Rescue therapy with Sofosbuvir /Velpatasvir/ Voxilaprevir in a patient infected with Hepatitis C virus multidrug resistant variant-a much needed option for DAA-treatment failures in Pakistan? A case-report.

Primary non-response to the currently available direct acting anti-viral (DAAs) in chronic hepatitis C virus (HCV) is rare and expected in approximately only 3-4% of the patients. Among the plausible explanations, HCV resistant variant may be one of the causes among the several other viral and host factors implicated in cases who do not achieve cure. Ever since the approval of licensed DAAs in 2014, focus has been mainly on high cure rates. Hence, significantly less attention has been given to the few difficult to treat cases. We present, herein, the case of a 50-year old male who had previously failed to respond to the currently available first and second-line DAA treatment and was then approved for a special treatment access programme. According to our knowledge this is the first case-report from Pakistan in favour of the physician's directive for special treatment access for HCV DAA-experienced patients.

Phenotypic identification of different ß-Lactamases in intrinsic and acquired colistin resistant uropathogenic gram negative bacteria.

Objective: Identification of MBL, AmpC and ESBLs in colistin intrinsic and acquired resistant uropathogenic gram negative bacteria. Method: Urine samples were collected from Hayatabad Medical Complex, Peshawar during 17 January to 30 June 2019. Collected urine samples were aseptically transported microbiology lab of Health Research Institution (HRI), National Institute of Health (NIH), Khyber Medical College, Peshawar and streaked on different media. Positive growth was identified by API-10s. Antibiotic sensitivity profile was done by Modified Kirby Bauer disc diffusion method. Detection of metallo ßlactamases (MBL) production by Imipenem EDTA synergy test, Double Disc Synergy Test (DDST) for detection of ESBLs and D-test for the detection of inducible AmpC beta lactamases test was used. Colistin resistance was identified via broth micro dilution according to CLSI manual. Colistin resistant bacteria was divided in two categories; acquired and intrinsic resistant bacteria according to CLSI manual. Results: Out of 2000 urine samples, 281(14%) gram-negative bacteria were isolated. Among positive samples, acquired colistin resistant bacteria were 241 and intrinsic resistant bacteria were 40 isolates. MBL was produce by twenty one (11.7%) E.coli and seventeen (40.5%) Pseudomonas aeruginosa. E. coli, Pseudomonas aeruginosa, Klebsiella Pneumoniae, Serratia Oderifora and Proteus Marblis were ESBLs producing bacteria. AmpC production was prevalent in fourteen (7.8%) E. coli and twelve (28.6%) Pseudomonas aeruginosa. Fifty-five samples showed resistance to colistin out of 241 samples. In colistin resistant bacteria, two E.coli were MBL, ESBLs, while one E.coli was ESBLs, AmpC co-producing bacteria. The most prevalent extended drug resistant bacteria were Pseudomonas aeruginosa (28.6%) and Escherichia coli (6.1%), While 155(86.6%) Escherichia coli, 25 (59.5%) Pseudomonas aeruginosa and 22 (95.7%) Serratia Oderifora was multi drug resistant bacteria. Conclusion: Current study concluded that ESBL, MBL AmpC enzymes and their co-expression was observed with colistin resistance in E.coli and Pseudomonas aeruginosa.

HepFREEPak: protocol for a multi-centre, prospective observational study examining efficacy and impact of current therapies for the treatment of hepatitis C in Pakistan and reporting resistance to antiviral drugs: study protocol.

