A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26,2023,at the Pakistan Kidney and Liver Institute&Research Centre(PKLI&RC)after initial con...A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26,2023,at the Pakistan Kidney and Liver Institute&Research Centre(PKLI&RC)after initial consultations with the experts.The Pakistan Society for the Study of Liver Diseases(PSSLD)and PKLI&RC jointly organised this meeting.This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma(hCCA).The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients.This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation.The diagnostic and staging workup includes high-quality computed tomography,magnetic resonance imaging,and magnetic resonance cholangiopancreato-graphy.Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis.However,histopathologic confirmation is not always required before resection.Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging.The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification.Selected patients with unresectable hCCA can be considered for liver transplantation.Adjuvant chemotherapy should be offered to patients with a high risk of recurrence.The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions.Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage.Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.展开更多
Hepatitis D virus(HDV)can infect HBsAg-positive individuals,causing rapid fibrosis progression,early decompensation,increased hepatocellular carcinoma risk,and higher mortality than hepatitis B virus(HBV)mono-infectio...Hepatitis D virus(HDV)can infect HBsAg-positive individuals,causing rapid fibrosis progression,early decompensation,increased hepatocellular carcinoma risk,and higher mortality than hepatitis B virus(HBV)mono-infection.Most countries lack high-quality HDV prevalence data,and the collection techniques employed often bias published data.In recent meta-analyses,HDV prevalence in HBsAg-positive patients reaches 5%-15%and is even significantly higher in endemic areas.Since HBV vaccination programs were implemented,HDV prevalence has decreased among younger populations.However,owing to immigrant influx,it has increased in some Western countries.The current practice of HDV screening in HBsAg-positive individuals is stepwise,based on physician’s discretion,and limited to at-risk populations and may require numerous visits.Double reflex testing,which includes anti-HDV testing in all HBsAg-positive individuals and then HDV RNA testing for anti-HDV-positive ones,is uncommon.Reflex testing can identify more HDV infection cases and link identified patients to further care and follow-up.Moreover,laboratory-based double reflex screening is less biased than physician-led testing.Therefore,health-care providers should learn about reflex testing,and federal and provincial hepatitis control programs should implement laboratory-based double reflex testing to obtain reliable HDV prevalence estimates.The test’s cost-effectiveness depends on the number of HBV-positive patients screened to identify one HDV-positive patient.Such testing may be viable in areas with low HBsAg but high HDV prevalence.However,its economic impact on areas with low HDV prevalence needs further study.展开更多
BACKGROUND Alpha-fetoprotein(AFP),a commonly used biomarker for hepatocellular carcinoma(HCC),is normal in up to one-third of patients.AIM To evaluate the diagnostic performance of des-gamma-carboxy-prothrombin(DCP)al...BACKGROUND Alpha-fetoprotein(AFP),a commonly used biomarker for hepatocellular carcinoma(HCC),is normal in up to one-third of patients.AIM To evaluate the diagnostic performance of des-gamma-carboxy-prothrombin(DCP)alone and in combination with AFP.METHODS In this study,202 patients with radiologically proven HCC were enrolled,and their DCP and AFP levels were evaluated for their diagnostic performance.RESULTS The mean age of the enrolled patients was 58.5 years;72.0%were male.DCP was elevated in 86.6%(n=175)of all patients,100.0%(n=74)of patients with portal vein thrombus,and 87.4%(n=111)of patients with multicentric HCC.AFP was elevated in 64.3%(n=130)of all the patients,74%(n=55)of the patients with portal vein thrombus,and 71.6%(n=91)of the patients with multicentric HCC(P=0.030,0.001,and 0.015,respectively).In tumors less than 2 cm in size(n=46),DCP was increased in 32(69.5%)patients,and AFP was increased in 25(54.3%)patients(P=0.801).There was good pairing between DCP and AFP for HCCs of 2 cm size or larger(P<0.001);however,the pairing among tumors<2 cm size was not significant(P=0.210).In 69 of the patients(34.1%),only one of the tumor markers was positive;DCP was elevated alone in 57/202(28.2%)of all patients,and AFP alone was elevated in 12/202(5.9%)of the patients.The areas under receiver operating characteristic curves(AUROC)for tumors>2 cm was 0.74 for DCP and 0.59 for AFP;combining both markers resulted in an AUROC of 0.73.For tumors<2 cm,the AUROC was 0.25 for DCP and 0.40 for AFP.CONCLUSION DCP,as an individual marker,had a better diagnostic performance in many cases of HCC.Hence,DCP may replace AFP as the primary HCC biomarker.展开更多
To determine the predictive performance of cholinesterase compared to existing prognostic models in evaluating liver function in patients with chronic hepatitis D. METHODSIn an observational, cross-sectional and retro...To determine the predictive performance of cholinesterase compared to existing prognostic models in evaluating liver function in patients with chronic hepatitis D. METHODSIn an observational, cross-sectional and retrospective study, consecutive patients with hepatitis D cirrhosis were evaluated. Demographic, clinical and laboratory parameters were recorded. Serum cholinesterase levels were correlated with existing scoring models for chronic liver disease and Liver function tests. Receiver operating characteristic (ROC) curves were constructed to find an optimal cholinesterase level predicting ascites, Child Turcotte Pugh (CTP) score ≥ 10, model for end stage liver disease (MELD) score ≥ 15, baseline-event-anticipation (BEA) score for hepatitis D ≥ 5 and the aspartate transaminase to Platelet Ratio Index (APRI) ≥ 1.5. RESULTSThis study investigated 233 patients with chronic liver disease due to hepatitis D; 192 were male, median age 42 (16-69 years). Fifty patients had ascites and 15 had encephalopathy. One hundred and sixty-seven (71.7%) were in Child class A, 52 (22.3%) in Child class B and 14 (5.0%) in class C. A MELD score of 15 or more was seen in 24 patients. Cholinesterase levels correlated well with the INR, albumin, CTP score, MELD, MELD sodium, BEA and APRI scores (P < 0.001 each). Area under the ROC curve for ascites, CTP ≥ 10, MELD ≥ 15, BEA ≥ 5, APRI ≥ 1.5 was 0.836, 0.966, 0.913, 0.871 and 0.825 respectively (P < 0.001 each). Cut off values of cholinesterase (IU/L) for predicting ascites, CTP ≥ 10, MELD ≥ 15, BEA ≥ 5 and APRI ≥ 1.5 were < 3812, < 2853, < 2829, < 4719 and < 3954 with a sensitivity of 80%, 100%, 91.67%, 82.50%, 58.0% and specificity of 81.97%, 84.79%, 87.56%, 77.06% and 55.64% respectively. CONCLUSIONSerum cholinesterase demonstrates promising correlations with serum albumin, INR and CTP, MELD, BEA and APRI scores and is predictive of liver reserves in hepatitis D cirrhosis.展开更多
AIM： To assess the clinical features, yield of the diagnostic tests and outcome of abdominal tuberculosis in non-HIV patients.METHODS： Adult patients with discharge diagnosis of abdominal tuberculosis （based upon; ...AIM： To assess the clinical features, yield of the diagnostic tests and outcome of abdominal tuberculosis in non-HIV patients.METHODS： Adult patients with discharge diagnosis of abdominal tuberculosis （based upon; positive microbiology, histo-pathology, imaging or response to trial of anti TB drugs） during the period 1999 to 2004 were analyzed. Patient＇s characteristics, laboratory investigations, radiological, endoscopic and surgical findings were evaluated. Abdominal site involved （intestinal, peritoneal, visceral, and nodal） and response to treatment was also noted.RESULTS： There were 209 patients enrolled. One hundred and twenty-three （59%） were females. Symptoms were abdominal pain 294 （93%）, fever 234 （64%）, night sweats 99 （48%）, weight loss 98 （47%）, vomiting 75 （36%）, ascites 74 （35%）, constipation 64 （31%）, and diarrhea 25 （12%）. Sub-acute and acute intestinal obstruction was seen in 28 （13%） and 12 （11%） respectively. Radiological evidence of pulmonary tuberculosis was found in 134 （64%） patients. Basis of diagnosis of abdominal tuberculosis were radiology （Chest and barium X-Rays, Ultrasound and CT scan abdomen） in 111 （53%） and histo-pathology （tissue obtained during surgery, colonoscopy, CT or ultrasound guided biopsy, laparoscopy and upper gastro intestinal endoscopy） in 87 （42%） patients. Mycobacterium culture was positive in 6/87 （7%） patients and response to therapeutic trial of anti tubercular drugs was the basis of diagnosis in 5 （2.3%） patients. Predominant site of involvement by abdominal TB was intestinal in 103 （49%） patients, peritoneal in 87 （42%） patients, solid viscera in 10 （5%） and nodal in 9 （4%） patients. Response to medical treatment was found in 158 （76%） patients and additionally 35 （17%） patients also underwent surgery. In a 425 ± 120 d follow-up period 12 patients died （eight post operative） and no case of relapse was noted.CONCLUSION： Abdominal TB has diverse and nonspecific symptomatology. No single test is adequate for diagnosis of abdominal tuberculosis in all patients. Abdominal TB in non-HIV patients remains an ongoing diagnostic dilemma requiring a high index of clinical suspicion.展开更多
