of 2017, 271,000 viremic infections were estimated. Of these, 58,400 were diagnosed and 10,200 treated. Modelling results showed that, with the current treatment paradigm in Turkey, by 2030 the total number of viremic HCV infections would decline by 35%, while liver-related deaths, hepatocellular carcinoma (HCC), and decompensated cirrhosis would decrease by 10–25%. In the increased treatment scenario, by 2030 viremic HCV infections would decrease by 50%; liver-related deaths, HCC and decompensated cirrhosis would decrease by 45–70%. In the WHO targets scenario, HCV infections would decrease by 80%; sequelae would decrease by 80–85%. Data on disease burden in micro-elimination target subpopulations are largely unavailable. Conclusions: To meet the WHO Global Health Sector Strategy targets for the elimination of HCV, Turkey needs to increase treatment. Better data are needed as well as countrywide access to DAAs

The cost-effectiveness of treating chronic hepatitis B patients in a median endemic and middle income country

BACKGROUND/AIMS: Chronic hepatitis B (CHB) infection is a serious public health problem due to its potential liver disease sequelae and highly expensive medical costs such as the need for liver transplantation. The aim of this study was to quantify the burden of active CHB in terms of mortality and morbidity, the eligibility of antiviral treatment and to assess various treatment scenarios and possible salvage combinations for cost-effectiveness.METHODS: A population cohort from a large data base of chronic hepatitis B patients was constructed and stratified according to 10-year age groups, the prevalence of HBsAg, HBV DNA level, ALT level, HBeAg status and the presence of cirrhosis. An age-specific Markov model for disease progression and cost-effectiveness analysis was constructed and calibrated for the specific population setting.RESULTS: Of about 3.2 million estimated HBsAg carriers, 25% are eligible for treatment. If the active cohort remains untreated, 31% will die due to liver related complications. Within a 20-year period, 11% will have developed decompensated cirrhosis, 12% liver cancer and 6% will need liver transplantation. Quality adjusted life years (QALYs) for the no treatment scenario ranged from 9.3 to 14.0. For scenarios with antiviral treatment, QALYs ranged from 9.9 to 14.5 for lamivudine, 13.0-17.5 for salvage therapy, and 16.6-19.0 for the third generation drugs entecavir and tenofovir.CONCLUSION: In a country with considerable amount of active CHB patients, monotherapy with a highly potent third generation drug has the most health-gain, and is cost-effective in both HBeAg-positive and negative in all stages of liver disease.</p

MRI quantification techniques in fatty liver: the diagnostic performance of hepatic T1, T2, and stiffness measurements in relation to the proton density fat fraction

PURPOSENonalcoholic fatty liver disease (NAFLD) can progress to liver cirrhosis and is predicted to become the most frequent indication for liver transplantation in the near future. Noninvasive assessment of NAFLD is important for diagnosis and patient management. This study aims to prospectively determine the liver stiffness and T1 and T2 values in patients with NAFLD and to compare the diagnostic performance of magnetic resonance elastography (MRE) and mapping techniques in relation to the proton density fat fraction (PDFF).METHODSEighty-three patients with NAFLD and 26 participants with normal livers were imaged with a 1.5 T scanner. PDFF measurements obtained from the multiecho Dixon technique were used to quantify the liver fat. MRE, native T1 mapping (modified Look-Locker inversion recovery [MOLLI] schemes 5(3)3, 3(3)3(3)5, and 3(2)3(2)5 and the B1-corrected variable flip angle [VFA] method), and T2 mapping values were correlated with PDFF. The diagnostic performance of MRE and the mapping techniques were analyzed and compared.RESULTST1 values measured with the MOLLI schemes and the B1-corrected VFA (P < 0.001), and the stiffness values from MRE (P = 0.047) were significantly higher in the NAFLD group. No significant difference was found between the groups in terms of T2 values (P = 0.127). In differentiation of the NAFLD and control groups, the B1-corrected VFA technique had slightly higher accuracy and area under the curve (AUC) than the MOLLI schemes. In the NAFLD group, there was a good correlation between the PDFF, MOLLI 3(3)3(3)5 and 3(2)3(2)5, and VFA T1 measurements (r=0.732; r=0.735; r=0.716, P < 0.001, respectively).CONCLUSIONLiver T1 mapping techniques have the potential to distinguish steatotic from nonsteatotic livers, and T1 values seem to have a strong correlation with the liver fat content

Real-world efficacy and safety of Ledipasvir plus Sofosbuvir and Ombitasvir/Paritaprevir/Ritonavir +/- Dasabuvir combination therapies for chronic hepatitis C: A Turkish experience

Background/Aims: This study aimed to evaluate the real-life efficacy and tolerability of direct-acting antiviral treatments for patients with chronic hepatitis C (CHC) with/without cirrhosis in the Turkish population.Material and Methods: A total of 4,352 patients with CHC from 36 different institutions in Turkey were enrolled. They received ledipasvir (LDV) and sofosbuvir (SOF)+/- ribavirin (RBV) ombitasvir/paritaprevir/ritonavir +/- dasabuvir (PrOD)+/- RBV for 12 or 24 weeks. Sustained virologic response (SVR) rates, factors affecting SVR, safety profile, and hepatocellular cancer (HCC) occurrence were analyzed.Results: SVR12 was achieved in 92.8% of the patients (4,040/4,352) according to intention-to-treat and in 98.3% of the patients (4,040/4,108) according to per-protocol analysis. The SVR12 rates were similar between the treatment regimens (97.2%-100%) and genotypes (95.6%-100%). Patients achieving SVR showed a significant decrease in the mean serum alanine transaminase (ALT) levels (50.90 +/- 54.60 U/L to 17.00 +/- 14.50 U/L) and model for end-stage liver disease (MELD) scores (7.51 +/- 4.54 to 7.32 +/- 3.40) (p<0.05). Of the patients, 2 were diagnosed with HCC during the treatment and 14 were diagnosed with HCC 37.0 +/- 16.0 weeks post-treatment. Higher initial MELD score (odds ratio [OR]: 1.92, 95% confidence interval [CI]: 1.22-2.38; p=0.023]), higher hepatitis C virus (HCV) RNA levels (OR: 1.44, 95% CI: 1.31-2.28; p=0.038), and higher serum ALT levels (OR: 1.38, 95% CI: 1.21-1.83; p=0.042) were associated with poor SVR12. The most common adverse events were fatigue (12.6%), pruritis (7.3%), increased serum ALT (4.7%) and bilirubin (3.8%) levels, and anemia (3.1%).Conclusion: LDV/SOF or PrOD +/- RBV were effective and tolerable treatments for patients with CHC and with or without advanced liver disease before and after liver transplantation. Although HCV eradication improves the liver function, there is a risk of developing HCC.Turkish Association for the Study of The Liver (TASL