Hep-net opinion about the management of patients with chronic hepatitis C in Pakistan in the era of available direct acting antivirals

In Pakistan, we have 4.9% prevalence of HCV in general population, with 79% genotype 3. Recently Sofosbuvir has been made available at compassionate price in Pakistan. Management of chronic hepatitis C includes counseling of HCV patients, their proper assessment to select those who need antiviral therapy, initiation of appropriate antiviral agents and duration of therapy, along-with careful monitoring for safety and efficacy. Hepatic status as well as previous history of HCV therapy needs to be taken in the consideration before starting antiviral therapy. Other factors include co-morbid conditions like obesity, DM, NASH, etc. Treatment of special populations like liver transplant patients, patients with HBV co-infection, chronic kidney disease and hemoglobinopathies need special considerations when initiating HCV therapy

Conventional interferon alfa-2b and ribavirin for 12 versus 24 weeks in HCV genotype 2 or 3

To determine the efficacy of 12 weeks therapy with conventional interferon and ribavirin in chronic hepatitis C genotype 2 and 3 naive patients. A randomized clinical trial. Postgraduate Medical Institute, Lady Reading Hospital, Peshawar, from January 2005 to October 2006. Two hundred and twenty seven patients with chronic hepatitis C genotype 2 or 3 naive patients were enrolled in the study. All the patients were started on conventional Interferon 3 MIU, S/C, three times a week plus Ribavirin 800 to 1200 mg in divided doses daily. HCV-RNA qualitative PCR was determined after 4 weeks. In case of undetected PCR, patients were randomized to Group-I [where antiviral therapy was given for 12 weeks, n=81] or Group-II [where antiviral therapy was given for 24 weeks, n=81]. In case of detected PCR, patients were given 24 weeks antiviral therapy, n=65 [Group-III]. HCV-RNA PCR was determined at the end of respective therapies and after 6 months later on. Efficacy was defined as number of patients who achieved Sustained Virological Response [SVR] i.e. HCV-RNA PCR remained undetected 6 months after the end of antiviral therapy. SVR was achieved in 66 patients [81.48%] in Group-I, 64 patients [79.01%] in Group-II, and 49 patients [75.35%] in Group-III. SVR rate was better in genotype 2 than genotype 3 in all the three groups [p=0.031, OR = 1.52]. Conventional Interferon and Ribavirin combination therapy remains an effective therapy in chronic hepatitis genotype 2 and 3 naive patients in our region. Determination of HCV-RNA qualitative PCR at 4 weeks seems to be an important predictor of SVR and should be used to tailor antiviral therapy to 12 or 24 weeks

Frequency of hepatitis B and C in selected groups of population in NWFP, Pakistan

To determine the frequency of hepatitis B and hepatitis C in selected groups of population in NWFP. Material and We analyzed our unpublished data as well as searched out local data, published till December 2006, to know the frequency of Hepatitis B and C in. NWFP in the following groups: 1] general population, 2] healthy blood donors, 3] pre-procedure screening, 4] patients with liver diseases, and 5] high risk populations like thalassaemia. We found 2.28% prevalence for hepatitis B virus [HBV] and 3.19% for hepatitis C virus [HCV] in general population, 1.83% [HBV] and 2.34% [HCV] in healthy blood donors, 2.09% [HBV] and 4.06% [HCV] in screening data, 27.55% [HBV] and 48.78% [HCV] in chronic hepatitis patients, 26.56% [HBV] and 51.09% [HCV] in liver cirrhosis, 14.28% [HBV] and 67.86% [HCV] in hepatoma, and 6.7% [HBV] and 40.9% [HCV] in children with thalassaemia requiring multiple transfusions. We conclude that HCV and HBV has become one of the major problems in NWFP like the rest of the country, resulting in chronic liver disease and its complications

Efficacy and safety of interferon alpha 2 B plus ribavirin combination in chronic hepatitis C patients with pulmonary tuberculosis

