Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality, and healthcare expenditure in patients with chronic liver disease in India. The Indian National Association for Study of the Liver (INASL) had published its first guidelines on diagnosis and management of HCC (The Puri Recommendations) in 2014, and these guidelines were very well received by the healthcare community involved in diagnosis and management of HCC in India and neighboring countries. However, since 2014, many new developments have taken place in the field of HCC diagnosis and management, hence INASL endeavored to update its 2014 consensus guidelines. A new Task Force on HCC was constituted that reviewed the previous guidelines as well as the recent developments in various aspects of HCC that needed to be incorporated in the new guidelines. A 2-day round table discussion was held on 5th and 6th May 2018 at Puri, Odisha, to discuss, debate, and finalize the revised consensus statements. Each statement of the guideline was graded according to the Grading of Recommendations Assessment Development and Evaluation system with minor modifications. We present here the 2019 Update of INASL Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri-2 Recommendations. Hepatocellular carcinoma (HCC) is one of the major causes of morbidity, mortality, and healthcare expenditure in patients with chronic liver disease in India. The Indian National Association for Study of the Liver (INASL) had published its first guidelines on diagnosis and management of HCC (The Puri Recommendations) in 2014, and these guidelines were very well received by the healthcare community involved in diagnosis and management of HCC in India and neighboring countries. However, since 2014, many new developments have taken place in the field of HCC diagnosis and management, hence INASL endeavored to update its 2014 consensus guidelines. A new Task Force on HCC was constituted that reviewed the previous guidelines as well as the recent developments in various aspects of HCC that needed to be incorporated in the new guidelines. A 2-day round table discussion was held on 5th and 6th May 2018 at Puri, Odisha, to discuss, debate, and finalize the revised consensus statements. Each statement of the guideline was graded according to the Grading of Recommendations Assessment Development and Evaluation system with minor modifications. We present here the 2019 Update of INASL Consensus on Prevention, Diagnosis, and Management of Hepatocellular Carcinoma in India: The Puri-2 Recommendations. Primary liver cancer or hepatocellular carcinoma (HCC) is one of the major causes of mortality among patients with chronic liver disease.1Kumar A. Acharya S.K. Singh S.P. et al.The Indian national association for study of the liver (INASL) consensus on prevention, diagnosis and management of hepatocellular carcinoma in India: the Puri recommendations.J Clin Exp Hepatol. 2014; 4: S3-S26https://doi.org/10.1016/j.jceh.2014.04.003Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar The incidence and prevalence of HCC is rising in India, mainly because of the epidemic of non-alcoholic fatty liver disease and is poised to become the leading cause of cancer in India.2Three year report of PBCR 2012-2014. http://ncdirindia.org/NCRP/ALL_NCRP_REPORTS/PBCR_REPORT_2012_2014/ALL_CONTENT/Printed_Version.htm. Accessed August 12, 2018.Google Scholar,3Younossi Z. Stepanova M. Ong J.P. et al.Nonalcoholic steatohepatitis is the fastest growing cause of hepatocellular carcinoma in liver transplant candidates.Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2019; 17 (e3): 748-755https://doi.org/10.1016/j.cgh.2018.05.057Abstract Full Text Full Text PDF PubMed Scopus (64) Google Scholar Although there are many consensus guidelines on HCC management from USA, Europe and Asia, most of these fail to address India specific issues on HCC.4Marrero J.A. Kulik L.M. Sirlin C.B. et al.Diagnosis, staging, and management of hepatocellular carcinoma: 2018 practice guidance by the American association for the study of liver diseases.Hepatol Baltim Md. 2018; 68: 723-750https://doi.org/10.1002/hep.29913Crossref PubMed Scopus (289) Google Scholar, 5Heimbach J.K. Kulik L.M. 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Singh S.P. et al.The Indian national association for study of the liver (INASL) consensus on prevention, diagnosis and management of hepatocellular carcinoma in India: the Puri recommendations.J Clin Exp Hepatol. 