Hepatitis C virus (HCV) infection is costly to treat and, has high morbidity and mortality. The addition of new protease inhibitors (i.e., boceprevir, telaprevir), to the standard dual therapy with pegylated interferon-α and ribavirin, for the treatment of HCV infection has demonstrated superior efficacy with shorter treatment duration, but at higher drug acquisition costs and incidence of adverse events. Robust economic data are required to inform healthcare decision for the optimal use of these expensive antiviral agents. Accordingly, this review will explore the clinical and economic aspects of boceprevir-based treatment strategies. Important considerations, challenges and gaps for future pharmacoeconomic research in this setting are highlighted.
Primary Biliary Cirrhosis (PBC) and Auto Immune Hepatitis (AIH) are autoimmune diseases of the liver which highlighted with slow destructive process of intra hepatic small bile ducts. As a result of these damages cholestasis and over the time tissue damage will happen, which leads to scarring, fibrosis and finally cirrhosis. Some patients may present with clinical and biochemical features of both conditions, which is called "Overlap syndrome". Here we are reporting a case of PBC-AIH overlap syndrome that primarily diagnosed as gallbladder carcinoma and went under operation and finally histological examination revealed to be PBC.
This study is an observational cross-sectional study aimed to examine the possible demographic and social characteristics of patients enrolled at the Methadone Maintenance Therapy Adherence Clinic (MMTAC) in Malaysia. Medical records from year 2009 - 2011 were Reviewed. Demographic, social characteristics and laboratory examinations such as age, gender, race, clinic attendances and urine analysis were recorded. Subjects were selected by means of convenient sampling but based on the specified inclusion and exclusion criteria. Data were analyzed by either Chi-square test, Fisher's exact test Mann-Whitney U-test, with the limit of significance was set at p < 0.05. Demographically, this study found that the ratio of Malays, Chinese and Indian enrolled to the MMTAC program is similar to the distribution of races in Malaysia. Their starting age for drug use was between 14-35 years and the age to enrolment between 30-58 years. Socially, many are unemployed, lowly educated and married. Most are drug users with a high percentage of HCV accompanied with impaired liver function. Retention rate was 87% but illicit drug use was at 57.50%. However, percentage of employment increased significantly after therapy. The study managed to identify several demographical and social distributions of patients attending the MMTAC. Although attendance rate was high, many were on illicit drug use. Nevertheless, employment rate improved significantly.
Study site: government methadone clinic in Klang, Selangor, Malaysia
Hepatitis B virus (HBV) is classified into eight genotypes (A to H). In this study, three genotyping methods were compared for their sensitivity and accuracy, namely PCR-RFLP on the S region, PCR-RFLP on the pre-S region and nested PCR with type specific primers. Sixty HBV samples from infected sera were genotyped. The nested PCR with type specific primers was found to be the most sensitive and produced substantial numbers of co-infections by genotypes B and C. The sensitivities for both PCR-RFLP methods were lower and did not reveal co-infections. Generally, the three methods produced consistent genotyping results in samples infected by single genotypes but for co-infections by genotypes B and C, the two PCR-RFLP methods yielded only single genotypic results. For the cases of single genotypic infections, genotypes ascertained by sequencing were in concordance across all three methods. However, when co-infections occurred, PCR analysis on clones revealed only single genotypic infections.
Lichen planus, a chronic autoimmune, mucocutaneous disease affects the oral mucosa (oral lichen planus or OLP) besides the skin, genital mucosa, scalp and nails. An immune mediated pathogenesis is recognized in lichen planus although the exact etiology is unknown. The disease most commonly affects middle-aged females. Oral lichenoid reactions (OLR) which are considered variants of OLP, may be regarded as a disease by itself or as an exacerbation of an existing OLP, by the presence of medication (lichenoid drug reactions) or dental materials (contact hypersensitivity). OLP usually presents as white striations (Wickham's striae), white papules, white plaque, erythema, erosions or blisters. Diagnosis of OLP is established either by clinical examination only or by clinical examination with histopathologic confirmation. Direct immunofluorescence examination is only used as an adjunct to the above method of diagnosis and to rule out specific autoimmune diseases such as pemphigus and pemphigoid. Histopathologic features of OLP and OLR are similar with suggestions of certain discriminatory features by some authors. Topical corticosteroids are the treatment of choice for OLP although several other medications have been studied including retinoids, tacrolimus, cyclosporine and photodynamic therapy. Certain OLP undergo malignant transformation and the exact incidence and mechanisms are still controversial. In this paper, etiopathogenesis, diagnosis, management and malignant transformation of OLP and OLR have been reviewed.