BACKGROUND: Pakistan has one of the highest burdens of Hepatitis C virus (HCV) infection globally. To achieve the World Health Organization's goals for HCV elimination, there is a need for substantial scale-up in testing, treatment, and a reduction in new infections. Data on the population impact of scaling up treatment is not available in Pakistan, nor is there reliable data on the incidence of infection/reinfection. This project will fill this gap by providing important empirical data on the incidence of infection (primary and reinfection) in Pakistan. Then, by using this data in epidemic models, the study will determine whether response rates achieved with affordable therapies (sofosbuvir plus daclatasvir) will be sufficient to eliminate HCV in Pakistan. METHODS: This prospective multi-centre cohort study will screen 25,000 individuals for HCV antibody (Ab) and RNA (if Ab-positive) at various centers in Pakistan- Karachi (Sindh) and Punjab, providing estimates of the disease prevalence. HCV positive patients will be treated with sofosbuvir and daclatasvir for 12-weeks, (extended to 24-weeks in those with cirrhosis) and the proportion responding to this first-line treatment estimated. Patients who test HCV Ab negative will be recalled 12 months later to test for new HCV infections, providing estimates of the incidence rate. Patients diagnosed with HCV (~ 4,000) will be treated and tested for Sustained Virological Response (SVR). Questionnaires to assess risk factors, productivity, health care usage and quality of life will be completed at both the initial screening and at 12-month follow-up, allowing mathematical modelling and economic analysis to assess the current treatment strategies. Viral resistance will be analysed and patients who have successfully completed treatment will be retested 12 months later to estimate the rate of re-infection. CONCLUSION: The HepFREEPak study will provide evidence on the efficacy of available and widely used treatment options in Pakistan. It will also provide data on the incidence rate of primary infections and re-infections. Data on incidence risk factors will allow us to model and incorporate heterogeneity of risk and how that affects screening and treatment strategies. These data will identify any gaps in current test-and-treat programs to achieve HCV elimination in Pakistan. STUDY REGISTRATION: This study was registered on clinicaltrials.gov (NCT04943588) on June 29, 2021.

Identification of colistin resistance and its bactericidal activity against uropathogenic gram negative bacteria from Hayatabad Medical Complex Peshawar.

Objectives: Identification of colistin resistance and its bactericidal activity against gram-negative bacteria isolated from urinary tract infection (UTI) patients. Methods: This 6-month cross sectional study was conducted in Hayatabad Medical Complex Peshawar from January 2019-June2019.. A total of 2000 urine samples were collected and transported to the Health Research Institute, NIH, Research Centre, Khyber Medical College Peshawar. Samples were streaked on different media and incubated at 37C° for 24hrs. Gram negative bacteria were identified through gram staining and Analytical Profile Index (API) 10s. Gram negative bacteria were subjected under antibiotic sensitivity profile through Kirby-Bauer disc diffusion method. Colistin resistance was found through broth microdilution method. Minimum bactericidal activity was performed to find out the lowest concentration of colistin required to kill gram-negative bacteria. Results: A total of 241(12.05%) uropathogenic gram negative bacteria were isolated and identified from 2000 urine samples while excluding intrinsically resistant bacteria. After broth microdilution, colistin resistance was found in 48(19.9%) Escherichia coli, 4(1.6%) Klebsiella pneumoniae and 3(1.3%) Pseudomonas aeruginosa respectively. Colistin resistant Escherichia coli were resistant to 77% Cephalosporins, 81% to Fluoroquinolones and 70% to Penicillin combinations. Colistin resistant Klebsiella pneumoniae were 100% resistant to Cephalosporins, Penicillin combinations and Fluoroquinolones while 75% were resistant to Carbapenems and Monobactams. Pseudomonas aeruginosa isolates were sensitive to all used antibiotics. Conclusion: E.coli was the mainly responsible uropathogen causing UTIs. Colistin resistance was found in 22.8% gram negative uropathogens. Klebsiella pneumoniae isolates exhibited highest resistance to antibiotics.

Azoles resistance of candida species causing vulvo-vaginitis in reproductive age women at a tertiary care setting.

Objectives: To study prevalence and resistance pattern to azoles of candida species causing vulvovaginitis in reproductive age women. Methods: Samples were collected from Hayatabad Medical Complex from November 2018 to May 2019. This cross-sectional study was conducted at the department of Microbiology, Institute of Pathology and Diagnostic Medicine, Khyber Medical University Peshawar, Pakistan. A total of 369 high vaginal swabs were collected. Candida was isolated by vaginal swabs inoculation on Sabouraud's dextrose agar (SDA). Colonies on SDA were inoculated on Candida CHROM agar to identify candida species. Wet film microscopy and Gram staining were performed. Biochemical identification was done with 20C AUX. Antifungal susceptibility testing was done by disc diffusion and broth micro-dilution methods to find the resistance pattern of azole drugs. Fluconazole, Clotrimazole, Miconazole, Voriconazole and Itraconazole were the azoles drugs used. Results: Among 43%(n=158) positive candida cases, 44%(n=85) were non pregnant women while 41%(n=73) were pregnant. The Candida species distribution of 158 isolates was as follow; Candida albicans (C. albicans) 46.2%(n=73), Candida krusei (C. krusei) 29.1%(n=46), Candida parapsilosis (C. parapsilosis) 19%(n=30) and Candida glabrata (C. glabrata) 5.7%(n=9). Overall Candida isolates were highly resistant 72%(n=113) to Fluconazole while least resistant 21.5 % (n=34) to Itraconazole. Conclusion: C. albicans is the most prevalent specie involved in Vulvovaginal candidiasis. Candida species were found to be least resistant to Itraconazole followed by Voriconazole, Miconazole, Clotrimazole and Fluconazole.

