Short interfering RNA-directed inhibition of hepatitis B virus replication

AbstractRNA interference (RNAi) is the process by which double-stranded RNA directs sequence-specific degradation of mRNA. In mammalian cells, RNAi can be triggered by 21-nucleotide duplexes of short interfering RNA (siRNA). We examined effects of siRNA on hepatitis B virus (HBV) replication. Human hepatoma cells were transfected with HBV DNA and siRNA against HBV-pregenome RNA. Transfection experiments demonstrated that the siRNA reduced the amount of HBV-pregenome RNA and resulted in reduction of the levels of replicative intermediates and viral protein. Our results indicate that siRNA-mediated gene silencing inhibits HBV replication through suppression of viral RNA, which may be useful as a potential therapeutic modality

Perioperative synbiotic treatment to prevent infectious complications in patients after elective living donor liver transplantation. A prospective randomized study.

BACKGROUND: Although the effect of synbiotic therapy using prebiotics and probiotics has been reported in hepatobiliary surgery, there are no reports of the effect on elective living-donor liver transplantation (LDLT). METHODS: Fifty adult patients undergoing LDLT between September 2005 and June 2009 were randomized into a group receiving 2 days of preoperative and 2 weeks of postoperative synbiotic therapy (Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides [the BLO group]) and a group without synbiotic therapy (the control group). Postoperative infectious complications were recorded as well as fecal microflora before and after LDLT in each group. RESULTS: Only 1 systemic infection occurred in the BLO group (4%), whereas the control group showed 6 infectious complications (24%), with 3 cases of sepsis and 3 urinary tract infections with Enterococcus spp (P = .033 vs BLO group). No other type of complication showed any difference between the groups. CONCLUSIONS: Infectious complications after elective LDLT significantly decreased with the perioperative administration of synbiotic therapy

Protein-Energy Malnutrition in Patients with Liver Cirrhosis

Protein-energy malnutrition (PEM) is frequently seen in patients with liver cirrhosis. This condition is associated with a poorprognosis and reduced survival. We investigated the protein and energy metabolic status, including serum albumin concentration,and resting energy expenditure (REE) and respiratory quotient (RQ) measured by indirect calorimetry in 23 patients withliver cirrhosis (8 men and 15 women; mean age, 60.3 years). The median value of %REE (measured REE / predicted REE)was highest in Child-Pugh grade A and lowest in grade C, and the range of RQ tended to be highest in Child-Pugh grade Aand lowest in grade C, although there were not statistically significant (p=0.871 and 0.664, respectively). Serum triglycerideconcentration was significantly lower in patients who had an RQ less than 0.85 than in patients who had an RQ of 0.85 ormore, and free fatty acid tended to be higher in patients who had an RQ less than 0.85 than in patients who had an RQ of 0.85or more. Of the 23 patients, 78.3% were in a state of protein and/or energy malnutrition and 47.8% had PEM. Our results suggestthat %REE and RQ were not significantly associated with liver function, but the oxidation rate of fat was increased in advancedliver cirrhosis. A longitudinal study in a large population is needed to determine the efficacy of %REE and RQ measurementsfor adequate nutritional treatment and improvement of patient outcome

The Relationship between Energy Expenditure and Type or Stage of Cancer

Malnutrition commonly occurs in patients with cancer. This situation can be associated with increased morbidity and mortality.The etiology is not clearly understood but decreased energy intake and increased energy expenditure may be involved. Weaimed to investigate the energy metabolic status including energy expenditure in patients with various cancers. The clinicalfeatures and energy metabolic status measured by indirect calorimetry of 74 patients with cancer (50 men and 24 women;mean age, 64.7 years) were obtained from the medical records. Hypermetabolism was more common and REE/kg (resting energyexpenditure / kg body weight) seems to be more reliable in estimating the true energy expenditure than %REE (measuredREE / predicted REE). The REE/kg and VO2 /kg (oxygen consumption per minute / kg body weight) varied among cancertypes, i.e., they were significantly higher in gastric cancer than in hepatocellular carcinoma. Moreover, REE/kg and VO2/kg wassignificantly higher in cancer stage IV than in stage I, or stages I and II. Patients with or at risk for malnutrition should receiveappropriate nutritional support, which has to be personalized according to tumor site, tumor stage, and the nutritional statusof the patient. This nutritional support should improve not only the patients\u27 quality of life but also their survival

Tubulointerstitial Nephritis Complicated by Fanconi Syndrome and Renal Tubular Acidosis Associated with three autoimmune diseases

A 45-year-old woman experiencing back pain showed signs of metabolic acidosis and electrolyte imbalances. The results of blood and urine tests indicated Fanconi syndrome and renal tubular acidosis. An x-ray showed vertebral fractures, which were thought to responsible for the back pain. In addition, the patient had proteinuria and renal dysfunction; therefore, renal biopsy was performed, and tubulointerstitial nephritis (TIN) was diagnosed. While investigating TIN, primary biliary cirrhosis and Sjögren’s syndrome were also detected. She had been previously diagnosed with chronic thyroiditis. We report a rare case of TIN and 3 autoimmune disorders with review of literature

Anti-hepatitis C virus activity of geranylgeranylacetone treatment in hepatitis C-infected patients