2014; 4: S3-S26https://doi.org/10.1016/j.jceh.2014.04.003Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar) in 2014, and these guidelines were very well received by the healthcare community involved in diagnosis and management of HCC in India and neighboring countries. However, since 2014 many new developments have taken place in the field of HCC diagnosis and management, hence INASL endeavored to update its 2014 consensus guidelines. A new Task Force on HCC. For the development of these revised guidelines, the task force reviewed the previous guidelines as well as the recent developments that have happened in various aspects of HCC that needed to be incorporated in the new guidelines. A 2-day round table discussion was held on 5th and 6th May 2018 at Puri, Odisha, to discuss, debate, and finalize the revised consensus statements. Each topic was discussed considering the most relevant data available in literature and the final consensus statements were formulated according to both scientific evidence and clinical expertise of the involved physicians. Only those statements were accepted which were unanimously approved by the majority of the members of the taskforce. Each statement of the guideline was graded according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) system with minor modifications.12Atkins D. Best D. Briss P.A. et al.Grading quality of evidence and strength of recommendations.BMJ. 2004; 328: 1490https://doi.org/10.1136/bmj.328.7454.1490Crossref PubMed Google Scholar The strength of recommendations (strong or weak) thus reflects the quality (grade) of underlying evidence (I, II-1, II-2, II-3, and III) (Table 1).Table 1Modified Grading of Recommendations, Assessment, Development and Evaluation (GRADE).Quality of evidenceCriteriaIRandomized controlled trialsII-1Controlled trials without randomizationII-2Cohort or case-control analytical studiesII-3Multiple time series, dramatic uncontrolled experimentsIIIOpinions of respected authorities, descriptive epidemiologyStrength of recommendationsCriteriaStrongFactors influencing the strength of the recommendation included the quality of the evidence, presumed patient-important outcomes, and costWeakVariability in preferences and values, or more uncertainty. Recommendation is made with less certainty, higher cost, or resource consumption Open table in a new tab HCC is among the leading causes of cancer death globally.11European Association for the Study of the LiverElectronic address: [email protected], European association for the study of the liver. EASL clinical practice guidelines: management of hepatocellular carcinoma.J Hepatol. 2018; 69: 182-236https://doi.org/10.1016/j.jhep.2018.03.019Abstract Full Text Full Text PDF PubMed Scopus (741) Google Scholar According to the Global Burden of Disease Study 2015, there were 854,000 incident cases of and 810,000 deaths due to liver cancer globally in 2015, contributing to 20,578,000 disability-adjusted life-years. Number of cases with incident liver cancer increased by 75% between 1990 and 2015; of this, 47% can be explained by changing population age structures, 35% by population growth, and −8% to changing age-specific incidence rates. The male-to-female ratio for age-standardized liver cancer mortality was 2.8. Globally, hepatitis B virus (HBV) is estimated to account for 33% of liver cancer deaths, alcohol for 30%, hepatitis C virus (HCV) for 21%, and other causes for 16%; these relative figures show substantial variation between countries.13Akinyemiju T. Abera S. et al.Global Burden of Disease Liver Cancer CollaborationThe burden of primary liver cancer and underlying etiologies from 1990 to 2015 at the global, regional, and national level: results from the global burden of disease study 2015.JAMA Oncol. 