Emerging trends of antimicrobial resistance in Helicobacter pylori isolates obtained from Pakistani patients: The need for consideration of amoxicillin and clarithromycin.

OBJECTIVE: To present antimicrobial susceptibility profile of helicobacter pylori isolated from gastric biopsies of dyspeptic patients. METHODS: The cross-sectional study was conducted from March 2008 to May 2013 at the Jinnah Postgraduate Medical Centre (JPMC), Karachi, and comprised patients with suspected peptic ulcer disease who underwent upper gastrointestinal endoscopy. Multiple gastric antral biopsies were taken. One sample was imbedded in the Campylobacter-like organism test, while other biopsies were processed for culture and confirmed on polymerase chain reaction. Isolates were subjected to antimicrobial susceptibility testing and minimum inhibitory concentrations of antimicrobial agents were estimated by Epsilometer test. SPSS 21 was used for statistical analysis. RESULTS: Of the 889 samples available, 254(28.6%) were positive after campylo-like organism test, of them, 92(36.2%) isolates were cultured. Susceptibility test showed 90(97.8%) resistance to metronidazole, 25(30.1%) ofloxacin, 6(16.2%) levofloxacin, 14(15.2%) furazolidone, 5(5.4%) clarithromycin, 4(4.3%) tetracycline and 2(2.2%) isolates showed resistance to amoxicillin. Resistance to more than one drug was observed in 37(40.2%) isolates. CONCLUSIONS: Low clarithromycin resistance was surprising since Pakistan is considered a hot bed of drug-resistant bacteria.

Dengue fever in patients admitted in tertiary care hospitals in Pakistan.

OBJECTIVES: To assess the gaps in the diagnosis and management of dengue fever cases. METHODS: The retrospective descriptive analytical study was done with a case record analysis of patients with dengue fever admitted from January to December 2010 at five tertiary care hospitals in different Pakistani cities. Using a questionnaire, information was gathered on demography, haematological profile, management, use of blood and platelet transfusions and the outcome. For comparison, data of serologically-confirmed dengue patients from a private laboratory in Islamabad was collected to see the age, gender and month-wise distribution of cases tested over the same period. SPSS 16 was used for statistical analysis. RESULTS: Out of the 841 confirmed dengue cases, 514 (79%) were males and 139 (21%) females. The overall mean age was 31.3 +/- 14.0 years. Dengue fever was seen in 653 (78%) and dengue haemorrhagic fever (DHF) in 188 (22%) patients. Most cases were between 20 and 49 years of age. A gradual increase in dengue fever and dengue haemorrhagic fever was seen from August, with a peak in October/November. Tourniquet test was done only in 20 (2.3%) cases, out of which 11 (55%) were positive and 9 (45%) were negative. Serial haematocrit was not done in any case. Total deaths were 5 (0.6%). CONCLUSIONS: Most cases were seen in October/November with the majority being in the 20-39 age group. Tourniquet test and serial haematocrit were infrequently used. No standard national guidelines were employed.

Factors associated with knowledge and awareness of Hepatitis B in individuals of Chinese descent: Results from a mass point of care testing and outreach campaign in Toronto, Canada.