Objectives:: To assess the efficacy of combination therapy of interferon alpha-2b plus Ribavirin in patients of chronic hepatitis C and pulmonary TB Material and Methods:: This retrospective study comprised of personal series of patients in Gastroenterology Unit, HMC Peshawar and Saidu Group of Teaching Hospitals Swat, from June 1999 to December 2002. Records of chronic hepatitis C and pulmonary TB, were analyzed for base-line parameters, response rates, and any adverse effects. Standard anti-TB was given uninterrupted along with close monitoring of all the patients. Results:: This study was conducted on 22 males and 11 females [33 patients] with chronic hepatitis C and pulmonary tuberculosis. End-treatment response: serum ALT levels became normal in 18 out of 22 male patients [81.81%], as compared to 10 out of 11 female patients [90.90%], [P > 0.05]. Serum HCV-RNA became negative in 17 out of 22 male patients [77.27%], as compared to 9 out of 11 female patients [81.81%], [P > 0.05]. Sustained viral response: Serum ALT levels remained normal and HCV-RNA PCR remained undetectable at the end of 6 months follow-up period in 15 out of 22 male patients [68.18%], as compared to 8 out of 11 female patients [72.72%], [P > 0.05]. Conclusion:: We conclude that Interferon plus Ribavirin combination therapy is an effective and safe therapy in the treatment of chronic hepatitis C patients having pulmonary TB

Review of 100 cases of intestinal amoebiasis in SWAT

The objective of this study was to find out the frequency of intestinal amoebiasis and the evaluation of clinical features and effectiveness of therapy in such patients. Material and This study was conducted in Saidu Group of Teaching Hospitals Swat from April to August 2001. An analysis of 100 patients with abdominal symptoms was done. Stool examination was performed by a specially trained technician. The stools were reported positive for Entamoeba histolytica in 70% of patients. These patients usually presented with chronic, low-grade upper abdominal pain and vague general abdominal discomfort, belching and flatulence. Bowel habits varied from continuous diarrhea to constipation alone. Frank dysentery with blood and mucous was rare. of treatment were good. The frequency of amoebiasis is high in Swat and stool examination may be diagnostic in majority of cases

Efficacy of conventional interferon alpha-2 b plus ribavirin combination in the treatment of chronic hepatitis C naive patients

To assess the efficacy of combination therapy of Conventional interferon alpha-2b plus ribavirin in patients of chronic hepatitis C. Records of 65 patients [43 males and 22 females] of chronic hepatitis C treated with combination therapy of interferon alpha-2b plus ribavirin from January 2003 to December 2003 were analyzed for base-line parameters, response rates and any adverse effects.End-treatment response was found in 86.04% male patients and 86.36% female patients. Sustained response was found in 81.39% male patients and 86.36% female patients.The study shows that conventional interferon plus ribavirin combination therapy remains an effective therapy in the treatment of chronic hepatitis C naive patients in our set-up

Use of antibiotics in hospitalized adult patients: an experience from NWFP

An audit of antibiotic use in the hospitalized adult patients in different wards and specialties in Khyber Teaching Hospital Peshawar. Records of all admitted patients, during the month of January 2002, were analyzed, to find out the age and sex-distribution, number of patients given antibiotics, routes of administration, types of antibiotics used, and brands of antibiotics used. Records of 750 patients were analyzed, with 55% males and 45% females. Mean age was 35.19 years and the mean hospital stay was 5.09 days. Antibiotic[s] were given in 590 patients [78.67%]: orally in 50.18%, intravenously in 24.40%, and both in 25.42% patients. The most three commonly prescribed antibiotics were Penicillin [30.96], 1st generation Cephalosporins [12.33%] and quinolones [9.78%]. Different groups of antibiotics and numerous brands are being used in hospital. Hospital based formulary is urgently needed to limit this irrational and diverse use of antibiotics

Non-steroidal-anti-inflammatory-drugs indiced gastrotoxicity

Non-Steroidal-Anti-Inflammatory-Drugs [NSAIDs] toxicity in the upper gastrointestinal tract is amongst the most common serious drug-induced toxicity. Enormous progress has been made in the understanding of NSAIDs-induced peptic ulcer disease in the last decade. Inhibitors in at-risk patients would require further investigation. The introduction of Cox-II specific agents offers the opportunity for safe and effective treatment for patients who are at high risk for developing GI complications. However, large, long-term, randomized and controlled studies are needed in the future to assess the overall safety of Cox-II specific inhibitors, especially in organs outside the GI tract. Whilst several matters of detail about use of Cox-II specific inhibitors persist, there is sufficient data to be confident that Cox-II specific inhibitors represent a therapeutic revolution capable of reducing NSAIDs associated gastric complications substantially. Whether such complications will be at placebo levels will require further study. The available data is still limited, particularly in the at-risk groups i.e., elderly, patients with previous history of GI complications, and are on corticosteroids

