Breakthrough hepatitis is common during lamivudine treatment for chronic hepatitis B, and usually develops before HBeAg seroconversion. We encountered a patient who received lamivudine due to acute exacerbation of chronic hepatitis B. Liver function tests became normalized gradually and HBeAg seroconversion was attained 6 months after the start of treatment. While lamivudine treatment was extended in order to ensure the response durability, breakthrough hepatitis accompanying the emergence of drug-resistant mutant (methionine-to-valine substitution at tyrosine-methionine-aspartate-aspartate motif of the HBV polymerase gene) occurred at the 10th month of therapy. G-to-A substitution at nucleotide 1896 of the precore region was detected at the same time. Our experience warrants attention in that the advocacy for additional lamivudine treatment to consolidate HBeAg seroconversion needs to be balanced against increasing risk of emerging resistant mutants.

Seroconversion

HBeAg

Hepatitis B

10.6557/gjt.200306_20(2).0004

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Pathogenesis and management of alcoholic liver cirrhosis: a review

Hepatic Medicine Evidence and Research (2010)

Jia‐Horng Kao Yi‐Wen Huang Yang

Abstract: Little is known about how alcohol causes liver disease and cirrhosis. The strongest evidence of the causality between alcohol and liver disease stems from epidemiological observations. Factors contributing to alcohol-induced fibrosis and cirrhosis include cytokines, oxidative stress, and toxic metabolites of ethanol. Patients with alcoholic cirrhosis generally have complications at diagnosis, and cirrhotic complications should be actively assessed because they are closely associated with subsequent morbidity as well as mortality. Abstinence is strictly required to prevent disease progression and is critical for eventual liver transplantation. In addition, nutritional therapy remains the mainstay of managing alcoholic cirrhosis. Keywords: alcohol, cirrhosis, complication, treatment

Pathogenesis

10.2147/hmer.s10265

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Citations (18)

Rituximab carries high risks of hepatitis B virus reactivation in hematologic and rheumatic patients with chronic or resolved hepatitis B

Journal of Gastroenterology and Hepatology (2024)

Kuan‐Chu Hou Tung‐Hung Su Chien‐Neng Kao Huei‐Ru Cheng Tai‐Chung Tseng

Abstract Background and Aim Rituximab therapy is associated with a high risk of hepatitis B virus (HBV) reactivation. We aimed to assess whether the risk of reactivation differed among various underlying diseases and between hepatitis B surface antigen (HBsAg) carriers and patients with resolved HBV infection. Methods We retrospectively analyzed patients with chronic or resolved HBV infection who received rituximab without prophylactic anti‐HBV therapy at a tertiary medical center. The risks of HBV reactivation, hepatitis, and hepatic decompensation were compared between the patients with hematologic and rheumatic diseases. Results There were 78 patients with hematologic diseases and 39 patients with rheumatic diseases included. Among them, 43 (59%) HBsAg‐positive patients and 24 (55%) patients with resolved HBV infection experienced HBV reactivation at a median of 14.6 months after rituximab therapy. After rituximab treatment, the 1‐year HBV reactivation rate among patients with hematologic and rheumatic diseases was 29% and 45% in HBsAg‐positive patients, respectively, while the rates were 38% and 17% in patients with resolved HBV infection. The reactivation risk continued to increase even 2 years after rituximab therapy and was comparable between hematologic and rheumatic patients. A higher baseline HBV DNA level (≥20 IU/mL vs <20 IU/mL) was an independent predictor for HBV reactivation (adjusted hazard ratio [aHR]: 10.9, 95% confidence interval [CI]: 1.1–107) and HBV‐associated hepatitis (aHR: 14.8, 95% CI: 1.4–158). Conclusions Rituximab therapy is associated with a 50–64% risk of HBV reactivation regardless of underlying diseases and HBsAg status. HBV DNA levels should be assessed before initiating rituximab.

Hepatitis B

10.1111/jgh.16725

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Four weeks of off-treatment follow-up is sufficient to determine virologic responses at off-treatment week 12 in patients with hepatitis C virus infection receiving pangenotypic direct-acting antivirals

Research Square (Research Square) (2024)