Background: Migrants from hepatitis B virus (HBV) endemic regions are at high risk of having chronic infection. Despite this, HBV knowledge and awareness programming, and low-barrier screening methods such as point of care (POC) testing, among this group have yet to become routine. Methods: We conducted a mass HBV POC screening and knowledge and awareness campaign for individuals of Chinese descent in Toronto, Canada. POC screening was administered, then participants completed a knowledge questionnaire. Logistic regression identified associations between demographic factors and participants' level of HBV knowledge. Results: From 2015 to 2018, 33 outreach events resulted in 891 individuals completing testing and the knowledge questionnaire. Individuals averaged 64.4 years old. Most, 62% (N = 552), were female, and 73.6% (N = 656) have been in Canada for <30 years. The average questionnaire score was 70.7% correct, with 65.2% (N = 581) demonstrating a high level of HBV knowledge. Post-secondary education (OR: 2.19, 95% CI: 1.41, 3.39), income of $50,000 to <$75,000 (OR: 2.74, 95% CI: 1.39, 5.43), and having familial history of HBV (OR: 1.72, 95% CI: 1.06, 2.78) were associated with high knowledge. The observed prevalence of HBV was 1.5%, with 13 individuals testing positive on the POC test and confirmatory laboratory testing. Conclusions: Improving knowledge and awareness of HBV is critical to empowering people, especially migrants who experience barriers to care, to pursue vaccination, testing, and treatment. Combining knowledge outreach and POC test campaigns, enabled discussion and screening for HBV with large numbers of people, and can be tailored for optimal effectiveness for specific groups.

Treatment of hepatitis B and C through national programme--an audit.

OBJECTIVES: To evaluate the response to treatment given on a large scale for hepatitis B and C through a nationwide programme. METHODS: Records of patients who received treatment of hepatitis B and C during past 2 years through the Prime Minister's programme for the Prevention and Control of Hepatitis Viral Infection was retrieved randomly from 12 sites after taking consent from the management and the site managers. Data confidentiality was ensured. All data was photocopied and brought to the Pakistan Medical Research Centre at the Jinnah Postgraduate Medical Centre, Karachi, where it was entered and analysed. The inclusion/exclusion criteria and the followup tests that were to be done before, during and after treatment were taken from the National programme manager so that actual data could be matched with the guidelines. Data was analysed through a specially developed programme. RESULTS: A total of 7752 patients received treatment at the 12 sites for hepatitis C. Adherence to inclusion/exclusion criteria or protocol was followed in 7572 (97.6%) patients. Out of 7572 patients, 3440 (45.4%) completed 6 months of interferon therapy, but the polymerase chain reaction test at the end of 6 months was available in 1686 (49%) cases. It was not detected at 6 months in 1133/1686 (67%) cases, while in 553 (33%) cases there was no response. Data for hepatitis B was collected from 8 sites. A total of 454 cases received treatment and 85 (18.72%) fulfilled the inclusion criteria. Treatment was completed by 9 (10.58%) cases, with 3 (3.52%) cases showing Hepatitis B 'e' antigen clearance and anti-HBe (antibody to hepatitis B 'e' antigen) production. CONCLUSION: Poor followup and inadequate documentation of serological/biochemical tests were the major drawbacks in both hepatitis B and C patients, resulting in wastage of huge human and financial resources without proper planning and accountability.

Cancer Registry - What is the Need to be Attentive and Why Now?

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Weight loss with interferon and ribavirin therapy in chronic hepatitis C patients.

Recommended treatment of chronic Hepatitis C virus (HCV) infection is interferon and ribavirin. Most patients develop side effects during treatment. Weight loss is one of the side effects of interferon therapy. Present study was conducted at Pakistan Medical and Research Centre (PMRC), Jinnah Postgraduate Medical Centre (JPMC), Karachi from January 1998 - December 2010, to find out the frequency, extent of weight loss, its recovery after interferon therapy and the impact of weight loss on treatment response. Body weight was recorded on regular outpatient visits i.e initially, then at 1, 3 and 6 months of treatment and six months post treatment. Out of 260 patients, 176 (67.7%) observed statistically significant weight loss (p<0.05), on completion of therapy as compared to initial visit. Weight loss during interferon therapy was found to be independent of age, gender, treatment outcome, serum albumin, haemoglobin, white blood cell (WBC) and platelet count. Body weight returned to baseline within six months after completion of treatment in most cases.

Response to different conventional interferons in treatment of chronic hepatitis C.

