Clinical characteristics of patients with non-alcoholic fatty liver disease (NAFLD) in Germany - First data from the German NAFLD-Registry.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) affects more than 18 million individuals in Germany. Real-world data help to better characterize the natural history of disease and standard of care. METHODS: The German NAFLD-Registry is a prospective non-interventional study initiated by the German Liver Foundation and aims to describe clinical characteristics and observe outcomes in patients with NAFLD recruited in secondary and tertiary care. RESULTS: From this ongoing study, baseline data of the first 501 patients (mean age 54 years, 48% women) were analysed. 13 % of the study population had a high risk for advanced fibrosis (FIB-4 ≥2.67), approximately one-third had a liver stiffness value ≥9.6kPa measured by transient elastography, and the clinical diagnosis of liver cirrhosis was present in 10%. Typical comorbidities were more prevalent in high risk as compared to low risk patients (FIB-4 <1.3) including arterial hypertension (85 vs. 42%), hypercholesterolemia (39 vs. 16%), and type 2 diabetes mellitus (T2DM) (69 vs. 26%). Patients with T2DM (192/501) had a higher NAFLD disease burden as shown by liver stiffness values ≥9.6 kPa (51%) and clinical diagnosis of cirrhosis (20%). Statins were used in 22% of the main population, while in diabetic patients, metformin, GLP-1 agonists, and SGLT2 inhibitors were used in 65, 17, and 17%, respectively. Uptake of life-style interventions such as physical exercise or nutritional counselling was generally low. CONCLUSION: First data of the German NAFLD registry show that approximately every 10th patient has advanced NAFLD, highlights T2DM patients as a high-risk group and gives insights in the use of comedication and life-style interventions in secondary and tertiary care.

Management of hepatic encephalopathy in Germany: a survey among physicians.

BACKGROUND: Hepatic encephalopathy (HE) is a severe complication of liver cirrhosis with impairment of quality of life and prognosis. Management patterns among physicians have not been investigated yet. METHODS: A questionnaire containing 17 questions was sent out to 1468 gastroenterologists and 120 general practitioners (GPs). It included questions regarding diagnostic, therapeutic, and management strategies used in patients with overt HE (OHE) and covert HE (CHE). RESULTS: The response rate was 12 % (n = 172) for gastroenterologists and 45 % (n = 54) for GPs. Of gastroenterologists, 26.7 % examine patients with an initial diagnosis of liver cirrhosis regarding HE. Gastroenterologists favored a combination of different testing strategies (27.9 %) and clinical examination (23.0 %), while the biggest part of the GPs use clinical examination (55.3 %); 63.7 % of gastroenterologists and 28.3 % of GPs give correct nutritional advices to patients with HE. Treatment strategies for acute bouts of OHE and secondary prophylaxis varied widely in both groups. Preferred medication was lactulose followed by rifaximin or a combination therapy. More than half of the GPs (53.7 %) were not familiar with minimal HE (MHE). About one-third of both groups never tried to diagnose MHE. CONCLUSION: Our data strongly indicate that management of HE is very heterogeneous among gastroenterologists as well as selected GPs working in Germany and not driven by evidence-based international guidelines. Thus, the national guideline is more than welcome.

Estimation of liver fibrosis by noncommercial serum markers in comparison with transient elastography in patients with chronic hepatitis C virus infection receiving direct-acting antiviral treatment.

Treatment decisions are based on extent of fibrosis in patients with chronic hepatitis C (HCV) infection. Noninvasive diagnostic tools may help to avoid liver biopsy. We investigated the diagnostic accuracy of noncommercial serum scores in comparison with transient elastography (TE). Data analysis was undertaken based on 2458 patients enrolled in the German Hepatitis C Registry, in a prospective, observational study. Aspartate aminotransferase-to-platelet ratio index (APRI), FORNS index and FIB-4 score were calculated and the diagnostic accuracy was compared to TE. As estimated by TE, 955 (38.9%) patients had absence of significant fibrosis (SF), 736 (29.9%) patients had SF, and 767 (31.2%) patients were shown to have cirrhosis. Patients with absence of SF had a sustained virological response (SVR) rate of 97.9%, whereas SVR was attained in 96.2% and 92.2% in those with SF and cirrhosis, respectively (P < 0.0001). The area under the receiver operator characteristic curve (AUROC), sensitivity and specificity in discriminating of SF were 0.789, 0.596 and 0.939 by APRI; 0.838, 0.852 and 0.748 by FORNS index; and 0.828, 0.658 and 0.946 by FIB-4 score. AUROCs for the prediction of cirrhosis, sensitivity and specificity were 0.881, 0.851 and 0.854 by APRI; 0.846, 0.948 and 0.628 by FORNS index; and 0.907, 0.907 and 0.848 by FIB-4 score. In conclusion, in the present multicentre real-world cohort, SF and cirrhosis were predicted with high accuracy with noncommercial serum markers using TE as reference. Further prospective long-term follow-up is necessary to compare biomarkers with TE concerning liver-related outcome and overall mortality.

Etiologies and outcomes of acute liver failure in Germany.