Cholangiocarcinoma

Cholangiocarcinoma represents the second most common primary liver cancer after hepatocellular carcinoma and accounts for 15% of primary liver malignancies. The incidence of cholangiocarcinoma in Asia is 50 times higher than Europe. Most patients report in advanced stage of cholangiocarcinoma at the time of presentation. However, it is classified by the location of tumor in biliary tree as intrahepatic [70%] and extrahepatic lesions [30%]. Cholangiocarcinoma is usually fatal because of the difficulty in its early diagnosis and lack of availability of effective therapy. The major identified risk factor for the development of cholangiocarcinoma is primary sclerosing cholangitis [PSC]. Liver transplantation is a viable therapeutic option for selected patients with early-stage cholangiocarcinoma. Use of pre-operative radiation and chemotherapy and ensuring the absence of metastases optimizes the outcome by an exploratory laparotomy

Hepatocellular carcinoma

Hepatocellular carcinoma [HCC] is a common cause of cancer mortality. Hepatitis B and C viruses, aflatoxin and alga toxin in the contaminated drinking water are the major etiological factors. Rapidly progressing medical imaging has resulted in the improved treatment results. Surgical resection has a major role for influencing prognosis of HCC. Local cancer therapies based on the advances in early diagnosis are progressing rapidly. Multimodality combination and sequential treatment has proved effective, unfortunately systemic chemotherapy for HCC remains disappointed. All of these have resulted in the improved prognosis of HCC

Outcome of endoscopic injection sclerotherapy with absolute alcohol for bleeding esophageal varices

Objective:To find out the long-term consequences of endoscopic injection sclerotherapy using absolute alcohol as a sclerosing agent. Design: Study was carried out retrospectively. Place and Duration:Department of Gastroenterology, HMC, Peshawar from January, 1988 to June, 2000. Subject and 620 patients admitted for bleeding esophageal varices were studied, emergency sclerotherapy was performed in 127 [20.48%] patients whereas elective sclerotherapy was performed after 24- 72 hours in 493 [79.52%] patients [p < 0.05]. Total sclerosis with survival was achieved in 573[92.41%] patients [p < 0.05], whereas 47[7.58%] patients died because of uncontrolled bleeding in 31[5%] patients, early rebleeding in 9[1.45%] patients, and encephalopathy in 7[1.12%] patients. Common complications included central chest pain [17%], esophageal ulceration [11%] and pyrexia [5%]. At the time of discharge from hospital, all the patients were given propranolol 20 mg QID as an adjuvant medical therapy for the secondary prophylaxis of variceal bleeding. The rate of complete eradication of esophageal varices was 92%. The overall recurrence rate of varices was 28% during follow-up period. The rate of recurrent bleeding and death was 9.42% and 3% respectively. We conclude that absolute alcohol and propranolol for bleeding esophageal varices are associated with low recurrence rate of varices, rebleeding and low mortality

Liver gene therapy: prospects in the new century

Novel and exciting techniques have been developed for the genetic modification of hepatocytes. There are five broadly defined indications for direct gene transfer in liver therapy: 1] Gene replacement therapy, 2] Gene expression therapy, 3] Viral enzyme prodrug therapy, 4] Inhibition of gene expression, and 5] Repair of abnormal genes. The two main methods of gene delivery to the liver are: 1] viral vectors including Retroviruses, Adenoviruses, Adeno-associated, Simian virus 40, hybrid virus vectors, and 2] non-viral methods involving attachment of a therapeutic gene to a carrier. These may be either polymer based cationic carriers [conjugates] or lipid based vectors [liposomes]. The last decade of the second millennium has seen a lot of research work done in the field of genetics. Based on the many advances in the field, we hope that there is bright future for clinical applications of gene therapy for hepatic diseases

Predictors of the outcome after the first episode of acute variceal bleeding in liver cirrhosis patients