Background. Geranylgeranylacetone (GGA), which is an isoprenoid compound, has been used orally as an antiulcer drug inJapan. GGA induces antiviral gene expression by stimulating the formation of interferon-stimulated gene factor 3 in humanhepatoma cells. This study verified the anti-hepatitis C virus (HCV) activity of GGA in chronic hepatitis C-infected patients.Methods. The present prospective study included 20 consecutive anti-HCV antibody-positive, HCV-genotype 1b, and chronicgastritis patients who visited Nagasaki University Hospital between January 1999 and December 1999. GGA (150 mg per day,which is the dose generally used for chronic gastritis) was taken orally for four weeks. We evaluated HCV-RNA titers and otherclinical parameters at pretreatment, posttreatment, and at the endpoint of the study. Pretreatment was the beginning point ofGGA treatment. Posttreatment was the termination point of GGA treatment. The endpoint was the point four weeks after theposttreatment point.Results. All patients completed four weeks of GGA treatment and four weeks of observation. HCV-RNA titers at postpointwere not significantly diminished compared to those at pretreatment. However, HCV-RNA titers were significantly diminishedat endtreatment compared to pretreatment. Unfortunately, we did not observe a case with no titer of HCV-RNA. Alanineaminotransferase values and other parameters were not affected by GGA treatment.Conclusion. GGA has anti-HCV activities in chronic hepatitis C-infected patients. In the future, it will be necessary to examinethe clinical effectiveness of the combination of treatment with both GGA and interferon in HCV patients

Living donor liver transplantation from a donor previously treated with interferon for hepatitis C virus: a case report

<p>Abstract</p> <p>Introduction</p> <p>Selecting a marginal donor in liver transplantation (LT) remains controversial but is necessary because of the small number of available donors.</p> <p>Case presentation</p> <p>A 46-year-old Japanese woman was a candidate to donate her liver to her brother, who had decompensated liver cirrhosis of unknown origin. Eight years before the donation, she had a mild liver dysfunction that was diagnosed as a hepatitis C virus (HCV) infection (serotype 2). She had received anti-viral therapy with interferon α-2b three times weekly for 24 weeks and had a sustained viral response (SVR). A biopsy of her liver before the donation showed normal findings without any active hepatitis, and her serum was negative for HCV-RNA. Only 67 patients have undergone LT from a cadaveric donor in Japan. The family in this case decided to have living donor LT. A careful selection for the liver graft donation was made; however, since she was the only candidate, we approved her as a living donor. She was discharged nine days after the liver donation. Her liver function recovered immediately. A computed tomography scan showed sufficient liver regeneration one year later. Her brother also had good liver function after LT and had no HCV infection 48 months after surgery and no <it>de novo </it>malignancy. Neither of the siblings has developed an HCV infection.</p> <p>Conclusions</p> <p>A patient with SVR status after interferon therapy might be considered a candidate for living donor LT but only if there are no other possibilities of LT for the recipient. A careful follow-up of the donor after donation is needed. The recipient also must have a very close follow-up because it is difficult to predict what might happen to the graft with post-transplant immunosuppression.</p

Macrophage-dominant sialadenitis in human T-cell leukemia virus type I-associated myelopathy after living-donor liver transplantation.

A 64-year-old man who suffered from human T-cell leukemia virus type I (HTLV-I)-associated myelopathy (HAM) after living-donor liver transplantation (LDLT) for liver cirrhosis due to hepatitis C virus infection complained of xerostomia. Although exocrine function test results were positive, autoantibodies including anti-SS-A/SS-B antibodies and sialography showed negative findings. Labial salivary gland biopsy revealing infiltration of 60 counts of mononuclear cells (MNCs) in minor salivary glands led to a diagnosis of Sjögren\u27s syndrome-like sialadenitis. Immunohistochemistry demonstrated dominant CD68 staining and major histocompatibility complex class II on the surface of infiltrating MNCs. Herein we have reported a rare condition of macrophage-dominant sialadenitis in a patient with HAM after LDLT

Indices calculated by serum creatinine and cystatin C as predictors of liver damage, muscle strength and sarcopenia in liver disease

Serum creatinine (Cr)-based glomerular filtration rate (CrGFR) is overestimated in liver disease. The present study evaluated whether the difference in CrGFR and cystatin C (CysC) GFR (dGFR) is significant in liver disease. The Cr-to-CysC ratio and sarcopenia index (SI) have been reported to correlate with muscle volume. An estimated total body muscle mass with Cr, CysC and calculated body muscle mass (CBMM) has also been reported to correlate with muscle mass. The applicability of dGFR, SI and CBMM for liver disease were evaluated. A total of 313 patients with liver damage were evaluated for Child-Pugh score, albumin-bilirubin (ALBI) score, model for end-stage liver disease, fibrosis-4, Cr, CysC, Cr-based estimated GFR (CreGFR), CysCGFR and grip strength. Of the 313 patients, 199 were evaluated using cross-sectional computed tomography (CT) of the third lumbar vertebra to determine the skeletal muscle (SM) mass. dGFR, CBMM and SI were compared to liver damage, muscle strength and muscle mass. In the 313 patients, dGFR was correlated with age, ALBI and grip strength; CBMM was correlated with body mass index (BMI) and grip strength; and SI was correlated with BMI and grip strength. In patients evaluated with CT, the correlation coefficients for CBMM and SI with SM were 0.804 and 0.293, respectively. Thus, CBMM and SI were associated with sarcopenia. The relationship between dGFR and ALBI does not differ with different grades of CrGFR-based chronic kidney disease (CKD). dGFR is a marker of liver damage and muscle strength regardless of CKD. CBMM and SI are markers for sarcopenia in liver disease