[Sonographic diagnostics of liver tumors]. / Sonographische Diagnostik bei Lebertumoren.

Liver tumors are often incidentally found during ultrasound examinations. The decision on further diagnostic imaging depends on the clinical context and the appearance in B mode ultrasound. This review highlights the role of grey scale and contrast-enhanced ultrasound (CEUS) and summarizes the ultrasonographic key features of the most common benign and malignant liver tumors. Conventional grey scale ultrasound is recommended in several guidelines for screening and follow-up of liver tumors in certain risk populations but its ability to characterize liver tumors is limited in most cases. The CEUS has an excellent tolerability and enables liver tumor characterization with a high sensitivity and specificity. The diagnostic value of CEUS is comparable to magnetic resonance imaging. In the case of unclear lesions, inconclusive findings by different imaging methods or if molecular targeted treatment is pursued, ultrasound-guided biopsy is often mandatory. Ultrasound is a rapidly and ubiquitously available method for the detection of liver tumors and CEUS is the only imaging method that enables real-time examination of all contrast phases in the liver. It should therefore be used as the first line imaging method for liver tumor characterization.

[Chronic hepatitis B and D (delta) : Current and future treatments]. / Chronische Hepatitis B und D (delta) : Gegenwärtige und zukünftige Therapien.

BACKGROUND: Worldwide, hepatitis B virus (HBV) infection is among the 30 leading causes of death, despite effective vaccination and therapeutic options. Chronic hepatitis delta (coinfection with hepatitis D virus) leads to a rapid disease progression. AIMS: Based on current international guidelines and studies, an overview about present and future therapeutic options for chronic hepatitis B and delta is provided. RESULTS: Therapy with nucleoside or nucleotide analogues leads to nearly complete HBV DNA suppression, which is associated with regression of liver fibrosis and a lower risk for the development of hepatocellular carcinoma. Therapy of chronic hepatitis delta with pegylated interferon alfa achieves only low response rates with high risk for virological relapse. Various therapeutic approaches are currently being investigated in preclinical and clinical studies and have led to a significant reduction of hepatitis B surface antigen (HBsAg) and HDV RNA. CONCLUSION: Current therapies of chronic HBV infection can effectively reduce subsequent complications. New therapeutic approaches promise functional cure (HBsAg loss) of HBV infection and effective treatment options for patients with chronic hepatitis delta.

[New direct-acting antiviral agents for the treatment of chronic hepatitis C in 2014]. / Neue direkt antivirale Medikamente zur Behandlung der chronischen Hepatitis C 2014.

BACKGROUND: The development of direct-acting antiviral agents (DAA) against the hepatitis C virus (HCV) has seen enormous progress in recent years. In 2011, the first protease inhibitors boceprevir (BOC) and telaprevir (TLV) were approved, which still need to be combined with pegylated interferon α (PEG-IFN α) and ribavirin (RBV) and are used only in patients with genotype 1. With sofosbuvir (SOF) and simeprevir (SMV), two new DAA are available. More DAA are in clinical development. OBJECTIVES: Which changes in the treatment of chronic hepatitis C infection can be expected with the approval of the new DAA in 2014? Relevant phase IIb and phase III studies for the approval in 2014 were considered for drugs approved by the FDA or EMA at the editorial deadline. CURRENT DATA: For patients with genotype 1, the combination of SOF, SMV or faldaprevir with PEG-IFN α and RBV was successfully evaluated in phase III studies. In contrast to previous treatment with PEG-IFN α, RBV and telaprevir (TLV) or boceprevir (BOC), therapy can be shortened in most cases with a significantly improved side-effect profile. Cure rates above 80 % are possible. Data are also available for an interferon-free therapy with either SOF and RBV or SOF and SMV in GT-1 patients. SVR rates exceeding 60 % and up to 90 % are possible. However, treatment experience with these combinations is low and an unrestricted interferon-free therapy for genotype 1 should not be expected before 2015. For patients with genotypes 2 and 3, valid data for interferon-free therapies are available. The combination of SOF and RBV for 12 weeks in genotype 2 and 24 weeks for genotype 3 is effective and shows equal or superior cure rates with fewer side effects than the PEG-IFN α/RBV therapy. CONCLUSION: For patients with genotype 1, the duration of therapy can be further reduced with better side effect profile. In certain situations, therapy without PEG-IFN α is possible and should be considered. For patients with genotypes 2 and 3, an interferon-free therapy will be standard of care in 2014.

Systematic analysis and evolution of 5S ribosomal DNA in metazoans.

Several studies on 5S ribosomal DNA (5S rDNA) have been focused on a subset of the following features in mostly one organism: number of copies, pseudogenes, secondary structure, promoter and terminator characteristics, genomic arrangements, types of non-transcribed spacers and evolution. In this work, we systematically analyzed 5S rDNA sequence diversity in available metazoan genomes, and showed organism-specific and evolutionary-conserved features. Putatively functional sequences (12,766) from 97 organisms allowed us to identify general features of this multigene family in animals. Interestingly, we show that each mammal species has a highly conserved (housekeeping) 5S rRNA type and many variable ones. The genomic organization of 5S rDNA is still under debate. Here, we report the occurrence of several paralog 5S rRNA sequences in 58 of the examined species, and a flexible genome organization of 5S rDNA in animals. We found heterogeneous 5S rDNA clusters in several species, supporting the hypothesis of an exchange of 5S rDNA from one locus to another. A rather high degree of variation of upstream, internal and downstream putative regulatory regions appears to characterize metazoan 5S rDNA. We systematically studied the internal promoters and described three different types of termination signals, as well as variable distances between the coding region and the typical termination signal. Finally, we present a statistical method for detection of linkage among noncoding RNA (ncRNA) gene families. This method showed no evolutionary-conserved linkage among 5S rDNAs and any other ncRNA genes within Metazoa, even though we found 5S rDNA to be linked to various ncRNAs in several clades.

