Remy Schwarzer

Unexpected high incidence of hepatocellular carcinoma in cirrhotic patients with sustained virologic response following interferon-free direct-acting antiviral treatment

Please cite this article as: Kozbial, K., Moser, S., Schwarzer, R., Laferl, H., Al-Zoairy, R., Stauber, R., Stättermayer, A.F., Beinhardt, S., Graziadei, I., Freissmuth, C., Maieron, A., Gschwantler, M., Strasser, M., Peck-Radosalvjevic, M., Trauner, M., Hofer, H., Ferenci, P., Unexpected high incidence of hepatocellular carcinoma in cirrhotic patients with SVR following IFN-free DAA treatment, Journal of Hepatology (2016), doi: http://dx.doi.org/10.1016/j.jhep. 2016.06.009

Sustained virologic response to interferon-free therapies ameliorates HCV-induced portal hypertension

BACKGROUND & AIMS We aimed to investigate the impact of sustained virologic response (SVR) to interferon (IFN)-free therapies on portal hypertension in patients with paired hepatic venous pressure gradient (HVPG) measurements. METHODS One hundred and four patients with portal hypertension (HVPG ⩾6mmHg) who underwent HVPG and liver stiffness measurement before IFN-free therapy (baseline [BL]) were retrospectively studied. Among 100 patients who achieved SVR, 60 patients underwent HVPG and transient elastography (TE) after antiviral therapy (follow-up [FU]). RESULTS SVR to IFN-free therapies significantly decreased HVPG across all BL HVPG strata: 6-9mmHg (BL: 7.37±0.28 vs. FU: 5.11±0.38mmHg; -2.26±0.42mmHg; p<0.001), 10-15mmHg (BL: 12.2±0.4 vs. FU: 8.91±0.62mmHg; -3.29±0.59mmHg; p<0.001) and ⩾16mmHg (BL: 19.4±0.73 vs. FU: 17.1±1.21mmHg; -2.3±0.89mmHg; p=0.018). In the subgroup of patients with BL HVPG of 6-9mmHg, HVPG normalized (<6mmHg) in 63% (12/19) of patients, while no patient progressed to ⩾10mmHg. Among patients with BL HVPG ⩾10mmHg, a clinically relevant HVPG decrease ⩾10% was observed in 63% (26/41); 24% (10/41) had a FU HVPG <10mmHg. Patients with Child-Pugh stage B were less likely to have a HVPG decrease (hazard ratio [HR]: 0.103; 95% confidence interval [CI]: 0.02-0.514; p=0.006), when compared to Child-Pugh A patients. In the subgroup of patients with BL CSPH, the relative change in liver stiffness (per %; HR: 0.972; 95% CI: 0.945-0.999; p=0.044) was a predictor of a HVPG decrease ⩾10%. The area under the receiver operating characteristic curve for the diagnosis of FU CSPH by FU liver stiffness was 0.931 (95% CI: 0.865-0.997). CONCLUSIONS SVR to IFN-free therapies might ameliorate portal hypertension across all BL HVPG strata. However, changes in HVPG seemed to be more heterogeneous among patients with BL HVPG of ⩾16mmHg and a HVPG decrease was less likely in patients with more advanced liver dysfunction. TE might be useful for the non-invasive evaluation of portal hypertension after SVR. LAY SUMMARY We investigated the impact of curing hepatitis C using novel interferon-free treatments on portal hypertension, which drives the development of liver-related complications and mortality. Cure of hepatitis C decreased portal pressure, but a decrease was less likely among patients with more pronounced hepatic dysfunction. Transient elastography, which is commonly used for the non-invasive staging of liver disease, might identify patients without clinically significant portal hypertension after successful treatment.

Interferon‐free regimens for chronic hepatitis C overcome the effects of portal hypertension on virological responses

Portal hypertension is the strongest predictor of virological response to pegylated interferon (IFN)/ribavirin in patients with chronic hepatitis C (CHC)‐related cirrhosis.