HBcAg (hepatitis B core antigen) is a nanoplex bioproduct that has a great potential in the development of therapeutic drugs and vaccines. In the present study, a continuous-flow bead milling for the disruption of Escherichia coli was optimized and a direct recovery protocol to isolate the recombinant HBcAg from the unclarified E. coli disruptate was developed. The optimal condition for continuous-flow bead milling for the release of HBcAg from E. coli was achieved at a feed flow rate of 15 litres/h, biomass concentration of 10% [ww/v (wet weight/vol.)] and impeller tip speed of 14 m/s. The sucrose-density-gradient analysis showed that the particulate form of the HBcAg released by this optimal condition is still preserved. In the direct purification of HBcAg from the unclarified disruptate, the AE-EBAC (anion-exchange expanded-bed adsorption chromatography) technique was employed. A 54% adsorption and 50.7% recovery of HBcAg were achieved in this direct recovery process. The purity of HBcAg recovered was 49.8%, which corresponds to a purification factor of 2.0. ELISA showed that the HBcAg recovered is functionally active.
Matched MeSH terms: Hepatitis B Core Antigens/isolation & purification*
OBJECTIVE: To describe the clinical manifestations and outcome of acute liver failure (ALF) associated with dengue viral infection, a rare but severe complication.
METHODS: One hundred and fifty five consecutive patients with ALF admitted to the national liver centre from 2001 to 2009 were reviewed retrospectively. Eight cases due to dengue infection were identified and their clinical characteristics are described.
RESULTS: All patients had severe dengue with one dengue shock syndrome. The median (minimum, maximum) age was 33.5 (17, 47) years with 50% female. The median (minimum, maximum) duration from the onset of fever to development of ALF was 7.5 (5, 13) days and the maximum hepatic encephalopathy (HE) grade were III in five patients and II in three patients. Three patients had systemic inflammatory responses (SIRS) on admission and were in grade III HE. The presence of SIRS on admission was associated with higher grade of HE and its development during the course of hospitalization was associated with worsening HE grade. The hepatitis was characterized by marked elevations in: alanine transaminase [median admission 1140.5 u/L (639, 4161); median peak 2487 u/L (998, 5181)], serum bilirubin [median admission 29 μmol/L (23, 291); median peak 127 μmol/L (72, 592)], and prothrombin time [median admission 16.8s (15.3, 26.2); median peak 22s (15.3, 40.7)]. The survival rate with standard medical therapy alone was 100%.
CONCLUSIONS: Dengue associated ALF manifest about one week after the onset of fever with severe hepatitis and encephalopathy. In our experience, the outcome with standard medical therapy alone is excellent.
The risk of liver cancer in patients infected with the hepatitis B virus (HBV) and their clinical response to interferon alpha therapy vary based on the HBV genotype. The mechanisms underlying these differences in HBV pathogenesis remain unclear. In HepG2 cells transfected with a mutant HBV(G2335A) expression plasmid that does not transcribe the 2.2-kb doubly spliced RNA (2.2DS-RNA) expressed by wild-type HBV genotype A, the level of HBV pregenomic RNA (pgRNA) was higher than that in cells transfected with an HBV genotype A expression plasmid. By using cotransfection with HBV genotype D and 2.2DS-RNA expression plasmids, we found that a reduction of pgRNA was observed in the cells even in the presence of small amounts of the 2.2DS-RNA plasmid. Moreover, ectopic expression of 2.2DS-RNA in the HBV-producing cell line 1.3ES2 reduced the expression of pgRNA. Further analysis showed that exogenously transcribed 2.2DS-RNA inhibited a reconstituted transcription in vitro. In Huh7 cells ectopically expressing 2.2DS-RNA, RNA immunoprecipitation revealed that 2.2DS-RNA interacted with the TATA-binding protein (TBP) and that nucleotides 432 to 832 of 2.2DS-RNA were required for efficient TBP binding. Immunofluorescence experiments showed that 2.2DS-RNA colocalized with cytoplasmic TBP and the stress granule components, G3BP and poly(A)-binding protein 1 (PABP1), in Huh7 cells. In conclusion, our study reveals that 2.2DS-RNA acts as a repressor of HBV transcription through an interaction with TBP that induces stress granule formation. The expression of 2.2DS-RNA may be one of the viral factors involved in viral replication, which may underlie differences in clinical outcomes of liver disease and responses to interferon alpha therapy between patients infected with different HBV genotypes.
Matched MeSH terms: Hepatitis B e Antigens/metabolism; Hepatitis B Surface Antigens/metabolism; Hepatitis B virus/genetics*; Hepatitis B, Chronic/virology
A thermo-responsive random copolymer, POEGMA (poly(oligoethylene glycol) methacrylate) grafted on cationized agarose adsorbent was used for size selective protein adsorption. The effects of OEGMA300 ((oligoethylene glycol) methyl ether methacrylate, Mn=300g/mol) content and temperature on the adsorption of bovine serum albumin (BSA) were evaluated. Increasing the content of OEGMA300 resulted a reduction in BSA adsorption due to the enhanced shielding effect of OEGMA300 chains. Grafting of POEGMA chains onto cationized agarose adsorbent reduced the BSA adsorption by more than 95% at 26.5°C, which is below the LCST (lower critical solution temperature) of POEGMA. The BSA adsorption capacities for adsorbents grafted with 10 and 20mol% of OEGMA300 decreased by 48% and 46% respectively at 38°C, a temperature higher than their LCSTs. The temperature-dependent adsorption of BSA on the adsorbents was attributed to changes in the polymer conformation. The thermal transition of grafted POEGMA conformation exposed the ligand when the temperature was increased. Myoglobin (Myo), which was smaller than BSA, its adsorption behavior was less dependent on the polymer conformation. The adsorption of myoglobin onto the adsorbent with and without POEGMA showed similar percentage of reduction whereas the adsorption of BSA onto the adsorbent with POEGMA decreased by 7.6 times compared to the one without POEGMA. The packed bed of POEGMA grafted adsorbent was used for flow through separation of a protein mixture consisted of virus-like particle, Hepatitis B virus-like particle (HBVLP), BSA and insulin aspart. The recovery of HBVLP in 20mol% of OEGMA300 grafted adsorbent was increased by 19% compared to ungrafted adsorbent. The flow through of BSA can be reduced by increasing the operating temperature above LCST of 20mol% of OEGMA300 while the smaller protein, insulin aspart, remained adsorbed onto the cationized surface. Hence, this thermo-responsive adsorbent has a potential for size-selective separation of protein especially for the recovery of large biomolecule.