Hepatitis D virus(HDV) is a defective RNA virus which requires the help of hepatitis B virus(HBV) virus for its replication and assembly of new virions. HDV genome contains only one actively transcribed open reading f...Hepatitis D virus(HDV) is a defective RNA virus which requires the help of hepatitis B virus(HBV) virus for its replication and assembly of new virions. HDV genome contains only one actively transcribed open reading frame which encodes for two isoforms of hepatitis delta antigen. Post-translational modifications of small and large delta antigens(S-HDAg and L-HDAg) involving phosphorylation and isoprenylation respectively con- fer these antigens their specific properties. S-HDAg is required for the initiation of the viral genome replica- tion, whereas L-HDAg serves as a principal inhibitor of replication and is essential for the assembly of new virion particles. Immune mediation has usually been implicated in HDV-associated liver damage. The patho- genesis of HDV mainly involves interferon-α signaling inhibition, HDV-specific T-lymphocyte activation and cytokine responses, and tumor necrosis factor-alpha and nuclear factor kappa B signaling. Due to limited protein coding capacity, HDV makes use of host cel- lular proteins to accomplish their life cycle processes, including transcription, replication, post-transcriptional and translational modifications. This intimate host- pathogen interaction significantly alters cell proteome and is associated with an augmented expression of pro-inflammatory, growth and anti-apoptotic factorswhich explains severe necroinflammation and increased cell survival and an early progression to hepatocellular carcinoma in HDV patients. The understanding of the process of viral replication, HBV-HDV interactions, and etio-pathogenesis of the severe course of HDV infection is helpful in identifying the potential therapeutic targets in the virus life cycle for the prophylaxis and treatment of HDV infection and complications.展开更多
AIM： To investigate the association between cytokine gene polymorphism and disease status in chronic hepatitis C genotype 3 by liver biopsy, ALl, HCV RNA levels and response to treatment. METHODS： Patients with chro...AIM： To investigate the association between cytokine gene polymorphism and disease status in chronic hepatitis C genotype 3 by liver biopsy, ALl, HCV RNA levels and response to treatment. METHODS： Patients with chronic hepatitis C genotype 3 were analyzed for single nucleotide polymorphisms of interleukin （IL）-10, IL-1 beta, interferon-gamma （IFN-y）, tumor necrosis factor-alpha （TNF-y） and transforming growth factor-beta （TGF-β） by polymerase chain reaction using sequence-specific oligonucleotide primers. Liver biopsies were assessed by modified histological activity index （HAI） scoring system using a scale of 0-18 for grading the necro-inflammatory activity and 0-6 for staging the fibrosis. HCV RNA levels were determined by bDNA assay. The patients were treated with interferon alpha and ribavirin for 6 mo. Sustained virological response was assessed 6 mo after the completion of the treatment. RESULTS： Out of the 40 patients analyzed, 26 were males. Mean age was 40.5±12.5 years （range 18- 65 years）. The frequencies of different dimorphic polymorphisms based on single nucleotide substitution were as follows： IL-10-1082 G/A 85%, A/A 12.5%, G/ G 2.5%; IL-10-819 A/C 87.5%, C/C 10%, A/A 2.5%; IL-10-592 C/A 72.5%, C/C 27.5%; IL-1 C 90%, U 10%; IFN-874 T/A 50%, T/T 27.5%, A/A 22.5%; TNF-308 A/G 95%, G/G 5%; TGF-10 T/C 52.5%, C/C 35%, T/T 12.5%. The mean grades of necroinflammatory activity of different genotypes of IL-10 at promoter site -1082 were A/A = 3.6, A/G = 5.0, and G/G = 10.0 and the difference was significant （P = 0.029）. The difference in the stage of disease at a scale of 0-6 was A/A 0.8, A/G 2.3, and G/G 4.0 （P = 0.079）. The difference in the HAI seemed to be related to the presence of allele -1082G.For IL-10 -819 genotypes, mean scores of fibrosis were A/A = 6.0, A/C = 2.2, and C/C = 1.0 （P = 0.020） though the inflammatory activity was not much different. No significant differences in HAI were noted among polymorphisms of other cytokines. Moreover, ALT and HCV RNA levels were not significantly different among different cytokine polymorphisms. There was a significant correlation of HAI and HCV RNA levels with the duration of disease. TGFI3 -10 genotype CC patients had a better end of treatment response than those with other genotypes （P = 0：020）. Sustained virological response to the treatment was not influenced by the cytokine polymorphism. No effect of other factors like viral load, degree of fibrosis, gender, steatosis, was observed on sustained virological response in this population infected with genotype 3. CONCLUSION： There is no significant correlation between cytokine polymorphisms and HAI except for the polymorphisms of anti-inflammatory cytokine IL-10, which may influence hepatic inflammatory activity and fibrosis in patients with chronic hepatitis C genotype 3. Sustained virological response in this genotype does not seem to be influenced by cytokine gene polymorphisms.展开更多
AIM: To determine the predictive factors for early aspiration in liver abscess. METHODS: A retrospective analysis of all patients with liver abscess from 1995 to 2004 was performed. Abscess was diagnosed as amebic in ...AIM: To determine the predictive factors for early aspiration in liver abscess. METHODS: A retrospective analysis of all patients with liver abscess from 1995 to 2004 was performed. Abscess was diagnosed as amebic in 661 (68%) patients, pyogenic in 200 (21%), indeterminate in 73 (8%) and mixed in 32 (3%). Multiple logistic regression analysis was performed to determine predictive factors for aspiration of liver abscess. RESULTS: A total of 966 patients, 738 (76%) male, mean age 43 ± 17 years, were evaluated: 540 patients responded to medical therapy while adjunctive percutaneous aspiration was performed in 426 patients. Predictive factors for aspiration of liver abscess were: age ≥ 55 years, size of abscess ≥ 5 cm, involvement of both lobes of the liver and duration of symptoms ≥ 7 d. Hospital stay in the aspiration group was relatively longer than in the non aspiration group. Twelve patients died in the aspiration group and this mortality was not statistically significant when compared to the non aspiration group. CONCLUSION: Patients with advanced age, abscess size > 5 cm, both lobes of the liver involvement and duration of symptoms > 7 d were likely to undergo aspiration of the liver abscess, regardless of etiology.展开更多