BACKGROUND: Sustained virological response to interferon therapy is a great challenge for patients of chronic Hepatitis C. Over 20 brands of interferons are available in the local market with each claiming over 80% response and a wide variation in the cost thus creating confusion for treating physicians as to which drug should be selected. METHODS: Chronic Hepatitis C patients attending outpatients department of Pakistan Medical Research Centre JPMC from January 1998-December 2010 were evaluated. Complete blood count, liver function tests, serum proteins, HCV-RNA were done in all cases before starting therapy. Side effects were also noted. RESULTS: Total of 851 cases received interferon 3 MIU three times a week for 6 months. There were 638 (75%) males and 213 (25%) females, mean age was 36.1 +/- 10.4 years. All were HCV-RNA positive prior to treatment, at the end of 6 months 666 (78.3%) became negative while 185 (21.7%) were non-responders with positive HCV RNA. End of treatment response (ETR) showed 84.7% with Bioferon (Argentina), 83.8% Hebron (Cuba), 82.2% INF (Argentina), 82.1% Ceron (China), 81% Viteron (Korea), 80.7% Leveron (Argentina), 81.5% Hepaferon, 79.1% Anferon (China), 77.4% Intron (Belgium), 75% Green alpha (Korea), 74% Roferon (Switzerland), 67.3% Uniferon (Lithuania), and 68.4% with others. Post-treatment 211 cases were lost to follow-up. In remaining 358/640 (55.9%) negative for HCV-RNA, at six months follow up, whereas 98 (15.3%) relapsed. Sustained virological response (SVR) Ceron 68.2%, Hebron 66.3%, Bioferon 65.2%, Leveron 60.5%, Intron 60.3%, Viteron 57%, Anferon 53.3%, Green alpha, Roferon, Hepaferon, and others 50%, INF 48.5% and Uniferon 41.9%. Average cost of these interferons was Rs. 6,000/month, except Hepaferon 5,000/month, Roferon 10,600/month. CONCLUSIONS: ETR ranged from 74-84.7% and SVR 41.9% to 68.2% and > 60% SVR was observed with Ceron, Hebron, Bioferon, Leveron, Intron and were cost effective.

Factors influencing the response of interferon therapy in chronic hepatitis C patients.

OBJECTIVE: To determine factors influencing response of interferon therapy in chronic hepatitis C patients. STUDY DESIGN: Descriptive, analytical study. PLACE AND DURATION OF STUDY: Pakistan Medical Research Centre, Jinnah Postgraduate Medical Centre, Karachi, from January 1998 to December 2009. METHODOLOGY: Patients of chronic hepatitis C treated with conventional interferon were retrospectively analyzed. End treatment response at 6 months for genotype 2 and 3 and one-year for genotype 1 and 4 was assessed. Sustained virological response was checked after 6 months of cessation of therapy. Non-compliant and incomplete follow-up cases were excluded. Factors influencing the response to therapy were analyzed by univariate and multivariate logistic regression analysis. RESULTS: A total of 932 cases received interferon therapy 103 were lost to follow-up and were excluded. Treatment was completed in 829 cases end treatment response was 74% (615 out of 829 cases). Six months post-treatment follow-up was available in 492 cases. Sustained virological response was seen in 63% (308 out of 492 cases). Univariate logistic regression analysis showed significantly better response in patients with <40 years of age, body weight>70 kg, normal platelet count, serum albumin>4.0 grams, non diabetic patients and those with a normal alanine aminotransferase (ALT) at 1st month of therapy. Multiple logistic regression analysis showed that only age<40 years was significantly important for sustained virological response. CONCLUSION: For conventional interferon therapy, age<40 years is the best predictor for sustained virological response, however, better response can be achieved in patients with <70 kg weight, normal platelet count, serum albumin>4.0 grams, non-diabetics and patients having normal ALT at 1st month of therapy.

Integration of informal medical practitioners in DOTS implementation to improve case detection rate.