BACKGROUND & AIMS: Acute liver failure (ALF) is a severe form of acute liver injury that can progress to multiple organ failure. We investigated causes and outcomes of ALF. METHODS: Eleven university medical centers in Germany were asked to report patients with (primary) severe acute liver injury (sALI) (international normalized ratio [INR] >1.5 but no hepatic encephalopathy) and primary ALF (INR >1.5 with overt hepatic encephalopathy) treated from 2008 to 2009. Data were analyzed from 46 patients with sALI and 109 patients with ALF. RESULTS: The most frequent etiologies of primary ALF were non-acetaminophen drug-induced (32%), indeterminate (24%), and viral (21%); acetaminophen ingestion was the cause of ALF in only 9% of patients. The support of a ventilator was required by 44% of patients with ALF, vasopressors by 38%, and renal replacement by 36%. Seventy-nine patients with ALF (72%) survived until hospital discharge, 38 (35%) survived without emergency liver transplantation (ELT), and 51 received ELT (47%); 80% of patients who received ELT survived until discharge from the hospital. CONCLUSIONS: In Germany, drug toxicity, indeterminate etiology, and viral hepatitis appear to be the major causes of primary ALF, which has high mortality. Patients with ALF are at great risk of progressing to multiple organ failure, but 80% of patients who receive ELT survive until discharge from the hospital.

Hepatitis D virus-specific cytokine responses in patients with chronic hepatitis delta before and during interferon alfa-treatment.

BACKGROUND: Hepatitis delta is caused by infection with the hepatitis D virus (HDV) and is considered the most severe form of viral hepatitis. Treatment options for hepatitis delta are limited, with only 25% of patients responding to interferon (IFN)-alfa-based therapies. The role of the adaptive immune system in controlling HDV infection during spontaneous or treatment-induced viral clearance is not well understood. METHODS: We studied HDV-specific cytokine production of peripheral blood mononuclear cells stimulated with HDV peptide pools as well as serum cytokine levels in well-characterized patients with chronic HDV infection before and during pegylated-interferon-alfa±adefovir therapy. RESULTS: Hepatitis D virus-specific interleukin (IL)-2, IFN-γ-, interferon-inducible protein-10 and IL-10-responses were detectable in 53%, 35%, 65% and 6% of hepatitis delta patients. HDV-specific IFN-γ responses tended to be more common in patients with low HDV viral loads. HDV-specific cytokine responses declined during pegylated (PEG)-IFNa therapy and patterns of changes were associated with the treatment response. Serum cytokine levels also showed distinct changes during PEG-IFNa treatment. CONCLUSION: We suggest that cellular HDV-specific immune responses contribute to the control of HDV infection and that cytokine responses may indicate response to type-I-IFN-based antiviral therapy of hepatitis delta.

Therapeutic vaccine IC41 as late add-on to standard treatment in patients with chronic hepatitis C.

We examined the effect of the hepatitis C virus (HCV) peptide vaccine IC41 on HCV-specific T-cell responses and virological relapse rates in patients with chronic HCV genotype 1 infection when added to pegylated interferon plus ribavirin standard therapy. 35 patients received 6 vaccinations with IC41 from weeks 28 to 48 of standard antiviral treatment and were followed-up for another 6 months. IC41 vaccination did not prevent HCV-RNA relapse in patients with ongoing interferon standard treatment but HCV-specific T-cell responses were inducible and were associated with lower relapse rates. An increase of HCV-specific T-cell responses occurred in 73% of patients, responses were more frequent and stronger in patients with sustained virologic response than in patients who relapsed. Optimized vaccine responses may enhance sustained virologic response rates obtained with standard treatment of chronic hepatitis C.

The hepatitis C virus NS5A protein and response to interferon alpha: mutational analyses in patients with chronic HCV genotype 3a infection from India.

The hepatitis C virus (HCV) non-structural (NS)5A protein is linked to interferon alpha resistance in vitro and higher numbers of NS5A amino acid (aa) variations in HCV 1a/b isolates are associated with virologic response to interferon alpha-based therapy in vivo. Here, we aimed to study NS5A aa variations in Indian patients undergoing interferon alpha/ribavirin treatment infected with HCV 3a. The NS5A region [aa 2194-2401, comprising interferon sensitivity determining region, protein kinase resource (PKR) binding domain, V3 region] was sequenced from pre-treatment sera of 24 patients with HCV 3a infection. Mean number and physicochemical properties of aa variations (conserved vs. non-conserved) were assessed. Additionally, published NS5A sequences [NS5A region (n = 61), PKR binding domain (n = 111)] of characterized HCV 3a isolates were analyzed. The mean number of NS5A aa variations was not correlated with treatment response in our cohort. When all available NS5A sequences were included, a higher number of non-conserved aa variations within PKR binding domain and an extended V3 region of NS5A was associated with virologic response (P = 0.004 and 0.05, respectively). Mutational analyses of a large number of NS5A sequences suggest, that a higher number of non-conserved aa variations within the PKR binding domain and the extended V3 region is correlated with virologic response in HCV 3a infected patients.