2017; 3: 1683-1691https://doi.org/10.1001/jamaoncol.2017.3055Crossref PubMed Scopus (241) Google Scholar Data on the epidemiology of HCC from India are sparse and of variable and uncertain quality. Data on incidence of HCC as reported by various population-based registries across the country show a marked (>30-fold) variation in crude and age-adjusted incidence rates of HCC. However, it is uncertain whether the data from these different registries can be directly compared. Estimates based on these data suggest that crude incidence rate of HCC in India in the year 2015 was 2.8 cases per 100,000 population per year (males: 3.9, females: 1.6), and the crude mortality rate was 2.7 per 100,000 population per year.2Three year report of PBCR 2012-2014. http://ncdirindia.org/NCRP/ALL_NCRP_REPORTS/PBCR_REPORT_2012_2014/ALL_CONTENT/Printed_Version.htm. Accessed August 12, 2018.Google Scholar The registry data also suggest a slight increase in the incidence of HCC over time, but whether this reflects a true increase remains uncertain. In the only observational study, incidence of HCC in patients with cirrhosis was 1.6 per 100 person-years of follow-up, with fairly wide confidence intervals (CIs) (0.55–2.64).14Paul S.B. Sreenivas V. Gulati M.S. et al.Incidence of hepatocellular carcinoma among Indian patients with cirrhosis of liver: an experience from a tertiary care center in northern India.Indian J Gastroenterol Off J Indian Soc Gastroenterol. 2007; 26: 274-278PubMed Google ScholarTabled 1Consensus statementsLevelGrade•Data on epidemiology of HCC from India are sparse and of variable and uncertain quality.•The available data suggest that crude incidence rate of HCC in India is 2.8 cases per 100,000 population per year (males: 3.9, females: 1.6), and crude mortality rate is around 2.7 per 100,000 population per year.II-2•One study reported the incidence of HCC in patients with cirrhosis is 1.6 per 100 person-years, with wide uncertainty bounds (95% CI: 0.55–2.64).II-2 Open table in a new tab Cirrhosis due to any cause may be complicated by development of HCC. The risk is higher in persons with cirrhosis due to chronic viral hepatitis than that due to other causes. 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Barbàra M. et al.A meta-analysis of single HCV-untreated arm of studies evaluating outcomes after curative treatments of HCV-related hepatocellular carcinoma.Liver Int Off J Int Assoc Study Liver. 2017; 37: 1157-1166https://doi.org/10.1111/liv.13357Crossref PubMed Scopus (33) Google Scholar A subsequent meta-analysis showed that there is no evidence that HCC occurrence or recurrence is different between patients receiving DAA or interferon (IFN) therapy.37Waziry R. Hajarizadeh B. Grebely J. et al.Hepatocellular carcinoma risk following direct-acting antiviral HCV therapy: a systematic review, meta-analyses, and meta-regression.J Hepatol. 2017; 67: 1204-1212https://doi.org/10.1016/j.jhep.2017.07.025Abstract Full Text Full Text PDF PubMed Scopus (144) Google Scholar In fact, sustained virological response (SVR) post DAA reduces the incidence of HCC. Cirrhosis, low albumin, low platelet, and alpha-fetoprotein (AFP) level posttreatment are indicators of high HCC occurrence even after SVR.38Guarino M. Sessa A. Cossiga V. et al.Direct-acting antivirals and hepatocellular carcinoma in chronic hepatitis C: a few lights and many shadows.World J Gastroenterol. 2018; 24: 2582-2595https://doi.org/10.3748/wjg.v24.i24.2582Crossref PubMed Scopus (16) Google Scholar Long-term follow-up studies are required to assess surveillance strategy in patients treated with DAA. Chronic alcohol consumption is an important risk factor for HCC development. However, the incidence of HCC associated with alcoholic cirrhosis is lower than the incidence associated with cirrhosis of other etiologies, including chronic HCV, chronic HBV, and hereditary hemochromatosis. It appears that the linkage between compensated alcoholic liver disease-associated cirrhosis and HCC is medium to high risk, with the risk increasing with age and with quantity and duration of alcohol consumption and is more pronounced in females. Studies evaluating HCC risk in patients with cirrhosis associated exclusively with alcohol consumption (with no evidence of ongoing viral hepatitis infection) have suggested that the 10-year cumulative incidence may range from 6.8 to 28.7%.39Joshi K. Kohli A. Manch R. Gish R. Alcoholic liver disease: high risk or low risk for developing hepatocellular carcinoma?.Clin Liver Dis. 2016; 20: 563-580https://doi.org/10.1016/j.cld.2016.02.012Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar There is increasing evidence from observational studies suggests that DM is an important risk factor for HCC. In a systematic review of 26 case–control and cohort studies, diabetes was associated significantly with HCC in 16 studies with a pooled odds ratio of 2.5. The significant association between HCC and diabetes was independent of alcohol use or viral hepatitis.40El-Serag H.B. Hampel H. Javadi F. The association between diabetes and hepatocellular carcinoma: a systematic review of epidemiologic evidence.Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc. 2006; 4: 369-380https://doi.org/10.1016/j.cgh.2005.12.007Abstract Full Text Full Text PDF PubMed Scopus (558) Google Scholar Presence of diabetes mellitus has also been shown to increase the risk of HCC in patients with chronic HCV and HBV infection.19Dyal H.K. Aguilar M. 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Nonalcoholic fatty liver disease and hepatocellular carcinoma: new insights on presentation and natural history.Hepatobiliary Surg Nutr. 2017; 6: 401-403https://doi.org/10.21037/hbsn.2017.07.07Crossref PubMed Google Scholar In a recent meta-analyses, Younossi et al. reported that in patients with NAFLD, the annual incidence of HCC was 0.44 per 1000 person-years, whereas for those with NASH, the annual incidence of HCC was 5.29 per 1000 person-years.50Younossi Z.M. Koenig A.B. Abdelatif D. Fazel Y. Henry L. Wymer M. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes.Hepatol Baltim Md. 2016; 64: 73-84https://doi.org/10.1002/hep.28431Crossref PubMed Scopus (1678) Google Scholar According to a recent meta-analysis, patients with autoimmune hepatitis (AIH)-related cirrhosis are at an increased risk for HCC while AIH patients without cirrhosis at index diagnosis, particularly
Summary Background Alopecia is a psychologically distressing condition. Androgenetic alopecia, which affects millions of men and women, is an androgen‐driven disorder. Here, Cuscuta reflexa Roxb is evaluated for hair growth activity in androgen‐induced alopecia. Methods Petroleum ether extract of C. reflexa was studied for its hair growth–promoting activity. Alopecia was induced in albino mice by testosterone administration for 20 days. Its inhibition by simultaneous administration of extract was evaluated using follicular density, anagen/telogen ratio, and microscopic observation of skin sections. To investigate the mechanism of observed activity, in vitro experiments were performed to study the effect of extract and its major component on activity of 5α‐reductase enzyme. Results Petroleum ether extract of C. reflexa exhibited promising hair growth–promoting activity as reflected from follicular density, anagen/telogen ratio, and skin sections. Inhibition of 5α‐reductase activity by extract and isolate suggest that the extract reversed androgen‐induced alopecia by inhibiting conversion of testosterone to dihydrotestosterone. Conclusions The petroleum ether extract of C. reflexa and its isolate is useful in treatment of androgen‐induced alopecia by inhibiting the enzyme 5α‐reductase.
Information on the antiviral treatment (pegylated interferon plus ribavirin) of chronic infection by hepatitis C virus (HCV) in patients on long-term dialysis is extremely limited. We evaluated the efficacy and safety of combination antiviral therapy (pegylated interferon plus ribavirin) in patients on long-term dialysis with chronic hepatitis C by performing a systematic review of the literature with a meta-analysis of clinical studies. The primary outcome was sustained virological response (SVR) (as a measure of efficacy); the secondary outcome was dropout rate (as a measure of tolerability). We used the random-effects model of DerSimonian and Laird, with heterogeneity and sensitivity analyses. We identified eleven clinical studies (287 unique patients), two of them being controlled clinical trials. The summary estimate for SVR and dropout rate was 0.60 (95% Confidence Intervals, 0.47; 0.71) and 0.18 (95% CI, 0.08; 0.35), respectively; studies being heterogeneous with regard to both the outcomes. Stratified analysis reported a higher SVR rate in controlled trials, 0.86 (95% CI, 0.27; 0.99). The most common sources of dropout were anaemia (11/46 = 23%) and infections (6/46 = 13%). Meta-regression analysis showed a detrimental impact of HCV genotype 1 (P = 0.036) and dropout (P = 0.0001) rate upon the frequency of SVR. Antiviral therapy based on pegylated interferon plus ribavirin for HCV gives encouraging results in terms of efficacy and safety among patients on long-term dialysis; such approach should be considered the current standard of care for HCV-infected individuals on regular dialysis.