Hepatitis D virus(HDV) is a defective circular shape single stranded HDV RNA virus with two types of viral proteins,small and large hepatitis D antigens,surrounded by hepatitis B surface antigen.Superinfection with HD...Hepatitis D virus(HDV) is a defective circular shape single stranded HDV RNA virus with two types of viral proteins,small and large hepatitis D antigens,surrounded by hepatitis B surface antigen.Superinfection with HDV in chronic hepatitis B is associated with a more threatening form of liver disease leading to rapid progression to cirrhosis.In spite of some controversy in the epidemiological studies,HDV infection does increase the risk of hepatocellular carcinoma(HCC) compared to hepatitis B virus(HBV) monoinfection.Hepatic decompensation,rather than development of HCC,is the first usual clinical endpoint during the course of HDV infection.Oxidative stress as a result of severe necroinflammation may progress to HCC.The large hepatitis D antigen is a regulator of various cellular functions and an activator of signal transducer and activator of transcription(STAT)3 and the nuclear factor kappa B pathway.Another proposed epigenetic mechanism by which HCC may form is the aberrant silencing of tumor suppressor genes by DNA Methyltransferases.HDV antigens have also been associated with increased histone H3 acetylation of the clusterin promoter.This enhances the expression of clusterin in infected cells,increasing cell survival potential.Any contribution of HBV DNA integration with chromosomes of infected hepatocytes is not clear at this stage.The targeted inhibition of STAT3 and cyclophilin,and augmentation of peroxisome proliferatoractivated receptor γ have a potential therapeutic role in HCC.展开更多
Hepatitis D virus (HDV) infection is present worldwide and affects all age groups. Around 18 million people are estimated to be infected with HDV. An important trend in HDV infection is global decline. HDV prevalence ...Hepatitis D virus (HDV) infection is present worldwide and affects all age groups. Around 18 million people are estimated to be infected with HDV. An important trend in HDV infection is global decline. HDV prevalence has decreased significantly in Europe since the 1970s and 1980s when it was f irst reported. The Asia-Pacif ic region now seems to be where HDV is a major health concern. There is a lack of available data from most of the countries from this region; hence, the true status of HDV cannot be determined. In South Asia, most of the countries have conditions that are favorable for the spread of hepatitis B and other related infections. Countries like Pakistan and Iran have shown an increase in HDV prevalence over a period of time. Other countries and region like China, Turkey, Australia, Japan, India and Taiwan, some of which had very high HDV prevalence in the past, have shown a decline in the incidence, but high prevalence persists in some. Intravenous drug abusers, homosexual men and women, prostitutes, and people on hemodialysis are the groups with very high HDV prevalence.展开更多
AIM: To determine the efficacy of gastric juice polymerase chain reaction (PCR) for the detection of H pylori infection in comparison with histology and gastric antral biopsy PCR in patients on a proton pump inhibitor...AIM: To determine the efficacy of gastric juice polymerase chain reaction (PCR) for the detection of H pylori infection in comparison with histology and gastric antral biopsy PCR in patients on a proton pump inhibitor (PPI). METHODS: Eighty-five consecutive patients with dyspeptic symptoms were enrolled. Gastric biopsies for histology, PCR and gastric juice were collected at endoscopy for PCR of the H pylori urease C gene (ure C). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, positive and negative likelihood ratio for PCR of gastric juice for the H pylori ure C gene was compared to histology and gastric antral biopsy H pylori ure C PCR in patients with and without PPI. RESULTS: Gastric juice PCR was positive in 66 (78%) patients. Histology showed H pylori associated gastritis in 57 (67%). Gastric biopsy PCR was positive in 72 (85%). In patients not taking PPI, the sensitivity, specificity, PPV, NPV, accuracy and positive and negative likelihood ratio for gastric juice PCR were 89%, 72%, 91%, 67%, 90%, 85%, 3.1 and 0.1 respectively. In patients on PPI these values were 86%, 100%%, 100%, 29%, 86%, 9.5 and 1.4, respectively. CONCLUSION: Gastric juice PCR for the diagnosis of H pylori infection has increased sensitivity compared to histology with PPI. The use of gastric juice PCR is recommended to confirm H pylori status in patients taking PPIs.展开更多
AIM： To assess the clinical presentation and genotypes of delta hepatitis in local population. METHODS： In this prospective study, 39 consecutive patients who were positive for HBsAg and hepatitis D virus （HDV） an...AIM： To assess the clinical presentation and genotypes of delta hepatitis in local population. METHODS： In this prospective study, 39 consecutive patients who were positive for HBsAg and hepatitis D virus （HDV） antibody were included. The patients were divided in two groups on the basis of presence or absence of HDV RNA and a comparative study was done. Genotype of HDV was determined in PCR positive patients. RESULTS： Overall there is male dominance, in which 34 patients out of 39 （87.2%） were male. Twenty （51%） patients were from the adjacent areas of three provinces; Sindh, Punjab and Balochistan indicating the higher prevalence of delta hepatitis in this mid region of Pakistan. Patients of all age groups were affected with delta hepatitis （median 31.5 years, range 12-75）. HDV RNA was detectable in 23 patients （59%）. All the HDV strains belonged to genotype I. HBV DNA was detectable only in 3 cases who were also HBeAg and HDV RNA positive. Patients with detectable HDV RNA were younger than patients with undetectable RNA; mean age 29.7±12.8 years vs 36.8±15.2. There were no statistically significant differences in the clinical presentation and routine biochemical profile of patients with detectable or undetectable HDV RNA. Clinical cirrhosis was present in 19 （49%） patients; 12 with detectable RNA and 7 with undetectable HDV RNA （P = 0.748）. Decompensated disease was seen in eight patients; five and three respectively from each group. Four patients with undetectable RNA and two patients with detectable RNA had normal ALT and ultrasound abdomen. CONCLUSION： HDV may infect at any age, usually young adult males. Genotype I is prevalent. With time some of the patients become HDV RNA negative or asymptomatic carrier. Most of the patients have suppressed HBV DNA replication. Significant numbers of patients have cirrhosis.展开更多
Hepatitis B is one of the leading causes of chronic hepatitis in developing countries, with 5% to 15% of the population carrying virus. The high prevalence is due to failure to adopt appropriate measure to confine the...Hepatitis B is one of the leading causes of chronic hepatitis in developing countries, with 5% to 15% of the population carrying virus. The high prevalence is due to failure to adopt appropriate measure to confine the spread of infection. Most hepatitis B patients present with advanced diseases. Although perinatal transmission is believed to be an important mode, most infections in the developing world occur in childhood and early adulthood. Factors in developing countries associated with the progression of chronic hepatitis B (CHB) include co-infections with human immunodeficiency virus, delta hepatitis virus, hepatitis C virus, alcohol intake and aflatoxin. Treatment protocols extrapolated from developed countries may need modifications according to the resources available. There is some controversy as to when to start treatment, with what medication and for how long? There is now enough evidence to support that hepatitis B patients should be considered for treatment if they show persistently elevated abnormal aminotransferase levels in the last 6 mo, checked on at least three separate occasions, and a serum hepatitis B virus DNA level of > 2000 IU/mL. Therapeutic agents that were approved by Pure Food and Drug Administration are now available in many developing countries. These include standard interferon (INF)-α, pegylated INF-α, lamivudine, adefovir, entecavir and telbivudine. Drug resistance has emerged as a major challenge in the management of patients with CHB. The role of the universal vaccination program for effective control of hepatitis B cannot be emphasized enough.展开更多
