Treating chronic hepatitis delta: The need for surrogate markers of treatment efficacy.

Chronic hepatitis delta represents the most severe form of chronic viral hepatitis. The current treatment of hepatitis delta virus (HDV) infection consists of the use of interferons and is largely unsatisfactory. Several new compounds are currently in development for the treatment of HDV infection. However, surrogate markers that can be used to develop clinical endpoints in HDV infection are not well defined. In the current manuscript, we aimed to evaluate the existing data on treatment of HDV infection and to suggest treatment goals (possible "trial endpoints") that could be used across different clinical trials.

Effect of crude extracts of selected actinomycetes on biofilm formation of A. schindleri, M. aci, and B. cereus.

Actinomycetes are well known group of gram positive bacteria for their potential to produce antibiotics. This study sought to assess the ability of the selected actinomycetes to control biofilm forming bacteria isolated from different dental plaque samples. On the basis of morphological differences three out of ten different dental plaque bacterial isolates were selected for further study. These isolates were biochemically and genetically characterized and were identified as Acinetobacter schinndleri, Moraxella aci, and Bacillus cereus. Antibiotic resistant profile was measured through disc diffusion method and found that all three isolates were moderately sensitive to ofloxacin and erythromycin and resistant to trimethoprim. Antibacterial activity of ten different Streptomyces strains was assessed through an agar plug and well diffusion method against three dental biofilm forming bacteria. Two Streptomyces strains named as S. erythrogriseus and S. labedae showed good antibacterial activity against Moraxella and Acinetobacter strains. Ability of the four active antibiotic producing strains to inhibit biofilm formation was assessed using microtiter biofilm detection assay. It was found that biofilm forming ability of Acinetobacter and Moraxella was inhibited by S. labedae an antibiotic producing strain, while S. macrosporeus can only inhibit biofilm formation by B. cereus.

Three years old child with juvenile hyaline fibromatosis presenting with rectal bleeding.

Juvenile hyaline fibromatosis is a rare inherited autosomal recessive disorder which is caused by mutation of CMG2 gene on chromosome 4q21. Mutation of this gene protein can disrupt the formation of basement membranes. Hyalinization of various body tissues like skin, joints, and bones leads to development of skin papules, gingival hyperplasia, osteolytic lesions in bones, and joint contractures. We had a case of a 3 years old female child with Juvenile Hyaline Fibromatosis who presented with rectal bleeding. She had a bleeding mucocutaneous lesion in anal canal along with papullonodular lesions on the face, gingival hypertrophy and flexion contractures of small joints of hands and feet. Excision of the anal lesion revealed histopathological features of Juvenile Hyaline Fibromatosis.

Interferon lambda-3 polymorphism and response to pegylated interferon in patients with hepatitis D.

BACKGROUND: Specific single nucleotide polymorphisms (SNPs) near the interferon lambda-3 (IFNλ3) gene (formerly interleukin 28B) influence the response to treatment with interferon in hepatitis C patients. We aimed to investigate such an influence in hepatitis D patients. METHODS: The study population consisted of hepatitis D patients who were previously treated with pegylated interferon for one year and who were spontaneous clearers of the virus post recent superinfection. The SNP of IFNλ3, rs12979860, was determined by polymerase chain reaction-restriction fragment length polymorphism protocol. RESULTS: The total number of patients was 64; median age was 30.5 years and 53 were male. The number of patients with sustained virological response 1 year post-treatment was 17, non-responders 29, relapsers 11 and spontaneous clearers post superinfection 7. Cirrhosis was present in 28 (44%). IFNλ3, rs12979860 genotype CC, was present in 41 (64.1%), CT in 21 (32.8%) and TT in 2 (3.1%). There was no difference in the body mass index, baseline alanine aminotransferase, hepatitis B e antigen and HBV DNA status among patients with sustained response and response failure (no response or relapse). The median age of response failures was 33.5 years compared to 26 in responders (P=0.024). They had higher gamma glutamyl transferase levels (P=0.030) and cirrhosis (P=0.003). Genotype CC was present in 29/40 of response failures compared to 9/17 of the responders (P=0.152). Logistic regression analysis showed that cirrhosis was the independent risk factor for failure to have a response (P=0.001). 4/7 patients with spontaneous clearance had genotype CC. CONCLUSIONS: IFNλ3 rs12979860 SNP does not have any significant influence on long-term hepatitis D clearance. Presence of cirrhosis may influence the response.

Hepatitis E: when to treat and how to treat.

HEV generally causes a self-limited acute infection and treatment remains supportive. However, severe hepatitis or fulminant hepatic failure may occur, more so during pregnancy. It is an important cause of acute-on-chronic liver failure in endemic areas. Chronic HEV infection and progressive disease has been reported in recipients of solid organ transplants, haematological malignancies, HIV patients and those on haemodialysis. Clearance of HEV may occur after reducing immunosuppressive therapy, especially those targeting T-cells, in about one third of cases. Antiviral therapy should be considered for patients for whom immunosuppressive therapy cannot be reduced and for those who do not achieve viral clearance after reducing immunosuppression. For the patients with severe infection, fulminant hepatic failure and acute-on-chronic infection, ribavirin monotherapy should be considered to expedite the viral clearance and recovery. Although ribavirin therapy is contraindicated in pregnancy owing to teratogenicity, the risks of untreated HEV to the mother and fetus are high and treatment may be offered. A twelve-week course of pegylated interferon, ribavirin or a combination of the two agents leads to viral clearance in about two-thirds of patients with chronic hepatitis E. Three- to twelve-month treatment with pegylated interferon clears virus in liver transplant recipients and patients on haemodialysis. In kidney and heart transplant patients where interferon may lead to organ rejection, ribavirin may be given.

Treatment of chronic hepatitis D patients with pegylated interferon: a real-world experience.

BACKGROUND: Published experience of treating chronic hepatitis D patients with pegylated interferon (PEG-IFN)-α is limited. The aim of this study was to determine the efficacy of 48 weeks of treatment with PEG-IFN in naive patients outside the clinical trial setting, in the real world. METHODS: Patients with chronic hepatitis D were treated with PEG-IFN. The primary end points were sustained clearance of HDV RNA and normal alanine aminotransferase (ALT) at 24 weeks post-treatment. RESULTS: The total number of patients treated with PEG-IFN was 104; 91 males, mean age ±SD 30.1 ±10.0 years (range 15-55). Cirrhosis was present in 41 patients. With an intention-to-treat analysis, end of treatment virological response (ETR) was achieved in 44 (42.3%), normalization of ALT in 38 (35%) and a combined response in 23 (22.1%) patients. Sustained virological response (SVR) at 24 weeks post-treatment was seen in 24 (23.1%) patients each for the virological and biochemical responses and in 13 (12.5%) as combined response. Both ETR and SVR were associated with a negative HDV RNA at 24 weeks of treatment (P=0.001 and P=0.000, respectively). Detectable HDV RNA at this point had a positive predictive value of 0.95 (range 0.85-0.99) for detectable RNA at 6 months post-treatment. End of treatment biological response, that is, normal ALT at the end of treatment was also a predictor of ETR and SVR (P=0.004 and P=0.041, respectively). CONCLUSIONS: Treatment with PEG-IFN for hepatitis D is of limited efficacy. Detectable HDV RNA at 24 weeks of treatment is a predictor for a failed SVR.