OBJECTIVE: To integrate informal registered medical practitioners (IRMP) in Directly Observed Therapy Short Course (DOTS) implementation to improve case detection rate. METHODS: This interventional study was conducted in the settlement area of Malir district whereas New Karachi was taken as control, between February to November 2005. All registered healthcare providers within 5 kilometer around Tuberculosis (TB) DOTS center Malir were included. New sputum positive and sputum direct smear negative cases of pulmonary Tuberculosis above 15 years residing in the catchments area were included as target population. Informal registered medical practitioners were trained for the referral of suspected cases to the TB DOTs center where three sputum samples were taken, and X-ray chest was done to confirm if sputum direct smear (D/S) was negative. Demographic data regarding age, gender, address, case number, onset of symptoms, treatment given, response, compliance to treatment was all collected. RESULTS: Out of 64 health care providers there were a drop out of 6 leaving 58 informal registered medical practitioners (36 homeopathic/22 Hakims) who referred 54 cases, of these 16 cases were actual suspects. Two out of these 16 (12.5%) were Tuberculosis positive. One was Sputum D/S positive and the other sputum direct smear negative with X-ray chest positive. Comparison of data (Malir and New Karachi diagnostic center) showed that by incorporating homeopathic and Hakims an increase in the proportion of case identification (0.477) was significantly higher in Malir (intervention area) vs New Karachi (non-intervention area) (0.316). CONCLUSION: Integration of informal registered medical practitioners was found to be effective in DOTS implementation hence they can be incorporated in other national programmes to improve public health.

Changing trend of viral hepatitis--"A twenty one year report from Pakistan Medical Research Council Research Centre, Jinnah Postgraduate Medical Centre, Karachi".

OBJECTIVE: To determine the frequency and pattern of Hepatitis B and C over the past twenty one years, in a liver research unit of Karachi. METHODS: Retrospective analysis of the records of PMRC, Research Centre, Jinnah Postgraduate Medical Centre, Karachi, from 1987 to 2007 were reviewed. A special flow sheet was made where information of all patients with viral liver disease was entered. Patients having complete information of viral markers were included in the analysis. Cases with HBsAg, Anti HBc IgM positive and raised ALT were considered as acute Hepatitis B. HBs Ag/Anti HBc IgG positive were considered as chronic Hepatitis B. Delta antibody positive with or without HBsAg were considered as Delta Hepatitis. Anti HCV positive and raised ALT more than ten times for less than 6 months were considered as acute Hepatitis C, whereas Anti HCV and HCV-RNA positive with or without raised ALT for more than six months were considered as chronic Hepatitis C. Anti HEV IgM and Anti HAV IgM positive were considered as acute Hepatitis E and A respectively. RESULTS: A total of 5193 cases fulfilling all criteria of viral hepatitis were seen in the past 21 years. Of the total 3247 (62.5%) were males and 1946 (37.5%) females giving a male to female ratio of 1.7 : 1. Hepatitis C was the most common infection seen in 2896 cases (55.8%), followed by Hepatitis B in 1691 cases (32.6%). Seventy five percent cases of Hepatitis B were males and 25% females while 55% Hepatitis C cases were males and 45% females. Hepatitis B was seen a decade earlier in different age groups than hepatitis C. Overall, out of the total 5193 cases, 2294 (44.2%) were of chronic hepatitis, 1430 (27.5%) cirrhosis, 1083 (20.8%) carriers and 346 (6.7%) had acute hepatitis (hepatitis B; 214 (61.8%), hepatitis C; 21 (6.0%). While hepatitis B and hepatitis C both were present in 3 (1.3%). Hepatitis E was 70 (20.2%), hepatitis A 12 (3.5%) and all markers were negative in 26 (7.5%) cases). Forty cases (0.8%) were of Hepatocellular carcinoma. Year wise analysis of proportion of hepatitis B and C showed gradual decline of Hepatitis B and rise of Hepatitis C with a transition period between 1995 and 1996. CONCLUSIONS: Hepatitis C is the most common viral hepatitis, followed by hepatitis B, both are more common in males. Hepatitis B is seen a decade earlier than hepatitis C. Rising trend of hepatitis C and declining evidence of hepatitis B could be due to increased awareness and detection of hepatitis C and effective vaccination for hepatitis B in the country.

Frequency of hepatitis C and D super infection in patients with hepatitis B related complex liver disorders.