Hepatitis D virus(HDV) is the smallest single stranded RNA virus infecting humans. The hepatitis B surface antigen envelope protein protects the HDV nucleocapsidantigen and provides a means for the virus to enter and ...Hepatitis D virus(HDV) is the smallest single stranded RNA virus infecting humans. The hepatitis B surface antigen envelope protein protects the HDV nucleocapsidantigen and provides a means for the virus to enter and exit the hepatocyte. Hepatitis B and D viruses exploit the human sodium taurocholate co-transporting polypeptide(NTCP), a receptor, for their entry into hepatocytes. Prenylation of the large delta antigen is a critical determinant of HDV particle assembly. Treatment with pegylated interferon results in sustained virological response six months post-treatment in one fourth of the patients. Nucleos(t)ide analogs(NAs) have been widely tested in hepatitis delta, but they appear to be ineffective. Combination treatment of NAs with interferon also proved to be disappointing so there is a need for novel therapeutic options. The receptor function of NTCP is blocked by Myrcludex B, a synthetic N-acylated pre S1 lipopeptide that competes with infectious virions for receptor binding. There are already some approved drugs available, including irbesartan, ezetimibe, and ritonavir and cyclosporin A, with documented inhibitory effects on NTCP's metabolic function. These drugs may have a role in HDV treatment. Interference with hostmediated post-translational changes of proteins that are crucial to the HDV life cycle, such as prenylation may become an important tool to control HDV infection and prevent replication. Lonafarnib, a prenylation inhibitor significantly reduces virus levels in hepatitis delta patients. Antisense oligodeoxynucleotides which are complementary to genomic HDV ribozyme self-cleavage site and stem?Ⅰ?regions can inhibit genomic HDV ribozyme activity.展开更多
AIM: To investigate the efficacy of pegylated interferon alfa(PEG-IFNα) therapy with and without entecavir in patients with chronic hepatitis D. METHODS: Forty hepatitis D virus(HDV) RNA positive patients were random...AIM: To investigate the efficacy of pegylated interferon alfa(PEG-IFNα) therapy with and without entecavir in patients with chronic hepatitis D. METHODS: Forty hepatitis D virus(HDV) RNA positive patients were randomized to receive either PEG-IFNα-2a 180 μg weekly in combination with entecavir 0.5 mg daily(n = 21) or PEG-IFNα alone(n =19). Patients who failed to show 2 log reduction in HDV RNA level at 24 wk of treatment, or had detectable HDV RNA at 48 wk of therapy were considered as treatment failure. Treatment was continued for 72 wk in the rest of the patients. All the patients were followed for 24 wk post treatment. Intention to treat analysis was performed.RESULTS: The mean age of the patients was 26.7 ± 6.8 years, 31 were male. Two log reduction in HDV RNA levels at 24 wk of therapy was achieved in 9(43%) patients receiving combination therapy and 12(63%) patients receiving PEG-IFNα alone(P = 0.199). Decline in hepatitis B surface antigen(HBs Ag) levels was insignificant. At the end of treatment, HDV RNA was negative in 8 patients(38%) receiving combination therapy and 10 patients(53%) receiving PEG-IFNα-2a alone. Virological response persisted in 7(33%) and 8(42%) patients, respectively at the end of the 24 wk follow-up period. One responder patient in the combination arm lost HBs Ag and became hepatitis B surface antibody positive. Six out of 14 baseline hepatitis B e antigen reactive patients seroconverted and four of these seroconverted patients had persistent HDV RNA clearance.CONCLUSION: Administration of PEG-IFNα-2a with or without entecavir, resulted in persistent HDV RNA clearance in 37% of patients. The addition of entecavir did not improve the overall response.展开更多
Side-effects associated with the cancer chemotherapy limit the scope of chemotherapeutic drugs and no data was available about these side effects in Pakistan. Moreover starvation based differential chemotherapy has be...Side-effects associated with the cancer chemotherapy limit the scope of chemotherapeutic drugs and no data was available about these side effects in Pakistan. Moreover starvation based differential chemotherapy has been proved to greatly reduce the side effects of chemotherapy depending on starvation time. The current study was conducted to survey the common side effects of the chemotherapeutic drugs and the role of starvation to reduce them. The study included total 100 subjects with multiple carcinomas. A comprehensive questionnaire about starvation inquiry, chemotherapy side effects and their basic information was filled by interviewers as told by patients. There were 48% patients with breast cancer and 11% with uterine cancer. Out of these patients 30%, 28%, 9% and 9% patients were agreed to starve for 12, 24, 36 and 48 hours respectively. The survey regarding the side effects of chemotherapy showed that 43% patients were suffering from headache, fatigue 90%, weakness 95%, hair loss 76%, nausea 77%, vomiting 75%, diarrhea 31%, abdominal cramps 40%, mouth sores 47%, dry mouth 74%, memory impairment 14%?and numbness 49%. Breast cancer is the most common cancer in Pakistan. Only 18% of the total patients were agreed to starve for more than one day. Chemotherapy-associated side effects vary greatly and it does not depend upon cancer type. But these side effects depend on multiple factors such as the type and dose of chemotherapeutic drug, patient’s health status and stage of cancer.展开更多
AIM:To assess the cost savings of reloading the multiband ligator in endoscopic esophageal variceal ligation (EVL) used on the same patient for subsequent sessions. METHODS:This single centre retrospective descriptive...AIM:To assess the cost savings of reloading the multiband ligator in endoscopic esophageal variceal ligation (EVL) used on the same patient for subsequent sessions. METHODS:This single centre retrospective descriptive study analysed patients undergoing variceal ligation at a tertiary care centre between 1st January, 2003 and 30th June, 2006. The multiband ligator was reloaded with six hemorrhoidal bands using hemorrhoidal ligator for the second and subsequent sessions. Analysis of cost saving was done for the number of follow-up sessions for the variceal eradication. RESULTS:A total of 261 patients underwent at least one session of endoscopic esophageal variceal ligation between January 2003 and June 2006. Out of 261, 108 patients (males 67) agreed to follow the eradication program and underwent repeated sessions. A total of 304 sessions was performed with 2.81 sessions per patient on average. Thirty-two patients could not complete the programm. In 76 patients (70%), variceal obliteration was achieved. The ratio of the costs for the session with reloaded ligator versus a session with a new ligator was 1:2.37. Among the patients who completed esophageal varices eradication, cost saving with reloaded ligator was 58%. CONCLUSION:EVL using reloaded multiband ligators for the follow-up sessions on patients undergoing variceal eradication is a cost saving procedure. Reloading the ligator thus is recommended especially for developing countries where most of the patients are not health insured.展开更多
OBJECTIVE： Helicobacter pylori is a Gram-negative organism. Its outer membrane protein Q（Hop Q） mediates host-pathogen interactions; Hop Q genotypes 1 and 2 are found associating with gastroduodenal pathologies. Th...OBJECTIVE： Helicobacter pylori is a Gram-negative organism. Its outer membrane protein Q（Hop Q） mediates host-pathogen interactions; Hop Q genotypes 1 and 2 are found associating with gastroduodenal pathologies. The authors measured the anti-adhesion effects of the extracts of Abelmoschus esculentus, Zingiber officinale, Trachyspermum ammi, Glycyrrhiza glabra, Curcuma longa and Capsicum annum against Hop Q genotypes and H. pylori cytotoxin-associated gene A（Cag A）.METHODS： DNA was extracted by polymerase chain reaction of the Hop Q genotypes（i.e., type 1, type 2 and Cag A） from 115 H. pylori strains. The effect of the extracts from selected dietary ingredients was determined using a gastric adenocarcinoma cell line and a quantitative DNA fragmentation assay. The anti-adhesive effect of these extracts on H. pylori was tested using an anti-adhesion analysis.RESULTS： C. annum, C. longa and A. esculentus showed prominent anti-adhesion effects with resultant values of 17.3% ± 2.9%, 14.6% ± 3.7%, 13.8% ± 3.6%, respectively, against Hop Q type 1 and 13.1% ± 1.7%, 12.1% ± 2%, 11.1% ± 1.6%, respectively, against Hop Q type 2. C. longa（93%）, C. annum（89%） and A. esculentus（75%） had better anti-adhesive activity against H. pylori with Hop Q type 1 compared to Hop Q type 2 with respective values of 70%, 64% and 51%. Extracts of C. annum（14.7% ± 4.1%）, A. esculentus（12.3% ± 4.1%） and Z. officinale（8.4% ± 2.8%） had an anti-adhesion effect against Cag A-positive H. pylori strains compared to Cag A-negative strains.展开更多