Chronic administration of cannabis extract (14 mg/kg body wt for 90 days) caused testicular lesions resulting in mass atrophy of the spermatogenic elements. RNA, protein and sialic acid contents of the testes and epididy-mides were reduced; whereas the alkaline phosphatase and cholesterol contents of the testes were elevated. Liver glycogen and adrenal ascorbic acid contents were low. Degranulation and vacuolization of hepatocytoplasm was conspicuous which was further reflected in elevated transaminases, bilirubin, NEFA, phospholipids, free and total cholesterol. Serum protein, alkaline and acid phosphatase, triglycerides, blood sugar, blood urea and creatinine phosphate levels were in normal range. Hematological studies did not reveal any deviation from the normal range except a rise in leucocyte counts.
After the recent approval of Trastuzumab (anti-HER2 antibody) for the treatment of HER2 overexpressed Gastric Adenocarcinoma (GA), importance of HER2 testing is increasingly recognized. However, there is paucity of studies for HER2 overexpression in the Indian patients of GA. Similarly, study of p53 expression in the Indian patients of GA is infrequent.To study immunohistochemical expression of HER2 and p53 in GA biopsy samples.This was a cross-sectional observational study. The expression of HER2 and p53 by immunohistochemistry were analyzed in 50 cases of GA. The HER2 expression was scored as negative (0 and 1+), equivocal (2+), and overexpression (3+). The p53 expression was quantified as negative (0-9% tumour cells) and positive (≥10% tumour cells). The intensity of p53 expression was assessed as strong and weak.Mean age of the patients was 56.8±14.8 years. Male:female ratio was 2:1. Histological types of adenocarcinoma were intestinal (68%), diffuse (28%), and indeterminate (4%). HER2 overexpression and equivocal results were present in 10% cases, each. Overall, a positive expression of p53 was seen in 72% (strong and weak intensities: 66.7% and 33.3% cases, respectively).As compared to HER2 overexpression, a higher incidence of p53 expression was seen (10% vs.72%) in GA.
Summary Background The hepatorenal syndrome is a severe and well‐known complication of end‐stage liver disease, but its management is controversial. Recent reports have shown the efficacy of terlipressin therapy, a vasopressin analogue, in hepatorenal syndrome patients. Aim To evaluate the efficacy and safety of terlipressin in the treatment of hepatorenal syndrome. Methods We performed a systematic review of the literature with a meta‐analysis of clinical trials. The primary outcome (as a measure of efficacy) was the rate of responder patients (i.e. patients who had hepatorenal syndrome reversal after terlipressin therapy). The secondary outcomes were the rate of responders who had hepatorenal syndrome recurrence after terlipressin withdrawal, and the drop‐out rate (as a measure of tolerability). We used the random effects model of DerSimonian and Laird with heterogeneity and sensitivity analysis. Results We identified 10 clinical trials (154 unique patients); two (20.0%) were randomized, controlled trials. The pooled rate of patients who reversed hepatorenal syndrome after terlipressin therapy was 0.52 (95% CI, 0.42; 0.61), P = 0.0001; I 2 = 24.6%. The pooled frequency of responder patients who showed hepatorenal syndrome recurrence after terlipressin withdrawal was 0.55 (95% CI, 0.40; 0.69), P = 0.00001; I 2 = 44.3%. The pooled rate of patients who showed side‐effects to terlipressin therapy was 0.29 (95% CI, 0.17; 0.42), P < 0.0001, I 2 = 66.6%. The drop‐out rate was 0%. The pooled OR for mortality rate in hepatorenal syndrome patients who were not responders to terlipressin vs. responder patients was 5.746 (95% CI, 1.5; 21.9). We did not find any predictive factor of response to terlipressin therapy. Conclusions This meta‐analysis shows efficacy and safety of terlipressin in the treatment of hepatorenal syndrome. However, a significant number of responder patients relapsed after terlipressin withdrawal. Further studies are in progress to address the link between terlipressin and survival in hepatorenal syndrome patients.
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