Effect of gender and ITPA polymorphisms on ribavirin-induced anemia in chronic hepatitis C patients

BACKGROUND & AIMS Single nucleotide polymorphisms (SNPs) in the inosine triphosphate pyrophosphatase (ITPA) gene protect patients from ribavirin induced anemia. To investigate other possible protective cofactors, gender differences were analyzed in patients with HCV genotype 1. METHODS Hemoglobin levels at baseline (Hb0) and the decline after 4 weeks of treatment (HbΔ4) were analyzed in 308 chronic hepatitis C patients participating in 5 Austrian trials (n=308, age 43.9 ± 11.1, male:185, female:123, BMI 25.3 ± 3.9, no cirrhosis: n=259, liver cirrhosis: n=49). All patients were treated with 180 μg peginterferon-alpha 2a and ribavirin [1000-1200 mg/d; females: mean (95% CI) 15.8 mg/kg (15.4-16.2); males 14.3 (14.1-14.5); p<0.001]. The SNPs rs6051702, rs1127354, rs7270101 and IL28B rs12979860 were analyzed by the StepOnePlus Real time PCR System. RESULTS 188 were major alleles homozygotes; 95 (30.8%) carried the minor allele (C) of rs6051702, 47 (15.3%) of rs1127354 (A), and 69 (22.4%) of rs7270101 (C). The overall Hb0 was 14.8 g/dl (14.6-14.9) [mean (95%CI); females 13.7 (13.5-13.9); males 15.5; 15.3-15.6; p<0.001]. The overall HbΔ4 was greater in major allele homozygotes [2.8 g/dl (2.6-3.0)] than in minor allele carriers [1.6 (1.4-1.9); p<0.001]. Irrespective of the ITPA genotypes HbΔ4 was smaller in female [2.0 (1.7-2.2)] than in male patients [2.6 (2.4-2.8); p<0.001] and among females in premenopausal [1.5 (1.3-1.8)] than in postmenopausal patients [2.7 (2.3-3.1); p<0.001]. CONCLUSIONS Irrespective of the protective effect of ITPA mutations, premenopausal females less likely develop ribavirin induced anemia.

Evaluation of a new balloon occlusion catheter specifically designed for measurement of hepatic venous pressure gradient

Despite the important clinical value of hepatic venous pressure gradient (HVPG) and its increasing use, no specific balloon occlusion catheters have been designed to cannulate liver veins. The aim of the study was to evaluate the clinical applicability of a novel balloon (NC) occlusion catheter specifically designed for HVPG measurement.

Follow-up of sustained virologic responders with hepatitis C and advanced liver disease after interferon/ribavirin-free treatment

The introduction of direct‐acting antivirals (DAA) has increased sustained virological response (SVR) rates in patients with advanced liver disease and chronic hepatitis C(CHC)infection. At present, data on clinical outcome and long‐term durability of viral eradication after successful DAA therapy are scarce.

Randomised clinical study: the effects of oral taurine 6g/day vs placebo on portal hypertension

The amino sulphonic acid taurine reduces oxidative endoplasmatic reticulum stress and inhibits hepatic stellate cell activation, which might lead to reduction of portal pressure in cirrhosis.

Endoscopic versus surgical management of biliary complications – Outcome analysis after 1188 orthotopic liver transplantations

BACKGROUND AND AIM After liver transplantation, the endoscopic approach has become the standard treatment modality for biliary complications. Aim of this study was to compare primary endoscopic with primary surgical management. PATIENTS AND METHODS A retrospective review on 1188 consecutive liver transplant patients between 1989 and 2009 was performed. Management strategies (endoscopic, surgical or combined approach) were evaluated for treatment success as well as patient survival. RESULTS Biliary complications after liver transplantation were diagnosed in 211 (18%) patients. Initial endoscopic approach (N=162, 77%) was successful in 97 of 162 (60%) patients. In 80% of patients, success was achieved within a median of four ERCPs. Sixty-one patients (38%) were referred to surgery after non-successful ERCP. Initial surgical approach was performed in 49/211 patients (23%) with successful management in 38/49 (78%) of patients. Patients presenting with intraluminal objects needed a significantly higher number of ERCPs to reach treatment success (median 3 versus 2 interventions, p=0.001) but had an equal endoscopic success rate (p=0.427). Patients with successful endoscopic treatment showed lower mortality compared to patients with primary surgical treatment (p=0.029). CONCLUSIONS Endoscopic management should be considered as the primary approach for biliary complications after liver transplantation.

Carvedilol for reducing portal pressure in primary prophylaxis of variceal bleeding: a dose‐response study

Sequential measurements of hepatic venous pressure gradient (HVPG) are used to assess the haemodynamic response to nonselective betablockers (NSBBs) in patients with portal hypertension.

Plasma renin concentration represents an independent risk factor for mortality and is associated with liver dysfunction in patients with cirrhosis

Plasma renin concentration (PRC) is increased in patients with cirrhosis. The aims of this study were to evaluate the relation of PRC to (i) portal hypertension, (ii) degree of liver dysfunction, and (iii) survival.