Hepatitis C virus (HCV) has emerged as a leading cause of hepatocellular carcinoma (HCC). In most cases, the virus causes HCC in the presence of chronic hepatic inflammation, advanced fibrosis, and cirrhosis. A combin...Hepatitis C virus (HCV) has emerged as a leading cause of hepatocellular carcinoma (HCC). In most cases, the virus causes HCC in the presence of chronic hepatic inflammation, advanced fibrosis, and cirrhosis. A combination of viral, environmental, and genetic factors are likely to determine the host immune response to the infection as well as the progression to HCC. Clinical and epidemiologic studies have identified many of the risk factors associated with HCC development in patients with chronic hepatitis C. Male sex and older age are considered as independent risk factors for HCC, while alcohol consumption accelerates fibrosis, increasing the risk for progression to HCC. Obesity, diabetes mellitus, nonalcoholic fatty liver disease, aflatoxin exposure and occult hepatitis B infection, all contribute to a higher HCC risk. HCV patients infected with HCV genotype 3 are also more likely to develop HCC and genetic variations such as single nucleotide polymorphisms, which may also alter the risk. Sustained virological response to the antiviral therapy results in significantly more favorable long-term outcomes. The incidence of HCC after HCV eradication is similar between patients treated with peginterferon plus ribavirin and direct-acting antiviral therapy.展开更多
文摘A consensus meeting of national experts from all major national hepatobiliary centres in the country was held on May 26,2023,at the Pakistan Kidney and Liver Institute&Research Centre(PKLI&RC)after initial consultations with the experts.The Pakistan Society for the Study of Liver Diseases(PSSLD)and PKLI&RC jointly organised this meeting.This effort was based on a comprehensive literature review to establish national practice guidelines for hilar cholangiocarcinoma(hCCA).The consensus was that hCCA is a complex disease and requires a multidisciplinary team approach to best manage these patients.This coordinated effort can minimise delays and give patients a chance for curative treatment and effective palliation.The diagnostic and staging workup includes high-quality computed tomography,magnetic resonance imaging,and magnetic resonance cholangiopancreato-graphy.Brush cytology or biopsy utilizing endoscopic retrograde cholangiopancreatography is a mainstay for diagnosis.However,histopathologic confirmation is not always required before resection.Endoscopic ultrasound with fine needle aspiration of regional lymph nodes and positron emission tomography scan are valuable adjuncts for staging.The only curative treatment is the surgical resection of the biliary tree based on the Bismuth-Corlette classification.Selected patients with unresectable hCCA can be considered for liver transplantation.Adjuvant chemotherapy should be offered to patients with a high risk of recurrence.The use of preoperative biliary drainage and the need for portal vein embolisation should be based on local multidisciplinary discussions.Patients with acute cholangitis can be drained with endoscopic or percutaneous biliary drainage.Palliative chemotherapy with cisplatin and gemcitabine has shown improved survival in patients with irresectable and recurrent hCCA.
文摘Hepatitis D virus(HDV)can infect HBsAg-positive individuals,causing rapid fibrosis progression,early decompensation,increased hepatocellular carcinoma risk,and higher mortality than hepatitis B virus(HBV)mono-infection.Most countries lack high-quality HDV prevalence data,and the collection techniques employed often bias published data.In recent meta-analyses,HDV prevalence in HBsAg-positive patients reaches 5%-15%and is even significantly higher in endemic areas.Since HBV vaccination programs were implemented,HDV prevalence has decreased among younger populations.However,owing to immigrant influx,it has increased in some Western countries.The current practice of HDV screening in HBsAg-positive individuals is stepwise,based on physician’s discretion,and limited to at-risk populations and may require numerous visits.Double reflex testing,which includes anti-HDV testing in all HBsAg-positive individuals and then HDV RNA testing for anti-HDV-positive ones,is uncommon.Reflex testing can identify more HDV infection cases and link identified patients to further care and follow-up.Moreover,laboratory-based double reflex screening is less biased than physician-led testing.Therefore,health-care providers should learn about reflex testing,and federal and provincial hepatitis control programs should implement laboratory-based double reflex testing to obtain reliable HDV prevalence estimates.The test’s cost-effectiveness depends on the number of HBV-positive patients screened to identify one HDV-positive patient.Such testing may be viable in areas with low HBsAg but high HDV prevalence.However,its economic impact on areas with low HDV prevalence needs further study.
文摘BACKGROUND Alpha-fetoprotein(AFP),a commonly used biomarker for hepatocellular carcinoma(HCC),is normal in up to one-third of patients.AIM To evaluate the diagnostic performance of des-gamma-carboxy-prothrombin(DCP)alone and in combination with AFP.METHODS In this study,202 patients with radiologically proven HCC were enrolled,and their DCP and AFP levels were evaluated for their diagnostic performance.RESULTS The mean age of the enrolled patients was 58.5 years;72.0%were male.DCP was elevated in 86.6%(n=175)of all patients,100.0%(n=74)of patients with portal vein thrombus,and 87.4%(n=111)of patients with multicentric HCC.AFP was elevated in 64.3%(n=130)of all the patients,74%(n=55)of the patients with portal vein thrombus,and 71.6%(n=91)of the patients with multicentric HCC(P=0.030,0.001,and 0.015,respectively).In tumors less than 2 cm in size(n=46),DCP was increased in 32(69.5%)patients,and AFP was increased in 25(54.3%)patients(P=0.801).There was good pairing between DCP and AFP for HCCs of 2 cm size or larger(P<0.001);however,the pairing among tumors<2 cm size was not significant(P=0.210).In 69 of the patients(34.1%),only one of the tumor markers was positive;DCP was elevated alone in 57/202(28.2%)of all patients,and AFP alone was elevated in 12/202(5.9%)of the patients.The areas under receiver operating characteristic curves(AUROC)for tumors>2 cm was 0.74 for DCP and 0.59 for AFP;combining both markers resulted in an AUROC of 0.73.For tumors<2 cm,the AUROC was 0.25 for DCP and 0.40 for AFP.CONCLUSION DCP,as an individual marker,had a better diagnostic performance in many cases of HCC.Hence,DCP may replace AFP as the primary HCC biomarker.
文摘To determine the predictive performance of cholinesterase compared to existing prognostic models in evaluating liver function in patients with chronic hepatitis D. METHODSIn an observational, cross-sectional and retrospective study, consecutive patients with hepatitis D cirrhosis were evaluated. Demographic, clinical and laboratory parameters were recorded. Serum cholinesterase levels were correlated with existing scoring models for chronic liver disease and Liver function tests. Receiver operating characteristic (ROC) curves were constructed to find an optimal cholinesterase level predicting ascites, Child Turcotte Pugh (CTP) score ≥ 10, model for end stage liver disease (MELD) score ≥ 15, baseline-event-anticipation (BEA) score for hepatitis D ≥ 5 and the aspartate transaminase to Platelet Ratio Index (APRI) ≥ 1.5. RESULTSThis study investigated 233 patients with chronic liver disease due to hepatitis D; 192 were male, median age 42 (16-69 years). Fifty patients had ascites and 15 had encephalopathy. One hundred and sixty-seven (71.7%) were in Child class A, 52 (22.3%) in Child class B and 14 (5.0%) in class C. A MELD score of 15 or more was seen in 24 patients. Cholinesterase levels correlated well with the INR, albumin, CTP score, MELD, MELD sodium, BEA and APRI scores (P < 0.001 each). Area under the ROC curve for ascites, CTP ≥ 10, MELD ≥ 15, BEA ≥ 5, APRI ≥ 1.5 was 0.836, 0.966, 0.913, 0.871 and 0.825 respectively (P < 0.001 each). Cut off values of cholinesterase (IU/L) for predicting ascites, CTP ≥ 10, MELD ≥ 15, BEA ≥ 5 and APRI ≥ 1.5 were < 3812, < 2853, < 2829, < 4719 and < 3954 with a sensitivity of 80%, 100%, 91.67%, 82.50%, 58.0% and specificity of 81.97%, 84.79%, 87.56%, 77.06% and 55.64% respectively. CONCLUSIONSerum cholinesterase demonstrates promising correlations with serum albumin, INR and CTP, MELD, BEA and APRI scores and is predictive of liver reserves in hepatitis D cirrhosis.