Chen‐Hua Liu Yu‐Ping Chang Ji‐Yuh Lee Chi-Yi Chen Wei-Yu Kao

Abstract Background: Early confirmation of sustained virologic response (SVR) or viral relapse after direct-acting antivirals (DAAs) for hepatitis C virus (HCV) infection is essential based on public health perspectives, particularly for patients with high risk of nonadherence to posttreatment follow-ups. Methods: A total of 1011 patients who achieved end-of-treatment virologic response, including 526 receiving pangenotypic DAAs, and 485 receiving genotype-specific DAAs, who had available off-treatment weeks 4 and 12 serum HCV RNA data to confirm SVR at off-treatment week 12 (SVR₁₂) or viral relapse were included in the analysis. The positive predictive value (PPV) and negative predictive value (NPV) of SVR₄ to predict patients with SVR₁₂ or viral relapse were reported. Furthermore, we analyzed the concordance rate between SVR₁₂ and SVR₂₄ in 943 patients with available SVR₂₄ data. Results: The PPV and NPV of SVR₄ to predict SVR₁₂ were 98.5% (95% confidence interval [CI]: 98.0%-98.9%) and 100% (95% CI: 66.4%-100%) in the entire population. The PPV of SVR₄ to predict SVR₁₂ in patients receiving pangenotypic DAAs was higher than those receiving genotype-specific DAAs (99.8% [95% CI: 98.9%-100%] versus 97.1% [95% CI: 96.2%-97.8%], p < 0.001). The NPVs of SVR₄ to predict viral relapse were 100%, regardless of type of DAAs. Moreover, the concordance rate between SVR₁₂ and SVR₂₄ was 100%. Conclusion: In patients with HCV who are treated with pangenotypic DAAs, an off-treatment week 4 serum HCV RNA testing is sufficient to provide an excellent prediction power of SVRor viral relapse at off-treatment week 12.

10.21203/rs.3.rs-3876749/v1

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Hepatitis B viral factors and treatment responses in chronic hepatitis B

Journal of the Formosan Medical Association (2013)

Chih‐Lin Lin Jia‐Horng Kao

Pegylated interferon

Hepatitis B

Nucleoside analogue

Entecavir

Antiviral Therapy

10.1016/j.jfma.2013.02.001

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Citations (38)

Genotypes of Hepatitis C Virus in Taiwan and the Progression of Liver Disease

Journal of Clinical Gastroenterology (1995)

Jia‐Horng Kao Pei‐Jer Chen Ming‐Yang Lai Pei‐Ming Yang Jin‐Chuan Sheu

The existence of four genotypes of hepatitis C virus (HCV) — types 1a, 1b, 2a, and 2b — has been suggested based on variations in nucleotide sequences of the core region. The aim of this study was to investigate the prevalence of HCV genotypes in chronic type C liver disease in Taiwan and correlate distinct genotypes to severity of liver disease. The genotypes of 175 patients with chronic type C liver disease were determined by a polymerase chain reaction with type-specific primers. The prevalence of each genotype in Taiwan was as follows: type 1a, n = 1 (0.6%); 1b, n = 125 (71.4%); 2a, n = 21 (12%); 2b, n = 6 (3.4%); mixed types, n = 18 (10.3%); and unclassified, n = 4 (2.3%). The demographic and clinical features were comparable between patients with different genotypes, except that the mean peak serum transaminase levels of patients with double viruses and type 1b HCV infections were significantly higher than were those of patients with type 2a virus. Moreover, type 1b HCV was more prevalent in patients with liver cirrhosis alone or with hepatocellular carcinoma. In conclusion, type 1b virus is the predominant genotype in chronic hepatitis C in Taiwan, and type 1b virus and mixed infection may trigger more severe liver disease.

Liver disease

Chronic liver disease

Hepatitis C

10.1097/00004836-199510000-00014

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Citations (53)

Benefits of long-term therapy with nucleos(t)ide analogues in treatment-naïve patients with chronic hepatitis B

Current Medical Research and Opinion (2016)

Lai Wei Jia‐Horng Kao

To assess the benefits of long-term nucleos(t)ide analogue (NA) therapy in reducing the severity and progression of liver disease in treatment-naïve patients with chronic hepatitis B (CHB).As complications of CHB, such as hepatic decompensation and hepatocellular carcinoma (HCC), take a long time to develop in patients with less advanced disease, the long-term benefits of NA therapy in such patients are more difficult to prove than short- or medium-term benefits. Thus, the recent literature was reviewed to evaluate the impact of NA therapy on the long-term outcomes of treatment-naïve CHB patients.A literature search of the MEDLINE/PubMed database was undertaken to identify studies published since 2010 of the long-term use of NAs with high potency and low drug resistance profiles in treatment-naïve CHB patients. A total of 22 studies were identified, many of which were retrospective analyses or case-control studies, as well as three meta-analyses and one systematic review.Analysis of the retrieved studies showed that long-term NA therapy in treatment-naïve CHB patients did prevent or delay the occurrence of complications, including hepatic decompensation, HCC, and liver-related death, in comparison with no treatment. However, it did not completely eliminate the risk of these complications, particularly in those with cirrhosis. Although long-term NA therapy improved the clinical status of patients with decompensated cirrhosis, the risk of cirrhotic complications including HCC, liver transplantation, and liver-related mortality remained significant in comparison with those with compensated cirrhosis.Long-term administration is generally advised in all CHB patients treated with NAs because of the high rates of virological and clinical relapse after stopping therapy. The findings of this analysis lend support to the choice of highly potent agents with a low drug resistance profile to maximize viral suppression in CHB patients and halt or delay progression to end-stage liver disease.

