To determine the feasibility of magnetic resonance imaging T2 mapping in the quantification of liver steatosis in patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), and to assess ...the effect of inflammation and fibrosis on T2 values of the liver.
Twenty-three consecutive patients with biopsy-proven NAFLD who underwent T2 mapping between December 2013 and September 2014 were included in this study. All patients underwent fast spin echo multi-echo sequence with eight echoes for T2 measurements.
The mean liver T2 value and percentage of histological steatosis was 64.9 ± 7.4 ms and 46.5 ± 27.6%, respectively. There was a good correlation between the liver T2 value and histology-determined steatosis (r = 0.780, p<0.001) and grade of steatosis (rs = 0.779, p<0.001). The mean T2 value in patients with definitive non-alcoholic steatohepatitis (NASH) was significantly higher in comparison with patients without NASH (69 ± 7.37 versus 61.73 ± 5.99 ms, p=0.016). The correlation between T2 value and NAFLD activity score (NAS) was significant (rs = 0.443, p=0.034); however, the correlation disappeared after adjustment for hepatic steatosis and fibrosis (r=0.131, p=0.572). There was a close inverse correlation between T2 value and fibrosis stage after adjusting for hepatic steatosis (r=–0.536, p=0.012).
T2 mapping can be used for quantification of hepatic steatosis, as there is a close correlation between T2 relaxation values and histology-determined steatosis. Patients with definite NASH have increased T2 values and there is an inverse correlation between the T2 value and fibrosis stage of the liver. T2 mapping in NAFLD may be a useful clinical tool for disease assessment and prognostication.
•There is a close correlation between histologic steatosis and T2 values of the liver.•T2 values are increased in patients with definite NASH.•T2 values are not correlated with NAS score after adjustment for steatosis and fibrosis.•There is an inverse relationship between T2 value and fibrosis stage of the liver.
Chronic delta hepatitis (CDH) represents a severe form of chronic viral hepatitis, induced by the hepatitis delta virus (HDV) in conjunction with the hepatitis B virus (HBV). Delta hepatitis may lead ...to disease in humans through co‐infection. The former leads to acute hepatitis which clinically can range from mild hepatitis to fulminant hepatitis and death. Severe or fulminant hepatitis is more often observed with HBV‐HDV co‐infection compared to HBV mono‐infection. Chronic infection after acute hepatitis B + D co‐infection is infrequent and similar to the rate in mono‐infected patients. CDH develops in 70–90% of patients with superinfection. CDH runs a more progressive course than chronic hepatitis B and may lead to cirrhosis within 2 years in 10–15% of patients. However, as with any immune‐mediated disease, different patterns of progression, ranging from mild to severe progressive disease, are observed. Active replication of both HBV and HDV may be associated with a more progressive disease pattern. Further, different HDV and HBV genotypes may contribute to various disease outcomes. CDH may be frequently associated with hepatocellular carcinoma development although recent studies provided conflicting results. The only established therapy for CDH is treatment with interferons for a duration of at least 1 year. On treatment, 6 month HDV RNA assessment may give clues as to whether to stop treatment at 1 year or continue beyond 1 year. New approaches to treatment of CDH are an urgent need of which the use of prenylation inhibitors appears the most promising.
Summary
Background
In patients with chronic hepatitis B, tenofovir disoproxil fumarate (TDF) plus pegylated interferon (PEG‐IFN) for 48‐weeks results in higher rates of hepatitis B surface antigen ...(HBsAg) loss than either monotherapy.
Aim
To identify baseline and on‐treatment factors associated with HBsAg loss at Week 72 and provide a model for predicting HBsAg loss in patients receiving combination therapy for 48 weeks.
Methods
A secondary analysis of data from an open‐label study where patients were randomised to TDF (300 mg/day, oral) plus PEG‐IFN (PI, 180 μg/week, subcutaneous) for 48 weeks (TDF/PI‐48w); TDF plus PEG‐IFN for 16 weeks, TDF for 32 weeks (TDF/PI‐16w+TDF‐32w); TDF for 120 weeks (TDF‐120w) or PEG‐IFN for 48 weeks (PI‐48w). Logistic regression methods were used to identify models that best predicted HBsAg loss at Week 72.