文摘AIM： To assess the clinical features, yield of the diagnostic tests and outcome of abdominal tuberculosis in non-HIV patients.METHODS： Adult patients with discharge diagnosis of abdominal tuberculosis （based upon; positive microbiology, histo-pathology, imaging or response to trial of anti TB drugs） during the period 1999 to 2004 were analyzed. Patient＇s characteristics, laboratory investigations, radiological, endoscopic and surgical findings were evaluated. Abdominal site involved （intestinal, peritoneal, visceral, and nodal） and response to treatment was also noted.RESULTS： There were 209 patients enrolled. One hundred and twenty-three （59%） were females. Symptoms were abdominal pain 294 （93%）, fever 234 （64%）, night sweats 99 （48%）, weight loss 98 （47%）, vomiting 75 （36%）, ascites 74 （35%）, constipation 64 （31%）, and diarrhea 25 （12%）. Sub-acute and acute intestinal obstruction was seen in 28 （13%） and 12 （11%） respectively. Radiological evidence of pulmonary tuberculosis was found in 134 （64%） patients. Basis of diagnosis of abdominal tuberculosis were radiology （Chest and barium X-Rays, Ultrasound and CT scan abdomen） in 111 （53%） and histo-pathology （tissue obtained during surgery, colonoscopy, CT or ultrasound guided biopsy, laparoscopy and upper gastro intestinal endoscopy） in 87 （42%） patients. Mycobacterium culture was positive in 6/87 （7%） patients and response to therapeutic trial of anti tubercular drugs was the basis of diagnosis in 5 （2.3%） patients. Predominant site of involvement by abdominal TB was intestinal in 103 （49%） patients, peritoneal in 87 （42%） patients, solid viscera in 10 （5%） and nodal in 9 （4%） patients. Response to medical treatment was found in 158 （76%） patients and additionally 35 （17%） patients also underwent surgery. In a 425 ± 120 d follow-up period 12 patients died （eight post operative） and no case of relapse was noted.CONCLUSION： Abdominal TB has diverse and nonspecific symptomatology. No single test is adequate for diagnosis of abdominal tuberculosis in all patients. Abdominal TB in non-HIV patients remains an ongoing diagnostic dilemma requiring a high index of clinical suspicion.
文摘Hepatitis D virus(HDV) is a defective RNA virus which requires the help of hepatitis B virus(HBV) virus for its replication and assembly of new virions. HDV genome contains only one actively transcribed open reading frame which encodes for two isoforms of hepatitis delta antigen. Post-translational modifications of small and large delta antigens(S-HDAg and L-HDAg) involving phosphorylation and isoprenylation respectively con- fer these antigens their specific properties. S-HDAg is required for the initiation of the viral genome replica- tion, whereas L-HDAg serves as a principal inhibitor of replication and is essential for the assembly of new virion particles. Immune mediation has usually been implicated in HDV-associated liver damage. The patho- genesis of HDV mainly involves interferon-α signaling inhibition, HDV-specific T-lymphocyte activation and cytokine responses, and tumor necrosis factor-alpha and nuclear factor kappa B signaling. Due to limited protein coding capacity, HDV makes use of host cel- lular proteins to accomplish their life cycle processes, including transcription, replication, post-transcriptional and translational modifications. This intimate host- pathogen interaction significantly alters cell proteome and is associated with an augmented expression of pro-inflammatory, growth and anti-apoptotic factorswhich explains severe necroinflammation and increased cell survival and an early progression to hepatocellular carcinoma in HDV patients. The understanding of the process of viral replication, HBV-HDV interactions, and etio-pathogenesis of the severe course of HDV infection is helpful in identifying the potential therapeutic targets in the virus life cycle for the prophylaxis and treatment of HDV infection and complications.
文摘AIM： To investigate the association between cytokine gene polymorphism and disease status in chronic hepatitis C genotype 3 by liver biopsy, ALl, HCV RNA levels and response to treatment. METHODS： Patients with chronic hepatitis C genotype 3 were analyzed for single nucleotide polymorphisms of interleukin （IL）-10, IL-1 beta, interferon-gamma （IFN-y）, tumor necrosis factor-alpha （TNF-y） and transforming growth factor-beta （TGF-β） by polymerase chain reaction using sequence-specific oligonucleotide primers. Liver biopsies were assessed by modified histological activity index （HAI） scoring system using a scale of 0-18 for grading the necro-inflammatory activity and 0-6 for staging the fibrosis. HCV RNA levels were determined by bDNA assay. The patients were treated with interferon alpha and ribavirin for 6 mo. Sustained virological response was assessed 6 mo after the completion of the treatment. RESULTS： Out of the 40 patients analyzed, 26 were males. Mean age was 40.5±12.5 years （range 18- 65 years）. The frequencies of different dimorphic polymorphisms based on single nucleotide substitution were as follows： IL-10-1082 G/A 85%, A/A 12.5%, G/ G 2.5%; IL-10-819 A/C 87.5%, C/C 10%, A/A 2.5%; IL-10-592 C/A 72.5%, C/C 27.5%; IL-1 C 90%, U 10%; IFN-874 T/A 50%, T/T 27.5%, A/A 22.5%; TNF-308 A/G 95%, G/G 5%; TGF-10 T/C 52.5%, C/C 35%, T/T 12.5%. The mean grades of necroinflammatory activity of different genotypes of IL-10 at promoter site -1082 were A/A = 3.6, A/G = 5.0, and G/G = 10.0 and the difference was significant （P = 0.029）. The difference in the stage of disease at a scale of 0-6 was A/A 0.8, A/G 2.3, and G/G 4.0 （P = 0.079）. The difference in the HAI seemed to be related to the presence of allele -1082G.For IL-10 -819 genotypes, mean scores of fibrosis were A/A = 6.0, A/C = 2.2, and C/C = 1.0 （P = 0.020） though the inflammatory activity was not much different. No significant differences in HAI were noted among polymorphisms of other cytokines. Moreover, ALT and HCV RNA levels were not significantly different among different cytokine polymorphisms. There was a significant correlation of HAI and HCV RNA levels with the duration of disease. TGFI3 -10 genotype CC patients had a better end of treatment response than those with other genotypes （P = 0：020）. Sustained virological response to the treatment was not influenced by the cytokine polymorphism. No effect of other factors like viral load, degree of fibrosis, gender, steatosis, was observed on sustained virological response in this population infected with genotype 3. CONCLUSION： There is no significant correlation between cytokine polymorphisms and HAI except for the polymorphisms of anti-inflammatory cytokine IL-10, which may influence hepatic inflammatory activity and fibrosis in patients with chronic hepatitis C genotype 3. Sustained virological response in this genotype does not seem to be influenced by cytokine gene polymorphisms.
文摘AIM: To determine the predictive factors for early aspiration in liver abscess. METHODS: A retrospective analysis of all patients with liver abscess from 1995 to 2004 was performed. Abscess was diagnosed as amebic in 661 (68%) patients, pyogenic in 200 (21%), indeterminate in 73 (8%) and mixed in 32 (3%). Multiple logistic regression analysis was performed to determine predictive factors for aspiration of liver abscess. RESULTS: A total of 966 patients, 738 (76%) male, mean age 43 ± 17 years, were evaluated: 540 patients responded to medical therapy while adjunctive percutaneous aspiration was performed in 426 patients. Predictive factors for aspiration of liver abscess were: age ≥ 55 years, size of abscess ≥ 5 cm, involvement of both lobes of the liver and duration of symptoms ≥ 7 d. Hospital stay in the aspiration group was relatively longer than in the non aspiration group. Twelve patients died in the aspiration group and this mortality was not statistically significant when compared to the non aspiration group. CONCLUSION: Patients with advanced age, abscess size > 5 cm, both lobes of the liver involvement and duration of symptoms > 7 d were likely to undergo aspiration of the liver abscess, regardless of etiology.
