Congenital viral hepatitis.Care & specialists in Italy

• •Persistently elevated ALT or AST on routine blood work without an obvious explanation
• •Unexplained fatigue lasting more than 4 weeks in someone with risk factors (injection drug use, multiple sexual partners, transfusion before 1992, healthcare exposure, birth in an endemic region)
• •Acholic (pale) stools and dark urine appearing together
• •New or worsening yellowing of the eyes or skin, especially with recent travel to a region with unsafe water
• •Vague right upper quadrant discomfort in adults with alcohol use disorder or metabolic syndrome

Diagnosis of hepatitis follows a structured pathway: confirm hepatocellular injury, identify the cause, assess severity, and characterize chronicity. Initial blood tests show elevated ALT and AST with variable bilirubin, albumin, and INR. Acute viral hepatitis typically produces ALT in the thousands; alcoholic hepatitis shows AST greater than ALT with a ratio above 2; autoimmune hepatitis shows moderate transaminase elevation with hypergammaglobulinemia. Serologic testing for each virus is essential: HAV IgM for acute hepatitis A; HBsAg, anti-HBc IgM, and anti-HBs for HBV (with HBeAg, HBV DNA, and anti-HDV in chronic disease); anti-HCV antibody followed by HCV RNA for HCV; anti-HEV IgM and HEV RNA in suspected cases. The 2020 CDC and AASLD-IDSA guidelines recommend at least one-time HBV and HCV screening for all adults, plus risk-based testing. Autoimmune hepatitis is identified by autoantibodies (ANA, ASMA, anti-LKM1, anti-LC1), elevated serum IgG, and confirmed by liver biopsy showing interface hepatitis. Acute alcoholic hepatitis is diagnosed by history (over 40 g/day for women or 60 g/day for men over several months), serum bilirubin above 3 mg/dL, and AST greater than ALT with AST under 500 IU/L. Imaging with ultrasound, transient elastography (FibroScan), or magnetic resonance elastography quantifies fibrosis non-invasively. Liver biopsy remains the gold standard for autoimmune hepatitis confirmation and for staging when non-invasive assessment is discordant. In chronic disease, twice-yearly ultrasound with alpha-fetoprotein measurement screens for hepatocellular carcinoma in cirrhotic patients and selected non-cirrhotic chronic HBV carriers.

• ✓Tenofovir disoproxil 300 mg, tenofovir alafenamide 25 mg, or entecavir 0.5-1.0 mg orally daily (chronic HBV)
• ✓Direct-acting antivirals for HCV (sofosbuvir-velpatasvir 400/100 mg daily, glecaprevir-pibrentasvir 300/120 mg daily)
• ✓Prednisolone induction with azathioprine maintenance (autoimmune hepatitis)
• ✓Prednisolone 40 mg daily for 28 days (severe alcoholic hepatitis)

Hepatitis A virus infection

Acquired by ingestion of food or water contaminated with fecal material. Outbreaks occur with contaminated produce, shellfish, or food handlers in non-vaccinated populations. The virus replicates in hepatocytes, causing T-cell-mediated injury and acute hepatitis without chronic carriage.

Hepatitis B virus infection

Transmitted by exposure to infected blood, semen, or vaginal fluids — through unprotected sex, shared needles, unsafe medical injections, mother-to-child transmission at birth, and rarely transfusion. HBV integrates and persists in hepatocytes, with chronicity rate depending heavily on age at exposure.

Hepatitis C virus infection

Transmitted predominantly by blood-to-blood contact — injection drug use, transfusion before 1992 routine screening, unsafe medical and tattoo procedures, occasional vertical and sexual transmission. Chronic infection follows in 75% of adults; without treatment, leads to cirrhosis in 15-30% over 20-30 years.

Hepatitis D, E and other viral hepatitides

Hepatitis D requires HBV surface antigen and infects only HBV-positive individuals, accelerating disease. Hepatitis E spreads by contaminated water (genotypes 1, 2) and zoonotically by pork or game meat (genotypes 3, 4). Other viruses (CMV, EBV, HSV) can cause hepatitis in immunocompromised patients.

Autoimmune attack on hepatocytes

T-cell-mediated destruction of hepatocytes driven by loss of self-tolerance and association with HLA-DR3 and HLA-DR4 in white populations. Characterized by autoantibodies, elevated IgG, and interface hepatitis on biopsy. Female predominance and bimodal age distribution (peri-adolescent and middle age).

Alcohol-related liver injury

Sustained alcohol intake (over 40 g/day in women, 60 g/day in men for years) produces steatosis, oxidative stress, and immune-mediated injury that can manifest as alcoholic hepatitis — sometimes severe and life-threatening, particularly when combined with HCV, MASLD, or HBV.

Drug- and toxin-induced liver injury

Acetaminophen overdose, antibiotics (amoxicillin-clavulanate, isoniazid), antiepileptics, statins, methotrexate, herbal preparations (kava, green tea extract, comfrey), and dietary supplements are leading causes of drug-induced liver injury. Acute presentation can resemble viral hepatitis.

Metabolic dysfunction-associated steatohepatitis (MASH)

Hepatic insulin resistance and lipotoxicity drive accumulation of free fatty acids and inflammation in hepatocytes. Now the most rapidly rising indication for liver transplant in the US and projected to overtake HCV as the leading cause of liver-related mortality.

Injection drug usemodifiable

Most important modifiable risk factor for hepatitis C transmission, accounting for over 60% of new HCV cases in high-income countries. Also raises HBV and HIV co-infection risk substantially.

Birth in an HBV-endemic regionnon-modifiable

Adults born in regions with HBV surface antigen prevalence above 2% (Asia, Africa, Pacific Islands, Eastern Europe) have prevalence rates of 5-15%. CDC recommends universal screening of all adults born in these regions.

Multiple sexual partners or unprotected sexmodifiable

Raises HBV transmission risk; lesser effect on HCV transmission except with traumatic anal intercourse or HIV co-infection. Condom use and vaccination of partners reduce risk.

Heavy alcohol usemodifiable

Daily intake over 30 g for men and 20 g for women raises risk of alcoholic hepatitis and accelerates fibrosis in any underlying liver disease. Abstinence is the single most effective intervention.

Obesity, type 2 diabetes, and metabolic syndromemodifiable

Drive metabolic dysfunction-associated steatohepatitis (MASH). Weight loss of 7-10% can reverse steatohepatitis in clinical trials.

Maternal HBV infection at birthnon-modifiable

• •Balanced Mediterranean-style diet with vegetables, fruits, whole grains, fish, and olive oil
• •Adequate protein (1.0-1.2 g/kg per day; up to 1.5 g/kg in cirrhotic patients with sarcopenia) to prevent muscle wasting
• •Coffee — 3-4 cups daily, associated with lower fibrosis progression and HCC risk in observational studies
• •Whole-grain complex carbohydrates and high-fiber foods to support glycemic control
• •Vitamin D-rich foods and supplementation to maintain 25-OH-D above 30 ng/mL

• •Alcohol in any amount with chronic hepatitis
• •Acetaminophen above 2 g daily, particularly with cirrhosis or chronic hepatitis
• •Herbal supplements (kava, green tea extract, comfrey, chaparral) which can cause drug-induced liver injury
• •Raw or undercooked shellfish, which can transmit hepatitis A and aggravate cirrhosis through vibriosis risk
• •Excessive sodium (over 2 g per day) in cirrhotic patients with ascites