Results
Rates of HBsAg loss at Week 72 were significantly higher in the TDF/PI‐48w group (6.5%) than in the TDF/PI‐16w+TDF‐32w (0.5%), TDF‐120w (0%) and PI‐48w (2.2%) groups (P = 0.09). The only baseline factor associated with response was genotype A. HBsAg decline at Week 12 or 24 of treatment was associated with HBsAg loss at Week 72 (P < 0.001). HBsAg decline >3.5 log10 IU/mL at Week 24 in the TDF/PI‐48w group resulted in a positive predictive value of 85% and a negative predictive value of 99% for HBsAg loss at Week 72.
Conclusions
HBsAg decline at Week 24 of TDF plus PEG‐IFN combination therapy may identify patients who, after completing 48 weeks of treatment, have a better chance of achieving HBsAg loss at Week 72.
Summary
The aim of this study was to determine the long‐term efficacy of entecavir (ETV) and tenofovir disoproxil fumarate (TDF) on the natural course of disease in chronic hepatitis B patients (CHB) ...with/without cirrhosis in clinical practice. A total of 355 treatment‐naïve CHB patients were enrolled into the study. The primary outcome measure was viral suppression as defined by serum HBV DNA level <20 IU/mL. A secondary outcome measure was to determine the development of Hepatocellular carcinoma (HCC). Virological and biochemical responses were similar between the two treatment groups over time. The presence of cirrhosis and hepatitis B e antigen (HBeAg) positivity did not appear to impact viral suppression. The cumulative probability of HBeAg loss was 41% at 4 years of therapy. Hepatitis B surface antigen (HBsAg) loss occurred in four patients. Model for End‐Stage Liver Disease score was significantly improved from baseline to week 48 and 96 under antiviral therapy (P = 0.013, P = 0.01). HCC was diagnosed in 17 patients (4.8%). The cumulative probability of the development of HCC was 3.3% at 1 year and 7.3% at 4 years of therapy. The development of HCC was independently associated with older age (P = 0.031) and the presence of cirrhosis (P = 0.004). Serum creatinine levels and creatinine clearance remained stable over time. ETV and TDF effectively maintained virological and biochemical responses in long‐term follow‐up of CHB patients with/without cirrhosis. HCC may still develop, although at a lower rate, and is more likely to develop in patients with cirrhosis, especially in older patients.
According to published data, the risk of developing lamivudine resistant HBV increases with duration of lamivudine treatment. 6 Resistance rates of 15-40% have been reported after two years of ...lamivudine treatment in immunocompetents with chronic HBV infection. 6 None of the individuals with haematological malignancy who received lamivudine in our experience developed a lamivudine resistant virus after a mean of 14 months of continuous lamivudine therapy. 5 This result was comparable with that of Rossi et al who reported no development of lamivudine resistance in HBV carriers with lymphoid malignancies treated with chemotherapy. 3 In conclusion, although the ideal protocol for lamivudine prophylaxis for the prevention of HBV reactivation in individuals receiving chemotherapy for haemato/oncological malignancies is not yet established, it would appear prudent to begin lamivudine at the time of initiation of chemotherapy and to continue it throughout the period of chemotherapy administration and for at least one but possibly two years following discontinuation of chemotherapy.