文摘Hepatitis D virus(HDV) is a defective circular shape single stranded HDV RNA virus with two types of viral proteins,small and large hepatitis D antigens,surrounded by hepatitis B surface antigen.Superinfection with HDV in chronic hepatitis B is associated with a more threatening form of liver disease leading to rapid progression to cirrhosis.In spite of some controversy in the epidemiological studies,HDV infection does increase the risk of hepatocellular carcinoma(HCC) compared to hepatitis B virus(HBV) monoinfection.Hepatic decompensation,rather than development of HCC,is the first usual clinical endpoint during the course of HDV infection.Oxidative stress as a result of severe necroinflammation may progress to HCC.The large hepatitis D antigen is a regulator of various cellular functions and an activator of signal transducer and activator of transcription(STAT)3 and the nuclear factor kappa B pathway.Another proposed epigenetic mechanism by which HCC may form is the aberrant silencing of tumor suppressor genes by DNA Methyltransferases.HDV antigens have also been associated with increased histone H3 acetylation of the clusterin promoter.This enhances the expression of clusterin in infected cells,increasing cell survival potential.Any contribution of HBV DNA integration with chromosomes of infected hepatocytes is not clear at this stage.The targeted inhibition of STAT3 and cyclophilin,and augmentation of peroxisome proliferatoractivated receptor γ have a potential therapeutic role in HCC.
文摘Hepatitis D virus (HDV) infection is present worldwide and affects all age groups. Around 18 million people are estimated to be infected with HDV. An important trend in HDV infection is global decline. HDV prevalence has decreased significantly in Europe since the 1970s and 1980s when it was f irst reported. The Asia-Pacif ic region now seems to be where HDV is a major health concern. There is a lack of available data from most of the countries from this region; hence, the true status of HDV cannot be determined. In South Asia, most of the countries have conditions that are favorable for the spread of hepatitis B and other related infections. Countries like Pakistan and Iran have shown an increase in HDV prevalence over a period of time. Other countries and region like China, Turkey, Australia, Japan, India and Taiwan, some of which had very high HDV prevalence in the past, have shown a decline in the incidence, but high prevalence persists in some. Intravenous drug abusers, homosexual men and women, prostitutes, and people on hemodialysis are the groups with very high HDV prevalence.
基金The research grants from Aga Khan University Research Committee to JY and SR
文摘AIM: To determine the efficacy of gastric juice polymerase chain reaction (PCR) for the detection of H pylori infection in comparison with histology and gastric antral biopsy PCR in patients on a proton pump inhibitor (PPI). METHODS: Eighty-five consecutive patients with dyspeptic symptoms were enrolled. Gastric biopsies for histology, PCR and gastric juice were collected at endoscopy for PCR of the H pylori urease C gene (ure C). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy, positive and negative likelihood ratio for PCR of gastric juice for the H pylori ure C gene was compared to histology and gastric antral biopsy H pylori ure C PCR in patients with and without PPI. RESULTS: Gastric juice PCR was positive in 66 (78%) patients. Histology showed H pylori associated gastritis in 57 (67%). Gastric biopsy PCR was positive in 72 (85%). In patients not taking PPI, the sensitivity, specificity, PPV, NPV, accuracy and positive and negative likelihood ratio for gastric juice PCR were 89%, 72%, 91%, 67%, 90%, 85%, 3.1 and 0.1 respectively. In patients on PPI these values were 86%, 100%%, 100%, 29%, 86%, 9.5 and 1.4, respectively. CONCLUSION: Gastric juice PCR for the diagnosis of H pylori infection has increased sensitivity compared to histology with PPI. The use of gastric juice PCR is recommended to confirm H pylori status in patients taking PPIs.
文摘AIM： To assess the clinical presentation and genotypes of delta hepatitis in local population. METHODS： In this prospective study, 39 consecutive patients who were positive for HBsAg and hepatitis D virus （HDV） antibody were included. The patients were divided in two groups on the basis of presence or absence of HDV RNA and a comparative study was done. Genotype of HDV was determined in PCR positive patients. RESULTS： Overall there is male dominance, in which 34 patients out of 39 （87.2%） were male. Twenty （51%） patients were from the adjacent areas of three provinces; Sindh, Punjab and Balochistan indicating the higher prevalence of delta hepatitis in this mid region of Pakistan. Patients of all age groups were affected with delta hepatitis （median 31.5 years, range 12-75）. HDV RNA was detectable in 23 patients （59%）. All the HDV strains belonged to genotype I. HBV DNA was detectable only in 3 cases who were also HBeAg and HDV RNA positive. Patients with detectable HDV RNA were younger than patients with undetectable RNA; mean age 29.7±12.8 years vs 36.8±15.2. There were no statistically significant differences in the clinical presentation and routine biochemical profile of patients with detectable or undetectable HDV RNA. Clinical cirrhosis was present in 19 （49%） patients; 12 with detectable RNA and 7 with undetectable HDV RNA （P = 0.748）. Decompensated disease was seen in eight patients; five and three respectively from each group. Four patients with undetectable RNA and two patients with detectable RNA had normal ALT and ultrasound abdomen. CONCLUSION： HDV may infect at any age, usually young adult males. Genotype I is prevalent. With time some of the patients become HDV RNA negative or asymptomatic carrier. Most of the patients have suppressed HBV DNA replication. Significant numbers of patients have cirrhosis.
文摘Hepatitis B is one of the leading causes of chronic hepatitis in developing countries, with 5% to 15% of the population carrying virus. The high prevalence is due to failure to adopt appropriate measure to confine the spread of infection. Most hepatitis B patients present with advanced diseases. Although perinatal transmission is believed to be an important mode, most infections in the developing world occur in childhood and early adulthood. Factors in developing countries associated with the progression of chronic hepatitis B (CHB) include co-infections with human immunodeficiency virus, delta hepatitis virus, hepatitis C virus, alcohol intake and aflatoxin. Treatment protocols extrapolated from developed countries may need modifications according to the resources available. There is some controversy as to when to start treatment, with what medication and for how long? There is now enough evidence to support that hepatitis B patients should be considered for treatment if they show persistently elevated abnormal aminotransferase levels in the last 6 mo, checked on at least three separate occasions, and a serum hepatitis B virus DNA level of > 2000 IU/mL. Therapeutic agents that were approved by Pure Food and Drug Administration are now available in many developing countries. These include standard interferon (INF)-α, pegylated INF-α, lamivudine, adefovir, entecavir and telbivudine. Drug resistance has emerged as a major challenge in the management of patients with CHB. The role of the universal vaccination program for effective control of hepatitis B cannot be emphasized enough.
文摘Hepatitis D virus(HDV) is the smallest single stranded RNA virus infecting humans. The hepatitis B surface antigen envelope protein protects the HDV nucleocapsidantigen and provides a means for the virus to enter and exit the hepatocyte. Hepatitis B and D viruses exploit the human sodium taurocholate co-transporting polypeptide(NTCP), a receptor, for their entry into hepatocytes. Prenylation of the large delta antigen is a critical determinant of HDV particle assembly. Treatment with pegylated interferon results in sustained virological response six months post-treatment in one fourth of the patients. Nucleos(t)ide analogs(NAs) have been widely tested in hepatitis delta, but they appear to be ineffective. Combination treatment of NAs with interferon also proved to be disappointing so there is a need for novel therapeutic options. The receptor function of NTCP is blocked by Myrcludex B, a synthetic N-acylated pre S1 lipopeptide that competes with infectious virions for receptor binding. There are already some approved drugs available, including irbesartan, ezetimibe, and ritonavir and cyclosporin A, with documented inhibitory effects on NTCP's metabolic function. These drugs may have a role in HDV treatment. Interference with hostmediated post-translational changes of proteins that are crucial to the HDV life cycle, such as prenylation may become an important tool to control HDV infection and prevent replication. Lonafarnib, a prenylation inhibitor significantly reduces virus levels in hepatitis delta patients. Antisense oligodeoxynucleotides which are complementary to genomic HDV ribozyme self-cleavage site and stem?Ⅰ?regions can inhibit genomic HDV ribozyme activity.