[Which treatment options are validated for chronic viral hepatitis?]. / Was ist gesichert in der Therapie der chronischen Virushepatitis?

BACKGROUND: In the last 10 years, a dramatic change has occurred in the treatment of chronic viral hepatitis, particularly in the area of hepatitis B and hepatitis C. OBJECTIVES: Which treatment options of viral hepatitis are scientifically validated and can be recommended for practical use in consideration of current studies on the treatment of viral hepatitis and the German and European guidelines, respectively. CURRENT DATA: The treatment of chronic hepatitis B continues to be based either on a long-term therapy with nucleos(t)ide analogues or a finite therapy with pegylated interferon alpha (PEG-IFN). Treatment of hepatitis D is also based on PEG-IFN; however, the relapse rate is high. The treatment of hepatitis C is currently based on the combination of PEG-IFN and ribavirin (RBV). To estimate the optimal duration of therapy and dosage, knowledge of previous treatments, genotype, and presence of cirrhosis is crucial. For genotype 1, the first direct acting antiviral drugs were approved in 2011. These drugs led to a significant increase in treatment success. In the upcoming years another dramatic change in the treatment of hepatitis C is anticipated, including an improved side effect profile, increased efficacy, and a greater degree of customization in difficult-to-treat patients. Acute hepatitis E is usually self-limiting, but can become chronic in immunocompromised patients, i.e., after organ transplantation. Reduction of immunosuppression may clear HEV and RBV shows antiviral efficacy. CONCLUSION: Currently available therapies have a high disease control or chance for cure in hepatitis B and C. In Hepatitis C treatment, a massive change in future therapies is foreseeable. The hepatitis D co-infection remains difficult to treat. For hepatitis E, RBV is a promising off-label treatment option.

Dominance of hepatitis C virus (HCV) is associated with lower quantitative hepatitis B surface antigen and higher serum interferon-γ-induced protein 10 levels in HBV/HCV-coinfected patients.

Different viral dominance patterns have been documented in coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) based on HBV DNA and HCV RNA quantification. In most cases, HCV is dominant and suppresses HBV replication. In vitro studies revealed that there is most probably no direct interference between HBV and HCV replication. We hypothesized that indirect mechanisms mediated by host immune responses might be responsible for the different dominance patterns. In this study we analysed quantitative hepatitis B surface antigen (HBsAg) as a marker for immune control of HBV and interferon γ-induced protein 10 (IP-10) as host marker for the endogenous interferon in 85 patients with HBV/HCV coinfection. Levels of HBsAg were closely associated with viral dominance patterns in 85 HBV/HCV-coinfected patients. HBsAg levels were lowest in patients with HCV dominance, even lower compared with HBV-monoinfected patients undergoing treatment with nucleos(t)ide analogues (NA) but comparable to low replicative HBsAg carriers. An increase in HCV RNA during follow up was associated with HBsAg decline. Patients with HCV dominance had significantly higher serum IP-10 levels compared with HBV-dominant patients or HBV-monoinfected patients treated with NA. Lower HBsAg and higher IP-10 levels in HCV-dominant HBV/HCV-coinfected patients suggest that HCV suppresses HBV DNA replication and also HBsAg production by immune mechanisms.

Improvement of liver function parameters in advanced HCV-associated liver cirrhosis by IFN-free antiviral therapies.

BACKGROUND: Successful antiviral treatment of decompensated hepatitis B with HBV polymerase inhibitors is associated with improvement of liver function. To what extent liver function also improves in cirrhotic patients with chronic hepatitis C receiving novel interferon-free (IFN-free) therapies is unknown. AIM: To study liver function in cirrhotic HCV patients receiving IFN-free therapies. METHODS: We here studied 80 consecutive patients with advanced HCV associated liver cirrhosis including 34 patients (43%) with Child B/C cirrhosis and 42 patients (53%) with platelet counts of <90.000/µL receiving different combinations of direct acting antivirals without interferon [sofosbuvir/ribavirin (n = 56), sofosbuvir/simeprevir ± ribavirin (n = 15) and sofosbuvir/daclatasvir ± ribavirin (n = 9)]. The majority of patients was infected with HCV genotype 1 (n = 50); HCV genotypes 2, 3 and 4 were present in 4, 24 and 2 patients, respectively. RESULTS: Liver function parameters including albumin, bilirubin, cholinesterase and prothrombin time all improved in the majority of patients during antiviral therapy irrespectively of the underlying HCV genotype, however, with different kinetics. MELD scores improved until post-treatment week 12 in 44% of the patients but worsened in 15%. A sustained virological response was achieved in 63% of the patients. HCV RNA relapse led to moderate ALT increases in 15/23 patients but was not associated with hepatic decompensations. CONCLUSION: This real-world single centre study showed that interferon-free treatment of hepatitis C patients with advanced liver cirrhosis restores liver function, and may thereby reduce the need for liver transplantations.