OBJECTIVE: To determine the frequency of super infection of hepatitis C and D in patients with hepatitis B related complex liver disorders and the distribution of HBV genotypes in these patients. STUDY DESIGN: Descriptive study. PLACE AND DURATION OF STUDY: The Gastroenterology Unit of PMRC in JPMC, Karachi, from July 2006 to June 2007. METHODOLOGY: All patients registered for HBV associated infections were selected. Blood was drawn from 180 patients who fulfilled the inclusion criteria. Those with an incomplete test profile were excluded. All clinical conditions were investigated through liver function tests, coagulation profile, and findings at abdominal ultrasonography, upper gastrointestinal endoscopy and liver biopsy. Liver cirrhosis and hepatocellular carcinoma (HCC) were diagnosed either on the basis of histology, or on a combination of radiological, endoscopic and laboratory data. Hepatitis B virus DNA was extracted from serum, and subjected to a nested PCR using the type specific primers for HBV genotype. Descriptive statistics were used for frequency and mean determination. RESULTS: The 129 patients finally selected for statistical analysis included 108 (84%) males and 21 (16%) females. The age ranged from 6- 68 years (mean=31.5 +/-12.39 years). There were 70 (54.2%) patients of non-cirrhotic, chronic hepatitis (CLD), 38 (29.4%) carriers, 12 (9.3%) cirrhotics and 9 (6.9%) HCC patients. Among the 129 patients, 45 (34.9%) were positive for double infection with HDV. These included 35 CLD cases, 7 cirrhotic and 3 carriers, 4 (3.1%) patients were positive for double infection with HCV including one with CLD, 2 with cirrhosis and one with HCC. Triple infection with HBV/HDV/HCV was present in 4 (3.1%) patients who had CLD. Approximately 59% (n=76) patients were not coinfected, though 9 had developed HCC. The genotype distribution of HBV was observed as D in 98 (76%) patients, A in 24 (18.6%), and AD mix in 7 (5.4%). Genotypes B, C, E or F were not found. Accordingly, genotype D strains were the predominant strains among all categories. CONCLUSION: The frequency of super infection of hepatitis C and D was found to be highest in HBV cirrhosis patients compared to patients having chronic liver disease (non-cirrhotics) and carriers. Genotype D of hepatitis B virus was found dominant in all hepatitis B related complex liver disorders.

YMDD mutation in Pakistani patients. The comparison of Eastern response with the Western response.

Lamivudine exhibits potent antiviral activity in chronic hepatitis B. YMDD mutations in west is around 32% (5 years) but reports from East are scarce. To evaluate frequency of lamivudine resistance and compare the results with the West, a total of 100 chronic hepatitis B patients were given Lamivudine 100 mg before breakfast. Out of 81 patients (19 no follow up), (85%) males and (15%) females. Wild type were 69 (85%) and 12 (14.8%) pre-core mutants. At 1 year 25/69 wild type (36.2%) lost their HBeAg and 18 (26%) seroconverted. At 2 years 30 (43.4%) became HBeAg negative and 22(31.8%) had positive anti-HBe. At 3 years 33 (47.8%) became HBeAg negative and 25 (36.2%) sero-converted. Of 12 precore mutants 8 (66.6%) lost HBV DNA within 24 weeks of therapy. At 36 months 44.4% showed sero-conversion with a YMDD mutation rate of 6% which is in contrast to 32% reported from the West.

Treatment of HBV and HDV co-infection using lamivudine.

OBJECTIVE: To see effect of Lamivudine on sero conversion of HBeAg positive cases co infected with Delta hepatitis. METHODS: Hepatitis B positive patients with deranged liver functions for 6 months were tested for HBeAg, HBV DNA and anti-Delta virus (HDV), using ELISA. Patients were divided into 2 groups, group 1: HBeAg, HBV DNA positive (wild type) but delta negative and group 2: HBeAg, HBV DNA positive (wild type) with delta positive. Lamivudine (100 mg) was advised to both groups till sero-conversion. RESULTS: Of 124 cases in year 1999-2005, 69 were in (Group 1), and 55 were in (Group 2). Eighty percent were males in both groups. ALT normalisation occurred in 75%, 24% cases within 6 months respectively. At the start of therapy mean HBeAg was 289 +/- 189 in group 1 and 142 +/- 160 in group 2. With treatment, the values did not change much till 12 months of therapy. The fall was significantly slow in delta positive cases. At 36 months 26 (38%) cases in group 1 and 9 (16.4%) cases in group 2 sero-converted. Nine cases in each group remained non-responders while 2 in each group relapsed. CONCLUSION: Wild type of HBV/HDV co-infected cases have a 16% chance of seroconversion which negates the concept that once infected with delta virus there is not much that can be done.