A review of the epidemiology of hepatitis A virus (HAV) infection over the last 20 years shows shifting patterns in the prevalence of antibodies to HAV (anti-HAV) throughout South-East Asia and China. A number of countries have shifted from high to moderate and from moderate to low endemicity, with a corresponding increase in the age of exposure from childhood to early adulthood. The changes have resulted from improvements in hygiene, sanitation and the quality of drinking water, reflecting improvements in living standards and socioeconomic progress. In general in the late 1970s and early 1980s, 85-95% of the population of developing countries like the Philippines, Korea, China and Thailand were anti-HAV-positive by age 10-15 years, compared with only about 50% in the more affluent countries like Malaysia and Singapore. In the early 1990s, 85-95% of the population were immune by age 30-40 years in the Philippines, Korea, China and Thailand, and by 50 years of age and above in Malaysia and Singapore. Similar trends were noted in Hong Kong, Taiwan and Japan. Exposure to HAV at a later age may be associated with an increase in hepatitis A morbidity and a greater propensity for outbreaks.
Anti-HCV antibody was detected in 1.9% of the blood donors in University Hospital. Among the risk groups, 33.3% of the patients with post-transfusion hepatitis were tested positive for anti-HCV antibody. The anti-HCV antibody was detected in 30% of the IDU. Haemodialysis patients, patients with acute and chronic hepatitis and patients with liver cirrhosis appeared to have increased risk of Hepatitis C virus infection. The results indicate that the frequency of HCV infection increases with the exposure to blood or blood products.
Two outbreaks involving 31 persons with jaundice are described. All had originally been diagnosed as having viral hepatitis. But subsequent investigations showed that all had been exposed to chloroform at work. Toxic jaundice from chemical exposure presents a similar clinical picture to that of viral hepatitis, but fever appears to be uncommon. Doctors who look after workers should be familiar with the type of work and health hazards of their patients. A knowledge of occupational medicine and epidemiology would enable doctors to help in detecting and preventing
occupational disease.
An abnormal, fast-moving 5'-nucleotide phosphodiesterase isozyme was found in 90.0% of 20 Malaysian patients with primary hepatoma and in 23.5% of 391 Malaysian patients with various malignant diseases; it was also discovered in 42.9% of 14 Malaysian and American patients with clinically active hepatitis B infection; in 16.7% of 18 healthy American blood bank donors who were positive for hepatitis B surface antigen (HBsAg); in 13.9% of 287 healthy Malaysian blood bank donors, some positive for HBsAg; and in none of 160 healthy American donors who were negative for HBsAg. A correlation of this abnormal isozyme with hepatoma and with infectious hepatitis B is clearly evident.
Analysis of diarrhoeal disease patterns in Malaysia from 1981-1986 suggested that infectious hepatitis ranked as the most predominant diarrhoeal disease followed by typhoid, food poisoning, dysentery and cholera. Although these five major food and water-borne diseases are still endemic in this country, diarrhoeal diseases per se no longer become an important public health problem in Malaysia. Enforcement of the cholera control program brought the incidence of the disease to a minimal. Unfortunately, this fatal form of diarrhoeal disease caused the greatest mortality compared to the others. Seasonal influence also played a part in controlling the occurrence of the disease. There was a preponderance of diarrhoeal diseases during the rainy season implicating contaminated water as a source of transmission. Although greater than half of the population has been supplied with piped water and sanitary latrines, a lot more has to be done before diarrhoeal diseases could be eliminated from this country.
Four recent cases of dengue fever with severe, unusual clinical manifestations are described. Two of these cases had features of fulminant hepatitis and encephalopathy; one of these cases was fatal. The two remaining cases showed hepatitis with renal impairment. The significance and importance of these unusual manifestations of dengue disease are discussed.
Chronic hepatitis C manifests with many extrahepatic features including renal involvement. However, less commonly, interferon therapy for chronic hepatitis C can also result in renal involvement and we describe a case when interferon therapy resulted in minimal change glomerulopathy, a form of involvement which, carries a good prognosis. Our patient developed nephrotic syndrome while on interferon therapy and HCV RNA levels were undetectable at that time. The disease showed excellent response to steroid therapy.