文摘AIM: To investigate the efficacy of pegylated interferon alfa(PEG-IFNα) therapy with and without entecavir in patients with chronic hepatitis D. METHODS: Forty hepatitis D virus(HDV) RNA positive patients were randomized to receive either PEG-IFNα-2a 180 μg weekly in combination with entecavir 0.5 mg daily(n = 21) or PEG-IFNα alone(n =19). Patients who failed to show 2 log reduction in HDV RNA level at 24 wk of treatment, or had detectable HDV RNA at 48 wk of therapy were considered as treatment failure. Treatment was continued for 72 wk in the rest of the patients. All the patients were followed for 24 wk post treatment. Intention to treat analysis was performed.RESULTS: The mean age of the patients was 26.7 ± 6.8 years, 31 were male. Two log reduction in HDV RNA levels at 24 wk of therapy was achieved in 9(43%) patients receiving combination therapy and 12(63%) patients receiving PEG-IFNα alone(P = 0.199). Decline in hepatitis B surface antigen(HBs Ag) levels was insignificant. At the end of treatment, HDV RNA was negative in 8 patients(38%) receiving combination therapy and 10 patients(53%) receiving PEG-IFNα-2a alone. Virological response persisted in 7(33%) and 8(42%) patients, respectively at the end of the 24 wk follow-up period. One responder patient in the combination arm lost HBs Ag and became hepatitis B surface antibody positive. Six out of 14 baseline hepatitis B e antigen reactive patients seroconverted and four of these seroconverted patients had persistent HDV RNA clearance.CONCLUSION: Administration of PEG-IFNα-2a with or without entecavir, resulted in persistent HDV RNA clearance in 37% of patients. The addition of entecavir did not improve the overall response.
文摘Side-effects associated with the cancer chemotherapy limit the scope of chemotherapeutic drugs and no data was available about these side effects in Pakistan. Moreover starvation based differential chemotherapy has been proved to greatly reduce the side effects of chemotherapy depending on starvation time. The current study was conducted to survey the common side effects of the chemotherapeutic drugs and the role of starvation to reduce them. The study included total 100 subjects with multiple carcinomas. A comprehensive questionnaire about starvation inquiry, chemotherapy side effects and their basic information was filled by interviewers as told by patients. There were 48% patients with breast cancer and 11% with uterine cancer. Out of these patients 30%, 28%, 9% and 9% patients were agreed to starve for 12, 24, 36 and 48 hours respectively. The survey regarding the side effects of chemotherapy showed that 43% patients were suffering from headache, fatigue 90%, weakness 95%, hair loss 76%, nausea 77%, vomiting 75%, diarrhea 31%, abdominal cramps 40%, mouth sores 47%, dry mouth 74%, memory impairment 14%?and numbness 49%. Breast cancer is the most common cancer in Pakistan. Only 18% of the total patients were agreed to starve for more than one day. Chemotherapy-associated side effects vary greatly and it does not depend upon cancer type. But these side effects depend on multiple factors such as the type and dose of chemotherapeutic drug, patient’s health status and stage of cancer.
文摘AIM:To assess the cost savings of reloading the multiband ligator in endoscopic esophageal variceal ligation (EVL) used on the same patient for subsequent sessions. METHODS:This single centre retrospective descriptive study analysed patients undergoing variceal ligation at a tertiary care centre between 1st January, 2003 and 30th June, 2006. The multiband ligator was reloaded with six hemorrhoidal bands using hemorrhoidal ligator for the second and subsequent sessions. Analysis of cost saving was done for the number of follow-up sessions for the variceal eradication. RESULTS:A total of 261 patients underwent at least one session of endoscopic esophageal variceal ligation between January 2003 and June 2006. Out of 261, 108 patients (males 67) agreed to follow the eradication program and underwent repeated sessions. A total of 304 sessions was performed with 2.81 sessions per patient on average. Thirty-two patients could not complete the programm. In 76 patients (70%), variceal obliteration was achieved. The ratio of the costs for the session with reloaded ligator versus a session with a new ligator was 1:2.37. Among the patients who completed esophageal varices eradication, cost saving with reloaded ligator was 58%. CONCLUSION:EVL using reloaded multiband ligators for the follow-up sessions on patients undergoing variceal eradication is a cost saving procedure. Reloading the ligator thus is recommended especially for developing countries where most of the patients are not health insured.
文摘OBJECTIVE： Helicobacter pylori is a Gram-negative organism. Its outer membrane protein Q（Hop Q） mediates host-pathogen interactions; Hop Q genotypes 1 and 2 are found associating with gastroduodenal pathologies. The authors measured the anti-adhesion effects of the extracts of Abelmoschus esculentus, Zingiber officinale, Trachyspermum ammi, Glycyrrhiza glabra, Curcuma longa and Capsicum annum against Hop Q genotypes and H. pylori cytotoxin-associated gene A（Cag A）.METHODS： DNA was extracted by polymerase chain reaction of the Hop Q genotypes（i.e., type 1, type 2 and Cag A） from 115 H. pylori strains. The effect of the extracts from selected dietary ingredients was determined using a gastric adenocarcinoma cell line and a quantitative DNA fragmentation assay. The anti-adhesive effect of these extracts on H. pylori was tested using an anti-adhesion analysis.RESULTS： C. annum, C. longa and A. esculentus showed prominent anti-adhesion effects with resultant values of 17.3% ± 2.9%, 14.6% ± 3.7%, 13.8% ± 3.6%, respectively, against Hop Q type 1 and 13.1% ± 1.7%, 12.1% ± 2%, 11.1% ± 1.6%, respectively, against Hop Q type 2. C. longa（93%）, C. annum（89%） and A. esculentus（75%） had better anti-adhesive activity against H. pylori with Hop Q type 1 compared to Hop Q type 2 with respective values of 70%, 64% and 51%. Extracts of C. annum（14.7% ± 4.1%）, A. esculentus（12.3% ± 4.1%） and Z. officinale（8.4% ± 2.8%） had an anti-adhesion effect against Cag A-positive H. pylori strains compared to Cag A-negative strains.
文摘Hepatitis C virus (HCV) has emerged as a leading cause of hepatocellular carcinoma (HCC). In most cases, the virus causes HCC in the presence of chronic hepatic inflammation, advanced fibrosis, and cirrhosis. A combination of viral, environmental, and genetic factors are likely to determine the host immune response to the infection as well as the progression to HCC. Clinical and epidemiologic studies have identified many of the risk factors associated with HCC development in patients with chronic hepatitis C. Male sex and older age are considered as independent risk factors for HCC, while alcohol consumption accelerates fibrosis, increasing the risk for progression to HCC. Obesity, diabetes mellitus, nonalcoholic fatty liver disease, aflatoxin exposure and occult hepatitis B infection, all contribute to a higher HCC risk. HCV patients infected with HCV genotype 3 are also more likely to develop HCC and genetic variations such as single nucleotide polymorphisms, which may also alter the risk. Sustained virological response to the antiviral therapy results in significantly more favorable long-term outcomes. The incidence of HCC after HCV eradication is similar between patients treated with peginterferon plus ribavirin and direct-acting antiviral therapy.
