Ethical dilemmas related to living donor liver transplantation in Asia.

Living donor liver transplantation (LDLT) has evolved rapidly in Asia with good outcomes for both donor and recipient. Nonetheless, LDLT remains a highly demanding technique and complex surgery. The potential risks to the donors provide the basis for many of the ethical dilemmas associated with LDLT. The transplant team must have a good knowledge of the principles of bioethics in order to handle these matters. To look after the need, donor's safety and the chance for good recipient outcomes, the principles of respect for the donor's autonomy, beneficence, and non-maleficence should be practiced. In accordance with the concept of equipoise, the risk to the donor must balance the benefit to the recipient. The transplant center should have adequate experience and proven expertise in LDLT. There are concerns regarding the validity of informed consent given by the donor. While donations to non-relative patients may, at first sight, indicate radical altruism, it is important to apply careful scrutiny. Though organ trading is strictly prohibited by the law, there seems to be an inherent risk with directed donations to strangers. Transplant tourism has flourished in some countries in spite of the existence of strict laws. There are reservations regarding transplantation done by foreign visiting teams. Donor websites facilitating patients and donors and Facebook pages bear no responsibility for the outcomes of their matches and cannot ensure sufficient and accurate information about donation, transplantation, and post-operation life. Telemedicine and virtual consultations appeared to work better when the clinician and the patient know and trust each other.

Co-treatment with pegylated interferon alfa-2a and entecavir for hepatitis D: A randomized trial.

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 (HBsAg) 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 HBsAg 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.

Pattern and profile of chronic liver disease in acute on chronic liver failure.

The etiology of the chronic liver disease (CLD) in patients with acute on chronic liver failure (ACLF) may vary from region to region. The major cause of underlying CLD is viral (hepatitis B and C) in the East, while it is alcohol related in the West and in some parts of the Indian subcontinent. Autoimmune liver disease and Wilson's disease are the major underlying etiologies in the pediatric age group. The patients with CLD without cirrhosis should be included when defining ACLF. Non-alcoholic fatty liver disease related chronic liver insult in patients with known risk factors for progressive disease should be taken as a chronic liver disease in the setting of ACLF, whereas fatty liver with normal aminotransferases in low risk patients should not. The patients with CLD and previous decompensation should be excluded. Diagnosis of chronic liver disease in the setting of ACLF is made by history, physical examination and previously available or recent laboratory, endoscopic or radiological investigations. A liver biopsy through the transjugular route may help in cases where the presence of underlying CLD or its cause is not clear. The need of liver biopsy in ACLF should, however, be individualized. Standardization of liver biopsy assessment is essential for a uniform approach to the diagnosis and treatment of CLD and acute insult. Tools to measure liver stiffness may aid in identifying patients with advanced fibrosis. Studies are needed to validate the performance of these tests in the setting of ACLF.

Hepatitis D and hepatocellular carcinoma.

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 proliferator-activated receptor γ have a potential therapeutic role in HCC.

Frequency and awareness of hepatitis B and C in visitors of Hepatitis Awareness Mela.

OBJECTIVE: To observe the frequency of Hepatitis B and C in a section of society that is presumably healthy and educated and to evaluate the awareness about the modes of transmission of hepatitis B and C, in this segment. METHODS: A total of 504 individuals visiting the Awareness Mela arranged to observe World Hepatitis Day were screened for Hepatitis B and C. In addition, 106 conveniently selected individuals of age 16 years or more were asked to fill out a questionnaire which enquired on the modes of transmission of the diseases. RESULTS: A total of 504 individuals were screened; 351 males (69.6%) and 153 females (30.4%). Mean age 34.2 +/- 11.7 years; range 11-66 years. Twenty nine (5.75%) were found positive for either hepatitis B or C, mean age being 28.43 years and 92% of the affected being males. Out of the 106 questionnaire takers, 25 were females (23.6%) and 81 males (76.4%). The mean age was 33.2 +/- 11.1 years. Majority (94.7%) believed that used syringes were amongst the main causes of spread of hepatitis B and C while 40.6% did not know about the risks of sharing toothbrushes and towels. Seventy three respondents did not have prior vaccination of Hepatitis B. In addition 2 males and 1 female of study subjects were anti-HCV positive and 1 male HBsAg positive. CONCLUSION: In the educated class, prevalence of hepatitis B and C appears lower than the general population. They have the knowledge of the mode of spread of these viruses though there is room for further improvement. Many still confuse it with orofaecal transmission. Knowledge on vaccination is also unsatisfactory.

Comparison of risk factors for hepatitis B and C in patients visiting a gastroenterology clinic.

OBJECTIVE: To find out and compare the risk factors for hepatitis B and C infections in patients visiting a gastroenterology clinic. DESIGN: A case-control study. PLACE AND DURATION OF STUDY: The Liver Stomach Clinic, Karachi, from July 2004 to September 2004. PATIENTS AND METHODS: Patients of hepatitis B and C visiting the clinic were interviewed and data were noted on a prescribed form. Patients with dyspeptic symptoms who were negative for both hepatitis B and C were taken as controls. Statistical analysis was done using SPSS package. RESULTS: Total numbers of patients interviewed were 148; 63 with hepatitis C, 41 with hepatitis B and 44 in the control group. These patients hailed from various parts of Pakistan with diverse ethnicity. Comparing hepatitis C with the control group, important risk factors identified were lower level of education, the occupational exposure to the blood and syringes, history of blood transfusions, taking therapeutic injections and intravenous drips, and habit of getting shaved by barbers. Patients of hepatitis B were younger as compared to the control group. Their knowledge about spread of infection was poor. These patients had not received hepatitis B vaccine during childhood. Less number of risk factors could be identified in this group, Shaving from the barber s shop was also found to be a risk factor just like in hepatitis C. CONCLUSION: There is a need to educate general population about the possible risk factors associated with the spread of hepatitis C and B. Proper screening of blood products and universal precautions against the spread of infections are recommended. Treatment by 1/V drips and getting shaved by barbers should be discouraged. Vaccination against hepatitis B is recommended.