Decompensation

Liver disease

Hepatitis B

Chronic liver disease

10.1080/03007995.2016.1264932

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Citations (16)

Hepatitis B Virus Reactivation in Patients Receiving Interferon-Free Direct-Acting Antiviral Agents for Chronic Hepatitis C Virus Infection

Open Forum Infectious Diseases (2017)

Chen‐Hua Liu Chun‐Jen Liu Tung‐Hung Su Yu‐Jen Fang Hung‐Chih Yang

Little is known about the risk of hepatitis B virus (HBV) reactivation in patients receiving interferon (IFN)-free direct-acting antiviral agents (DAAs) for hepatitis C virus (HCV).Patients who were seropositive for HBV core antibody and who received IFN-free DAAs for HCV were enrolled. Hepatitis B virus reactivation was defined as reappearance of serum HBV deoxyribonucleic acid (DNA) ≥100 IU/mL in patients with baseline undetectable viral load, or ≥2 log10 IU/mL increase of HBV DNA in patients with baseline detectable viral load. Hepatitis B virus-related alanine aminotransferase (ALT) flare was defined as ALT ≥5 times upper limit of normal or ≥2 times of the baseline level. Hepatitis B virus-related hepatic decompensation was defined as presence of jaundice, coagulopathy, hepatic encephalopathy, or ascites.Compared with no HBV reactivation in 81 HBV surface antigen (HBsAg)-negative patients, 2 of 12 HBsAg-positive patients had HBV reactivation (0% [confidence interval {95% CI}, 0%-4.5%] vs 16.7% [95% CI, 4.7%-44.8%], P = .015). No patients had ALT flare or hepatic decompensation. Baseline HBsAg level at a cutoff value of 500 IU/mL was associated with HBV reactivation in HBsAg-positive patients. There was no HBsAg seroreversion in HBsAg-negative patients.Hepatitis B virus reactivation is limited to HBsAg-positive patients receiving IFN-free DAAs for HCV. Higher baseline HBsAg levels are associated with HBV reactivation. The risk of ALT flares or hepatic decompensation is low in these patients.

HBeAg

Hepatitis B

10.1093/ofid/ofx028

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Citations (48)

Pegylated Interferon Alfa‐2a Monotherapy for Hemodialysis Patients with Acute Hepatitis C

Clinical Infectious Diseases (2010)

Chen‐Hua Liu Cheng‐Chao Liang Chun‐Jen Liu Jou‐Wei Lin Shih‐I Chen

Hemodialysis patients are at risk of hepatitis C virus (HCV) infection. However, little is known about the efficacy and safety of pegylated interferon (IFN) therapy for hemodialysis patients with acute hepatitis C.From 2005 through 2008, 35 hemodialysis patients with acute hepatitis C who did not have spontaneous clearance of HCV by 16 weeks were treated with pegylated IFN alfa-2a at a dosage of 135 microg weekly for 24 weeks. In contrast, 7 patients with clearance of HCV by 16 weeks were under observation only. Thirty-six hemodialysis patients from 2002-2005 who had acute hepatitis C but did not receive treatment served as historical controls. The primary efficacy and safety end points were sustained virologic response (undetectable HCV RNA levels at 24 weeks after therapy) by intention-to-treat analysis and treatment-related withdrawal.The rate of sustained virologic response in the treatment group was significantly higher than the rate of spontaneous HCV clearance in the control group (88.6% vs 16.7%; P < .001). Two patients (5.7%) prematurely terminated treatment at 8 and 10 weeks because of constitutional symptoms, and both did not have sustained virologic response. All but one patient had rapid virologic response (undetectable HCV RNA levels at 4 weeks of therapy), and all patients who received >12 weeks of therapy had early and end-of-treatment virologic responses. All patients who had clearance of HCV by 16 weeks had undetectable HCV RNA levels until the end of follow-up.Pegylated IFN alfa-2a monotherapy is safe and efficacious for hemodialysis patients with acute hepatitis C. It is suggested that patients without spontaneous clearance of HCV by week 16 should receive therapy.

Pegylated interferon

Hepatitis C

10.1086/655682

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Citations (37)

Hepatitis B Virus Genotypes and Variants

Cold Spring Harbor Perspectives in Medicine (2015)

C.-L. Lin Jia‐Horng Kao

Chih-Lin Lin1,2 and Jia-Horng Kao3,4,5,6 1Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei 106, Taiwan 2Department of Psychology, National Chengchi University, Taipei 106, Taiwan 3Department of Internal Medicine, National Taiwan University Hospital, Taipei 100, Taiwan 4Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 100, Taiwan 5Hepatitis Research Center, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 100, Taiwan 6Department of Medical Research, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei 100, Taiwan Correspondence: kaojh{at}ntu.edu.tw

HBeAg

Hepatitis B

Liver disease

Seroconversion

Orthohepadnavirus

10.1101/cshperspect.a021436

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Citations (221)