To determine the independent predictors of morbidity, mortality and survival after the first episode of acute variceal bleeding in patients with liver cirrhosis. Design: A longitudinal study done on 115 cases. Place and Duration of Study: It was conducted in Hayatabad Medical Complex, Peshawar, from January, 1996 to December, 1998 and followed-up till June, 2000. Subjects and One hundred and fifteen cirrhotic patients, 88 men and 27 women, having a mean [' SD] age of 52.4'5.4 years [range 37- 67 years], with first episode of acute variceal bleeding and admitted to the hospital, were studied. All the patients were positive for the virological markers i.e. 73[63.48%] for anti-HCV and 42[36.52%] HBsAg. The mean follow-up was 41 ' 4.3 months with the range of 30 to 54 months. Forty-three [39.81%] patients developed complications during the hospitalization period. These included encephalopathy [n =16], progression of a pre-existent hepatic encephalopathy [n =21] and renal failure [n = 6]. Seven [6.08%] patients died within 48 hours despite therapy. Causes of death included hypovolemic shock in six patients and unsuccessful control of bleeding in one patient. Age, hepatic encephalopathy, renal failure, hepatocellular carcinoma and Child's grade were the independent factors that predicted prognosis at 6 weeks. At the end of observation period, 88[92.63%] patients were alive while 7[7.37%] had died. Conclusions: We conclude that occurrence of a first episode of acute variceal bleeding alters the natural history of liver cirrhosis because it is associated with high morbidity and the frequent development of life-threatening complications especially during the first 6 weeks. Long-term survival in such cases needs to be determined in prolonged studies

Efficacy of intrahepatic absolute alcohol in unresectable hepatocellular carcinoma

To determine efficacy of intrahepatic absolute alcohol injection in unresectable hepatocellular carcinoma. Design: A randomized, controlled, experimental and interventional clinical trial. Place and Duration of Study: Gastroenterology Department, PGMI, Hayatabad Medical Complex, Peshawar during the period from June, 1998 to June, 2000. Subjects and Thirty patients were treated by percutaneous, intrahepatic absolute alcohol injections in repeated sessions, 33 patients were not given or treated with alcohol to serve as control. Both the groups were comparable for age, sex, and other baseline characteristics. Absolute alcohol therapy significantly improved quality of life of patients, reduced the tumor size and mortality as well as showed significantly better results regarding survival [P< 0.05] than the patients of control group. We conclude that absolute alcohol is a beneficial and safe palliative treatment measure in advanced hepatocellular carcinoma [HCC]

Prospects of anti-fibrotic therapy for liver diseases

Research on antifibrotic strategies has blossomed during the last decade of second millennium. Over the past 30 years methods have been developed for isolating the principal cell types of liver. These have made it possible to analyze in detail the injury response of liver quantitatively, which underlies the scarring process known as fibrosis. Potential antifibrotic strategies may be enlisted as follows: 1] to remove the cause of injury, 2] to use anti-inflammatory agents, 3] to use immunomodulators, 4] to use direct inhibitors of stellate cell activation, and 5] cell-targeted antifibrotic therapy. Patients with advanced disease, as well as those with reasonable liver function but progressive fibrosis, may be excellent candidate for anti-fibrotic therapy

Endoscopic management of bleeding peptic ulcers

Peptic ulcers account for more than half of the cases of non-variceal upper gastrointestinal [GI] bleeding and therefore, are the focus of most of the methods of endoscopic hemostasis. Surgical intervention is now largely reserved for patients in whom endoscopic hemostasis has failed. A variety of endoscopic techniques have been employed to stop bleeding and reduce the risk of rebleeding, with no major differences in outcome between these methods. These include injection therapy, fibrin injection, heater probe, monopolar electrocautery, bipolar electrocautery, lasers and mechanical hemoclipping. The most important factor in determining outcome after gastrointestinal bleeding is rebleeding or persistent bleeding. The endoscopic appearance of an ulcer, however, provides the most useful prognostic information for rebleeding. Recurrent bleeding after initial endoscopic hemostasis occurs in 15-20% of patients with a bleeding peptic ulcer. The best approach to these patients remains controversial; the current options are repeat endoscopic therapy with the same or a different technique, emergency surgery or semi-elective surgery after repeat endoscopic hemostasis. The combination of epinephrine injection with thermal coagulation may be more effective than epinephrine injection alone. Newer modalities such as fibrin injection or the application of hemoclips appear promising and comparative studies are awaited