Summary
Chronic hepatitis D is caused by coinfection of hepatitis B and hepatitis D virus. While HDV is the dominant virus over HBV in the majority of cases, mechanisms and consequences of viral ...dominance are largely unknown. We aimed to investigate associations between viral dominance patterns and patients’ characteristics and inflammatory features; 109 HDV‐infected patients treated with PEG‐IFNa‐2α within the international multicentre, prospective HIDIT‐2 trial were studied. Patients were classified as D‐ or B‐dominant if the viral load of one virus exceeded that of the other virus by more than 1log10. Otherwise, no viral dominance (ND) was described. We used Luminex‐based multiplex technology to study 50 soluble immune mediators (SIM) in pretreatment samples of 105 HDV RNA‐positive patients. Dominance of HDV was evident in the majority (75%) of cases. While only 7% displayed B‐dominance, 17% showed nondominance. D‐dominance was associated with downregulation of 4 interleukins (IL‐2ra, IL‐13, IL‐16 and IL‐18) and 5 chemokines/cytokines (CTACK (CCL27), MCP‐1 (CCL2), M‐CSF, TRAIL and ICAM‐1) while no analyte was increased. In addition, D‐dominance could be linked to a delayed HDV RNA response to pegylated interferon as patients with B‐dominance or nondominance showed higher early HDV RNA responses (61% at week 12) than D‐dominant patients (11%; P < .001). In conclusion, this study revealed unexpected effects of viral dominance on clinical and immunological features in chronic hepatitis delta patients. Individualizing PEG‐IFNa‐2α treatment duration should consider viral dominance. Overall, our findings suggest an activated but exhausted IFN system in D‐dominant patients.
Summary
Background Currently, although only a few therapies normalize the liver test abnormalities with/without improving the liver histology, no pharmacologic therapy has proved to be effective for ...the treatment of non‐alcoholic steatohepatitis.
Aim To investigate the role of insulin sensitizers in the treatment of individuals with non‐alcoholic steatohepatitis (NASH).
Methods A total of 74 individuals with NASH (male/female, 44/30; mean age, 47.2 ± 9.0 years) were enrolled. Participants were divided into two distinct groups: group 1 (n = 25) participants were administered a conventional diet and exercise programme while those in group 2 (n = 49) were administered the diet and exercise programme plus insulin sensitizers.
Results With respect to baseline metabolic, biochemical and histological parameters, no significant differences were observed between the two groups (P > 0.05). Insulin sensitizers significantly improved metabolic parameters (homeostasis model assessment‐insulin resistance score, P < 0.05), serum aminotransferase levels aspartate aminotransferase (AST): 45.9 ± 24.2 to 33.3 ± 17.7 IU/L, P < 0.01; alanine aminotransferase (ALT): 78.2 ± 46.3 to 47.3 ± 34.5 IU/L, P < 0.001 and histological features (median non‐alcoholic fatty liver disease activity score: 5.0–3.0, P = 0.01), while diet and exercise improved serum aminotransferase levels (AST: 39.3 ± 11.1 to 30.0 ± 8.6 IU/L, P < 0.01; ALT: 66.9 ± 28.9 to 42.0 ± 16.2 IU/L, P < 0.001) at the end of the 48 weeks when compared to baseline. Insulin sensitizers improved the high‐sensitivity C‐reactive protein levels (P < 0.01). No serious adverse effects of insulin sensitizers were observed.
Conclusion Insulin sensitizers can lead to improvement in metabolic, biochemical and histological abnormalities of NASH as a result of improved insulin sensitivity.
Living donor liver transplantation is a widely accepted option to treat liver diseases in several indications. Risk of liver donation is being discussed and quality of life of donors is also studied. ...Changes and the change pattern of quality of life were analyzed in this prospective longitudinal study.
Fifty-five donors were included. The Medical Outcomes Study Short Form 36 (SF-36) was fulfilled either in-person or during a telephone interview each donor preoperatively and at the end of the third, sixth, and 12th months.
Physical subdomain scores of SF-36 decreased significantly in the third postoperative month compared to preoperative score. The scores recovered in the sixth postoperative month, except for the bodily pain domain. The pain score recovered at the end of the 12th month. While social functioning score among mental subdomains of SF-36 temporarily decreased and recovered at postoperative 12th month, other mental subdomain scores and mental composition summary scores did not show a significant change.
The quality of life of living liver donors is not permanently affected by donation. There are well-defined changes in the physical aspects of the quality of life that all seem to recover within 1 year. Donors should be preoperatively informed about this temporary change as well as complications.
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